November 4 - 7, 2007
Orlando, Florida, USA
INTRODUCTION
Cold-, humidity- and in general bad weather-related diseases can be easily managed by a move to warm Florida, or by taking the adequate medication indicated for each disorder. Sunny warm Orlando was again the site for the annual scientific sessions of the American Heart Association, with most hotels within the International Drive axis lodging the high number of attendees that such a major meeting attracts, and medicines for heart and vascular diseases were among the main topics discussed during the four days of oral and poster presentations.
HEART FAILURE
Besides cardiac resynchronization therapy, which has been shown to improve cardiopulmonary performance and renal function, prevent hospitalizations and improve arrhythmia-related survival with a low risk for permanent atrial fibrillation [Anand, I.S. et al., Abst 1600; Miyazaki, C. et al., Abst 1602; Madaric, J. et al., Abst 1603; Thelen, A.M. et al., Abst 1604; Shen, X. et al., Abst 1605; Miyazaki, C. et al., Abst 1606; Yuasa, T. et al., Abst 1607; Hara, T. et al., Abst 1608; Foley, P.W. et al., Abst 1609; Boerrigter, G. et al., Abst 1889; Markowitz, S.M. et al., Abst 1890; Di Biase, L. et al., Abst 1891; Di Biase, L. et al., Abst 1892; Boehmer, J. et al., Abst 1893; Gasparini, M. et al., Abst 1894; Epstein, A. et al., Abst 1895; Upadhyay, G.A. et al., Abst 1896; Adelstein, E. & Saba, S., Abst 1897; Linde, C. et al., Abst 1898; Choi, A.D. et al., Abst 2506; Tournoux, F. et al., Abst 2507; Al Chekakie, M.O. et al., Abst 2508; Lavi, N. et al., Abst 2509; Lopez-Salazar, B. et al., Abst 2711; Ishizu, T. et al., Abst 2712; Rasmusson, K.D. et al., Abst 2714; Goldman, D. et al., Abst 2716; Ridocci-soriano, F. et al., Abst 2717; Waggoner, A.D. et al., Abst 2718; van Bommel, R.J. et al., Abst 2719; Chen-Tournoux, A. et al., Abst 2720; Ellison, K.E. et al., Abst 3072; Ando, K. et al., Abst 3073; Gras, D. et al., Abst 3074; Parsai, C. et al., Abst 3075; Wang, Y.C. et al., Abst 3076; Leclercq, C. et al., Abst 3077; Umar, S. et al., Abst 3078; Ypenburg, C. et al., Abst 3079; Sridhar, A. et al., Abst 3080; Toggweiler, S. et al., Abst 3282; Miske, G. et al., Abst 3283; Ousdigian, K.T. et al., Abst 3284; Soliman, O.I. et al., Abst 3285; Furugen, A. et al., Abst 3286; Beshai, J., presented at the Late-Breaking Clinical Trials III session], a number of therapies are available to improve the overall status of patients with heart failure, including notably β-blockers but also a wide range of other medications.
While improving coronary flow reserve in patients with idiopathic dilated cardiomyopathy [Sugioka, K. et al., Abst 2083] and lowering cardiac troponin I levels and preventing myocardial damage and left ventricular dysfunction in patients with Duchenne’s muscular dystrophy [Nishizawa, T. et al., Abst 2498], experimental data with carvedilol suggested sensitization of β receptors in the myocardium through an inhibitory effect on phosphatidylinositol-3 kinase- and phosphodiesterase-4-mediated pathways [Maack, C. et al., Abst 767]. Metoprolol also showed efficacy in the overall management of patients with heart failure regardless of renal function [Ghali, J. et al., Abst 2503]. An alternative β-blocker, nebivolol proved as effective in managing symptoms of heart failure and reducing left ventricular dysfunction in 160 hypertensive subjects with chronic heart failure [Marazzi, G. et al., Abst 2499] (Fig. 1). In the case of bucindolol, the impact on cardiovascular mortality and morbidity showed dependency on β1 receptor polymorphisms, with better response in the BEST trial in the Arg389Arg gene variant carriers [White, M. et al., Abst 901]. Regarding purely mechanistic data, clenbuterol offered a profile distinct from other β2-blockers by predominantly activate Gi protein in ventricular myocytes [Siedlecka, U. et al., Abst 2492].
Fig. 1. Mean change in the New York Heart Association functional class in chronic heart failure patients treated with carvedilol or nebivolol [Marazzi, G. et al., Abst 2499].
While nesiritide was reported to improve hemodynamics during dilated cardiomyopathy in a placebo-controlled study of 20 children [Behera, S.K. et al., Abst 2555], combined with nesiritide, the vasopressin-2 receptor blocker tolvaptan enhanced urinary output and electrolyte/free water excretion more than either monotherapy in experimental models of congestive heart failure [Costello-Boerrigter, L.C. et al., Abst 1599]. On the other hand, furosemide use at emergency room in accordance with the AHA guidelines for heart failure care decreased length of stay [Faillace, R.T. et al., Abst 2710], while torasemide improved left ventricular remodeling without sympathetic nerve system activation compared to azosemide in a series of 40 patients with mild symptomatic chronic heart failure [Harada, K. et al., Abst 3396]. Use of adjunctive carperitide in patients with acute myocardial infarction and chronic kidney disease improved chronic left ventricular function [Asakura, M. et al., Abst 3381]; the drug was also reported to prevent contrast-induced nephropathy in 170 patients with chronic renal failure undergoing angiographic explorations [Morikawa, S. et al., Abst 1690]. In that respect, use of iodixanol during percutaneous coronary interventions was associated with decreased risk for contrast-induced nephropathy compared to alternative contrast agents in 12,951 patients [Eichhöfer, J. et al., Abst 1694].
Data was reported also in Orlando regarding cibenzoline, which was shown to reduce left ventricular outflow tract obstruction and improve diastolic function in 11 patients with hypertrophic obstructive cardiomyopathy [Saito, M. et al., Abst 2076]. Similarly, new results were discussed with levosimendan, which reduced mortality and low output syndrome compared to placebo in 221 patients with low ejection fraction undergoing cardiac surgery [Levin, R.L. et al., Abst 3044] and improved right ventricular function in 25 critically ill patients with cardiogenic shock after myocardial infarction [Russ, M.A. et al., Abst 3380].
Adjuvant therapies for heart failure include renin-angiotensin-aldosterone system inhibitors, in which respect candesartan induced significant regression of left ventricular hypertrophy and improved left ventricular function and exercise tolerance compared to placebo in 24 patients with nonobstructive hypertrophic cardiomyopathy [Penicka, M. et al., Abst 3392] (Fig. 2) and once- and twice-daily valsartan offered similar benefits and safety profile in the 105 patients with heart failure included in the DESTINY-HF trial [Anand, I.S. et al., Abst 3398]. However, a meta-analysis of six randomized trials did not demonstrate global benefits for angiotensin receptor blockers in heart failure patients on standard therapy, although a significant impact was noted on death/hospitalization [Rasty, S. & Vaghayenegar, M., Abst 3465]. Antagonism of aldosterone with eplerenone attenuated left ventricular remodeling after acute myocardial infarction in 100 patients with left ventricular systolic dysfunction [Weir, R.A. et al., Abst 2496]. In that respect, potassium supplementation increased hospitalization rates without affecting mortality in patients with chronic heart failure, which points to the need to maintain normopotassemia during aldosterone antagonist therapy [Ahmed, A. et al., Abst 3395]. On the other hand, the direct renin inhibitor aliskiren was shown to suppress plasma renin activity in 302 patients on β-blocker therapy [Pitt, B. et al., Abst 2491]. Statins also offered a beneficial role in the management of patients with heart failure, with improved long-term outcomes and survival even in subjects with end-stage disease [Tousoulis, D. et al., Abst 2704].
Fig. 2. Percent change in left ventricular mass at 12 months in patients treated with candesartan or placebo [Penicka, M. et al., Abst 3392].
A recombinant human brain-type natriuretic peptide-serum albumin fusion protein showed longer-lasting renal enhancing activity than native human brain natriuretic peptide in experimental animals [Chen, H.H. et al., Abst 1382]. A novel designer natriuretic peptide, a fusion peptide of C-type natriuretic peptide and the C- and N-termini of urodilatin named CU-NP, was described and characterized as effective in dose-dependently increasing natriuresis, dieresis and glomerular filtration rate, decreasing cardiac filling pressures and inhibiting the renin-angiotensin system without causing hypotension [Lee, C.Y. & Burnett, J.C., Abst 2493]. A similar fusion protein consisting of C-type natriuretic peptide and the C-terminus of Dendroaspis natriuretic peptide also showed enhanced natriuretic, diuretic, glomerular filtration rate-enhancing and cardiac-unloading activities [Lee, C.Y. et al., Abst 2495].
Through inhibition of ρ kinase, fasudil improved diastolic heart failure in hypertensive animals [Fukui, S. et al., Abst 672]. In further experimental studies, acetylcysteine attenuated cardiac hypertrophy and fibrosis while preventing arrhythmias in models of hypertrophic cardiomyopathy [Lombardi, R. et al., Abst 903]. Cardioprotection was also demonstrated in experimental animal studies with curcumin through inhibition of histone acetyltransferase [Morimoto, T. et al., Abst 1510].
Interventional strategies for specific forms of heart failure and cardiomyopathy were also discussed during the meeting in Florida. Septal ethanol ablation was reported effective against obstructive hypertrophic cardiomyopathy, although with a risk of proarrhythmia [Sorajja, P. et al., Abst 1699; Coakley, E. et al., Abst 1739; Das, S. et al., Abst 1740], and radiofrequency ablation was confirmed as a feasible approach in a number of studies reported at the meeting, including studies in atrial arrhythmia [Dickfeld, T. et al., Abst 2243; Lim, B. et al., Abst 2244; Okumura, Y. et al., Abst 2245; Sharma, A. et al., Abst 2246; Henz, B. et al., Abst 2247; Chevalier, P. et al., Abst 3375].
CORONARY ARTERY DISEASE
Medical intervention, even without percutaneous interventions, has proved effective in preventing death and major cardiovascular events in patients with stable coronary artery disease [Boden, W.E. et al., Abst 2447; Boden, W.E. et al., Abst 2449], although revascularization has brought about significant improvements in survival [Jeremias, A. et al., Abst 2448].
Aspirin has been the mainstay in primary and secondary cardioprevention, and was reported to improve coronary endothelial function even in healthy people with normal coronary arteries [Teragawa, H. et al., Abst 2042]. Clopidogrel is a further effective complement to aspirin for cardioprotection, reducing cardiovascular event rates in men and women with higher frequency of bleeding complications in women and larger reduction of myocardial infarction in women [Berger, J.S. et al., Abst 2220]. Prolonged therapy for at least one year, or even two years according to some registries, offered marked benefits in terms of cardiovascular morbidity and mortality in a number of settings, including post-drug-eluting stent implantation [Stone, G.W. et al., Abst 2357; Lasala, J.M et al., Abst 2560] with cost effective benefits [Berg, J. et al., Abst 3504], while use of clopidogrel or the time of stopping it before a coronary artery bypass graft intervention was not a risk factor for in-hospital death, massive bleeding or other adverse early outcomes [Singh, S.K. et al., Abst 3049]. In fact, subanalysis of the ACUITY trial demonstrated improved one-year outcomes in patients receiving thienopyridine at least 120 hours prior to undergoing coronary artery bypass graft surgery [Ebrahimi, R. et al., Abst 3204], although exposure to clopidogrel within five days of intervention was associated with significantly higher reoperation and major bleeding rates [Berger, J.S. et al., Abst 3221]. On the other hand, low inflammatory activity, or lower C-reactive protein levels, was suggestive of increased benefit from clopidogrel treatment, as demonstrated in a subanalysis of the CHARISMA trial [Weber, M.W. et al., Abst 3539].
Although underresponse or resistance to both aspirin and clopidogrel has been reported [Schaefer, A. et al., Abst 2041; Daniels, L.B. et al., Abst 2213; Dichiara, J. et al., Abst 2358; Wetzel, T. et al., Abst 2359; Saw, J. et al., Abst 2363; Daniels, L.B. et al., Abst 3476; Faraday, N. et al., Abst 3477], dual therapy with aspirin and clopidogrel has been extensively used for secondary prevention of cardiovascular events, with long-term follow-up data suggesting an increased likelihood for bleeding [Serebruany, V.L. et al., Abst 3478] but a risk of severe bleeding of under 2% per year [Verheugt, F.W. & Clappers, N., Abst 2040]. The antiplatelet effect of clopidogrel in patients undergoing percutaneous coronary intervention was reduced in subjects carrying the cytochrome P450 2C19*2 gene variant [Trenk, D. et al., Abst 455]. Use of higher than currently recommended doses has been advocated to overcome resistances and improve antiplatelet efficacy, improving efficacy in regards to prevention of ischemic complications without significantly increasing the risk of complications [Kalyanasundaram, A. et al., Abst 1933; Pranno, N. et al., Abst 2360; Aronow, H. et al., Abst 2361]. In that respect, high, 150-mg/day doses proved effective in maintaining platelet inhibition in some patients underresponding to standard doses [Angiolillo, D.J. et al., Abst 1032], and offered more effective platelet inhibition in patients undergoing percutaneous coronary interventions with drug-eluting stent implantation [Abu Zahra, M. et al., Abst 2828]. Alternatives do exist, as exemplified by the greater inhibition of P2Y12 receptor-dependent platelet aggregation and improved clinical outcomes with prasugrel compared to clopidogrel, even with concomitant aspirin, in 110 patients [Varenhorst, C. et al., Abst 3201; Erlinge, D. et al., Abst 3217]. However, the higher antiplatelet efficacy of prasugrel compared to clopidogrel translated into progressive reduction of ischemic events with a matching significant increase in serious bleeding in the TRITON-TIMI 38 trial [Antman, E.M. et al., presented at the Late-Breaking Clinical Trials session I] (Fig. 3). A further active alternative to clopidogrel, ticlopidine, is available, the discontinuation of which after sirolimus-eluting stent implantation was associated with poorer angiographic outcomes [Nishino, M. et al., Abst 3329], while the agent was shown to effectively prevent thrombosis in a cohort of 15,216 sirolimus-eluting stent recipients [Nakagawa, Y. et al., Abst 3343].
Fig. 3. TIMI major non-coronary artery bypass graft-related bleeding rates during 450 days of treatment with clopidogrel or prasugrel [Antman, E.M. et al., presented at the Late-Breaking Clinical Trials session I].
Triple antiplatelet therapy with cilostazol was explored in the DECLARE-DIABETES trial, in which 400 patients with diabetes undergoing drug-eluting stent implantation showed decreased angiographic stenosis and late luminal loss compared to dual therapy with aspirin and clopidogrel alone [Park, S.W. et al., Abst 2355]. However, triple antiplatelet therapies have been associated with excess bleeding complications in stent recipients, especially in those with chronic kidney disease [Uchida, Y. et al., Abst 3474].
Regarding glycoprotein IIb/IIIa inhibitors, benefits on morbidity and mortality were confirmed in patients with ST segment-elevated myocardial infarction [Kouz, R. et al., Abst 3165] and significant reductions in target vessel revascularization, but not death, were demonstrated with abciximab after primary stenting for acute myocardial infarction in a meta-analysis [Vasu, S. et al., Abst 1998], while data from an ACUITY substudy suggested better outcomes after cath lab-initiated abciximab compared to double-bolus eptifibatide [Kirtane, A.J. et al., Abst 2830], although no differences between the two strategies were noted in the EVA-AMI trial, which included 220 patients undergoing percutaneous interventions for acute ST segment-elevated myocardial infarction [Zeymer, U., presented at the Late-Breaking Clinical Trials I session]; furthermore, the BRIEF-PCI trial suggested the possibility of shortened eptifibatide infusion for uncomplicated nonemergent percutaneous coronary interventions to less than two hours without loss of effectiveness or safety concerns but reduced postprocedural bleeding [Fung, A., presented at the Late-Breaking Clinical Trials I session]. Intracoronary bolus of abciximab was reported superior to standard intravenous therapy in the LIPSIAbciximab-STEMI trial regarding infarct size, microvascular obstruction and perfusion after percutaneous intervention [Thiele, H. et al., Abst 3008]. With no differences noted between upstream tirofiban and eptifibatide regarding clinical outcomes in other subanalyses of the ACUITY trial [Kirtane, A.J. et al., Abst 3219], further analyses from the APEX-AMI trial registry confirmed the benefits of glycoprotein IIb/IIIa inhibitors on epicardial and myocardial perfusion after ST segment-elevated myocardial infarction, resulting in reduced 90-day mortality [Huber, K. et al., Abst 3007]. A further large randomized study, FINESSE, is being conducted to evaluate abciximab alone or combined with half-dose reteplase versus placebo as facilitation for percutaneous interventions [Tendera, M. et al., Abst 3009].
Looking for alternative antiplatelet strategies, the von Willebrand factor-inhibiting aptamer ARC-1779 showed feasibility and optimal pharmacokinetic and pharmacodynamic profiles in human subjects, including patients with acute myocardial infarction, offering promising new therapeutic avenues [Jilma, B. et al., Abst 2214; Gilbert, J.C. et al., Abst 3218].
Anticoagulants are useful in the acute management of coronary syndromes, and in fact triple therapy with aspirin, clopidogrel and oral anticoagulants was deemed safe during 30 days postdischarge in 427 patients with ST segment-elevated myocardial infarction initially treated with fibrinolytics [Nguyen, M.C. et al., Abst 2221], although some data pointed to higher rates of major bleeding complications [Rogacka, R. et al., Abst 2356]. Regarding oral anticoagulation, the Couma-Gen trial suggested improved warfarin initiation with a pharmacogenetic- and clinical factor-based algorithm, although without lowering the percent of out-of-range international normalized anticoagulation ratio [Anderson, J.L. et al., presented at the Late-Breaking Clinical Trials IV session]. With data suggesting common use of heparin doses outside of the recommended range in patients with high-risk non-ST segment-elevated acute coronary syndromes [Melloni, C. et al., Abst 1800], use of low-molecular-weight heparins was associated with a reduced risk of bleeding complications and prolonged survival compared to unfractionated heparin [Durand, E. et al., Abst 2218], while individual drug comparisons suggested weaker antithrombotic activity for fondaparinux compared to enoxaparin or otamixaban [Walenga, J. et al., Abst 2219]; in that respect, fondaparinux was deemed not sufficient to prevent heart catheter thrombosis in a further comparative study in 10 men, but in combination with half-therapeutic doses of heparin offered a valid strategy [Schlitt, A. et al., Abst 3205], whereas a pharmacoeconomic evaluation indicated enoxaparin to be a cost-effective strategy to reduce death and prevent myocardial reinfarction after ST segment-elevated infarction [Zhang, Z. et al., Abst 3774]. The anticoagulant bivalirudin was reported to induce negative effects on endothelial nitric oxide bioavailability through an effect on neutrophil myeloperoxidase [Rudolph, V. et al., Abst 234] and proved superior to enoxaparin with glycoprotein IIb/IIIa inhibitors in reducing death rates after acute coronary syndromes in the ACUITY trial [Manoukian, S.V. et al., Abst 2217; Mehran, R. et al., Abst 2222], while in diabetic cohorts no differences in outcomes were apparent between bivalirudin monotherapy and heparin plus glycoprotein IIb/IIIa inhibitors [Feit, F. et al., Abst 3220]. A combination of bivalirudin and eptifibatide proved superior to bivalirudin alone in inhibiting platelet reactivity [Gurbel, P. et al., Abst 2364]. However, no differences in major bleeding and 12-month outcomes were noted between bivalirudin or heparin with glycoprotein IIb/IIIa inhibitors in 1,231 patients undergoing percutaneous coronary interventions with adequately activated clotting time-targeted heparin dosing [Steinberg, D.H. et al., Abst 2831]. Among novel anticoagulants, while argatroban was confirmed effective for anticoagulation in 140 patients undergoing percutaneous coronary interventions [Roessig, L. et al., Abst 2781] (Fig. 4), mechanistic data with terutroban indicated inhibition of thromboxane A2-dependent tissue factor expression, procoagulant activity and NADP(H) oxidase activation in endothelial cells [Del Turco, S. et al., Abst 713], while eribaxaban prolonged prothrombin time and prevented thrombosis during vein stenting [McBane, R. et al., Abst 717]. The second-generation antisense oligonucleotide against prothrombin ISI-401025 also prolonged prothrombin time independently of vitamin K [Monia, B. et al., Abst 716], while the first-in-class oligonucleotide drug-antidote complex REG1 safely regulated coagulation via specific factor IXa activity [Chan, M.Y. et al., Abst 2780]. Looking for safer alternatives, the thrombin receptor blocker SCH-530348 proved safe and offered sustained inhibition of thrombin-dependent platelet aggregation [Jennings, L.K. et al., Abst 3010], while initial data with the selective Part1 blocker F-16618 suggested antithrombotic activity with minor risk of bleeding [Letienne, R. et al., Abst 526], offering activity in the prevention of vasoconstriction and restenosis after reperfusion for coronary atherosclerosis in experimental animals [Bocquet, A. et al., Abst 1030].
Fig. 4. Percent of patients undergoing percutaneous coronary interventions reaching target activated clotting time after treatment with argatroban (A) or unfractionated heparin (H) [Roessig, L. et al., Abst 2781].
An effect of ranolazine in decreasing brain natriuretic peptide levels was suggested in the MERLIN-TIMI 36 study as an explanation for the reduced morbidity and mortality in patients with non-ST segment-elevated myocardial infarction treated with the drug [Morrow, D.A. et al., Abst 1798; Mega, J.L. et al., Abst 2451]. Ranolazine also lowered ischemia as assessed by Holter monitoring [Scirica, B. et al., Abst 1799] and improved hemoglobin A1c levels in diabetic subjects and prevented new-onset diabetes [Morrow, D.A. et al., Abst 2453] (Fig. 5).
Fig. 5. Percent of diabetic patients at target hemoglobin A1c levels after treatment with ranolazine or placebo and percent of nondiabetic patients developing diabetes during treatment [Morrow, D.A. et al., Abst 2453].
With alternative mechanisms of action, trimetazidine was shown to lower mortality and the risk for hospitalization during a four-year follow-up in 61 patients with ischemic cardiomyopathy [Di Napoli, P. et al., Abst 1598], nicorandil prevented microvascular dysfunction and myocardial damage in 62 patients undergoing percutaneous coronary intervention [Hirohata, A. et al., Abst 1682] and prevented left ventricular remodeling compared to placebo when given before reperfusion to 213 patients with acute myocardial infarction [Ishii, H. et al., Abst 3161], intracoronary ticagrelor inhibited erythrocyte adenosine uptake and improved coronary blood flow after local ischemia in experimental studies [Björkman, J.A. et al., Abst 245], sarpogrelate improved vascular function, exercise tolerance, insulin resistance and long-term outcomes in diabetic patients with stable angina [Watanabe, H. et al., Abst 2452], edaravone suppressed plasma monocyte chemoattractant protein-1 production after reperfusion [Nakamura, Y. et al., Abst 2617], pexelizumab inhibited terminal but preserved proximal complement activation pathway in patients with ST segment-elevated myocardial infarction [Martel, C. et al., Abst 3216] and teprenone induced heat shock protein-70i and improved left ventricular functional recovery after experimental myocardial ischemia [Robinson, B. et al., Abst 3353]. In specific settings, low-dose hormone replacement therapy in postmenopausal women with myocardial ischemia brought about decreases in chest pain and menopausal symptoms and improved the quality of life in the WISE study [Bairey Merz, C. et al., Abst 2450]. On the contrary, glucose-insulin-potassium offered no benefit on the cardiovascular event risk after reperfusion therapy in 19,222 patients with acute myocardial infarction [Katragadda, S. et al., Abst 3734].
Regarding experimental findings, the calcium channel blocker and RyR2/FKBP12.6 complex antagonist K-201 reversed calcium abnormalities in Purkinje cells during experimental myocardial ischemia [Hirose, M. et al., Abst 489], and the interleukin-1 receptor blocker anakinra showed an effect against apoptosis during myocardial infarction [Abbate, A. et al., Abst 1324]. Sildenafil protected against ischemia-reperfusion injuries in isolated cardiomyocytes [Das, A. et al., Abst 217] and in animals lacking apolipoprotein E [Dussault, S. et al., Abst 461], improved cardiac function, suppressed cardiac hypertrophy while inhibiting protein kinase Cα translocation in animals with advanced cardiac hypertrophy [Nagayama, T. et al., Abst 318] and attenuated disease progression and improved left ventricular function in experimental ischemic cardiomyopathy [Salloum, F.N. et al., Abst 2271]; in isolated cardiomyocytes, the drug suppressed hypertrophy through inhibition of canonical transient receptor potential cation channel-6 expression [Koitabashi, N. et al., Abst 537]. Similarly, intravenous immunoglobulin attenuated reperfusion injury and remodeling in experimental models of myocardial ischemia [Ueno, K. et al., Abst 554], while a novel antifibrotic drug, FT-011 improved left ventricular function and prevented fibrosis after experimental myocardial infarction [Elsik, M. et al., Abst 562]. Prevention of ischemia/reperfusion was also obtained with thymosin β4 [Hinkel, R. et al., Abst 698] and the CYP2C9-inhibiting sulfaphenazole [Khan, M. et al., Abst 1396], while epoetin improved postresuscitation myocardial dysfunction and survival [Huang, C.H. et al., Abst 2629] prevented postischemic remodeling through an effect on the erythropoietin receptor signaling pathway [Ueda, K. et al., Abst 1061], upregulated stem cell chemoattractant gene expression, improving angiogenesis, reducing inflammation and restoring cardiac function after a myocardial infarction [Klopsch, C. et al., Abst 1063] and stimulated tetrahydrobiopterin biosynthesis through an effect on the phosphatidylinositol 3-kinase/protein kinase B signaling pathway [d’Uscio, L.V. et al., Abst 1493]. The type IIA secretory phospholipase A2 inhibitor PX-18 also proved cardioprotective against myocardial infarction, with pre- and postconditioning activity [Ockaili, R.A. et al., Abst 1554], and a study with gadolinium also suggested efficacy in limiting myocardial infarction through JAK-2 and p44 mitogen-activated protein kinase-related pathways [Nicolosi, A.C. et al., Abst 1573]. On the other hand, the 5-HT2A receptor blocker APD-791 improved coronary patency in experimental models of recurrent coronary thrombosis [Przyklenk, K. et al., Abst 1034] and the adenosine A2A receptor blocker ATL-313 reduced infarct size and prevented postinfarct left ventricular remodeling after experimental myocardial ischemia/reperfusion [Beyers, R.J. et al., Abst 3424]. On the contrary, caffeine blunted the protective effects of statins against ischemia-reperfusion injury [Abu Said, G.H. et al., Abst 1399].
Cell therapy is rapidly gaining interest as a treatment option for myocardial infarction, with experimental data suggesting feasibility and potential for cardiac [Tang, X.L. et al., Abst 207], skeletal [Idris, N.M. et al., Abst 708], bone marrow-derived [Kim, H. et al., Abst 241; Li, T.S. & Hamano, K., Abst 853; Sheikh, A.Y. et al., Abst 856; Sato, M. et al., Abst 1112; Dohmann, H. et al., Abst 1113; Zuba-Surma, E.K. et al., Abst 1276; Dai, Y. et al., Abst 1278], mesenchymal [Page, B. et al., Abst 517; Timmers, L. et al., Abst 706; Huang, J. et al., Abst 707; Suzuki, G. et al., Abst 711; Fazel, S. et al., Abst 861; Toma, C. et al., Abst 1109; Wang, T. et al., Abst 2838] and embryonic [Wojakowski, W. et al., Abst 697; Kara, R.J. et al., Abst 854; Zuba-Surma, E.K. et al., Abst 1023; Adler, E. et al., Abst 1111; Rajasingh, J. et al., Abst 1277; Schrickel, J.W. et al., Abst 1350] stem cells as well as endothelial cells cocultured with tissue-engineered cardiomyocytes [Sekine, H. et al., Abst 1854], while neural stem cells offered activity in peripheral nerve repair [Sekiguchi, H. et al., Abst 467]. Clinical feasibility has already been demonstrated with bone marrow-derived progenitor cells in patients with nonischemic dilated cardiomyopathy [Fischer-Rasokat, U. et al., Abst 699; Campos de Carvalho, A.C. et al., Abst 3401] or myocardial infarction [Koestering, M. et al., Abst 1406; Assmus, B. et al., Abst 3352; Schachinger, V. et al., Abst 3378; Koestering, M. et al., Abst 3400; Rolf, A. et al., Abst 3419; Huikuri, H.V. et al., presented at the Late-Breaking Clinical Trials IV session], although some studies failed to demonstrated an improvement in contractility [Ang, K.L., presented at the Late-Breaking Clinical Trials IV session], mesenchymal stem cells in subjects with myocardial infarction [Zambrano, J. et al., Abst 1014], autologous CD34-positive stem cells in patients with dilated cardiomyopathy awaiting a heart transplant [Vrtovec, B. et al., Abst 1860] and skeletal myoblasts in people with ischemic cardiomyopathy [Dib, N., presented at the Late-Breaking Clinical Trials IV session]. In that regard, induction of endothelial progenitor cells was demonstrated with telmisartan through activation of peroxisome proliferator-activated receptor-γ-dependent phosphatidylinositol kinase/Akt pathways [Honda, A. et al., Abst 223], while cyclophosphamide enhanced ischemia-induced endothelial progenitor cell mobilization through CD26-dependent mechanisms [Wang, C.H. et al., Abst 228]. In relation to that, enhanced cord blood CD34-positive cell differentiation towards endothelial cell was enhanced by exposure to valproate [Avitabile, D. et al., Abst 466]. Further observations reported in Orlando suggested improvements in postmyocardial infarction cardiac function, fibrosis and hyperexcitability after treatment with ivabradine [Milliez, P. et al., Abst 567].
Regarding stenting for coronary artery disease, while a special joint AHA/Japanese Cardiology Society joint symposium in which the American and Japanese perspectives presented benefits from stenting for chronic total coronary occlusion provided optimal techniques were adhered to [Kathoh O. & Rutherford, B., both presented at the Symposium CVS.86], new studies have confirmed the effectiveness of sirolimus- and paclitaxel-eluting stents [Kawamura, Y. et al., Abst 1691; Nakazawa, G. et al., Abst 1928; Suzuki, N. et al., Abst 1930; Roukoz, H. et al., Abst 2140; Moreno, R. et al., Abst 2141; Gandhavadi, M. et al., Abst 2143; van Boven, A.J. et al., Abst 2146; Schampaert, E. et al., Abst 2150; Kelbck, H. et al., Abst 2151; Silber, S. et al., Abst 2152; Turco, M.A. et al., Abst 2153; Ormiston, J.A. et al., Abst 2154; Obata, J.E. et al., Abst 2158; Inoue, K. et al., Abst 2159; Levisay, J.P. et al., Abst 2160; Mulhearn, M. et al., Abst 2161; Chacko, R.S. et al., Abst 2162; Alfonso, F. et al., Abst 2163: Chieffo, A. et al., Abst 2566; Kim, J.S. et al., Abst 2775; Roy, P. et al., Abst 2776; Sera, F. et al., Abst 2777; Awata, M. et al., Abst 2778; Nakazawa, G. et al., Abst 2824; Vaquerizo, B. et al., Abst 2978; Chieffo, A. et al., Abst 2981; Wood, F. et al., Abst 2982; Cosgrave, J. et al., Abst 3137; Roy, P. et al., Abst 3138; Dai, K. et al., Abst 3164; Shirai, S. et al., Abst 3344; Hong, Y.J. et al., Abst 3345; Carrié, D. et al., Abst 3346; Atmakuri, S.R. et al., Abst 3347; Ormiston, J.A. et al., Abst 3348; Sharma, S.K. et al., Abst 3350; Beusekom, H.M. et al., Abst 3440], with many studies reporting superiority over bare metal stents [Yachi, S. et al., Abst 1685; Marroquin, O.C. et al., Abst 2142; Daemen, J. et al., Abst 2144; Iijima, R. et al., Abst 2147; Maresta, A. et al., Abst 2148; Park, S.W. et al., Abst 2149; Nakamura, S. et al., Abst 2975; Kim, Y.H. et al., Abst 2980; Kubo, T. et al., Abst 3322; Mauri, L. et al., presented at the on Outcomes Research: Implications for Clinical Practice special session; Kimura, T. & Waksman, R., both presented at the Symposium CVS.86] (Fig. 6) and some studies suggesting an advantage for sirolimus over paclitaxel stents [Nakamura, S. et al., Abst 2164; Nakamura, S. et al., Abst 2976] (Fig. 7), although such interventions have been related with endothelial dysfunction in the distal coronary vessels [Sorop, O. et al., Abst 1424], arterial aneurysm [Yu, C.W. et al., Abst 1929] and late thrombosis [Slottow, T.L.P. et al., Abst 2561; Kim, S.H. et al., Abst 2562; Boignard, A. et al., Abst 2563; Aoki, J. et al., Abst 2564; Voudris, V. et al., Abst 2565; Shah, A.P. et al., Abst 2567; Suh, J. et al., Abst 2568], and stent fractures have not been an uncommon cause for thrombosis and restenosis [Umeda, H. et al., Abst 1926; Lee, S.Y. et al., Abst 2156] with a remarkable incidence of 28% of drug-eluting stent fractures noted at autopsy in 116 consecutive cases [Nakazawa, G. et al., Abst 1925]. Efficacy was reported in the clinical setting also with novel drug-eluting stents, including those based on zotarolimus [Drzymala, L. et al., Abst 2155; Waseda, K. et al., Abst 2157; Waseda, K. et al., Abst 2773], everolimus [Sakurai, R. et al., Abst 2770; Yamasaki, M. et al., Abst 2771], biolimus A9 [Shimohama, T. et al., Abst 2774] and, for the first time in humans, bevacizumab [Toutouzas, K. et al., Abst 3133], with possible advantages over sirolimus- and/or paclitaxel-based stents reported for the former two stents. In the experimental animal setting, initial favorable data was reported for an imatinib nanoparticle-eluting stent [Masuda, S. et al., Abst 3443]. Increased risk of stent thrombosis with drug-eluting stents was related to monocyte chemoattracting protein-1 polymorphisms, with higher likelihood in carriers of the -2578G/G variant [Hwang, S.J. et al., Abst 907]. On the other hand, drug-eluting stents have been also suggested as an approach for cerebrovascular disease [Mehta, N.J. et al., Abst 1942], and α-lipoid acid was suggested effective in inhibiting stent restenosis through an effect on vascular smooth muscle cell proliferation based on observations in experimental animals [Jeong, M.H. et al., Abst 3444].
Fig. 6. Death and combined death/myocardial infarction/revascularization rates at 2 years in drug-eluting (DESA) and bare metal (BMS) stent recipients [Mauri, L. et al., presented at the Outcomes Research: Implications for Clinical Practice special session].
Fig. 7. Major adverse cardiovascular event rates in patients receiving sirolimus- or paclitaxel-eluting stents [Nakamura, S. et al., Abst 2164].
CARDIAC ARRHYTHMIA
Although implantable cardioverter defibrillators have been proven effective against atrial fibrillation/flutter [Vyas, A.K. et al., Abst 2429], drug therapies to prevent and treat such supraventricular arrhythmias have been developed. In patients with typical atrial flutter, use of nifekalant brought about prolongations of the effective atrial refractory period without prolonging the flutter cycle length, thus facilitating flutter termination [Tanaka, Y. et al., Abst 2025], while vernakalant proved effective in converting atrial fibrillation and flutter to sinus rhythm after cardiac surgery in 190 patients compared to placebo [Kowey, P.R. et al., Abst 2860] (Fig. 8). Efficacy was also reported with amiodarone, specifically in preventing atrial fibrillation after cardiac surgery [Gu, S. et al., Abst 3250], which in contrast to sotalol equally decreased epi- and endocardial atrial fibrillation inducibility in experimental animals [Bolderman, R.W. et al., Abst 2861], and coadministration of statins, but not thiazolidinediones, further reduced the odds for atrial fibrillation in patients undergoing cardiothoracic surgery with prophylactic amiodarone [Anglade, M.W. et al., Abst 2863]. A preventive effect of statins against arrhythmia was confirmed in additional analyses [Bhavnani, S. et al., Abst 3237]. Sotalol was similarly reported effective for suppressing rhythm disorders in patients with atrial fibrillation, but was associated with an increased likelihood for life-threatening tachycardia and mortality [Konietzko, A. et al., Abst 3236]. Other options for atrial fibrillation include catheter ablation [Wazni, O.M. et al., Abst 2437; Otomo, K. et al., Abst 2438; Reddy, V.Y. et al., Abst 2439; Vogt, J. et al., Abst 2440; Augello, G. et al., Abst 2441; Bunch, T.J. et al., Abst 2442; Di Biase, L. et al., Abst 2445; Lockwood, E.E. & Nademanee, K., Abst 2446], in which regard isoproterenol proved highly sensitive and specific for inducing atrial fibrillation during the intervention [Oral, H. et al., Abst 2443]. In preclinical states of development, consistent efficacy on atrial fibrillation/flutter inducibility was reported with the gap junction modifier GAP-134 [Rossman, E.I. et al., Abst 1837].
Fig. 8. Sinus rhythm conversion rates at 90 minutes in patients treated with vernakalant or placebo [Kowey, P.R. et al., Abst 2860].
Current options for ventricular arrhythmias have been extended with the availability of the A1 receptor blocker CVT-510, which in experimental animals provided effective rate control, being as effective as digoxin and superior to metoprolol [de Haan, S. et al., Abst 2865]. Also in the experimental arena, dantrolene blocked catecholaminergic polymorphic ventricular tachycardia in animal models [Kobayashi, S. et al., Abst 2930]. Implantable defibrillators also improved survival in patients with ventricular tachyarrhythmias [Alsheikh-Ali, A.A. et al., Abst 2434].
Use of pilsicainide in patients with Brugada’ syndrome enhanced the arrhythmogenic endocardial substrate, offering a new diagnostic tool for the disorder [Fukuda, K. et al., Abst 1824].
Regarding adjuvant therapies, a meta-analysis of 133 clinical trials including 34,794 patients confirmed a role of statins in preventing ventricular tachyarrhythmias in patients with coronary artery disease or nonischemic cardiomyopathy [Shah, K. et al., Abst 2643]. The prophylactic benefit of statins in patients with a history of atrial fibrillation undergoing cardiac surgery was confirmed in a systematic review of clinical trials [Fauchier, L. et al., Abst 2864]. On the other hand, ramipril and especially valsartan were reported more effective than amlodipine in preventing recurrent atrial fibrillation due to reduction of P-wave dispersion [Fogari, R. et al., Abst 2862] (Fig. 9).
Fig. 9. Atrial fibrillation rates during 6 months of treatment with amlodipine, ramipril and valsartan [Fogari, R. et al., Abst 2862].
VALVULAR HEART DISEASE
Metoprolol decreased heart rate and systolic pressure in 25 patients with asymptomatic moderate to severe mitral regurgitation, but failed to improve regurgitant volume [Stewart, R.A. et al., Abst 3038]. On the other hand, angiotensin-converting enzyme inhibition with ramipril improved systolic left ventricular function in adults with pulmonary regurgitation and repaired Fallot’s tetralogy [Babu-Narayan, S.V. et al., Abst 3122].
CARDIAC SURGERY
While desmopressin was related to reduced blood loss during cardiac surgery compared to placebo in 150 patients submitted to cardiovascular bypass [Hajjar, L.A. et al., Abst 1853], the safety of aprotinin regarding morbidity and mortality in patients undergoing coronary artery bypass graft surgery was demonstrated in the ROOBY trial [Zenati, M. et al., Abst 1851], with additional studies suggesting higher rates of perioperative complications and intermediate mortality only in higher-risk patients [Ad, N. et al., Abst 1852]. However, aprotinin was noted to increase the risk of acute kidney injury following cardiac surgery in 106 children [Dent, C.L. et al., Abst 1920]. On the other hand, use of low-dose heparin proved safe in 70 infants undergoing cardiac surgery, but did not prevent catheter-related thrombosis and prolonged the partial thromboplastin time [Schroeder, A.R. et al., Abst 2354].
Nonsteroidal antiinflammatory drug use in 555 patients undergoing cardiothoracic surgery was associated with decreased risk for postoperative atrial fibrillation and reduced red blood cell transfusion requirements without negatively affecting the risk of myocardial infarction or stroke [Ruffin, R.T. et al., Abst 3047].
Regarding other thoracoabdominal interventions, cerebrospinal fluid drainage and naloxone were reported to decrease the risk of paraplegia in people undergoing endovascular thoracoabdominal aortic aneurysm repair surgery [Kuratani, T. et al., Abst 3052].
On the other hand, A meta-analysis of 24 studies involving a total of 3,454 patients confirmed a role of perioperative β-blockers in reducing cardiovascular events in patients undergoing high-risk noncardiac surgery [Mapakshi, N. et al., Abst 3468]. In that respect, the POISE trial suggested that metoprolol would prevent 15 myocardial infarctions, three cardiac revascularizations and seven new atrial fibrillation per 1,000 interventions, at the cost of eight extra deaths, five strokes, 53 episodes of hypotension and 42 of bradycardia [Devereaux, P.J. et al., presented at the Late-Breaking Clinical Trials IV session].
PULMONARY HYPERTENSION
Use of intravenous sildenafil was successful for controlling postoperative pulmonary hypertension in 18 children undergoing surgical repair of congenital heart disease [Fraisse, A. et al., Abst 1671]. The agent was safe and well tolerated, with optimal pharmacokinetics, in 36 critically ill neonates with persistent pulmonary hypertension [Steinhorn, R.H. et al., Abst 2768].
Nebulized iloprost inhalation was deemed safe and effective for reducing pulmonary vascular tone in patients with heart failure and elevated pulmonary vascular resistance undergoing cardiac catheterization [Baran, D. et al., Abst 1597].
However, endothelin receptor blockers have been the most actively researched compounds for the treatment of pulmonary hypertension during the last few years, with new data reported during this year’s AHA meeting suggesting safety and efficacy of sitaxsentan in patients with Eisenmenger’s syndrome [Rosenzweig, E.B. et al., Abst 2108]. In experimental animal models, synergistic activity was demonstrated with sitaxsentan and sildenafil in attenuating increases in pulmonary vein resistance and media thickness and prevent overcirculation-induced pulmonary hypertension [Rondelet, B. et al., Abst 2964].
Nicorandil attenuated pulmonary artery endothelial damage in animal models of pulmonary hypertension [Sahara, M. et al., Abst 661]. On the contrary, simvastatin alone or combined with sirolimus did not reverse monocrotaline-induced pulmonary hypertension in animal studies [McMurtry, M. et al., Abst 2298].
STROKE
Thrombolytics have been among the best studied therapies for the acute treatment of stroke, with a role in preventing thrombosis and improving revascularization now reported for fibrin-targeted streptokinase-activated nanoparticles [Marsh, J.N. et al., Abst 1943].
On the other hand, an interesting case-control analysis in 151,930 patients suggested reduced risk of stroke following influenza infection in patients treated with oseltamivir, especially in those aged over 40 years [Madjid, M. et al., Abst 2375].
In the experimental arena, anakinra attenuated the functional impairment resulting from spinal cord ischemia in experimental animals [Akuzawa, S. et al., Abst 2679], while the calpain inhibitor CEP-3453 showed neuroprotective activity after global brain ischemia [Chen, Z. et al., Abst 2837].
PERIPHERAL VASCULAR DISEASE
Scarce and sundry news on therapy for peripheral vascular diseases were reported during the AHA meeting this year in Orlando, including analysis from the 10,101 patients included in the RUTH study that demonstrated no further reduction in the risk for venous thromboembolic events by adding dual antiplatelet therapy to raloxifene [Duvernoy, C.S. et al., Abst 3114] and results of the PROVIDENCE-1 trial, which demonstrated no benefit of rifalazin in Chlamydia-seropositive patients with intermittent claudication, suggesting no role of Chlamydia pneumoniae in peripheral arterial disease [Jaff, M.R. et al., presented at the Late-Breaking Clinical Trials IV session]. On the other hand, observations in 1,435 patients confirmed the safety profile of cilostazol in patients with peripheral arterial disease [Hiatt, W.R. et al., Abst 3119], while therapeutic analysis in 93 patients on hemodialysis revealed improvements in long-term patency after transluminal angioplasty for peripheral arterial disease [Kumada, Y. et al., Abst 3312]. A role of β-blockers in preventing inflammation and lung oxygenation impairment in patients with distal-type acute aortic dissection was reported [Jo, Y. et al., Abst 3307]. On the other hand, as for coronary artery disease, autologous transplantation of peripheral blood mononuclear cells was suggested effective in patients with peripheral arterial disease [Tateno, K. et al., Abst 3319].
CARDIOVASCULAR RISK FACTORS
Hypertension
Many drugs from several drug families are currently available for the management of high blood pressure, and besides new information available for a number of compounds, as reported in the meeting and summarized below, a STITCH strategy was discussed that using low-dose combination or either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with diuretics, uptitrated if required, with the addition of a calcium channel blocker as third step and, if still not reaching target blood pressure the addition of an α- or β-blocker or spironolactone, enhanced the use and acceptance of fixed-dose combination therapies and improved blood pressure control in the family practice setting [Feldman, R.D. et al., presented at the special session on Outcomes Research: Implications for Clinical Practice].
Diuretics, and especially thiazides, continue to be the subject of clinical research as effective therapies for hypertension. In that regard, a comparative study based on data from 218,360 patient-years of treatment suggested no significant differences but a trend for better protection against acute myocardial infarction, stroke and death for chlorthalidone compared to hydrochlorothiazide [Nagge, J. & Juurlink, D.N., Abst 2118].
β-Blockers have been effective in treating hypertension and preventing hypertensive heart failure, with the effect showing strong dependence on blood pressure reduction [Bangalore, S. et al., Abst 2110]. While the activity of esmolol as a cardioplegic was suggested from studies in isolated ventricular myocytes [Fallouh, H.B. et al., Abst 1556], alprenolol conferred cardioprotection by stimulating β-arrestin-mediated epidermal growth factor receptor transactivation and antagonizing G-protein signaling [Kim, I.M. et al., Abst 1335].
Calcium channel blockers have been extensively used in the treatment of hypertension, though data from a meta-analysis of seven trials suggested an increased risk for new-onset heart failure [Shibata, M.C. et al., Abst 3397]. Among the calcium channel blockers, a favorable impact of amlodipine was reported in diabetic individuals undergoing percutaneous angioplasty for coronary artery disease, with reductions in adverse cardiovascular event rates [Yokoi, H. et al., Abst 2047] (Fig. 10), whilst the compound was shown to improve endothelial function and metabolic parameters compared to placebo in 45 hypertensive individuals [Koh, K.K. et al., Abst 3429]. Experimental data with benidipine demonstrated enhanced coronary angiogenesis and reduced left ventricular stiffness and death in hypertensive animals [Nishizawa, T. et al., Abst 1242].
Fig. 10. Major adverse cardiovascular event rates in the overall cohort and diabetic patients from the CAVEFT-Kokura trial treated with amlodipine or placebo [Yokoi, H. et al., Abst 2047].
Angiotensin-converting enzyme inhibitors were the only first-line antihypertensive drugs proved to slow the progression of aortic stenosis in subjects with high blood pressure [Wakabayashi, K. et al., Abst 2522], while also being effective in improving renal outcomes in patients undergoing coronary artery bypass graft surgery [Benedetto, U. et al., Abst 3046]. Morning administration of captopril offered stronger inhibition of the angiotensin-converting enzyme and more robust organ protection than evening administration in hypertensive animal models [Tsujino, T. et al., Abst 182]. Captopril also restored insulin sensitivity in the heart of obese animals [Tabbi-Anneni, I. et al., Abst 654], while perindopril was shown to reduce large artery stiffness and left ventricular outflow tract diameter in 17 patients with Marfan’s syndrome [Ahimastos, A.A. et al., Abst 2958], with an effect independent of renal failure in subjects with stable coronary artery disease in the EUROPA trial [Brugts, J.J. et al., Abst 3462]. In the experimental setting, ramipril was shown to retard aortic valve stenosis in experimental animal models [Ngo, D.T. et al., Abst 3034].
Angiotensin receptor blockers (ARBs) have been highly effective and well tolerated in the treatment of hypertension, and uncertainties regarding their efficacy in preventing coronary events were cleared by the results of the HIJ-CREATE study, in which a 11% reduction in the risk of major adverse cardiovascular events was demonstrated with candesartan compared no non-ARB-based therapy in 2,049 patients [Kasanuki, H., presented at the Late-Breaking Clinical Trials IV session] (Fig 11). Basic science data with candesartan demonstrated upregulation of the transcriptional regulator Yin Yang 1 leading to blockade of leukocyte-endothelial cell interaction [Ishii, H. et al., Abst 1422]. While showing activity in improving vascular failure in hypertensive chronic kidney disease [Watanabe, H. et al., Abst 2119] and preventing atrial fibrillation recurrence in hypertension more effectively than carvedilol at equihypotensive doses [Galzerano, D. et al., Abst 2521] (Fig. 12), and independently of receptor blockade, telmisartan inhibited CD4-positive lymphocyte migration through an effect on peroxisome proliferator-activated receptor-γ activity [Walcher, D. et al., Abst 1202]. Along with blood pressure-lowering activity, olmesartan increased cerebral blood flow compared to amlodipine at equiantihypertensive doses, suggesting potential in patients with a history of stroke [Matsumoto, S. et al., Abst 2114] (Fig. 13); the favorable impact of olmesartan on left ventricular remodeling during experimental hypertension-induced heart failure was enhanced by coadministration of azelnidipine [Cheng, X.W. et al., Abst 2523].
Fig. 11. Major adverse cardiovascular event rates during 4.2 years of treatment with candesartan or non-angiotensin receptor blocker-based therapies [Kasanuki, H., presented at the Late-Breaking Clinical Trials IV session].
Fig. 12. Recurrent atrial fibrillation rates in hypertensive patients treated with telmisartan or carvedilol [Galzerano, D. et al., Abst 2521].
Fig. 13. Change in cerebral blood flow after treatment with olmesartan and amlodipine at doses reducing systolic and blood pressure to the same extent [Matsumoto, S. et al., Abst 2114].
The direct renin inhibitor aliskiren is arising as a further active antihypertensive compound, with marked, dose-dependent effects on renal vasodilatation [Fisher, N.D. & Hollenberg, N.K., Abst 2520]. Also acting on the angiotensin system, the CYT006-AngQb vaccine was tested dose-dependently positive in reducing blood pressure in 72 mild to moderate hypertensive patients [Tissot, A.C., et al., Abst 2519].
Among other news related to hypertension, the mineralocorticosteroid receptor blocker eplerenone was shown to reduce inflammation biomarkers in 16 patients with hypertension [Savoia, C. et al., Abst 1626] while sapropterin lacked antihypertensive activity in patients with pretreated hypertension in the CONTROL study [Quyyumi, A. et al., Abst 2115]. On the other hand, the first-in-class cyclooxygenase-inhibiting nitric oxide donor naproxcinod showed a superior profile compared to naproxen in 131 hypertensive individuals, with consistently lower blood pressure values [Townsend, R. et al., Abst 2744].
In the experimental setting, through inhibition of aldosterone synthase, FAD-286 prolonged survival and attenuated organ damage in experimental models of hypertension [Liu, J. et al., Abst 175] while a caveolin-1 mimetic peptide prevented pulmonary artery medial and myocardial hypertrophy in animals lacking caveolin-1 [Jasmin, J.F. et al., Abst 176].
Hypercholesterolemia and atherosclerosis
Statins are the most commonly used drugs for the treatment of hypercholesterolemia, with clear benefits on atherosclerosis progression [Mizukoshi, M. et al., Abst 3324] that may be more pronounced in patients with decreased renal function [Ishizu, T. et al., Abst 389] or diabetes [Kojima, S. et al., Abst 3763], and in fact a role in lowering blood pressure [Kumaravelu, P.G. et al., Abst 2524] and improving endothelial function through renoprotective effects has been suggested based on clinical observations [Sukhija, R. et al., Abst 532]. Furthermore, while discontinuation of fluvastatin, simvastatin, pravastatin or atorvastatin during major vascular surgery in 298 patients was associated with an increased risk for perioperative cardiac events [Schouten, O. et al., Abst 185], use of statins was associated with improved outcomes in patients with or without renal impairment undergoing vascular surgery [Welten, G. et al., Abst 533] or percutaneous coronary interventions [Lipinski, M.J. et al., Abst 1592; Chan, B. et al., Abst 2043]. New analysis of trials comparing intensive versus moderate statin therapy have confirmed the benefits of intensive therapy in preventing adverse outcomes [Brilakis, E.S. et al., Abst 1515], while early therapy was associated with reduced risk of arrhythmic complications [Bunch, T.J. et al., Abst 1544], although the activity of the statins showed dependency on ABCA1 cholesterol transporter variants in the STRENGTH study, with higher LDL-cholesterol-lowering activity in carriers of the rs16936183 single-nucleotide polymorphism [Voora, D. et al., Abst 909].
While fluvastatin added to standard calcium channel blocker reduced coronary spasm in 78 patients with coronary artery disease in the CAST trial [Mizuno, Y. et al., Abst 3206], clinical data with simvastatin demonstrated reduction of adioponectin levels and insulin sensitivity [Koh, K.K. & Quon, M.J., Abst 3516] and treatment-related sleep impairment [Golomb, B.A. et al., Abst 3725] (Fig. 14), while experimental data suggested improved LDL-cholesterol lowering in carriers of alternative splicing of the hydroxymethylglutaryl-coenzyme A gene [Medina, M.W. et al., Abst 905]. Mechanistic data suggested an effect in blocking angiotensin II-induced neovascularization [Zhang, Y. et al., Abst 1036] and suppressing dendritic cell-induced myocarditis [Nobuyoshi, F. et al., Abst 1408]. The benefits demonstrated with pravastatin in the MEGA study in patients with metabolic syndrome were increased by concomitant dietary intervention, resulting in effective prevention of cardiovascular disease, whilst this particular statin markedly reduced cardiovascular event rates in hypercholesterolemic individuals with mild to moderate chronic kidney disease [Matsushima, T. et al., Abst 2373; Nakamura, H., Abst 3731]. In the experimental setting, synergy was demonstrated with pravastatin and olmesartan in preventing vascular calcification in chronic kidney disease [Iijima, K. et al., Abst 969]
Fig. 14. Placebo-adjusted change in sleep quality and sleep problems during treatment with simvastatin or pravastatin [Golomb, B.,A. et al., Abst 3725].
According to substudies from the REVERSAL trial, both atorvastatin and pravastatin significantly increased the oxidized phospholipid contents of apolipoprotein B100 and decreased immune complexes and oxidized LDL autoantibodies regardless of their effects on atheroma volume or vessel wall remodeling [Choi, S.H. et al., Abst 475]. Atorvastatin was also shown to stabilize coronary atherosclerotic plaques [Okada, K. et al., Abst 3330], improve coronary flow reserve [Hong, S.J. et al., Abst 3339], lower aortic augmentation index [Hughes, A. et al., Abst 2747], accelerate DNA repair in atherosclerosis through activation of Nbs1-dependent mechanisms [Mahmoudi, M.M. et al., Abst 780], attenuate oxidative stress and improve neuronal nitric oxide synthase activity in the brain stem during heart failure [Francis, J. et al., Abst 814], improve most if not all cardiovascular risk factor components in the metabolic syndrome [Deedwania, P. et al., Abst 3729], reduce intracerebral hemorrhage after an experimental stroke [Elewa, H.F. et al., Abst 1944], prevent structural and electrical atrial remodeling in animal models of hypertensive heart failure [Okazaki, H. et al., Abst 740], improve endothelial function in patients with established congestive heart failure [Tousoulis, D. et al., Abst 1591] and inhibit c-jun N-terminal kinase and matrix metalloproteinase expression in abdominal aortic aneurismal wall cells [Kajimoto, K. et al., Abst 1031]. Intensive, high-dose therapy offered incremental effect in preventing cardiovascular disease [Tikkanen, M. et al., Abst 2455] and also brought about slight but significant improvements in renal function in the cohort of patients with stroke or transient ischemic attack from the SPARCL trial, especially in those with concomitant type 2 diabetes [Campese, V.M. et al., Abst 2173]. However, high doses of atorvastatin were noted to induce myocardial hypertrophy in animals through an effect on adiponectin and Akt [Boodhwani, M. et al., Abst 1859].
The results from the METEOR trial demonstrated reduction of atherosclerosis progression during 12 months of treatment with rosuvastatin [Bots, M.L. et al., Abst 194; Evans, G.W. et al., Abst 3730], while the drug was shown to restore nitric oxide-dependent endothelial function in mechanistic studies through effects on peroxisome proliferator-activated receptor-γ and superoxide dismutase [Desjardins, F. et al., Abst 474]. Rosuvastatin also improved left ventricular ejection fraction and skeletal muscle revascularization in patients with chronic heart failure through an effect on circulating stem and progenitor cells, which also brought about improvements in endothelial function [Erbs, S. et al., Abst 1884]. The effect of the drug on clinical outcomes in older patients with ischemic heart disease was established in the CORONA trial, which demonstrated no significant reduction in the combined endpoint of total mortality, coronary events, sudden death or death from worsening heart failure, but did significantly reduce cardiovascular hospitalizations and heart failure hospitalizations compared to placebo [Hjalmarson, Å. et al., presented at the Late-Breaking Clinical Trials II session].
Pitavastatin was also the subject of research reported in Orlando, which suggested improvements in angiotensin II-induced cardiorenal failure in experimental animal models [Yagi, S. et al., Abst 1423].
Besides clinical data, a number of experimental findings were reported with several statins during the basic science poster presentations. Simvastatin inhibited proliferation and migration of pulmonary artery smooth muscle cells in patients with pulmonary hypertension [Nakamura, K. et al., Abst 659], while either alone or combined with simvastatin, valsartan exerted an effect in stabilizing or reducing atherosclerotic plaque inflammation in experimental animals [Chatzizisis, Y.S. et al., Abst 123]. Simvastatin, like pitavastatin, also inhibited monocyte chemotactic protein-1, -2 and -3 and CXCL-5 secretion [Yoshimura, K. et al., Abst 603]. On the other hand, pravastatin improved hypoxia-induced pulmonary hypertension via downregulation of stromal cell-derived factor-1 [Nakano, M. et al., Abst 660].
As a complement to statins, the cholesterol absorption inhibitor ezetimibe has enhanced the overall activity of statins in a number of studies, and novel data presented in Orlando suggested efficacy in improving phytosterol levels over two years in patients with homozygous sitosterolemia [Musliner, T. et al., Abst 529] and promoting macrophage to feces reverse cholesterol transport in experimental animals [Briand, F. et al., Abst 823]. The compound also showed an effect in preventing atherosclerotic plaque formation, as demonstrated in a high-field magnetic resonance imaging study in experimental animals [Dietrich, T. et al., Abst 1913]. Furthermore, a lower than usual 5-mg dose was equipotent compared to the standard 10-mg dose, offering potential savings in the management of dyslipidemia [Baruch, L. et al., Abst 3728].
Besides statins, other options for lipid intervention include notably niacin and fibrates. Among the latter, fenofibrate reduced the risk of acute coronary syndrome, silent myocardial infarction and amputation in type 2 diabetic patients in the FIELD trial [Burgess, D. et al., Abst 3693] and lowered postprandial nonesterified fatty acid and lipoprotein levels in hypertriglyceridemic individuals [Rosenson, R.S., Abst 3733]. The drug’s activity on triglycerides showed pharmacogenomic variability, with glucuronidation and hence activity depending on the UDO-glucuronosyltransferase 2B7 A327G genotype [Straka, R.J. et al., Abst 908].
Niacin induced strong, opposed effects on HDL-cholesterol and complement C3 levels [Dunbar, R.L. et al., Abst 187] and combined with simvastatin showed marked benefits on the overall lipid profile [Ballantyne, C. et al., Abst 188] (Fig. 15). Similarly, a combination of niacin with the prostaglandin D2 receptor blocker laropiprant showed robust lipid efficacy with improved flushing profile compared to niacin alone or placebo in 1,398 and 1,613 dyslipidemic individuals [Maccubbin, D. et al., Abst 191; Gleim, G. et al., Abst 683]. In that respect, a novel niacin receptor partial agonist, MK-0354, strongly improved free fatty acid levels with no benefits on LDL- or HDL-cholesterol or triglycerides [Lai, E. et al., Abst 190].
Fig. 15. Change in LDL- and HDL-cholesterol levels in patients receiving simvastatin (S) alone or combined with niacin (N) [Ballantyne, C. et al., Abst 188].
Peroxisome proliferator-activated receptor α agonists have been used in the treatment of dyslipidemia. A novel compound within the family, LY-518674 significantly elevated apolipoprotein A1 and A2 in 28 patients with metabolic syndrome [Millar, J.S. et al., Abst 681]. A novel peroxisome proliferator-activated receptor δ, GW-501516 improved the overall lipid profile and fatty acid uptake and oxidation compared to placebo in patients with metabolic syndrome [Olson, E.J. et al., Abst 676; Sprecher, D.L. et al., Abst 677] (Fig. 16).
Fig. 16. Change in lipid parameters in patients receiving GW-501516 or placebo [Olson, E.J. et al., Abst 676].
Improvements in HDL-cholesterol are the main objective of treatment with torcetrapib, a cholesteryl ester transfer protein (CETP) inhibitor that also improved plaque progression in the ILLUSTRATE trial, but resulted in a relative excess of mortality and morbidity due to unknown mechanisms [Nicholls, S.J. et al., Abst 684; Barter, P.J., presented at the Late-Breaking Clinical Trials II session], while an effect of torcetrapib in inducing blood pressure elevation was deemed independent of CETP inhibition [Forrest, M.J. et al., Abst 4020].
Without an effect on lipids, the anti-CCR2 monoclonal antibody MLN-1022 decreased C-reactive protein levels and improved inflammatory status in patients with atherosclerosis [Davidson, M. et al., Abst 874], while the CXCR3 antagonist attenuated plaque formation in LDL receptor-deficient animal models [van Wanrooij, E.J. et al., Abst 878]. A further strategy for controlling lipid and C-reactive protein levels was the squalene synthase inhibitor lapaquistat, which was well tolerated alone or combined with atorvastatin in groups of 361 and 448 subjects with primary hypercholesterolemia [Davidson, M.H. et al., Abst 193; Bays, H.E. et al., Abst 682] (Fig. 17).
Fig. 17. Change in lipid parameters in patients receiving atorvastatin combined with either lapaquistat or placebo [Davidson, M.H. et al., Abst 193].
A rise in HDL-cholesterol was the main benefit derived from treatment with the novel p38 mitogen-activated protein kinase inhibitor KC-706, as demonstrated in a double-blind trial including 115 patients [Miller, S.G. et al., Abst 680] (Fig. 18).
Fig. 18. Change in HDL-cholesterol levels in patients receiving KC-706 or placebo [Miller, S.G. et al., Abst 680].
Another therapeutic intervention demonstrated to improve triglyceride levels was ω3 fatty acid supplementation, which combined with simvastatin offered strong activity against apolipoprotein CIII, triglycerides and LDL particle size [Davidson, M. et al., Abst 192]. Furthermore, eicosapentaenoic acid supplementation was noted to suppress ventricular fibrillation in animal models of acute myocardial infarction [Tsuburaya, R. et al., Abst 3222] and prevented endothelin-1-induced cardiomyocyte hypertrophy in in vitro studies through an effect on peroxisome proliferator-activated receptor-α [Shimojo, N. et al., Abst 3660].
Novel cholesterol ester transfer protein inhibitors, including CP-800569, PF-868348, CP-524515, CP-532623, CP-532624 and MK-859, were among further putative strategies for improving dyslipidemia that are currently under preclinical investigation [Keiser, J., Abst 4021]. In additional experimental studies, the farnesoid X receptor agonist FXR-450 prevented diet-induced dyslipidemia [Evans, M.J. et al., Abst 584], the liver X receptor (LXR) ligand WAY-252623 lowered LDL-cholesterol in experimental animals [Quinet, E. et al., Abst 585] and LXR-623, another LXR ligand, showed neutral lipid effects but inhibited atherosclerosis progression [Nambi, P. et al., Abst 1453]. The apolipoprotein A1 mimetic peptide D-4F scavenged myeloperoxidase-derived hypochlorous acid [Wake, A. et al., Abst 237] and, along with other apolipoprotein A1 mimetic peptides such as L-4F, improved HDL antiinflammatory properties through binding to oxidized lipids [Van Lenten, B.J. et al., Abst 581]; the apolipoprotein 1 expression enhancer RVX-208 also improved HDL-mediated cholesterol efflux in experimental animals [Krimbou, L. et al., Abst 679], while the thyroid hormone mimetic KAT-681 promoted reverse cholesterol transport in macrophages and prevented atherosclerosis [Tancevski, I. et al., Abst 1450] and the lipoprotein-associated phospholipase A2 inhibitor darapladib attenuated coronary atherosclerosis in diabetic animals [Wilensky, R.L. et al., Abst 266]. On the other hand, the γ-secretase inhibitor LY-411575 prevented diet-induced atherosclerosis in animals through an effect on Notch signaling [Aoyama, T. et al., Abst 913].
Diabetes, impaired glucose tolerance and insulin resistance
The importance of diabetes on the cardiovascular risk profile widened with observations from the French FAST-MI registry, in which despite decreases in mortality following an acute myocardial infarction in diabetic individuals, a persistent gap compared with nondiabetic subjects was identified, so that mortality among the diabetic population in 2005 was similar to that noted among the nondiabetic population 10 years before [Danchin, N. et al., Abst 2391], while novel studies have confirmed the detrimental effects of diabetes on long-term outcomes in patients undergoing percutaneous coronary interventions for coronary artery disease, even in drug-eluting stent recipients, although treatments remained effective [Park, D.W. et al., Abst 2827]. Glucose-lowering therapies in diabetes have been associated with improved outcomes [Anselmino, M. et al., Abst 3735; Anselmino, M. et al., Abst 3736], and tight glycemic control has been reported to improve cardiovascular outcomes, with differences between individual treatment strategies, as exemplified by the lower risk of subsequent myocardial infarctions with insulin glargine compared to NPH insulin [Kosiborod, M. et al., Abst 3737].
Metformin offered cardioprotection through AMP-activated protein kinase/endothelial nitric oxide synthase-dependent pathways [Calvert, J.W. et al., Abst 1260].
Add-on thiazolidinedione therapy improved endothelial function and reduced arterial wall thickness in type 2 diabetic patients with coronary artery disease receiving statin therapy [Murakami, T. & Kokado, H., Abst 2454], but treatment was not able to reduce one-year event rates in 598 diabetic subjects undergoing percutaneous coronary intervention, according to a retrospective registry [Sheikh, A. et al., Abst 3760]. Among the thiazolidinediones, pioglitazone was shown to increase the number and function of endothelial progenitor cells in coronary artery disease patients even with normal glucose tolerance [Werner, C. et al., Abst 2046], offering significant protection against adverse cardiovascular outcomes related to benefits on the lipid profile [Nagajothi, N. et al., Abst 3732], and to protect against hypertensive cerebrovascular injuries in animals [Nakamura, T. et al., Abst 2179]. Furthermore, add-on pioglitazone significantly improved myocardial glucose utilization and myocardial blood flow in nondiabetic patients with familial combined hyperlipidemia [Leccisotti, L. et al., Abst 3304]. Use of rosiglitazone in 108 patients with type 2 diabetes lowered C-reactive protein levels, but did not significantly attenuate the frequency of rapid angiographic progression of coronary lesions [Finn, A. et al., Abst 1675]. However, a cardioprotective effect of rosiglitazone against myocardial ischemic injury was related to an effect on adiponectin [Ma, X. et al., Abst 547]; the effect was accompanied by improvements in myocardial insulin sensitivity and protection against cardiomyopathy [Bhashyam, S. et al., Abst 1507]. Improved production of adipocytokines through depression of oxidative stress was also reported with mulberry leaf [Sugimoto, M. et al., Abst 1125].
Diet has an obvious impact on the risk of developing and the course of diabetes, and supplementation of ω3 fatty acids was noted to improve insulin sensitivity in obese adolescents, although only in females [Chen, Y. et al., Abst 2366]. Vitamin E supplementation was also reported to reduce cardiovascular events in diabetic individuals with the haptoglobin 2/2 genotype [Milman, U. et al., Abst 2365].
While observational data from 38,716 women free from diabetes, cancer and cardiovascular disease revealed no benefit of low-dose aspirin in preventing type 2 diabetes [Pradhan, A. et al., Abst 3503], further experimental insights demonstrated attenuation of atherosclerosis development in hyperglycemic animals receiving daily valproate [Bowes, A.J. et al., Abst 1312].
Diet and the cardiovascular risk
In addition to salt intake and its impact on blood pressure, resulting in current recommendations of reduced dietary salt to prevent cardiovascular disease [Okuda, N. et al., Abst 3643], a number of observations regarding the cardiovascular implications of diet and dietary supplements were discussed during this year’s meeting in Orlando. As an example, while the DASH-style diet was confirmed to reduce the risk of coronary heart disease and stroke during a 22-year follow-up of 88,517 middle-aged women [Fung, T. et al., Abst 2369], use of whole grains brought about decreases in lipid risk factors, including total and small LDL particles [Mellen, P. et al., Abst 2374].
The common benefits of ω3 fatty acid intake, which reportedly lowered pulse wave velocity in obese adolescents [Dangardt, F. et al., Abst 3646], were further explored in a case-control study that suggested lower intake in heart failure patients with anxiety and depressive symptoms [Payne-Emerson, H. et al., Abst 2423]. On the contrary, higher plasma levels of ω3 polyunsaturated fatty acids was associated with a reduced risk of heart failure in women [Yamagishi, K. et al., Abst 3607]. Regarding dietary management of patients with proarrhythmic states, ω3 fatty acid supplementation was reported to reduce the risk of atrial fibrillation after a myocardial infarction [Macchia, A. et al., Abst 2367].
While moderate alcohol consumption was confirmed to improve endothelial function, rise HDL lipoprotein subclass particle levels and reduce the risk of angina within the year following an acute myocardial infarction in the PREMIER registry [Buchanan, D.M. et al., Abst 3586; Suzuki, K. et al., Abst 3644; Harriss, L.R. et al., Abst 3645], resveratrol induced mitochondrial translocation of Gsk-3β [Xi, J. et al., Abst 168] and attenuated oxidative/nitrative stress through inhibition of tumor necrosis factor-α [Zhang, H. et al., Abst 1025] offering protection against reperfusion injury in the heart. Furthermore, the benefits of red wine, now reported to increase circulating endothelial progenitor cells and improve endothelial function in obese type 2 diabetes patients [Seck, C.L. et al., Abst 3785], were extended to white wine, which also offered cardioprotection in ischemic reperfused myocardium [Thirunavukkarasu, M. et al., Abst 3714].
In the experimental arena, flavonoid-rich dark chocolate’s benefits were further confirmed with observations of acute improvements in coronary circulation in healthy adults, which were independent of effects on oxidative stress, blood pressure and lipids [Shiina, Y. et al., Abst 1747]. Similarly, flavonoids from chocolate or green tea were reported to improve lipid profiles and cardioprotective defenses in healthy volunteers [Hamed, M.S. et al., Abst 3662].
On independent grounds, high folic acid intake attenuated cardiac dysfunction during ischemia [Moens A.L. et al., Abst 3664] and given during pregnancy reduced prevalence of severe congenital heart disease, according to a registry in Quebec [Ionescu-Ittu, R. et al., Abst 1777].
Regarding adverse dietary habits, sugar-sweetened beverages increased the coronary heart disease risk in middle-aged women [Fung, T. et al., Abst 3663].
Smoking and cardiovascular disease
With no major news in the field, a randomized, placebo-controlled trial demonstrated a correlation between smoking abstinence and antibody titers after immunotherapy with a conjugate nicotine vaccine in 301 smokers [Rennard, S.I. et al., Abst 3712].
HEART TRANSPLANTATION
While tacrolimus-based immunosuppression was confirmed effective and well tolerated in preventing rejection and improving survival in patients undergoing heart transplantation, with a low risk of infections [Baran, D.A. et al., Abst 2458], tacrolimus had no negative impact on endothelial-dependent vasorelaxation and sensitivity to vasospasm, but offered beneficial effects on nitric oxide/endothelin homeostasis, decreased sensitivity to endothelin and preserved endothelial-dependent vasomotor function in experimental animals [Tepperman, E. et al., Abst 2581]. Clarithromycin effectively inhibited matrix metalloproteinase-9 activation and attenuated acute and chronic rejection of cardiac allografts in experimental animals [Suzuki, J. et al., Abst 1410].
MISCELLANEOUS
In the experimental arena, atorvastatin was demonstrated to downregulate the ρ/ρ kinase pathway, resulting in blockade of influenza virus infection [Haidari, M., et al., Abst 147].
Sulfasalazine was shown to inhibit neointimal formation through induction of heme oxygenase-1 activity via an effect on nuclear factor erythroid 2-related factor and Jnk kinase signaling mediated by attenuation of reactive oxygen radical availability [Kim, J.Y. et al., Abst 157].
Ciclosporin normalized β-adrenergic responsiveness in spontaneously hypertensive animals [MacDonnell, S.M. et al., Abst 178].
Estradiol inhibited cardiomyocyte hypertrophy through estrogen receptor-dependent mechanisms [Donaldson, C. et al., Abst 202].
Amitriptyline was noted to activate cardiac ryanodine receptors, suggesting a role in a role in the management of complex arrhythmias and sudden death [Chopra, N. et al., Abst 490].
Resveratrol inhibited coronary smooth muscle cell proliferation and restenosis in experimental animals [Khandelwal, A.R. et al., Abst 601].
Inhibition of DNA methyltransferase with azacitidine blocked angiotensin II-induced increase in blood pressure, vascular remodeling and target organ damage [Bacanamwo, M. et al., Abst 668].
Donepezil promoted angiogenesis in experimental models of limb ischemia [Kakinuma, Y. et al., Abst 819] and prevented left ventricular dysfunction after myocardial ischemia [Arikawa, M. et al., Abst 1416].
A role of icosapent in upregulating adiponectin expression in animal models was reported [Matsumoto, M., Abst 1040].
Despite offering benefits on mortality during cardiac surgery, acetylcysteine carries a risk of impaired hemostasis as demonstrated in 177 patients with preoperative renal failure [Wijeysundera, D.N. et al., Abst 1567].
A novel magnetic resonance contrast agent, BMS-753951 was described that enhanced aortic images by allowing luminal perimeter, exterior perimeter and wall area to be reliably measured [Onthank, D. et al., Abst 1914]. Another related new contrast modality described during the meeting consisted in apolipoprotein E-derived lipopeptide-containing gadolinium mixed micelles [Vucic, E. et al., Abst 1915].
While human data suggested a correlation between adrenaline levels before epinephrine administration and the incidence of postresuscitation syndrome in patients with cardiac arrest [Nishikawa, K. et al., Abst 2012], endotracheal and intravenous epinephrine were shown equieffective for cardiopulmonary resuscitation after asphyxia in experimental animals [Barber, C.A. & Wyckoff, M.H., Abst 2005]. Mechanistic data suggested α1 receptors as mediators of the reduction of cerebral perfusion brought about by epinephrine during cardiopulmonary resuscitation [Ristagno, G. et al., Abst 2839].
Doxycycline proved superior to atenolol in preventing aortic aneurysms in experimental animal models of Marfan’s syndrome, an effect that was related to activity on calcification and matrix metalloproteinases, resulting in improved aortic elastic properties [Chung, A.W. et al., Abst 2676].
Bevazicumab induced vitreal vascular endothelial cell apoptosis and increased matrix metalloproteinase levels in the platelets after intravitreal injection in patients with diabetic retinopathy [Benzerroug, M. et al., Abst 3764].
Report prepared by: X. Rabasseda, Prous Science Medical Information Department