March 29 - April 1 , 2008
Chicago, Illinois, USA
INTRODUCTION
Despite the drizzle and cold temperatures, on Sunday, on March 30, 30,000 runners and walkers lined up to participate in the 29th annual Bank of America Shamrock Shuffle across downtown Chicago, partly blocking all traffic connections between the Magnificent Mile and area hotels, and McCormick place, site of the American College of Cardiology�s annual scientific session. However, this run, which is but one more issue in cardiovascular prevention, did not impede attendees from crowding the meeting halls, wherein a major call for �Quality first� in cardiology was issued, along with suggestions on what cardiologists should do to improve cardiovascular management and offer the best treatment options to all patients. In that sense, and specifically regarding pharmacotherapy for cardiovascular disease and prevention, an independent evaluation among the poster presentations at the meeting concluded that the probability of a clinically meaningful benefit on mortality was higher for lifestyle compared to pharmacological interventions, highlighting the importance of lifestyle and education programs in modulating the cardiovascular risk [Eshaghian, S. et al., Abst 1012-138]. However, drug therapies are required both for prevention and treatment of cardiovascular disease in many patient populations, and news on that topic are summarized in the following report.
CONTENT
Heart Failure
Both beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers are indicated in the treatment of heart failure, both drug families bringing about improvements in symptoms and cardiac remodeling, resulting in better survival [Bhatt, S. et al., Abst 1009-6]. In the case of beta-blockers, preoperative treatment reduced mortality in patients with systolic heart failure undergoing coronary artery bypass graft surgery [Chiong, J.R. et al., Abst 1009-17]. Among the beta-blockers, atenolol and carvedilol seemed to be associated with reduced mortality compared to metoprolol in a comparative trial in 1,162 patients with low ejection fraction [Kapoor, J.R. & Heidenreich, P.A., Abst 1009-27] (Fig. 1), with no relationship between beta-receptor genotype and survival during treatment with carvedilol or metoprolol in further studies [Sehnert, A.J. et al., Abst 807-8]; both agents improved left ventricular function and suppressed myocardial proinflammatory cytokines during experimental ischemia [Le, D.T. et al., Abst 1003-54]. Carvedilol was further reported to prevent nitrate tolerance in subjects receiving chronic therapy with an organic nitrate [Nakahira, A. et al., Abst 1007-173]. Combination of beta-blockers with selective serotonin reuptake inhibitors further improved survival in patients with end-stage heart failure and major depression [Tousoulis, D. et al., Abst 1009-26].
Fig. 1. All cause mortality during 6 months in patients treated with atenolol, carvedilol or metoprolol [Kapoor, J.R. & Heidenreich, P.A., Abst 1009-27].
Diuretic therapy is also useful, and bolus furosemide treatment nonsignificantly shortened hospitalization compared to continuous infusion in 51 patients [Allen, L.A. et al., Abst 1009-25]. On the other hand, addition of nitroglycerin to diuretic therapy improved mortality in patients with acute decompensated heart failure and chronic kidney disease [Aziz, E.F. et al., Abst 1016-1].
Aldosterone receptor blockers have been gaining interest in the treatment of heart failure. New mechanistic experimental data suggested an impact on gene expression in the myocardium and post-myocardial infarction heart failure, with selective responsiveness in females compared to males [Kanashiro-Takeuchi, R.M. et al., Abst 1002-40].
Levosimentan is another widely recognized therapy for heart failure. New clinical observations revealed cardioprotective activity in advanced chronic heart failure patients compared to placebo [Parissis, J. et al., Abst 1009-14].
Other observations regarding treatment for heart failure included the PROTECT trial, which suggested efficacy of rolofylline in preventing worsening of renal function, delaying death or hospitalization, improving symptoms and decreasing readmission rates compared to placebo in 152 patients with acute heart failure and renal impairment [O�Connor, C.M. et al., Abst 1009-20; Massie, B.M. et al., Abst 413-7] (Figs. 2 and 3); the HORIZON-HF study, in which istaroxime improved hemodynamics and diastolic function compared to placebo in 61 patients with decompensated acute heart failure [Gheoghiade, M. et al., Abst 413-8]; and a study showing that the guanylate cyclase activator BAY-58-2667 improved cardiopulmonary hemodynamics in acutely decompensated heart failure [Lapp, H. et al., Abst 1009-8]. Meanwhile, in the ACCLAIM trial, immunomodulating therapy did not significantly improve endothelial function in patients with advanced chronic failure [Shechter, M. et al., Abst 1009-9]; however, immunosuppression offered advantages over conventional heart failure therapy against autoreactive myocarditis in the ESETCID study [Maisch, B. et al., Abst 1023-10]. Treatment with the isosorbide dinitrate/hydralazine fixed combination lowered blood pressure in patients with diastolic heart failure, without offering benefits on cardiac remodeling [Wilson, R.M. et al., Abst 1002-12]. Further studies suggested acute response to dysopiramide in patients with obstructive hypertrophic cardiomyopathy, with higher responses depending on age, anterior mitral valve leaflet length and resting gradient [Musat, D. et al., Abst 1016-40]. In the experimental arena, chronic sildenafil therapy modulated gene expression more efficiently in the kidneys than the heart, with a marked decrease in atrial natriuretic peptide gene expression [Huntley, B.K. et al., Abst 1002-37; Huntley, B.K. et al., Abst 1016-5], while the cardioprotective effects of the agent against ischemia/reperfusion were abrogated by parecoxib [Salloum, F.N. et al., Abst 813-4]; the apolipoprotein A1 mimetic peptide L-4F improved cardiac performance [Zhang, Z. et al., Abst 1002-39]; and the cardiac myosin activator CL-452 improved left ventricular function and reduced filling pressure in animals with left ventricular hypertrophy and heart failure [Shen, Y.T. et al., Abst 1016-4]. On the other hand, low- but not high-dose epoetin showed efficacy in animal models of nonanemic dilated cardiomyopathy [Kono, T. et al., Abst 1016-9]. On the other hand, mechanistic data with diazoxide identified ATP-dependent potassium channels as putative target for improving heart�s response to stress and calcium handling in experimental models of calcium overload-mediated cardiac dysfunction [Sagar, S. et al., Abst 1021-206].
Fig. 2. Death/heart failure hospitalization rates in patients receiving rolofylline or placebo in the PROTECT trial [Massie, B.M. et al., Abst 413-7].
Fig. 3. Improvement of dyspnea at 24 hours after treatment with KW-3902 or placebo [O�Connor, C.M. et al., Abst 1009-20].
While in human subjects improvements in heart function were obtained with bone marrow cell [van Ramshorst, J. et al., Abst 901-261] and autologous skeletal myoblast [Duckers, H. et al., Abst 2411-9] transplantation, experimental findings discussed this year in the McCormick convention center confirmed the feasibility of mesenchymal stem cell [Nakanishi, C. et al., Abst 1002-1; Pazzine, M. et al., Abst 1002-38; Hatzistergos, K.E. et al., Abst 1002-40A; Cheng, Y. et al., Abst 807-7; Kim, Y.S. et al., Abst 1003-55; Tsuji, H. et al., Abst 1003-57; Gyongyosi, M. et al., Abst 1010-43], bone marrow-derived mononuclear cell [Gyongyosi, M. et al., Abst 1030-36; Mathieu, M. et al., Abst 1003-63; Moldovan, N.I. et al., Abst 1010-47], fetal cardiomyocyte [Landa, N. et al., Abst 807-3] and adipose tissue-derived stem cell [Cai, L. et al., Abst 1010-45] therapies for heart failure. Other nonpharmacological approaches to selected forms of heart failure included percutaneous septal ablation [Welge, D. et al., Abst 1016-27] or percutaneous transvalvular endomyocardial septal cryoablation [Hynes, B. Et al., Abst 1016-28] for symptomatic hypertrophic obstructive cardiomyopathy.
Coronary Artery Disease
Primary percutaneous coronary intervention has been advocated as the best option for the treatment of some forms of acute myocardial infarction, provided quick transfer of the patient is attained [Miedema, M.D. et al., Abst 1017-67; Bair, T.L. et al., Abst 1017-68; Fosbol, E.L. et al., Abst 1017-83; Lee, L.C. et al., Abst 1017-85; Ellis, S.G. et al., Abst 806-4; Kalla, K. et al., Abst 1024-46]; however, at least in ST segment-elevated infarction, the EUROTRANSFER registry suggested an increased risk for in-hospital death when the intervention was performed during the night shift [Siudak, Z. et al., Abst 1017-54]. However, primary percutaneous intervention was associated with lower rates of heart failure, stroke and death compared to rescue percutaneous intervention [Burjonroppa, S.C. et al., Abst 1017-77].
Fibrinolytic drugs are among the most immediate therapies for patients with myocardial ischemia, and should be first-line treatment in most patients, including notably patients with prosthetic valve thrombosis [Narang, S. et al., Abst 1034-95]. Cardiogenic shock, age, intracranial hemorrhage, heart rate and lack of predischarge revascularization were identified as the main predictors of death [Giugliano, R.P. et al., Abst 1017-84].
According to the TRACS registry, upstream glycoprotein IIb/IIIa receptor blockade resulted in in-hospital mortality benefits in patients with acute coronary syndrome [Amin, A.P. et al., Abst 1017-42; Nathan, S. et al., Abst 1017-43]. Specific studies reported during this year�s meeting included the ON-TIME-2 study, which demonstrated the benefits of prehospital tirofiban in improving ST segment resolution before and after primary percutaneous interventions in patients with acute myocardial infarction [Hamm, G.W. et al., Abst 413-5]; results from the MULTISTRATEGY trial demonstrating equiefficacy for tirofiban and abciximab, both markedly reducing major adverse cardiovascular event rates after sirolimus-eluting stent implantation [Valgimigli, M. et al., Abst 2404-11] (Fig. 4); and data showing that early abciximab does not result in reduced infarct size, but increased myocardial salvage and reduced mortality after percutaneous interventions [Petronio, A.S. et al., Abst 1017-53; Rakowski, T. et al., Abst 1017-64; Mehillio, J. et al., Abst 2407-4], while intracoronary administration was suggested superior to standard intravenous bolus regarding infarct size, extent of obstruction and perfusion after primary percutaneous intervention [Thiele, H. et al., Abst 806-7]. Through a different mechanism of action, the anti-complement agent pexelizumab has also been studied in the treatment of ST segment-elevated myocardial infarction, but a substudy of the APEX-AMI trial suggested a paradoxical increase in the formation of C5b-9 with no impact on cell apoptosis [Martel, C. et al., Abst 1017-60]. On the other hand, the recombinant human interleukin-1 receptor blocker anakinra inhibited myocardial apoptosis in experimental models of myocardial infarction [Abbate, A. et al., Abst 1002-8] and improved endothelial function and coronary flow reserve through an effect on nitroxidative stress and endothelin release [Ikonomidis, I. et al., Abst 903-268].
Fig. 4. Major adverse cardiovascular event rates at 8 months in patients treated with tirofiban or abciximab [Valgimigli, M. et al., Abst 2404-11].
Prolonged dual antiplatelet therapy with aspirin and clopidogrel is the current standard in many patients with coronary artery disease, without the use of clopidogrel being a marked hemorrhagic risk in case of coronary artery bypass surgery if stopped less than five days prior to the intervention [Kim, J.H.J. et al., Abst 813-7]. While adherence to the drug as prescribed was associated with significant benefits in the risk of myocardial infarction in coronary stent bearers [Tamariz, L. et al., Abst 1026-148; Dangas, G.D. et al., Abst 2407-7] (Figs. 5 and 6), intended clopidogrel therapy duration of at least 12 months resulted in reduced all-cause mortality compared with intended duration of up to six months after drug-eluting stent implantation [Butler, M.J. et al., Abst 1033-129]. According to the EUROTRANSFER registry, early administration of clopidogrel combined with aspirin, with or without abciximab, was associated with a marked decrease in the risk of major adverse cardiovascular events in patients with ST segment-elevated myocardial infarction undergoing primary percutaneous intervention [Legutko, J. et al., Abst 1024-43] (Fig. 7), but data from 550 patients undergoing drug-eluting stent implantation revealed lower rates of major adverse cardiovascular events without excess major bleeding with warfarin, low-dose aspirin and alternate-day clopidogrel compared to standard dual therapy with daily aspirin/clopidogrel [Akhter, M.W. et al., Abst 1028-176]. Confirmation of the benefit of aspirin in the primary cardiovascular prevention in patients with diabetes was obtained in a meta-analysis including five studies in a total population of 5,594 patients [Berwanger, O. et al., Abst 1035-207], and the agent was shown to decrease wave reflections, an independent cardiovascular risk factor, in untreated hypertensive patients even over the short term [Pietri, P. et al., Abst 1035-224]. Furthermore, specific mechanistic data on clopidogrel revealed an effect in abolishing the increase of plasminogen activator inhibitor-1 after coronary stent implantation in 51 patients [Katsaros, K.M. et al., Abst 1007-214], while a mechanistic study with aspirin revealed an effect in preventing cholesterol crystallization, which could be a potential mechanism of plaque stabilization [Vedre, A. et al., Abst 1021-187].
Fig. 5. Stent-related myocardial infarction rates over a 20.3-month follow-up in patients prescribed clopidogrel who adequately or inadequately received the drug [Tamariz, L. et al., Abst 1026-148].
Fig. 6. One-year death and myocardial infarction rates in patients on and off clopidogrel after drug-eluting stent implantation [Dangas, G.D. et al., Abst 2407-7].
Fig. 7. Death, death/repeated myocardial infarction and death/repeated myocardial infarction/revascularization rates at 30 days in patients receiving aspirin alone, aspirin/clopidogrel, aspirin/abciximab or aspirin/clopidogrel/abciximab early before the procedure [Legutko, J. et al., Abst 1024-43].
Aspirin [Majeed, F. et al., Abst 1023-16; Matetzky, S. et al., Abst 1017-63; Zairis, M. et al., Abst 1024-79; Bednar, F. et al., Abst 813-5; Kassab, R.Y. et al., Abst 1031-63] and/or clopidogrel [Kim, W. et al., Abst 1010-54; Mega, J.L. et al., Abst 1017-69; Buonamici, P. et al., Abst 1024-69; Patti, G. et al., Abst 1026-155; Gladding, P.A. et al., Abst 1028-163; Gorog, D.A. et al., Abst 1028-172] resistance or underresponsiveness have been detected in a significant proportion of patients, resulting in poorer outcomes; at least with clopidogrel, better responses were noted in current smokers compared to nonsmokers, an effect that could be mediated by increased CYP1A2 activity [Desai, N.R. et al., Abst 1017-59], while higher antiplatelet activity could be obtained by using 600 mg as loading dose followed by 150 mg/day [Trenk, D. et al., Abst 1031-48; Trenk, D. et al., Abst 1031-49; Gladding, P.A. et al., Abst 1028-162; Di Sciascio, G. et al., Abst 2411-11] and also with clopidogrel, reloading with higher doses, which proved effective in the RELOAD study [Landivier, A. et al., Abst 1017-88], or with dosing adjusted to platelet monitoring using the VASP index [Bonello, L. et al., Abst 1026-135; Bonello, L. et al., Abst 2401-9]. However, data from the TRITON-TIMI 38 study suggested more rapid, consistent and greater inhibition of platelet aggregation and larger reductions in the risk for stent thrombosis with prasugrel compared to clopidogrel at the standard 300/75 mg doses [Wiviott, S.D. et al., Abst 2401-11] (Fig. 8). Novel inhibitors of platelet activation acting on the P2Y1 and P2Y12 receptors were described, including diadenosine P1,P4-tetraphosphate and some tetraphosphonate derivatives [Chang, H. et al., Abst 1007-171].
Fig. 8. Cardiovascular death/myocardial infarction/stroke and major bleeding rates over 450 days in patients receiving prasugrel or clopidogrel [Wiviott, S.D. et al., Abst 2401-11].
Bleeding complications have been related to excess heparin dosing in patients with myocardial infarction receiving fibrinolytic therapy [Wang, T.Y. et al., Abst 1017-58], and the agent has been frequently associated with thrombocytopenia, which when used for preventing venous thromboembolism prophylaxis has resulted in poorer outcomes [Wang, T.Y. et al., Abst 803-5]; however, according to a systematic Bayesian meta-analysis, low-molecular-weight heparins can achieve marked reductions in reinfarction and a marginal benefit on mortality compared to unfractionated heparin in patients with ST segment-elevated acute myocardial infarction [Lang, C. et al., Abst 1024-49]. The low-molecular-weight heparin dalteparin offered long-term benefits on cardiovascular morbidity and mortality compared to placebo in patients with acute myocardial infarction, with no benefits over unfractionated heparin [Bahekar, A.A. et al., Abst 1017-52], and bridging oral anticoagulation with low-molecular-weight heparin was successful in patients with renal failure [Omran, H. et al., Abst 1028-218]. With a different approach, use of the direct thrombin inhibitor ximelagatran attenuated the increase in soluble P-selectin levels after acute myocardial infarction compared to placebo in the ESTEEM trial [Christersson, C. et al., Abst 1024-44] (Fig. 9), while through the same mechanism of action, bivalirudin was as effective as heparin with glycoprotein IIb/IIIa inhibitors regarding ischemic events, while reducing bleeding and shortening length of hospitalization in patients with acute coronary syndromes undergoing early invasive therapy [Pinto, D.S. et al., Abst 1024-71] (Fig. 10), and specifically in patients with end-stage kidney disease undergoing percutaneous coronary interventions [Krishnamurthy, P. et al., Abst 1033-135], but in the case of troponin-negative patients undergoing percutaneous intervention for unstable angina bivalirudin did not improve the clinical benefit of unfractionated heparin, although it was associated with a significant reduction in bleeding [Kastrati, A. et al., Abst 2401-3]. Novel anticoagulants are being developed, such as the antithrombin-dependent thrombin and factor Xa inhibitor SR-123781A, which in 1,243 patients provided protection against ischemic events comparable to that of heparin combined with abciximab [Lincoff, A.M. et al., Abst 806-8] (Fig. 11) and offered protection against thromboembolic events after total hip replacement surgery in the DRIVE study comparable to that of enoxaparin [Lassen, M.R. et al., Abst 803-4] (Fig. 12). Furthermore, EP3 receptor blockade arouse as a further target for antithrombotic agents according to results with sulprostone and DG-041 [Heptinstall, S. & Hartman, D., Abst 1021-203].
Fig. 9. Change in soluble P-selectin levels at 1 week and 6 months after treatment with ximelagatran or placebo [Christersson, C. et al., Abst 1024-44].
Fig. 10. Major adverse cardiovascular event (death, myocardial infarction or urgent revascularization) and major bleeding rates in patients receiving heparin alone (with glycoprotein IIb/IIia inhibitors at the catheterization laboratory), heparin with upstream glycoprotein IIb/IIIa inhibitors, or bivalirudin monotherapy [Pinto, D.S. et al., Abst 1024-71].
Fig. 11. Combined rates of all-cause death, myocardial infarction or urgent repeat target vessel revascularization within 7 days in patients with non-ST segment-elevated acute coronary syndrome treated with SR-123781A or heparin/abciximab. Data for the full intention-to-treat population and patients undergoing percutaneous coronary intervention are shown [Lincoff, A.M. et al., Abst 806-8].
Fig. 12. Combined rates of deep vein thrombosis, symptomatic venous thromboembolism or venous thromboembolism-related death in undergoing total hip replacement surgery receiving SR-123781A or enoxaparin [Lassen, M.R. et al., Abst 803-4].
Additional reports on pharmacotherapy for coronary artery disease included a study according to which intravenous nesiritide had more rapid, stronger and longer-lasting effects on (nor)epinephrine, renin, angiotensin II and aldosterone levels than nitroglycerin in patients with acute myocardial infarction resulting in cardiac dysfunction [Fu, X. et al., Abst 1017-78], with additional data suggesting that the preserving effect of the agent on glomerular filtration rate during cardiac surgery could result in reduced dialysis and all-cause death rates [He, J. et al., Abst 1031-83]. A novel chimeric natriuretic peptide, CD-NP proved safe in a first trial in humans, while activation of natriuretic and diuretic activity was confirmed [Lee, C.Y.W. et al., Abst 1021-212]; a further vasopressin antagonist-like peptide under preclinical research, ABC-NP, also demonstrated putative aquaretic, natriuretic and cardiac unloading activity with no impact on blood pressure [Chen, H.H. et al., Abst 1021-207]. Data were presented from a controlled study in which quercetin showed cardioprotective effects accompanied by a decrease in proinflammatory activation [Kozhukhov, S. & Parkhomenko, A., Abst 1017-87]; results from the MERLIN-TIMI 36 trial suggested that ranolazine effectively reduced angina and recurrent ischemia and can significantly improve health status and quality of life in patients with coronary artery disease [Arnold, S.V. et al., Abst 1024-54; Wilson, S.R. et al., Abst 1031-45] (Fig. 13); and data from a further study demonstrated the safety and feasibility of intracoronary anisodamine to treat slow reflow after percutaneous interventions for acute myocardial infarction [Fu, X. et al., Abst 1026-152].
Fig. 13. Exercise tolerance at 8 months in patients with chronic angina receiving ranolazine or placebo [Wilson, S.R. et al., Abst 1031-45].
Regarding new and experimental findings, lavender aromatherapy was reported to improve coronary blood velocity reserve in healthy subjects [Shina, Y. et al., Abst 903-267]. In the experimental arena, the protein kinase C inhibitor KASI-9803 offered protection against reperfusion injury [Sho, E. et al., Abst 1003-86]. Novel indole and quinoline aromatic heterocyclic derivatives of nicorandil that offer preconditioning in experimental animals were presented [Andreadou, I. et al., Abst 1003-64].
The increasing interest in drug-eluting stents during the recent years continues, as reflected by the number of oral and poster presentations in Chicago confirming the feasibility, efficacy and safety of sirolimus- and paclitaxel-eluting stents [Wojakovski, W. et al., Abst 1003-88; Harada, M. et al., Abst 1010-53; Gupta, S. et al., Abst 1010-86; Berger, P.B. et al., Abst 813-8; Marketou, M. et al., Abst 1031-46; Marketou, M. et al., Abst 1031-47; Rihal, C. et al., Abst 1005-148; Singh, M. et al., Abst 1012-145; Ko, D.T. et al., Abst 1012-146; Nadar, S. et al., Abst 1026-143; Kumbhani, D.J. et al., Abst 1026-144; Park, D.W. et al., Abst 1026-150; Alidjan, F.M. et al., Abst 1026-151; Malenka, D.J. et al., Abst 1026-156; Voudris, V. et al., Abst 1033-130; Byrne, R.A. et al., Abst 1033-138; Legrand, V.M. et al., Abst 1033-139; Moreira, A. et al., Abst 1033-143; Teragawa, H. et al., Abst 1014-219; Shinke, T. et al., Abst 1014-221; Taniguchi, T. et al., Abst 1028-187; Shinke, T. et al., Abst 1028-203; Bair, T.L. et al., Abst 1036-322; Mauri, L. et al., Abst 2404-13; Roe, M.T. et al., Abst 806-8; Unverdorben, M. et al., Abst 2407-11], with effective options progressively expanding to everolimus- [Serruys, P.W. et al., Abst 1026-147; Serruys, P.W., Abst 2407-9], pimecrolimus- [Ormiston, J.A: et al., Abst 1003-62; Dawkins, K.D. et al., Abst 2902-7; Verheye, S,. et al., Abst 2407-13] and bevacizumab-eluting [Toutouzas, K. et al., Abst 1033-134] stents and a salicylate-based bioabsorbable/biodegradable coronary stent [Jabara, R. et al., Abst 2900-52]. However, the use of drug-eluting stents for non-ST segment-elevated myocardial infarction was noted to be declining over recent years [Roe, M.T. et al., Abst 806-8].
Cardiovascular Risk Factors
Hypertension
Hypertension is one of the major cardiovascular risk factors, and an extensive armamentarium of blood pressure-lowering drugs is currently available, with most drugs offering additional benefits beyond antihypertensive activity. In that respect, while a lower prescription of diuretics was significantly associated with a higher likelihood for uncontrolled blood pressure in a cohort of 4,551 patients with metabolic syndrome [Arcucci, O. et al., Abst 1028-185], new data from the LIFE study revealed a special benefit of hydrochlorothiazide in inducing regression of left ventricular hypertrophy, more so in patients receiving concomitant losartan compared to atenolol [Okin, P.M. et al., Abst 805-3] (Fig. 14). On the other hand, compared to a calcium channel blocker and an angiotensin receptor blocker, use of the beta-blocker atenolol resulted in significant reduction in adiponectin and a trend towards reduced HDL-cholesterol [Cho, Y.S. et al., Abst 1028-216] (Fig. 15), although such compounds offered survival benefits in patients with severe aortic regurgitation [Sampat, U. et al., Abst 1036-319]. Regarding calcium channel blockers, no major news were reported during the meeting, except for the superiority of amlodipine/benazepril over hydrochlorothiazide/benazepril combinations in reducing morbidity and mortality at similar blood pressure-lowering doses in 11,462 hypertensive patients [Jamerson, K. et al., Abst 407-7] (Fig. 16). On the other hand, a study was reported suggesting preserved antihypertensive activity when coadministered with nonsteroidal antiinflammatory drugs or etoricoxib, while coadministration with other antihypertensive drugs tended to result in systolic blood pressure rebound [Krum, H. et al., Abst 1036-321]. In that respect, increase in cardiovascular risk was also demonstrated with celecoxib, regardless of concomitant therapies, but the increase was highest in patients with the highest baseline risk [Solomon, S.D. et al., Abst 407-15].
Fig 14. Change in left ventricular hypertrophy (Cornell product) after 1-4 years of treatment with atenolol or losartan combined or not with hydrochlorothiazide [Okin, P.M. et al., Abst 805-3].
Fig. 15. Change in adiponectin levels after treatment with atenolol, amlodipine or candesartan [Cho, Y.S. et al., Abst 1028-216].
Fig. 16. Major adverse cardiovascular event rates during 5 years of treatment with benazepril combined with either amlodipine or hydrochlorothiazide [Jamerson, K. et al., Abst 407-7].
While overall, angiotensin-converting enzyme inhibitors were associated with reduced risk for heart failure in patients with diabetic nephropathy [Bahekar, A.A. et al., Abst 1035-175], the SOLVD study demonstrated reduced long-term cardiovascular morbidity and mortality with early enalapril therapy in patients with asymptomatic left ventricular systolic dysfunction [Jong, P. et al., Abst 1019-129], and overall angiotensin-converting enzyme inhibitors were reported to prevent aortic dilatation after an acute, type A aortic dissection [Krähenbühl, E.S. et al., Abst 1014-212 ]. In the HYVET trial the use of perindopril combined with indapamide reduced the risk of all-cause and stroke-related mortality in very elderly patients with hypertension [Beckett, R. et al., Abst 407-9]. Regarding angiotensin receptor blockers, while higher blood pressure-lowering activity was demonstrated compared with other antihypertensive drugs in monotherapy according to a primary care survey in the U.K. [Sharplin, P. et al., Abst 1028-178], losartan was demonstrated to confer protection against exercise-induced myocardial ischemia in sedentary patients with chronic stable ischemic disease [Longobardi, G. et al., Abst 1021-221], while valsartan reversed collagen formation and improved diastolic function after an acute myocardial infarction, especially when combined with spironolactone [Fu, X. et al., Abst 1028-164]. With the ONTARGET study suggesting equiefficacy but superior tolerability in lowering blood pressure and preventing cardiovascular outcomes compared to ramipril in patients with coronary artery disease or diabetes and additional cardiovascular risk factors [Yusuf, S. et al., Abst 407-5] (Fig. 17), telmisartan was shown to prevent adverse effects of anti-HIV protease inhibitors on adipocyte function, which included insulin resistance, oxidative stress and inflammation and were related to deregulation of AT1 and AT2 receptors [Boccara, F. et al., Abst 1021-205]. Also acting on the renin-angiotensin system, aliskiren provided significant control of blood pressure for over 24 hours more effectively than irbesartan or ramipril in 654 patients, even after missing one dose [Palatini, P. et al., Abst 817-8], and the ALOFT study demonstrated that addition of aliskiren to angiotensin-converting enzyme inhibitor- or angiotensin receptor blocker-based therapy decreased plasma rennin activity and induced beneficial effects on brain natriuretic peptide levels [Latini, R. et al., Abst 1028-201]. The ALLAY trial further demonstrated an effect of aliskiren in reducing left ventricular mass more effectively than losartan, with the combination of both agents offering no advantage [Solomon, S.D. et al., Abst 409-3] (Fig. 18).
Fig. 17. Cardiovascular death/myocardial infarction/stroke/heart failure-related hospitalization rates in patients receiving telmisartan or ramipril in the ONTARGET trial [Yusuf, S. et al., Abst 407-5].
Fig. 18. Change in left ventricular mass index after treatment with aliskiren and/or losartan [Solomon, S.D. et al., Abst 409-3].
On the other hand, while atrasentan demonstrated potent antihypertensive and renoprotective activity with a favorable metabolic effect in patients with multiple cardiovascular risk factors [Raichlin, E. et al., Abst 1028-192], bosentan offered benefits to patients with Eisenmenger�s syndrome similar to those demonstrated in other groups of patients with pulmonary hypertension [Iversen, K. et al., Abst 1032-117].
Hypercholesterolemia
Lipid-lowering therapy has been increasingly used in cardiovascular prevention, and statins have proved effective in preventing or regressing coronary atherosclerosis [Galla, J.M. et al., Abst 1028-170], and prior statin therapy in patients suffering from an ST segment-elevated acute myocardial infarction was associated with lower probability of plaque rupture, independently of LDL-cholesterol levels [Otsuka, F. et al., Abst 814-6]. Furthermore, adherence with such therapies has been confirmed to slow progression of atherosclerosis [Sanwar, A.B. et al., Abst 907-260]. However, statins have provided additional benefits by directly protecting the myocardium through enhanced thrombolysis [Kiyokuni, M. et al., Abst 1017-62], limiting infarct size [Bauer, T. et al., Abst 1017-66], preventing exercise-induced ventricular arrhythmias [Dewey, F.E. et al., Abst 909-270] and improving survival in patients with end-stage heart failure [Tousoulis, D. et al., Abst 1028-161]. In that respect, while both simvastatin and pravastatin were able to reduce fast-migrating LDL particles, a marker of inflammation and atherogenesis [Zhang, B. et al., Abst 1028-158], rosuvastatin induced regression of coronary artery stenosis in the ASTEROID trial [Ballantyne, C.M. et al., Abst 407-11], improved glucose homeostasis and lipid, prothrombotic and inflammatory parameters in type 2 diabetic patients in the VICTOR study, without an impact on atherosclerosis over a 12-month period [Bertrand, O.F. et al., Abst 413-4] (Fig. 19), and improved diastolic stiffness in animal models of hypertensive heart failure with preserved ejection fraction [Chang, S.A. et al., Abst 1036-305]. A major program on cholesterol control, the ORBITAL, which included 8,108 patients randomized to rosuvastatin with or without a compliance-enhancing program, confirmed the feasibility of achieving LDL-cholesterol levels under 115 mg/dl in most patients within three months [Willich, S.N. et al., Abst 1012-148]. However, statins have a plethora of pleiotropic effects extending beyond LDL-cholesterol-lowering activity. In specific instances of trials reported at the meeting, atorvastatin significantly attenuated atherosclerotic plaque inflammation [Tang, T.Y. et al., Abst 409-6], reduced oxidative stress biomarker levels in patients with metabolic syndrome [Jialal, I. et al., Abst 1014-209], inhibited hypercholesterolemia-induced glomerular proliferation and matrix production [Manca, T. et al., Abst 1014-161], attenuated bioprosthetic heart valve calcification in animal models [Rajamannan, N.M. et al., Abst 816-7] and showed efficacy as an antiischemic drug when combined with amlodipine in the DUAAL trial, through complementary mechanisms that could be at the patient�s advantage for coronary artery disease and transient myocardial ischemia [Deanfield, J. et al., Abst 1031-42]. Benefits were also reported with simvastatin, which in hypercholesterolemic patients improved endothelial function and flow-mediated vasodilatation independently of the dose, but also reduced adiponectin levels [Koh, K.K. et al., Abst 1007-172]. Reduced mortality [de Waha, A. et al., Abst 1035-228] and improvements in endothelial function [Traina, M.I. et al., Abst 1007-191] were also demonstrated in patients with stable coronary artery disease with a highly purified omega 3 fatty acid derivative. While statin therapy was associated with increased myocardial glucose uptake in chronic heart failure [Khan, B.V. et al., Abst 1009-29], administration of rosuvastatin to 39 patients with clinically stable heart failure attenuated inflammation and reduced plasma levels of myeloperoxidase [Andreou, I. et al., Abst 1009-28], an effect that was also demonstrated with atorvastatin in 61 patients and was independent of lipid changes [Greig, D. et al., Abst 1009-37]. Furthermore, the benefits of statin therapy on the cardiovascular risk profile in diabetic individuals was enhanced by coadministration of vitamin E, as suggested by the results of the ICARE placebo-controlled trial [Blum, S. et al., Abst 1021-226].
Fig. 19. Change in glycosylated hemoglobin A1c levels after 12 months of treatment with rosuvastatin or placebo in type 2 diabetic individuals [Bertrand, O.F. et al., Abst 413-4].
Fig. 20. Major cardiovascular event rates according to treatment with statins or statins plus antioxidant vitamin E [Blum, S. et al., Abst 1021-226].
Fibrates are also effective hypocholesterolemic drugs, and the novel compound ABT-335 was shown to significantly improve HDL-cholesterol and triglyceride levels when added to atorvastatin or simvastatin, the combinations offering superiority over the respective monotherapies on the atherogenic profile [Goldberg, A.C. et al., Abst 1021-222; Mohiuddin, S.M. et al., Abst 1021-223] (Figs. 21 and 22).
Fig. 21. Change in lipid levels after 12 weeks of treatment with ABT-335, atorvastatin or the combination [Goldberg, A.C. et al., Abst 1021-222].
Fig. 22. Change in lipid levels after 12 weeks of treatment with ABT-335, simvastatin or the combination [Mohiuddin, S.M. et al., Abst 1021-223].
Niacin is a further option for the treatment of dyslipidemia, with specific benefits on HDL-cholesterol and an overall cardiovascular preventive effect [Siongh, S. et al., Abst 1035-210]. However, a negative impact of niacin-induced flushing on treatment adherence has been suggested, and underuse of aspirin to prevent flushing was noted in a real-world study [Trovato, A.T. et al., Abst 1019-150]; a similar negative flushing effect was noted with the fixed niacin/laropiprant combination, although gradual uptitration of dose allowed quick attainment of effective doses with good tolerability [Koren, M.J. et al., Abst 1021-214], while both niacin monotherapy and the combination with laropiprant significantly lowered systolic and diastolic pressure in dyslipidemic individuals, without a clinically significant risk of hypotension [Bays, H. et al., Abst 1021-216] (Fig. 23). A triple combination of niacin/laropiprant and simvastatin markedly improved the atherogenic lipoprotein profile in an additional study in dyslipidemic patients [Ballantyne, C. et al., Abst 1021-217; McKenney, J. et al., Abst 1028-168] (Fig. 24).
Fig. 23. Change in systolic and diastolic pressure after 24 weeks of treatment with niacin, niacin/laropiprant or placebo [Bays, H. et al., Abst 1021-216].
Fig. 24. Percent change in lipid levels alter treatment with niacin/laropiprant, simvastatin or the triple combination [Ballantyne, C. et al., Abst 1021-217].
Ezetimibe, a cholesterol (re)absorption inhibitor, has been extensively tested for its activity in enhancing the effect of statins regarding reduction of LDL-cholesterol and other lipid and inflammatory markers, while also improving other markers of cardiovascular risk, as exemplified by results in 100 patients with established coronary artery disease, in which coadministration of ezetimibe and atorvastatin markedly improved pulse wave velocity and, hence, arterial elasticity [Deshpande, N.V. et al., Abst 1007-216] (Fig. 25). However, a double-blind, crossover trial demonstrated no direct effect of ezetimibe on endothelial function, which was improved by rosuvastatin therapy [Gounari, P. et al., Abst 1031-58] (Fig. 26), and in the ENHANCE study the coadministration of ezetimibe and simvastatin was superior to simvastatin monotherapy in improving lipid levels, but no differences in atherosclerosis progression were noted between the two therapies [Kastelein, J.J.P., Abst 404-12]. Ezetimibe/simvastatin fixed dose combination is currently available for the aggressive treatment of hypercholesterolemia, and addition of extended-release niacin further improved lipid control in type IIa/b hyperlipidemic patients with good tolerability, except for niacin-associated flushing [Fazio, S. et al., Abst 1021-215; Guyton, J.R. et al., Abst 1021-229] (Fig. 27).
Fig. 25. Percent change in carotid-femoral, heart-brachial and brachial-ankle pulse wave velocity after treatment with atorvastatin combined with ezetimibe or niacin [Deshpande, N.V. et al., Abst 1007-216].
Fig. 26. Percent change in flow mediated vasodilatation after treatment with rosuvastatin or ezetimibe [Gounari, P. et al., Abst 1031-58].
Fig. 27. Percent change in lipid and C-reactive protein levels alter treatment with ezetimibe/simvastatin, niacin or the triple combination [Fazio, S. et al., Abst 1021-215].
Additional putative strategies � experimental results with which suggest potential in the treatment of dyslipidemic atherosclerotic complications � include an antisense oligonucleotide against apolipoprotein B100 [Merki, E. et al., Abst 1014-157] and a human apolipoprotein B100-related peptide vaccine [Zhao, X. et al., Abst 1028-207]. On the other hand, despite the negative effect of torcetrapib, dalcetrapib had no impact on blood pressure in experimental animals overexpressing renin-angiotensin system-related genes [Stroes, E.S. et al., Abst 1021-204] and proved safe and well tolerated alone or combined with pravastatin, atorvastatin or simvastatin in phase II trials [Steiner, G. et al., Abst 1028-166; Stein, E.A. et al., Abst 1028-167]. On the other hand, pyridoxal, a natural metabolite of vitamin B6 with lipid- and blood-lowering activity, offered cardioprotective effects in patients undergoing high-risk coronary artery bypass graft surgery in the MEND-CABG II trial [Alexander, J.H. et al., Abst 413-3].
Non-lipid-lowering drugs may also have a role in the management of atherosclerosis and related disorders, and examples were reported during the meeting in the windy city. Darapladib, a lipoprotein-associated phospholipase A2 inhibitor, dose-dependently reduced interleukin-6 and C-reactive protein levels in patients with coronary heart disease or equivalent risk already receiving atorvastatin [Mohler, E.R. et al., Abst 1007-168] (Fig. 28). A related compound, varespladib also markedly reduced soluble phospholipase A2, LDL-cholesterol levels and inflammatory markers in adults with stable coronary artery disease [Rosenson, R.S. et al., Abst 409-8].
Fig. 28. Percent change of highly sensitive C-reactive protein and interleukin-6 levels after treatment with darapladib or placebo [Mohler, E.R. et al., Abst 1007-168].
Hyperglycemia and diabetes
While treatment with low-dose metformin in experimental animal models of heart failure improved cardiac function [Gundewar, S. et al., Abst 1002-33], in patients with type 2 diabetes and heart failure its use was associated with marked decreases in mortality and hospitalizations [Al Zadjali, M.A. et al., Abst 1009-4]. Among the sulfonylureas, glibenclamide but not glimepiride blocked the infarct size-limiting effects of pioglitazone in experimental animals [Ye, Y. et al., Abst 1003-41]. While pioglitazone enhance the HDL-cholesterol-increasing effect of niacin in patients with metabolic syndrome [Dunbar, R.L. et al., Abst 1021-228], it prevented atherosclerosis progression in patients with type 2 diabetes in the PERISCOPE trial [Nissen, S.E., Abst 407-13] (Fig. 29) and furthermore prevented neointimal proliferation and target lesion revascularization after coronary stent implantation [Takagi, T. et al., Abst 1028-174]. By increasing adiponectin levels, hence activating AMP-dependent protein kinase and preserving GLUT4 translocation, rosiglitazone helped preserve myocardial structure and function during ischemia [Poormima, I.G. et al., Abst 1002-29], although the drug has been related to edema attributable at least in part to expansion of plasma volume, with no meaningful untoward effect on cardiac structure or function [Strean, A.R. et al., Abst 1021-213]. Regarding alpha-glucosidase inhibition, acarbose showed beneficial effects on oxidative stress markers and platelet activation in 48 subjects with early type 2 diabetes [Santilli, F. et al., Abst1007-225]. New insights from live animal studies revealed a preventive effect of lipoic acid against insulin resistance and adipocyte inflammation [Sun, Q. et al., Abst 1014-158], while potentiation of insulin resistance was described with short-term exposure to air pollution [Yue, P. et al., Abst 1014-159]. Also in the experimental arena, a degradation product of glycogen-like peptide-1, GLP1do offered protection against cardiac ischemia/reperfusion injury in diabetic animals [Gundewar, S. et al., Abst 1036-311].
Fig. 29. Change in percent atheroma volume after 18 months of treatment with pioglitazone or glimepiride [Nissen, S.E., Abst 407-13].
Obesity
Visceral obesity is a major cardiovascular risk factor, and drugs for the specific treatment of obesity have been recently developed. While in the STRADIVARIUS trial rimonabant effectively improved body weight, waist circumference and the metabolic/inflammatory profile, although no benefits were noted on atheroma volume [Nissen, S.E., Abst 412-5] (Fig. 30), one-year results from a trial with taranabant were reported that demonstrated clinically meaningful weight loss and overall improvements in the metabolic profile in 1,502 obese individuals with a favorable risk:benefit profile [Gantz, I. et al., Abst 1021-220] (Fig. 31).
Fig. 30. Change in percent atheroma volume after 18 months of treatment with rimonabant or placebo [Nissen, S.E., Abst 412-5].
Fig. 31. Weight loss after 1 year of treatment with taranabant or placebo [Gantz, I. et al., Abst 1021-220].
Diet, alcohol consumption and tobacco smoking
Diet has a major impact on the cardiovascular risk. Chronic consumption of olive oil was associated with improved short-term prognosis in patients undergoing open-chest heart surgery [Sifakaki, M. et al., Abst 1031-84].
Although consumption of alcoholic beverages has a negative impact on human health, including the cardiovascular health, moderate drinkers were shown to have better post-myocardial infarction long-term outcomes compared to nondrinkers in a survey that included 1,033 patients [Lee, J.H. et al., Abst 1019-146].
Regarding smoking, ex vivo results confirmed a negative impact of cigarette smoke on clot formation, increasing fibrin cross-links and hastening clot formation and strength [Barua, R.S. et al., Abst 1007-157]. In that respect, treatment with dextromethorphan was shown to attenuate endothelial dysfunction, inflammation and oxidative stress in 40 male smoking volunteers compared to placebo [Liu, P.Y. et al., Abst 1028-175]. On the other hand, adherence to treatment with varenicline improved smoking abstinence rates, which suggested the need for patient information and discussion on adherence to improve the success with tobacco cessation interventions [Hays, J.T. et al., Abst 1032-216].
ARRHYTHMIA
Novel therapies for the treatment of arrhythmia were discussed this year at McCormick Place convention center. In that respect, a first placebo-controlled, randomized, double-blind trial with celivarone in 153 patients with implantable cardioverter defibrillators demonstrated a significant effect in preventing ventricular fibrillation/flutter episodes [Kowey, P.R. et al., Abst 1001-94] (Fig. 32). Similarly, but in the case of atrial fibrillation, vernakalant effectively recovered sinus rhythm with good tolerability in randomized, placebo-controlled trials [Vidaillet, H.J. et al., Abst 1008-101]. Regarding thrombotic prophylaxis in patients with atrial fibrillation, discontinuation of warfarin was common according to a series of 4,395 patients, with fewer INR tests, higher bleeding rates and poorer INR control, but not older age, associated with increased discontinuation rates [Fang, M.C. et al., Abst 1005-138]. In the case of children, use of warfarin for cardiac conditions was also highly unadhered to, and very few children achieved adequate anticoagulation [Todd, J., Abst 1005-141]. On the other hand, treatment with renin-angiotensin system inhibitors was shown to prevent atrial fibrillation after cardiothoracic surgery in a retrospective patient-chart study [Kalus, J.S. et al., Abst 1015-91].
Fig. 32. Cumulative incidence of ventricular arrhythmia episodes during 180 days of treatment with celivarone or placebo [Kowey, P.R. et al., Abst 1001-94].
While in patients with long QT syndrome it shortened repolarization and improved myocardial relaxation [Moss, A.J. et al., Abst 1015-93], in the experimental arena, ranolazine suppressed ectopic activity in isolated left atria [Wolkowicz, P.E. et al., Abst 1001-105], prevented ischemia-induced ST segment changes [Wang, W.Q. et al., Abst 1003-69], attenuated palmitoyl-l-carnitine-induced ventricular diastolic dysfunction [Wu, Y. et al., Abst 1003-47], increased glucose-stimulated insulin secretion [Dhalla, A.K. et al., Abst 1021-198] and reduced myocardial infarct size during experimental ischemia/reperfusion [Hale, S.L. et al., Abst 1003-60]. Long-lasting dromotropic activity was demonstrated with the adenosine A1 receptor agonist INO-8875 [Etzion, Y. et al., Abst 1001-101], while acacetin (a component of Xuelainhua, a Chinese medicine) was shown to prolong atrial refractory period and prevent atrial fibrillation [Li, G.R. et al., Abst 1001-99]. According to additional mechanistic data presented during the meeting, blockade of calcium currents with verapamil slowed propagation of ventricular fibrillation wavefronts in experimental animals [Jin, Q. et al., Abst 1001-89] and thiazolidinediones blocked cardiac ATP-dependent potassium channels and increased propensity for ischemic ventricular fibrillation [Lu, L. et al., Abst 1015-97]. Other miscellaneous observations regarding experimental electrophysiology discussed in Chicago this spring included stronger blockade of HERG potassium channels with levo- than dextromethadone [Lin, C. et al., Abst 1001-90], and an effect of highly purified omega 3 fatty acid derivatives in reducing QT dispersion without modifying corrected QT interval in patients with stable coronary artery disease [Meymandi, S.K. et al., Abst 1029-114].
Regarding nonpharmacological therapies, ablation has repeatedly been reported effective in the management of atrial fibrillation and other arrhythmias [Russo, A.M. et al., Abst 1001-113; Santinelli, V. et al., Abst 1008-94A; Vogt, J. et al., Abst 1008-110; Ernst, S. et al., Abst 1008-114; Kiser, A.C. et al., Abst 1008-115; Chun, J.K.R. et al., Abst 1015-90; Khaykin, Y. et al., Abst 1015-92], and experimental data suggested termination of ventricular fibrillation upon chemical ablation of subendocardial and Purkinje fibers [Dosdall, D.J. et al., Abst 1001-108] and prevention of paroxysmal atrial tachyarrhythmias upon cryoablation of extrinsic cardiac sympathovagal nerves [Tan, A.Y. et al., Abst 1001-106]. Cardiac resynchronization therapy and implantable defibrillator cardioverters are other commonly used antiarrhythmic approaches [Fung, J.W.H. et al., Abst 1001-112; Jhanjee, R. et al., Abst 1001-114; Lim, P. et al., Abst 802-3; Asorvatham, S.J. et al., Abst 802-4; Ching, C.K. et al., Abst 802-5; Mehmood, F. et al., Abst 1029-89; Lindsay, B. et al., Abst 1029-90; Catanzarop, J.N. et al., Abst 1029-91; Birkett, R.T. et al., Abst 1029-94; Gold, M.R. et al., Abst 1029-94A; Kaufman, C.L. et al., Abst 1030-20; Linde, C. et al., Abst 412-9], despite an established risk for complications, including mitral regurgitation, decompensated heart failure, intraventricular conduction delay and device infection [Ypenburg, C. et al., Abst 802-6; Koplan, B.A. et al., Abst 802-7; Maskoun, W. et al., Abst 1029-92; Baman, T.S. et al., Abst 1029-93].
MISCELLANEOUS
Decreased antibody responses to influenza vaccination were described in patients with heart failure [Vardeny, O. et al., Abst 1002-35].
Vincristine was shown to attenuate doxorubicin cardiotoxicity in cultured cardiac myocytes [Kanu, C. et al., Abst 1016-12]. Doxorubicin cardiotoxicity was also attenuated by endothelial progenitor cell-mediated lentiviral erythropoietin gene therapy [Park, R.K. et al., Abst 1016-35].
The cardiotoxic potential of trastuzumab was analyzed, revealing a 140% increase in the risk of cardiotoxicity [Panjrath, G.S. et al., Abst 1016-34].
Indomethacin combined with statin therapy proved feasible and effective in reducing inflammation in 55 patients with acute pericarditis [Parrinello, G. et al., Abst 1016-39].
Sildenafil was noted to improve hemodynamics during exercise in patients with Fontan circulation, resulting in higher exercise capacity [Giardini, A. et al., Abst 808-6], and along with vardenafil showed a myocardial infarction-limiting effect that was accompanied by reduction of apoptosis and improved postischemic ventricular function [Salloum, F.N. et al., Abst 1003-43].
Intraosseous infusion of TRM-645, an artificial oxygen carrier consisting in liposome-encapsulated hemoglobin, was superior to erythrocyte wash in its antishock effect during resuscitation from lethal hemorrhagic shock in experimental animals [Takase, B. et al., Abst 1031-77].
In the topic of contrast imaging, an iso-osmolar agent such as iodixanol was as nephrotoxic as a low osmolar agent as iomeprol [Wessely, R. et al., Abst 2411-13]. Hydration with sodium bicarbonate offered short- and long-term benefits on the renal function in patients undergoing coronary procedures [Masuda, M. et al., Abst 1026-142], and prevented acute kidney injuries during cardiopulmonary bypass interventions [Haase, M. et al., Abst 1036-318]. In a dissimilar way, acetylcysteine was not effective in preventing acute renal injuries during cardiac surgery in patients with preexisting chronic kidney disease [Adabag, A.S. et al., Abst 1013-81].
Nonsignificantly lower recurrent stroke/death rates were noted with warfarin compared to aspirin in patients with previous stroke and large aortic plaques, which showed high event rates despite all preventive efforts [Russo, C. et al., Abst 1021-186].
The effects of estrogen/progestagen in postmenopausal women on inflammatory, thrombotic and metabolic biomarker levels were confirmed in a large randomized trial including 16,608 subjects, but no biomarker was related to increased risk for early coronary heart disease [Hsia, J. et al., Abst 1021-209].
The Chinese medicine Antrodia camphorate exerted inhibitory effects on smooth muscle cell proliferation, migration and formation in experimental models of arterial injury [Li, Y.H. et al., Abst 1021-211].
Prasterone induced unfavorable changes in lipoproteins in hypoadrenal women, with marked reductions in HDL cholesterol [Srinavasan, M. et al., Abst 1021-230].
Methotrexate improved not only disease activity, but also aortic stiffness in patients with rheumatoid arthritis [Gravos, A. et al., Abst 1028-160].
Clopidogrel and dipyridamole promoted angiogenesis and increased blood flow in patients with critical limb ischemia [Venkatesh, P.K. et al., Abst 1028-202].
Use of binodenoson stress was as effective as adenosine for identifying perfusion defects and ischemia in the VISION study [Udelson, J.E. et al., Abst 409-5].
Report prepared by: X. Rabasseda, Prous Science Medical Information Department