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Hallmark Clinical Trials

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Cardiac Drug Therapy

Part of the book series: Contemporary Cardiology ((CONCARD))

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Abstract

Results that dictate a reduction in end points observed in a few hallmark and other recent randomized clinical trials (RCTs) are given. The appropriate reference source is given so that the reader can explore the details of the RCT if required. Because of the constraints of available space, only a brief comment is given in the text regarding the results and their implications.

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References

  • ACE Inhibitor Myocardial Infarction Collaborative Group. Indications for ACE inhibitors in the early treatment of acute myocardial infarction. Systematic overview of individual data from 100,000 patients in randomized trials. Circulation. 1998;97:2202–12.

    Article  Google Scholar 

  • AFIRM: The Atrial Fibrillation Follow-up Investigation of Rhythm Management Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med. 2002;347: 1825.

    Google Scholar 

  • A-HeFT, Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:2049–57.

    Article  CAS  PubMed  Google Scholar 

  • AIM-HIGH Investigators. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365:2255–67.

    Article  Google Scholar 

  • Antman EM, Califf RM, Kupersmith J. Tools for assessment of cardiovascular tests and therapies. In: Antman EM, editor. Cardiovascular therapeutics. 2nd ed. Philadelphia, PA: WB Saunders; 2002. p. 1–19.

    Google Scholar 

  • Antman EM, Morrow DA, McCabe CH, et al. with fibrinolysis for ST-elevation myocardial infarction for the ExTRACT-TIMI 25 Investigators. N Engl J Med. 2006; 354:1477–88.

    Google Scholar 

  • ARISTOTLE, Granger CB, Alexander JH, McMurray JJV, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981–92.

    Article  CAS  PubMed  Google Scholar 

  • ASTEROID, Nissen SE, Nicholls SJ, Sipahi I, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:1556–65.

    Article  CAS  PubMed  Google Scholar 

  • Bach DS. Angiotensin-converting enzyme inhibitor therapy at the time of coronary artery bypass surgery when a friend turns meanspirited. J Am Coll Cardiol. 2009;54(19):1785–6.

    Article  CAS  PubMed  Google Scholar 

  • Björkman J-A, Kirk I, van Giezen JJ. AZD6140 inhibits adenosine uptake into erythrocytes and enhances coronary blood flow after local ischemia or intracoronary adenosine infusion. Circulation 2007;116 Suppl II: II–28, (abstr).

    Google Scholar 

  • Blumenthal RS, Kapur NK. Can a potent statin actually regress coronary atherosclerosis? JAMA. 2006;295:1583–4.

    Article  CAS  PubMed  Google Scholar 

  • Califf RM. Fondaparinux in ST-segment elevation myocardial infarction. The drug, the strategy, the environment, or all of the above? JAMA. 2006;295:1579–80.

    Article  CAS  PubMed  Google Scholar 

  • Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504.

    Article  CAS  PubMed  Google Scholar 

  • CAPRICORN Investigators. Effect of carvedilol on outcome after MI in patients with left ventricular dysfunction; the CAPRICORN randomized trial. Lancet 2001;357:1385–90.

    Google Scholar 

  • CARE: For the Cholesterol and Recurrent Events Trial Investigators. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med. 1996;335:1001.

    Google Scholar 

  • COMMIT (Cl Opidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group. Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366:1607–21.

    Article  Google Scholar 

  • COMMIT/CCS-2 (Clopidogrel and Metoprolol in Myocardial Infarction Trial) Collaborative Group. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: Randomised placebo-controlled trial. Lancet 2005;366:1622–32.

    Google Scholar 

  • Connolly SJ, Ezekowitz MD, Yusuf S, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med. 2009;361:1139–51,(Erratum, N Engl J Med 2010;363:1877).

    Google Scholar 

  • COPERNICUS: Carvedilol Prospective Randomized Cumulative Survival Study Group. Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med. 2001;344:1651–8.

    Article  Google Scholar 

  • COURAGE trial, Boden WE, O’Rourke RA, Teo KK, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007;356:1503–16.

    Article  CAS  PubMed  Google Scholar 

  • EPHESUS: Pitt B, Remme W, Zannad F, et al. for the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators. Eplerenone, a selective aldosterone blocker, in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 2003;348:1309–21.

    Google Scholar 

  • EUROPA: The European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease Investigators. Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomized, double-blind, placebo-controlled, multicenter trial. Lancet. 2003;362:782–88.

    Article  Google Scholar 

  • Fox KAA, Clayton TC, Damman P, et al. for the FIR Collaboration. Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome. A meta-analysis of individual patient data. J Am Coll Cardiol. 2010;55: 2435–45.

    Google Scholar 

  • GEMINI, Bakris GL, Fonseca V, Katholi RE, et al. Metabolic effects of carvedilol vs metoprolol in patients with type 2 diabetes mellitus and hypertension: a randomized controlled trial. JAMA. 2004;292:2227–36.

    Article  CAS  PubMed  Google Scholar 

  • Giles TD, Weber MA, Basile J, et al. for the NAC-MD-01 Study Investigators. Efficacy and safety of nebivolol and valsartan as fixed-dose combination in hypertension: a randomised multicentre study. Lancet 2014;383:1889–98.

    Google Scholar 

  • Giugliano RP. Niacin at 56 years of age — time for an early retirement? N Engl J Med. 2011;365:2318–20.

    Article  CAS  PubMed  Google Scholar 

  • Grosser T, Fries S, Lawson JA, et al. Drug resistance and pseudoresistance an unintended consequence of enteric coating aspirin. Circulation. 2013;127:377–85.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gurbel PA, Bliden KP, Butler K, et al. Randomized double-blind assessment of the ONSET and OFFSET of the antiplatelet effects of ticagrelor versus clopidogrel in patients with stable coronary artery disease: the ONSET/OFFSET study. Circulation. 2009;120:2577–85.

    Article  CAS  PubMed  Google Scholar 

  • Guyatt GH, Sackett DL, Cook DJ. The medical literature: users’ guide to the medical literature: II. How to use an article about therapy or prevention. B. What were the results and will they help me in caring for my patients? JAMA. 1994;271:59–63.

    Article  CAS  PubMed  Google Scholar 

  • Halverson S, Andreotti F, ten Berg HM, et al. Aspirin therapy in primary cardiovascular disease prevention: a position paper of the European Society of Cardiology Working Group on Thrombosis. J Am Coll Cardiol. 2014;64(3):319–27.

    Article  Google Scholar 

  • Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:7–22.

    Article  Google Scholar 

  • HOPE 2: The Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567–77.

    Article  Google Scholar 

  • HOPE: Heart Outcomes Prevention Evaluation Study Investigators. Effects of an angiotensin-converting enzyme inhibitor, ramipril, on cardiovascular events in high risk patients. N Engl J Med. 2000;342:145–53.

    Article  Google Scholar 

  • HORIZONS-AMI: Stone GW, Witzenbichler B, Guagliumi G, et al. Heparin plus a glycoprotein IIb/IIIa inhibitor versus bivalirudin monotherapy and paclitaxel-eluting stents versus bare-metal stents in acute myocardial infarction: final 3-year results from a multicentre, randomised controlled trial. Lancet. 2011;377(9784):2193–204.

    Google Scholar 

  • Imazio M, Brucato A, Ferrazzi P, et al. Colchicine reduces postoperative atrial fibrillation: results of the colchicine for the prevention of the postpericardiotomy syndrome (COPPS) atrial fibrillation substudy. Circulation. 2011;124(21):2290–5.

    Article  CAS  PubMed  Google Scholar 

  • Imazio M, Belli R, Brucato A. Efficacy and safety of colchicine for treatment of multiple recurrences of pericarditis (CORP-2): a multicentre, double-blind, placebo-controlled, randomised trial. Lancet. 2014;383(9936):2232–7.

    Article  CAS  PubMed  Google Scholar 

  • Kastrati A, Neumann F-J, Schulz S, et al. for the ISAR-REACT 4 Trial Investigators. Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med. 2011; 365:1980–89.

    Google Scholar 

  • Khan MG. Hallmark clinical trials. In: Cardiac drug therapy 7e. New York: Springer; 2007. p. 391.

    Google Scholar 

  • Lindholm D, Varenhorst C, Cannon C. Ticagrelor versus clopidogrel in patients with non-ST-elevation acute coronary syndrome: results from the PLATO trial. Am Coll Cardiol. 2013;61(10 S).

    Google Scholar 

  • LIPID Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349–57.

    Article  Google Scholar 

  • Maffei A, Lembo G. Nitric oxide mechanisms of nebivolol. Ther Adv Cardiovasc Dis. 2009;3(4):317–27.

    Article  PubMed  Google Scholar 

  • Mega JL. A new era for anticoagulation in atrial fibrillation. N Engl J Med. 2011;365:1052–4.

    Article  CAS  PubMed  Google Scholar 

  • Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med. 2012;366:9–19.

    Article  CAS  PubMed  Google Scholar 

  • MERIT-HF Study Group. The metoprolol CR/XL randomized intervention trial in CHF. Effects of controlled-release metoprolol on total mortality, hospitalizations and well-being in patients with heart failure. JAMA. 2000;283:1295–302.

    Article  Google Scholar 

  • Miceli A, Capoun R, Fino C, et al. Effects of angiotensinconverting enzyme inhibitor therapy on clinical outcome in patients undergoing coronary artery bypass grafting. J Am Coll Cardiol. 2009;54:177–84.

    Article  Google Scholar 

  • Montalescot G, Zeymerc U, Silvain J, et al. for the ATOLL Investigators. Intravenous enoxaparin or unfractionated heparin in primary percutaneous coronary intervention for ST-elevation myocardial infarction: the international randomised open-label ATOLL trial. Lancet 2011;378(9792):693–703

    Google Scholar 

  • Murphy SA, Cannon CP, Wiviott SD, et al. Reduction in recurrent cardiovascular events with intensive lipid-lowering statin therapy compared with moderate lipid-lowering statin therapy after acute coronary syndromes: from the PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy – Thrombolysis in Myocardial Infarction 22) trial. J Am Coll Cardiol. 2009;54:2358–62.

    Article  CAS  PubMed  Google Scholar 

  • Nicholls SJ, Ballantyne CM, Barter PJ, et al. Effect of two intensive statin regimens on progression of coronary disease. N Engl J Med. 2011;365:2078–87.

    Article  CAS  PubMed  Google Scholar 

  • Nidorf SM, Eikelboom JW, Budgeon CA, et al. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013;61(4):404–10.

    Article  CAS  PubMed  Google Scholar 

  • Nissen SE (2010) Angiotensin-receptor blockers and cancer: urgent regulatory review needed. Lancet Oncol. doi:10.1016/S1470-2045(10)70142-XCite, Early Online Publication

    Google Scholar 

  • OASIS-6 Trial Investigators. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction. The OASIS-6 randomized trial. JAMA 2006;295: 1519–1530.

    Google Scholar 

  • O’Rourke RA. Optimal medical therapy is a proven option for chronic stable angina. J Am Coll Cardiol. 2008b;52:905–7.

    Article  PubMed  Google Scholar 

  • ONTARGET Investigators. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med. 2008;358:1547–59.

    Article  Google Scholar 

  • Pizarro G, Fernandez-Friera L, Fuster V. Long-term benefit of early pre-reperfusion metoprolol administration in patients with acute MI: results from the METOCARD-CNTC trial (effect of metoprolol in cardioprotection during an acute myocardial infarction). J Am Coll Cardiol. 2014;63(22):2356–62.

    Article  CAS  PubMed  Google Scholar 

  • PLATO: Cannon CP, Harrington RA, James S, et al. for the PLATelet inhibition and patient Outcomes investigators. Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes: a randomised double-blind study. Lancet 2010;375(9711):283–93.

    Google Scholar 

  • PRoFESS :Yusuf S, Diener H-C, Sacco RL et al Telmisartan to preventrecurrent stroke and cardiovascular events. N Eng J Med 2008 359(12):1225–1237.

    Google Scholar 

  • PROSPECT :Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease: A randomised controlled trial. Lancet 2002;360:1623–1630.

    Google Scholar 

  • PROVE IT-TIMI 22: Ray KK, Cannon CP, McCabe CH, et al. for the PROVE IT-TIMI 22 Investigators. Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: Results from the PROVE IT-TIMI 22 trial. J Am Coll Cardiol 2005;46:1405–1410.

    Google Scholar 

  • RALES: The Randomized Aldactone Evaluation Study Investigators. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med 1999;341:709–717.

    Google Scholar 

  • ROCKET: Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–891.

    Google Scholar 

  • SENIORS: Flather MD, Shibata MC, Coats AJ, et al. Randomized trial to determine the effect of nebivolol on mortality and cardiovascular hospital admission in elderly patients with heart failure. Eur Heart J. 2005;26:215–25.

    Google Scholar 

  • SENIORS Investigators, van Veldhuisen DJ, Cohen-Solal A, Bohm M, et al. Beta-blockade with nebivolol in elderly heart failure patients with impaired and preserved left ventricular ejection fraction: data from SENIORS (study of effects of nebivolol intervention on outcomes and rehospitalization in seniors with heart failure). J Am Coll Cardiol. 2009;53:2150–58.

    Google Scholar 

  • Sipahi I, Debanne SM, Rowland DY (2010) Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomised controlled trials. Lancet Oncol. doi:10.1016/S1470-2045(10)70106-6, Early Online Publication.

    Google Scholar 

  • Stone GW. Ticagrelor in ACS: redefining a new standard of care? Lancet 2010;375(9711):263–5.

    Article  PubMed  Google Scholar 

  • Stone GW, McLaurin BT, Cox DA, et al. for the ACUITY Investigators. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006;355:2203–16.

    Google Scholar 

  • The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981–2997.

    Google Scholar 

  • TIMACS: Mehta SR, Granger CB, Boden WE et al. for the TIMACS Investigators (2009) Early versus delayed invasive intervention in acute coronary syndromes. N Engl J Med 360:2165–2175

    Google Scholar 

  • TRANSCEND: Yusuf S, Teo K, Anderson C et al for the Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet 2008, 372:1174–1183.

    Google Scholar 

  • Tuncer M, Fettser DV, Gunes Y, et al. Comparison of effects of nebivolol and atenolol on P-wave dispersion in patients with hypertension. Kardiologiia. 2008;48:42–5 (in Russian).

    CAS  PubMed  Google Scholar 

  • Val-HeFT, Cohn JN, Tognoni G. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med. 2001;345:1667–75.

    Article  CAS  PubMed  Google Scholar 

  • Van Gelder IC, Groenveld HF, Crijns HJGM et al. For the RACE II Investigators (2010) Lenient versus strict rate control in patients with atrial fibrillation. N Engl J Med 362:1363–73

    Google Scholar 

  • Wallentin L, Varenhorst C, James S, et al. Prasugrel achieves greater and faster P2Y12 receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease. Eur Heart J. 2008;29:21–30.

    Article  CAS  PubMed  Google Scholar 

  • Weinsaft JW. Effect of ramipril on cardiovascular events in high risk patients. N Engl J Med. 2000;343:64–6.

    Article  CAS  PubMed  Google Scholar 

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Khan, M.G. (2015). Hallmark Clinical Trials. In: Cardiac Drug Therapy. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-61779-962-4_22

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  • DOI: https://doi.org/10.1007/978-1-61779-962-4_22

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