Overall, the evolution of the management of a broad spectrum of cardiovascular disease states has occurred primarily as a result of randomized, controlled clinical trials that have been conducted and published over time. During the past two years, the results of numerous clinical trials have certainly had a significant impact on the ways in which practitioners have treated conditions such as chronic heart failure, cardiac arrhythmias, ischemic heart disease, dyslipidemias, and hypertension. This review article summarizes the results of several key clinical trials that evaluated various treatment strategies for these five cardiovascular disease states and attempts to provide insight as to how these findings can be incorporated into clinical practice.
American Heart Association. 2000 Heart and Stroke Statistical Update. Dallas, TX: American Heart Association, 1999.
2.
CIBIS Investigators and Committees. A randomized trial of β-blockade in heart failure: the Cardiac Insufficiency Bisoprolol Study (CIBIS). Circulation. 1994;90:1765-1773.
3.
CIBIS-II Investigators and Committees. The cardiac insufficiency bisoprolol study II (CIBIS-II): a randomised trial. Lancet.1999;353:9-13.
4.
MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL randomised intervention trial in congestive heart failure (MERIT-HF). Lancet.1999;353:2001-2007.
5.
Packer M, Bristow MR, Cohn J, et al. for the US Carvedilol Heart Failure Study Group. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med. 1996;334:1349-1355.
6.
Australia New Zealand Heart Failure Research Collaborative Group. Randomised placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischemic heart disease. Lancet. 1997;349:375-380.
7.
Guideline Committee for the Heart Failure Society of America. HFSA guidelines for the management of patients with heart failure caused by left ventricular systolic dysfunction: pharmacological approaches. Pharmacotherapy. 2000;20:495-522.
8.
Packer M.COPERNICUS Trial. 73rd Scientific Session of the American Heart Association. November 17, 2000. New Orleans, Louisiana.
9.
Smith NL, Psaty BM, Pitt B, et al. Temporal patterns in the medical treatment of congestive heart failure with angiotensin-converting enzyme inhibitors in older adults, 1989 through 1995. Arch Intern Med. 1998;158:1074-1080.
10.
Cohn JN, Johnson G, Ziesche S, et al. A comparison of enalapril with hydralazineisosorbide dinitrate in the treatment of chronic congestive heart failure. N Engl J Med.1991;325:303-310.
11.
The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). N Engl J Med. 1987;316:1429-1435.
12.
The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. N Engl J Med. 1991;325:293-302.
13.
Packer M, Poole-Wilson PA, Armstrong PW, et al. Comparative effects of low and high doses of the angiotensin-converting enzyme inhibitor, lisinopril, on morbidity and mortality in chronic heart failure. Circulation.1999;100:2312-2318.
14.
Cleland J, Semple P, Hodsman P, et al. Angiotensin II levels, hemodynamics, and sympathoadrenal function after low-dose captopril in heart failure. Am J Med.1984;77:880-886.
15.
Cleland JGF, Dargie HJ, Hodsman GP, et al. Captopril in heart failure: a double blind controlled trial. Br Heart J. 1984;52:530-535.
16.
Pitt B, Segal R, Martinez FA, on behalf of the ELITE Study Investigators. Randomised trial of losartan versus captopril in patients over 65 with heart failure. Lancet.1997;349:747-752.
17.
Pitt B, Poole-Wilson PA, Segal R, on behalf of the ELITE II Study Investigators. Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: a randomised trial—the Losartan Heart Failure Survival Study ELITE-II. Lancet.2000;355:1582-1587.
18.
Cohn JN. Val-HeFT. 73rd Scientific Session of the American Heart Association. November 15, 2000. New Orleans, Louisiana.
19.
Staessen J, Lijnin P, Fagard R, et al. Rise in plasma concentration of aldosterone during long-term angiotensin II suppression. J Endocrinol. 1981;91:457-465.
20.
Pitt B, Zannad F, Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. N Engl J Med. 1999;341:709-717.
21.
Elkayam U, Amin J, Mehra A, et al. A prospective, randomized, double-blind crossover study to compare the safety and efficacy of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation. 1990;82:1954-1961.
22.
Goldstein RE, Boccuzzi SJ, Cruess D, et al. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. Circulation.1991;83:52-60.
23.
Packer M.Calcium channel blockers in chronic heart failure: the risks of “physiologically rational” therapy. Circulation. 1990;82:2254-2257.
24.
Packer M, O’Connor CM, Ghali JK, et al., for the Prospective Randomized Amlodipine Survival Evaluation (PRAISE) Study Group. Effects of amlodipine on morbidity and mortality in severe chronic heart failure. N Engl J Med.1996;335:1107-1114.
25.
Packer M.PRAISE-2 Study. 49th Scientific Session of the American College of Cardiology. March 15, 2000. Anaheim, California.
26.
Connolly SJ, Gent M, Roberts RS, et al., for the CIDS Investigators. Canadian Implantable Defibrillator Study (CIDS): a randomised trial of the implantable cardioverter defibrillator against amiodarone. Circulation. 2001; 101:1297-1302.
27.
The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from near-fatal ventricular arrhythmias. N Engl J Med. 1997;337:1576-1583.
28.
Kuck KH, Cappato R, Siebels J, et al., for the CASH Investigators. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation.2000;102:748-754.
29.
Buxton AE, Lee KL, Fisher JD, et al., for the Multicenter Unsustained Tachycardia Trial Investigators. A randomized study of the prevention of sudden death in patients with coronary artery disease. N Engl J Med. 1999;341:1882-1890.
30.
Moss AJ, Hall WJ, Cannom DS, et al., for the Multicenter Automatic Defibrillator Implantation Trial Investigators. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med. 1996;335:1933-1940.
31.
Strickberger SA. AMIOVIRT. 73rd Scientific Session of the American Heart Association. November 15, 2000. New Orleans, Louisiana.
32.
Roy D, Talajic M, Dorian P, for the Canadian Trial of Atrial Fibrillation Investigators. Amiodarone to prevent recurrences of atrial fibrillation. N Engl J Med. 2000;342:913-920.
33.
Planning and Steering Committees of the AFFIRM Study, for the NHBL AFFIRM Investigators. Atrial fibrillation follow-up investigation of rhythm management: the AFFIRM Study design. Am J Cardiol. 1997;79:1198-1202.
34.
Greenbaum RA, Campbell TJ, Channer RS, et al. Conversion of atrial fibrillation and maintenance of sinus rhythm by dofetilide: the EMERALD (European and Australian Multicenter Evaluative Research on Atrial Fibrillation Dofetilide) study [abstract]. Circulation.1998;98 (suppl):I-633.
35.
Singh S, Zoble RG, Yellen L, et al. Efficacy and safety of oral dofetilide in converting and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the Symptomatic Atrial Fibrillation Investigative Research on Dofetilide (SAFIRE-D) study. Circulation2000; 102:2385-2390.
36.
Kober L, Bloch -Thomsen PE, Moller M, et al. Effect of dofetilide in patients with recent myocardial infarction and left-ventricular dysfunction: a randomised trial. Danish Investigations of Arrhythmia and Mortality on Dofetilide (EMERALD) Study Group. Lancet2000; 356:2052-2058.
37.
Torp-Pedersen C, Møller M, Bloch-Thomsen PE, for the Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. N Engl J Med. 1999;341:857-865.
38.
The 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;342:145-153.
39.
The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N Engl J Med.1992;327:685-691.
40.
Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction: results of the Survival and Ventricular Enlargement trial. N Engl J Med. 1992;327:669-677.
41.
Kober L, Torp-Pedersen C, Carlsen JE, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. N Engl J Med. 1995;333:1670-1676.
42.
Hansson L, Lindholm LH, Niskanen L, et al. Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPP) randomised trial. Lancet.1999;353:611-616.
43.
Ruggenenti P, Perna A, Gherardi G, et al. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Lancet.1998;352:1252-1256.
44.
Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet.1994;344:1383-1389.
45.
Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med.1996;335:1001-1009.
46.
The Long-Term Intervention with Pravastatin in Ischaemic Disease (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;339:1349-1357.
47.
Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA.1993;269:3015-3023.
48.
Rubins HB, Robins SJ, Collins D, et al. Distribution of lipids in 8500 men with coronary artery disease. Am J Cardiol. 1995;75:1196-1201.
49.
Rubins HB, Robins SJ, Collins D, for the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med. 1999;341:410-418.
50.
Manninen V, Elo MO, Frick MH, et al. Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. JAMA. 1988;260:641-651.
51.
Schwartz G.MIRACL Trial. 73rd Scientific Session of the American Heart Association. November 17, 2000. New Orleans, Louisiana.
52.
Lipid Research Clinics Program. The Lipid Research Clinics coronary primary prevention trial results, I: reduction in the incidence of coronary heart disease. JAMA. 1984;251:351-364.
53.
Levine GN, Keaney JF, Vita JA. Cholesterol reduction in cardiovascular disease, clinical benefits, and possible mechanisms of action. N Engl J Med. 1995;332:512-521.
54.
Davidson MH, Dillon MA, Gordon B, et al. Colesevelam hydrochloride (cholestagel): a new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects. Arch Intern Med. 1999;159:1893-1900.
The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs. chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA.2000;283:1967-1975.
