Overview of Congestive Heart Failure
E. Balbona M.D.
The effective treatment of heart failure goes back 200 years to William Withering’s introduction of digitalis, obtained from foxglove leaves. William Withering conducted his practice, in England in 1875, where he collaborated closely with medical and non-medical colleagues who were pioneers of intellectual thought during the industrial revolution. Because of his profound botanical knowledge, he was able to identify Digitalis purpurea as the essential ingredient in a prescription dispensed by a herbalist, and systematically proceeded to show its value in patients with cardiac failure.
1992 SAVE Study - Eugene Braunwald, M.D. (Harvard Univ)
Left ventricular dilatation and dysfunction after myocardial infarction are major predictors of death. In experimental and clinical studies, long-term therapy with the angiotensin-converting—enzyme inhibitor captopril attenuated ventricular dilatation and remodeling. Within 3 to 16 days after myocardial infarction, 2231 patients with ejection fractions of 40 percent or less but without overt heart failure or symptoms of myocardial ischemia were randomly assigned to receive double-blind treatment with either placebo (1116 patients) or captopril (1115 patients) and were followed for an f 42 months.
Conclusions: In patients with asymptomatic left ventricular dysfunction after myocardial infarction, long-term administration of captopril was associated with an improvement in survival and reduced morbidity and mortality due to major cardiovascular events. These benefits were observed in patients who received thrombolytic therapy, aspirin, or beta-blockers, as well as those who did not, suggesting that treatment with captopril leads to additional improvement in outcome among selected survivors of myocardial infarction. (N Engl J Med 1992;327
1996 Carvedilol Study – Cohn J (Columbia Univ.)
N Engl J Med. 1996 May 23;334(21):1349-55.The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. Controlled clinical trials have shown that beta-blockers can produce hemodynamic and symptomatic improvement in chronic heart failure, but the effect of these drugs on survival has not been determined. METHODS: 1094 patients with chronic heart failure in a double-blind, placebo-controlled, stratified program, in which patients were assigned to one of the four treatment protocols on the basis of their exercise capacity. Within each of the four protocols patients with mild, moderate, or severe heart failure with left ventricular ejection fractions < or = 0.35 were randomly assigned to receive either placebo (n = 398) or the beta-blocker carvedilol (n = 696);
Carvedilol therapy was accompanied by a 27 percent reduction in the risk of hospitalization for cardiovascular causes (19.6 percent vs. 14.1 percent, P = 0.036), as well as a 38 percent reduction in the combined risk of hospitalization or death (24.6 percent vs, 15.8 percent, P < 0.001). Worsening heart failure as an adverse reaction during treatment was less frequent in the carvedilol than in the placebo group.
Conclusions: Carvedilol reduces the risk or death as well as the risk of hospitalization for cardiovascular causes in patients with heart failure who are receiving treatment with digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor.
1999, RALES Study - Pitt Bertram (Univ of Mich)
Randomized Aldactone Evaluation Study.
The Randomized Aldactone Evaluation Study (RALES) was organized to explore the role of combination therapy with spironolactone in patients with heart failure. Patients with New York Heart Association Functional Class II-IV heart failure and left ventricular ejection fractions < or = 40% who were on regimens comprising an ACE inhibitor, loop diuretic, and, possibly, digoxin were randomized to receive placebo or spironolactone in doses of 12.5, 25, 50, or 75 mg per day.
Even at the lowest dose of spironolactone, a significant decrease in plasma N-terminal pro-atrial natriuretic peptide occurred.. The RALES Mortality Trial will follow up 1400 similar patients for 3 years to determine the effect of the addition of spironolactone on combined mortality and hospitalization for heart failure.
RALES was a double-blind study which enrolled 1.663 patients with severe heart failure and a left ventricular ejection fraction of no more than 35 percent who were being treated with an angiotensin-converting-enzyme inhibitor, a loop diuretic and, in most cases, digoxin. A total of 822 patients were randomly assigned to receive 25 mg of spironolactone daily and 841 to receive placebo. The primary end point of the study was death from all causes. The trial was discontinued early after a mean follow-up of 24 months because an interim analysis determined that spironolactone was efficacious. There were indeed 386 deaths in the placebo group (46%) and 284 in the spironolactone group (35%) (relative risk of death: 0.70; 95% confidence interval, 0.60-0.82; p < 0.001).
Conclusions: The 30% reduction of mortality among patients in the spironolactone group was attributable to a lower risk of sudden cardiac death and of death from progressive heart failure. Patients treated by spironolactone had a lower hospitalization rate for worsening heart failure; they also had a significant improvement in the symptoms of heart failure as assessed by the New York Heart Association functional class.