Calcium channel blockers in heart failure with reduced ejection fraction
- Wilson S Colucci, MD
Wilson S Colucci, MD
- Section Editor — Heart Failure
- Professor of Medicine
- Boston University School of Medicine
Calcium channel blockers should generally be avoided in patients with heart failure with reduced ejection fraction (HFrEF) since they provide no functional or mortality benefit and some first generation agents may worsen outcomes .
The clinical trials that have evaluated the use of calcium channel blockers in patients with HFrEF will be reviewed here. Calcium channel blockers have a better defined role in the treatment of HF due to diastolic dysfunction, which is discussed separately. (See "Treatment and prognosis of heart failure with preserved ejection fraction", section on 'Calcium channel blockers'.)
FIRST GENERATION AGENTS
Calcium channel blockers might be expected to have beneficial effects in systolic HF by reducing peripheral vasoconstriction and thereby reducing left ventricular afterload. However, these agents also have negative inotropic activity and several studies demonstrated greater clinical deterioration in patients treated with nifedipine and diltiazem compared to placebo or isosorbide dinitrate [2,3]. As a result, these drugs have generally been avoided in patients with systolic HF, even for the treatment of coexisting angina or hypertension.
Nifedipine — The effect of nifedipine in heart failure with reduced ejection fraction (HFrEF) depends, in part, upon the baseline hemodynamic status of the patient. Short-term use of the drug can cause hemodynamic deterioration when there is evidence of more severe HF, as manifested by high plasma renin activity, hyponatremia, and elevated right atrial pressure .
The adverse effects of long-term therapy with nifedipine were illustrated in a randomized, double-blind, crossover study of 28 patients with New York Heart Association (NYHA) class II or III HFrEF (table 1); nifedipine, with and without isosorbide dinitrate, was compared to isosorbide dinitrate alone . Eight weeks of therapy with nifedipine alone or in combination with isosorbide dinitrate resulted in a significantly higher incidence of hospitalization (24 and 26 versus 0 percent with isosorbide dinitrate alone), episodes of worsening HF (9 and 21 versus 5), and premature discontinuation of therapy due to clinical deterioration or other side effects (29 and 19 versus 5 percent).
- WRITING COMMITTEE MEMBERS, Yancy CW, Jessup M, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2013; 128:e240.
- Elkayam U, Amin J, Mehra A, et al. A prospective, randomized, double-blind, crossover study to compare the efficacy and safety of chronic nifedipine therapy with that of isosorbide dinitrate and their combination in the treatment of chronic congestive heart failure. Circulation 1990; 82:1954.
- Goldstein RE, Boccuzzi SJ, Cruess D, Nattel S. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group. Circulation 1991; 83:52.
- Packer M, Lee WH, Medina N, et al. Prognostic importance of the immediate hemodynamic response to nifedipine in patients with severe left ventricular dysfunction. J Am Coll Cardiol 1987; 10:1303.
- Effect of verapamil on mortality and major events after acute myocardial infarction (the Danish Verapamil Infarction Trial II--DAVIT II). Am J Cardiol 1990; 66:779.
- The effect of diltiazem on mortality and reinfarction after myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group. N Engl J Med 1988; 319:385.
- Kostis JB, Lacy CR, Cosgrove NM, Wilson AC. Association of calcium channel blocker use with increased rate of acute myocardial infarction in patients with left ventricular dysfunction. Am Heart J 1997; 133:550.
- Hager WD, Davis BR, Riba A, et al. Absence of a deleterious effect of calcium channel blockers in patients with left ventricular dysfunction after myocardial infarction: The SAVE Study Experience. SAVE Investigators. Survival and Ventricular Enlargement. Am Heart J 1998; 135:406.
- Figulla HR, Gietzen F, Zeymer U, et al. Diltiazem improves cardiac function and exercise capacity in patients with idiopathic dilated cardiomyopathy. Results of the Diltiazem in Dilated Cardiomyopathy Trial. Circulation 1996; 94:346.
- Cohn JN, Archibald DG, Ziesche S, et al. Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study. N Engl J Med 1986; 314:1547.
- Cohn JN, Ziesche S, Smith R, et al. Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group. Circulation 1997; 96:856.
- de Vries RJ, van Veldhuisen DJ, Dunselman PH. Efficacy and safety of calcium channel blockers in heart failure: focus on recent trials with second-generation dihydropyridines. Am Heart J 2000; 139:185.
- Packer M, O'Connor CM, Ghali JK, et al. Effect of amlodipine on morbidity and mortality in severe chronic heart failure. Prospective Randomized Amlodipine Survival Evaluation Study Group. N Engl J Med 1996; 335:1107.
- Data presented at the 49th Annual Scientific Session of the ACC, Anaheim, CA, March, 2000.
- O'Connor CM, Carson PE, Miller AB, et al. Effect of amlodipine on mode of death among patients with advanced heart failure in the PRAISE trial. Prospective Randomized Amlodipine Survival Evaluation. Am J Cardiol 1998; 82:881.
- Udelson JE, DeAbate CA, Berk M, et al. Effects of amlodipine on exercise tolerance, quality of life, and left ventricular function in patients with heart failure from left ventricular systolic dysfunction. Am Heart J 2000; 139:503.
- Littler WA, Sheridan DJ. Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group. Br Heart J 1995; 73:428.