HEART FAILURE
Clinical Overview

Investigational Pharmacological Strategies

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Rationale for use⁵

• arteriolar dilatation --> reduce afterload
• antiischemic effects
• favorable effects on left ventricular relaxation and diastolic dysfunction

Potential problems⁵

• decrease myocardial contractility
• activate renin-angiotensin system
• activate sympathetic nervous system
• no effect on venous dilatation (preload)

First generation⁵ :

nifedipine

• potent arteriolar-dilating effect with negative inotropic effect
• prospective studies show worsening of heart failure due to overriding negative inotropic effect

verapamil

• not studied extensively in heart failure due to negative inotropic effects
• post-myocardial infarction studies show no difference from placebo for heart failure patients

diltiazem

• no large studies in heart failure patients
• small studies show clinical deterioration in some heart failure patients

Second generation⁵ :

felodipine

• the V-HeFT III study showed no mortality differences between placebo and felodipine when administered with ACE inhibitors
• safe to administer for heart failure patients who require calcium channel blocker for other indications

amlodipine

• the PRAISE trial suggests that amlodipine reduces morbidity and mortality in heart failure patients with nonischemic heart failure
• PRAISE II trial underway to confirm results

Systolic dysfunction⁵

First generation CCBs should not be used as primary therapy for patients with systolic dysfunction. The primary problem is the neurohormonal activation that occurs in response to the hypotension that these agents cause. Verapamil may be safe for treatment of hypertension or ischemia in these patients. The second generation CCBs have arteriolar dilatation effects without negative inotropic effects. While felodipine and amlodipine are safe to use in heart failure patients with systolic dysfunction, improvement in clinical outcomes has yet to be confirmed for these agents.

Diastolic dysfunction⁶
Calcium channel blockers are the most commonly used class of drugs in ventricular diastolic dysfunction. These agents relieve symptoms by:

• controlling blood pressure
• slowing heart rate
• regression of left ventricular hypertrophy
• reducing myocardial oxygen demands
• dilating coronary microcirculation

When administering calcium channel blockers in patients with diastolic dysfunction, beware of hypotension and decreased cardiac output. CCBs may be detrimental to the patient's condition if both systolic and diastolic dysfunction are present. In addition, combining CCBs with beta-blockers may cause severe bradycardia.

CCB controversy
In 1995, a report by Furberg et al. suggested a relationship between short-acting nifedipine and an increase in mortality in patients with coronary artery disease and suggested that this relationship may extend to other short-acting calcium channel blockers. Braun et al.⁷ conducted their own study to support this report. However, their analysis did not support any relationship between short-acting calcium channel blockers and an increase in mortality. In 1996, an FDA expert panel on cardiovascular drugs examined all studies and data concerning this controversy and deemed calcium channel blockers safe for use. They did ask for enforced labeling on nifedipine capsules to discourage use for hypertension.⁸  

 © 1999 Geriatric Consultant Resources LLC.

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