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University of Ottawa The Ottawa Hospital, Ottawa, ON, Canada
Calcium Antagonists Cause an Increased Incidence of HF and MI: True or False?
Calcium antagonists without doubt cause an increased incidence of heart failure (HF) as observed in several well-run randomized controlled trials (RCTs):
Amlodipine in Antihypertensive and Lipid-Lowering Treatment (ALLHAT 2002): HF 38 % vs. diuretic.
Nifedipine in Intervention as a Goal in Hypertension Treatment (INSIGHT 2000): HF 46 % vs. diuretic.
Verapamil in Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE 2003): HF 30 %.
Amlodipine in Prospective Randomized Amlodipine Survival Evaluation (PRAISE 1996) caused significant increased pulmonary edema in patients with left ventricular (LV) dysfunction. These patients, however, did have left ventricular dysfunction.
Diltiazem caused a significant increase in HF in a non-Q-wave infarction study (Multicenter Diltiazem Postinfarction Trial 1989).
The short-acting preparations of nifedipine and other dihydropyridines used (1985–1995) have been shown in RCTs to cause an increased incidence of myocardial infarction (MI). These formulations are no longer used.
Although the sustained release formulations have been shown to be much safer than the rapid-acting older preparations, these agents are contraindicated in patients with unstable angina or acute MI. Verapamil is contraindicated in patients with acute ST elevation MI (STEMI) and non-STEMI.
Diltiazem is contraindicated in patients with LV dysfunction, prior heart failure, or EF <40 % but may be used in patients with unstable angina if beta-blockers are contraindicated and systolic function is normal.
Newer Calcium Antagonists Are Better Than Older Agents: True or False?
Lercanidipine was introduced into the United Kingdom a few years ago. It appeared to have advantages over amlodipine and older dihydropyridines. Because the drug dilates both afferent and efferent arterioles, the high incidence of peripheral edema caused by older calcium antagonists was reportedly reduced more than 50 %. The balanced effect of lercanidipine and manidipine on efferent and afferent arterioles was believed to be important in renoprotection; older calcium antagonists dilate only afferent arterioles.
Lercanidipine is only indicated for hypertension and is contraindicated in patients with LV dysfunction, sick sinus syndrome (if pacemaker not fitted), hepatic impairment, aortic stenosis, unstable angina, uncontrolled HF, within 1 month of MI, and renal impairment. Adverse effects include flushing, peripheral edema, palpitations, tachycardia, headache, dizziness, and asthenia, also gastrointestinal disturbances, hypotension, drowsiness, myalgia, polyuria, and rash.
Conclusion: newer agents are not more effective and do not possess more safety than older agents. Most importantly, the combination of lercanidipine and digoxin is potentially hazardous.
Are Calcium Antagonists Safe for Hypertensives with CAD?
Calcium antagonists are widely used in patients to treat coronary artery disease (CAD) events, particularly stable angina. Their role in patients with unstable angina is limited, and caution is required for acute MI. Post-MI prophylaxis with verapamil has been advocated by few in the field and remains controversial and is not recommended by the Author.
Their use in hypertensive patients with unsuspected or stable CAD has been widespread for more than two decades because they cause more effective and consistent lowering of blood pressure than angiotensin-converting enzyme (ACE) inhibitors/ARBs, beta-blockers, and diuretics.
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