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Safety of calcium antagonists in patients with congestive heart failure
1Heart Failure Center, Columbia-Presbyterian Medical Center, New York, New York, USA.
Abstract:
Continuing high morbidity and mortality have spurred an ongoing search for new therapeutic agents for patients with congestive heart failure. Calcium antagonists (CAs) have been under active investigation in patients with heart failure since their introduction into clinical medicine, because their anti-ischemic and vasodilator properties were thought to be of potential benefit in this patient population. However, review of published clinical trials of CAs in patients with heart failure reveals that some of these drugs are associated with detrimental effects, including acute hemodynamic deterioration, increased symptoms of heart failure, and increased mortality. The adverse effects of short-acting CAs in patients with heart failure include negative inotropic effects and neurohormonal activation. Long-acting CAs, such as amlodipine and felodipine, had fewer negative inotropic effects, showed less evidence of neurohormonal activation, and were better tolerated in clinical trials. Amlodipine, in combination with an angiotensin-converting enzyme inhibitor, had a neutral effect in patients with ischemic heart failure and an unexplained benefit in a subgroup of patients with non-ischemic cardiomyopathy. Although the preliminary experience with long-acting dihydropyridine CAs in heart failure has been encouraging, safety concerns raised by past trials dictate that no CA can be recommended for the treatment of heart failure at this time.
Insights
Calcium antagonists (CAs) show mixed results for heart failure treatment. While long-acting CAs like amlodipine appear safer, current evidence does not support recommending any CA for heart failure therapy.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Congestive heart failure (CHF) remains a leading cause of morbidity and mortality.
- Calcium antagonists (CAs) were investigated for CHF due to their anti-ischemic and vasodilator properties.
Purpose of the Study:
- To review the efficacy and safety of calcium antagonists in patients with congestive heart failure.
- To evaluate the impact of short-acting versus long-acting CAs on heart failure outcomes.
Main Methods:
- Systematic review of published clinical trials involving calcium antagonists in heart failure patients.
- Analysis of adverse effects, hemodynamic changes, and mortality associated with different CA formulations.
Main Results:
- Short-acting CAs demonstrated detrimental effects, including negative inotropy and neurohormonal activation.
- Long-acting CAs, such as amlodipine and felodipine, were better tolerated with fewer adverse effects.
- Amlodipine showed neutral effects in ischemic heart failure and potential benefit in non-ischemic cardiomyopathy when combined with ACE inhibitors.
Conclusions:
- Preliminary data on long-acting dihydropyridine CAs in heart failure are encouraging.
- Despite potential benefits, safety concerns from past trials preclude recommending any CA for heart failure treatment at present.