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Ongoing clinical outcome studies of calcium antagonists
Opie1
1Heart Research Unit, Cape Heart Centre, University of Cape Town Medical School, Cape Town, Republic of South Africa.
Insights
Short-acting calcium antagonists like nifedipine may increase mortality in the elderly, especially with high doses. Long-acting agents and combination therapies offer safer alternatives for hypertension management.
Area of Science:
- Cardiology
- Pharmacology
- Geriatrics
Background:
- Calcium antagonists remain relevant for hypertension treatment despite safety concerns.
- Recent studies raise questions about the long-term cardiovascular impact of certain calcium antagonists.
Purpose of the Study:
- To evaluate the safety and efficacy of different calcium antagonists in elderly hypertensive patients.
- To compare the risks associated with short-acting versus long-acting calcium antagonists.
Main Methods:
- Analysis of a well-designed cohort study in a very elderly population.
- Review of recent studies on calcium antagonist combinations and specific agents like nitrendipine.
Main Results:
- Short-acting nifedipine linked to increased mortality in the elderly, particularly at high doses and with lower initial blood pressure.
- Short-acting verapamil showed risks comparable to beta-blockade.
- Long-acting dihydropyridine agents and combinations (verapamil/ACE inhibitor, nitrendipine) show promise in reducing cardiovascular events.
Conclusions:
- Preference for long-acting calcium antagonists that minimize adrenergic stimulation is recommended.
- Combination therapies (e.g., verapamil/ACE inhibitor) may mitigate adverse effects and improve outcomes.
- Further large-scale trials are needed to confirm long-term safety and efficacy.
Abstract:
Calcium antagonists continue to have a place in the treatment of hypertension, despite recent concerns regarding their safety and long-term capacity to alter the natural history of cardiovascular disease. Results of a well-designed cohort study concerning a very elderly population suggested that administration of shorft-acting nifedipine is linked to an increase in mortality, particularly when a high dose is administered and when the initiaol blood pressure is below 160/90 mmHg. The risk of using short-acting verapamil, however, was no greater than that of beta-blockade. These differences can be attributed at least in part to the low catecholamine profile of verapamil and to the marked rapid adrenergic activation with short-acting nifedipine. Current evidence sujggests that less catecholamine activation occurs during the chronic use of long-acting dihydropyridine agents. Two recent studies have shown that the combination of verapamil and an angiotensin converting enzyme inhibitor reduces numbers of cardiovascular disease events among postinfarct patients with heart failure, and that the dihydropyridine nitrendipine reduces poor outcome measures, such as stroke incidence, in treating systolic hypertension in the elderly. In my view, apparent hazards such as the precipitation of myocardial infarction and cancer are discounted by the available evidence. While we await further major trials concerning outcomes, general safety can be related to a preference for administering those long-acting agents that do not stimulate and may even inhibit adrenergic responses, and the avoidance of possible adverse effects through the use of combination therapies, such as verapamil plus an angiotensin converting enzyme inhibitor or nifedipine plus a beta-blocker.