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What, if anything, is controversial about calcium antagonists?
1Department of Internal Medicine, Ochsner Clinic and Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121, USA.
Insights
Recent studies question calcium antagonist safety for hypertension and post-heart attack patients. However, newer long-acting formulations are safe and effective for heart disease and blood pressure management.
Area of Science:
- Cardiology
- Pharmacology
- Clinical Trials
Background:
- Recent publications have raised concerns regarding the safety and efficacy of calcium antagonists, particularly in hypertension and post-myocardial infarction patients.
- These concerns stem from retrospective studies suggesting paradoxical increases in heart attack and mortality rates.
- However, these studies have methodological limitations and are based on older, short-acting formulations.
Purpose of the Study:
- To address the safety and efficacy concerns surrounding calcium antagonists.
- To evaluate the role of newer, long-acting calcium antagonists in cardiovascular disease management.
- To provide an updated perspective on the use of calcium antagonists in hypertension and heart conditions.
Main Methods:
- Review of recent publications and meta-analyses questioning calcium antagonist safety.
- Analysis of methodological drawbacks in cited retrospective studies (meta-analysis, case-control, cohort).
- Examination of evidence from recent clinical trials (e.g., PRAISE, VHeFT-III, DEFIANT II, APSIS, STONE) and ongoing trials (e.g., ALLHAT, INSIGHT, HOT, SYST-EUR, STOP II, NORDIL).
Main Results:
- Retrospective studies cited have significant limitations, including data errors, borderline significance, outdated drug information, and inadequate patient management.
- Recent trials with newer, long-acting calcium antagonists demonstrate their safety and efficacy across a spectrum of heart diseases.
- Ongoing trials are expected to provide further morbidity and mortality data for hypertension management.
Conclusions:
- Concerns regarding calcium antagonist safety are largely based on flawed studies of short-acting agents.
- Newer, long-acting calcium antagonists are safe and effective for lowering blood pressure and managing symptomatic angina.
- Current evidence supports the continued use of long-acting calcium antagonists in patients with cardiovascular conditions.
Abstract:
Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospective, and have various drawbacks. Specifically, the metaanalysis of Furberg et al is fraught with mistakes, of borderline significance, and based on old data pertaining to short-acting nifedipine only (which should not be given in patients who have suffered an acute heart attack). The case control study of Psaty et al suggested that hypertensive patients who were treated with short-acting verapamil, diltiazem, and nifedipine had an excessive rate of myocardial infarction when compared with patients who were treated with diuretics. Two out of the three calcium antagonists that were used in this study were not approved for the treatment of hypertension by the US Food and Drug Administration. Some patients were taking these drugs only once a day whereas, because of their short duration of action, at least a three or four times daily regimen would be required to achieve an acceptable blood pressure control throughout a 24-h period. The cohort study of Pahor et al suggested distinct differences among various calcium antagonists with regard to survival. Blood pressure was controlled in < 40% of all patients, and in some patients blood pressure was never even measured. Recent studies, such as the Prospective Randomized Amlodipine Survival Evaluation (PRAISE), the third Vasodilator-Heart Failure Trial (VHeFT-III), the second Doppler Flow and Echocardiography in Functional Cardiac Insufficiency Assessment of Nisoldipine Therapy (DEFIANT II), the Angina Prognosis Study in Stockholm (APSIS), and the Shanghai Trial of Nifedipine in the Elderly (STONE), attest to the safety and efficacy of the newer long-acting calcium antagonists in patients with a wide spectrum of heart disease. Several ongoing trials including the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with amlodipine, the International Nifedipine-GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT) with nifedipine, the Hypertension Optimal Treatment study (HOT) with felodipine, the Systolic Hypertension in the Elderly in Europe Trial (SYST-EUR) with nicardipine, the Second Swedish Trial in Old Patients with Hypertension (STOP II) with felodipine, and Nordic Diltiazem Study (NORDIL) with diltiazem, will give us morbidity and mortality data in patients with high blood pressure within the next few years. Until these results are available, we can be confident that the lowering of blood pressure and providing relief of patients with symptomatic angina can be achieved safely and efficiently with the presently available long-acting calcium antagonists.