For several years the treatment of ...

For several years the treatment of angina has been based forward combinations of nitrates, beta blocker and calcium antagonists. In the mid 1990 there was matter about the long-term safety of calcium antagonists. Poole-Wilson and colleagues studied the purport of the long-acting calcium agonist nifedipine (Procardia) in succession patients with stable angina pectoris in the ACTION contemplation (A Coronary disease Trial Investigating issues with Nifedipine Gastrointestinal Therapeutic System)

More than 7600 patients with stable angina pectoris from 291 treatment facilities in 19 countries were recruited for the consideration Patients were 35 years or older and required oral or transdermal therapy to interrupt or control symptoms. Reasons for exclusion included left ventricular ejection fraction les than 40 percent manifest cardiac failure, major cardiovascular end or intervention in the previous three month significant cardiac valvular or pulmonary disease, and unstable insulin-dependent diabetes mellitus.

Nifedipine or placebo was added to passing from hand to hand therapy depending on randomization. The initial dose of nifedipine was 30 mg daily. If tolerated, this was increased to 60 mg daily within six weeks. Other medications were continued at the discretion of the treating physician with the exception of for calcium antagonists, cardiac glycosides (except for supraventricular arrhythmia), positive inotropic agents, antiarrhythmic agents in classes I or III other than amiodarone (Cordarone) or sotalol (Betapace), cimetidine (Tagamet), antipsychotic agents, antiepileptic remedys and rifampin (Rifadin). Randomization was made following baseline assessment that included a abounding medical history, echocardiography, blood press assessment, and classification into a of recent origin York Heart Association (NYHA) category. At each six-month follow-up clinical assessment included NYHA status, vital signs, and monitoring for adverse issues The study assessed survival without a major cardiovascular conclusion This was measured as time to casualty of acute myocardial infarction, refractory angina, novel overt heart failure, debilitating visitation peripheral revascularization procedure, or death from any cause. The primary combined endpoint was death from any cause, acute myocardial infarction, and debilitating rap Other cardiovascular events were predefined as secondary outcomes

The 3825 patients randomized to nifedipine were comparable with the 3840 randomized to placebo. The average age was 635 years, and 79 percent of participants were men united half of the participants had experienced myocardial infarction, and undivided fourth had undergone a coronary revascularization conduct Nearly 70 percent had significant lesions upon coronary angiography, and 46 percent had NYHA classification of II or III. according to six weeks, 88 percent of patients were taking the glutted dose of medication. Sixteen percent of patients reduc nifedipine to half-dose. Therapy was discontinued from 34 percent of patients taking nifedipine and 31 percent of those receiving placebo. The in the greatest degree common adverse events leading to discontinuation of nifedipine were peripheral edema and headache.

The mean follow-up achieved was almost five years. Patients taking nifedipine experienced significant increases in heart rate and reductions of vital fluid pressure compared with the placebo dispose Cardiovascular and noncardiovascular death rates were similar in the pair groups. Patients treated with nifedipine had significant reductions in just discovered overt heart failure, coronary angiography, and bypass surgery Overall, nifedipine put offed mean event-free survival by 41 days, mainly because of a reduction in coronary angiography.

The authors end that nifedipine is safe in patients with stable angina pectoris already using conventional treatments and is associated with a reduction in coronary transactions and interventions. The death rate in patients assigned to nifedipine was 11 for 1,000 patient-years greater than the placebo assign places to but most of these deaths were not because of cardiovascular causes. No evidence was establish indicating that nifedipine induces myocardial infarction or heart failure.

ANNE D WALLING, MD

Poole-Wilson PA, et al. result of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomized controll trial. Lancet 2004;364:849-57

COPYRIGHT 2005 American Academy of Family Physicians

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