Evolution of infarct size during the early use of nifedipine in patients with acute myocardial infarction: the Norwegian Nifedipine Multicenter Trial.

Abstract

In a multicenter double-blind study, 227 THE CALCIUM ANTAGONIST nifedipine has been shown during the last decade to be effective in the treatment of angina pectoris' and more recently in the treatment of hypertension2 and heart failure.3 A cardioprotective effect of nifedipine has also been demonstrated after experimental coronary occlusion.4 6 There are several reasons why nifedipine might limit myocardial damage in patients with acute myocardial infarction (AMI). By reducing systemic vascular resistance, nifedipine might improve left ventricular unloading and reduce left ventricular workload.7 Dilatation of coronary arteries9 10 might enhance collateral flow to the ischemic region and possibly restore blood flow in situations in which spasm contributes to the ischemia. " Furthermore, nifedipine might inhibit detrimental cellular uptake of Ca ++ during ischemia. 2 This trial was primarily designed to investigate MethodsPatient selection and recruitment. All patients who were admitted to the four participating hospitals with suspected AMI during the trial period (885 patients) were screened for inclusion. Inclusion criteria were (1) severe central chest pain for at least 30 min, continuing on admission or until an analgesic was given, or (2) electrocardiographic changes suggesting an AMI (not previously recognized ST segment elevation >0.2 mV in precordial leads or >0.1 mV in extremity leads, or a Q wave >-0.04 sec that had not been previously recognized). These inclusion criteria were fulfilled by 623 patients, 396 (64%) of whom were excluded (table 1).Allocation and treatment. After informed consent was obtained, eligible patients of both sexes were randomly assigned to treatment with either nifedipine (10 mg capsules) or placebo. Patients at each center were assigned in blocks of 10 and given capsules from prenumbered bottles. A patient was considered to be included in the trial when he or she took the first capsule sublingually. Subsequent doses were 10 mg orally and were begun 30 min after the first dose unless systolic blood pressure was below 90 mm Hg. For the first 2 days 10 mg was given five CIRCULATION

Prolonged protective effect of the calcium antagonist anipamil on the ischemic reperfused rabbit myocardium: Comparison with verapamil

“…Although most of the studies performed in animal models have shown calcium antagonists to be effective in reducing myocardial ischemia, the results of the available clinical trials have been disappointing [10][11][12][13][14]. The failure of these trials to provide unequivocal evidence of protection has emphasized the need to use these substances as prophylactic agents [15,16].…”

Effects of calcium channel blocker on responses of blood flow, function, arrhythmias, and extent of infarction following reperfusion in conscious baboons.

“…In support of this concept, while prior studies in primates and humans with myocardial ischemia have been controversial, 21 -41^48 -62 most of these studies have failed to demonstrate salutary effects of calcium channel blockers. [41][42][43][44][45][46][47][48] It is also clear that administration of any therapeutic intervention during ischemia must occur soon enough, i.e., prior to development of complete necrosis. Another possibility that must be considered is that upon reperfusion, further injury occurs.…”

Dihydropyridine Calcium Antagonists: Beneficial or Adverse Effects in the Setting of Myocardial Ischaemia/Reperfusion?

“…The fact that up to now all clinical studies failed to demonstrate an improvement in survival following acute myocardial infarction [39][40][41][42] requires explanation. Pos sible reasons may be the administration of the calcium antagonist too late during myocardial ischaemia, unfa vourable changes in systemic haemodynamics which may promote pro-ischaemic effects as discussed above, the fact that clinical trials often use only surrogate measures of infarct size (morbidity and mortality), and the concern that even the larger clinical trials undertaken to date have had insufficient statistical power to detect moderately sized treatment effects.…”