The combination of slow-release nifedipine and atenolol for stable angina

Beta-adrenoceptor antagonists, such as atenolol and the dihydropyridine calcium antagonist nifedipine, have antianginal actions that should prove complementary when the drugs are used in combination. Atenolol acts primarily by reducing myocardial oxygen demand, while the vasodilator effects of nifedipine can both reduce demand and increase oxygen supply. The slow-release tablet formulation of nifedipine (Nifedipine Retard) provides more persistent plasma concentrations than the conventional capsule formulation, which may prolong the duration of action. There is increasing evidence that the plasma nifedipine concentration is closely related to efficacy, although the absolute concentration required to improve exercise tolerance in patients with angina varies between individuals. Clinical studies indicate that for many patients the duration of action of slow-release nifedipine, particularly when added to atenolol, is less than 12 hours. This reflects the extensive but variable first-pass metabolism of nifedipine, leading to subtherapeutic trough concentrations. To achieve 24-hour symptom relief, slow-release nifedipine will often need to be given three times daily to patients with angina.