Secondary preventive potential of nitrates in ischaemic heart disease

Nitrates exert their anti-anginal activity by a number of mechanisms. By reducing venous return and left ventricular end-diastolic pressure they lower myocardial oxygen demand and at the same time enhance blood flow to the sub-endocardium. They also directly increase myocardial oxygen supply by dilating the coronary artery stenoses and increasing collateral blood flow. These pharmacodynamic attributes are clinically efficacious in all the ischaemic myocardial syndromes. In stable angina pectoris, nitrates reduce myocardial ischaemia and ischaemic pain and increase exercise tolerance. In unstable angina, nitrates similarly reduce electrocardiographic evidence of myocardial ischaemia and relieve anginal pain. Following acute myocardial infarction, nitrates reduce ventricular dilatation and by so doing reduce pulmonary congestion and mitral regurgitation. The weak anti-aggregatory effect of nitrates on platelets may also play an adjuvant role in their anti-ischaemic activity. Early small-scale studies with both intravenous and oral nitrates demonstrated a trend to reduced mortality and reinfarction in survivors of acute myocardial infarction. However, the later and larger ISIS-4 and GISSI-3 trials have not confirmed this trend possibly due to the smaller doses of nitrates used and the diluting effect of the widespread use of open-label nitrates in the placebo group. In patients with congestive heart failure, including those of ischaemic aetiology, nitrates together with hydralazine have clearly demonstrated a significant reduction in the medium term mortality risk. Nitrates have the undoubted ability, probably greater than any other single anti-anginal drug, to rapidly and often completely relieve the pain and breathlessness associated with myocardial ischaemia. They are haemodynamically efficacious in reducing dilatation of the ischaemic left ventricle and enhancing coronary blood flow to ischaemic areas. Although their preventative impact in survivors of acute myocardial infarction awaits clarification, they have been shown in combination with hydralazine to extend survival in patients with congestive heart failure, including those of ischaemic origin.