Implications of recent end-point trials on future management of hypertension and dyslipidaemia

Abstract

A significant proportion of patients with hypertension are likely to have additional cardiovascular (CV) risk factors, such as hypercholesterolaemia. Several trials have demonstrated that lipid lowering can provide significant benefits in terms of reduced risk of CV mortality and morbidity. Trials such as the Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP) trial have shown regression of atherosclerosis after aggressive lipid-lowering treatment with statins. The Heart Protection Study (HPS) also demonstrated a significant reduction in the incidence of major vascular events in high-risk patients, irrespective of baseline cholesterol levels, after treatment with a statin. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) is of particular significance because it investigated the impact of combining the effects of antihypertensive therapy with a statin. ASCOT was a multi-centre, 2×2 factorial design, randomized trial comparing two blood pressure (BP)-lowering regimens in the antihypertensive arm, and double-blind atorvastatin (10 mg) versus placebo in a separate lipid-lowering arm (LLA). The objective of the LLA was to compare the effects of low-dose atorvastatin versus placebo for the combined end-point of nonfatal myocardial infarction and fatal coronary heart disease (CHD) in hypertensive patients with normal to mildly elevated cholesterol levels (total cholesterol ≤6.5 mmoll−1; ≤250 mgdl−1). The ASCOT–LLA represents the first study to assess the benefits of lipid lowering in the primary prevention of CHD in well-controlled hypertensive patients who are not conventionally deemed dyslipidaemic. Secondary end-points included all-cause mortality, fatal and nonfatal stroke and total coronary events. The ASCOT–LLA, which had a 5-year planned follow-up, was terminated prematurely by the Data Safety Monitoring Board, after a median follow-up of 3.3 years due to a highly significant reduction in the primary end-point of 36% compared with placebo (P=0.0005). ASCOT and other end-point studies suggest that controlling both BP and dyslipidaemia may have a synergistic benefit on CV mortality and morbidity. Future treatment strategies should therefore be aimed at addressing global CV risk in each patient and not just individual risk factors.