The ASCOT trial: clarifying the role of ACE inhibition in the reduction of cardiovascular events in patients with hypertension.

Hypertension remains one of the primary causes of preventable death in developed countries. Universally accepted clinical practice guidelines based on well designed trials are needed to ensure standardized treatment for these patients. It has been hypothesized that agents such as calcium channel antagonists and ACE inhibitors may be more effective than beta-adrenoceptor antagonist (beta-blocker)- or diuretic-based regimens. However, until recently, there have been limited data on the efficacy of 'newer' antihypertensive regimens, particularly combination therapy, relative to standard therapeutic options. The ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm), a prospective, randomized, controlled trial in >19 250 patients with hypertension, highlights the benefit of a combined amlodipine plus perindopril regimen over an atenolol plus diuretic-based combination in terms of significant reductions (p < 0.05) in all-cause mortality, total cardiovascular events and procedures, and fatal and nonfatal stroke. The ASCOT-BPLA trial underlines the cardiovascular benefit of ACE inhibitors, specifically perindopril, beyond that provided by BP reduction, and potentially reflects a mechanistic feature of the ACE inhibitors. It also suggests that the combination of amlodipine plus perindopril may provide broad-spectrum cardiovascular protection, as well as reduce the incidence of new-onset diabetes mellitus and renal impairment, in addition to its efficacy in lowering BP. The ASCOT-BPLA trial provides evidence of the need to reconsider traditional prescribing recommendations in patients with hypertension, particularly conclusions reached in the US after the publication of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) study. The recently published National Institute for Health and Clinical Excellence (NICE) guidelines in the UK emphasize the efficacy of ACE inhibitors as first-line agents for hypertensive patients <55 years of age and recommend ACE inhibitor therapy at any stage of hypertension management.