Toward improved antihypertensive therapy with calcium channel blockers

Outcome trials are the scientific method of determining if an antihypertensive agent really works; and for a therapy to work well, it should reduce mortality. The FDA requires only that blood pressure be controlled safely, but current evidence-based medicine demands answers to the mortality/morbidity question. We need this outcome trial information on all the classes of antihypertensives, including calcium channel blockers. For example, we often rely on surrogate endpoints such as control of blood pressure or control of PVCs. If we treat hypertensives with PVCs using beta-blockers or calcium channel blockers, we may see both control of blood pressure and suppression of PVCs. However, as we learned from the CAST trial with flecainide and encainide, PVCs can be controlled, but mortality may increase. On the other hand, the Lewis trial demonstrated that captopril, an ACE inhibitor, reduced proteinuria, which is another surrogate endpoint in diabetic hypertensives with nephropathy, although blood pressure was controlled with diuretic and conventional therapy. Importantly, captopril also reduced morbidity and mortality without influencing blood pressure. Unfortunately, there are no outcome trials measuring mortality endpoints for most of the antihypertensive agents in use today, especially in patients with uncomplicated hypertension.