Blood pressure control and benefits of antihypertensive therapy: does it make a difference which agents we use?

This article debates the important question of whether blood pressure lowering alone is responsible for the benefits accrued from antihypertensive therapy as demonstrated in many multicenter randomized clinical trials with different antihypertensive agents or whether there is evidence that some agents have special properties that result in benefits that go beyond those resulting from lowering blood pressure. Over the past >/=30 years, it has been demonstrated beyond any doubt that lowering blood pressure in severe forms of hypertension, and more recently in systolic and even mild hypertension, will result in reduced incidence of stroke and slower progression of heart and renal failure. These effects have been easier to demonstrate in sicker patients, because enough end points may be counted in the 3 to 5 years that these clinical trials last. However, risk attributable to high blood pressure comes, to a greater degree, from the much larger group of hypertensive individuals who have less severe forms of hypertension. Blood pressure lowering offers less protection from coronary heart disease, which is highly prevalent in hypertensive patients, than from stroke. With the introduction of agents such as renin-angiotensin system inhibitors or calcium channel blockers, it has been demonstrated that hypertensive vascular remodeling and endothelial dysfunction may be corrected. It has therefore been suggested that benefits beyond blood pressure lowering may be achieved with the use of specific drugs to lower blood pressure. Although some evidence suggests that this may be the case, it is difficult to extrapolate from mechanistic studies to prevention of hard end points in outcome trials and vice versa. The question remains for the time being largely unanswered.