Outcome beyond blood pressure control?

The last two decades witnessed the publication of a large number of clinical outcome trials of blood pressure lowering agents in hypertensive patients or normotensive subjects with a high cardiovascular risk profile. Placebo-controlled trials of antihypertensive drug treatment in middle-aged or older hypertensive patients predominantly with diastolic hypertension1 proved that a 5–6mmHg decline in diastolic pressure maintained over 5 years diminished the incidence of stroke by nearly 40% and that of coronary endpoints by 15%. Similarly, in older patients with isolated systolic hypertension, pharmacological intervention during 4 years reduced systolic pressure on average by 10mmHg and decreased cardiovascular mortality by 18%, all cardiovascular complications by 26%, stroke by 30%, and coronary events by 23%.2 Until recently, the consensual interpretation of the evidence produced by the outcome trials in hypertensive patients3–39 was that blood pressure is a risk factor amenable to intervention, lower levels leading to fewer complications. However, the HOPE trial40,41 gave rise to the hypothesis that angiotensin-converting enzyme inhibitors (ACEIs) might reduce cardiovascular complications beyond blood pressure control. Subsequently published trials of angiotensin II receptor blockers (ARBs) in hypertensive patients with renal failure42–44 or left ventricular hypertrophy45,46 turned this concept into a major argument for drug marketing. The objectives of this editorial are to highlight the contribution of blood pressure lowering in the prevention of cardiovascular complications and to propose from a scientific perspective new research priorities for clinical trials in hypertension. We recently reviewed nine outcome trials in 62,605 hypertensive patients, who had been randomized to conventional therapy with diuretics or β-blockers or to initial treatment with newer classes of antihypertensive drugs, such as calcium-channel blockers (CCBs), ACEIs, or α-blockers.47 Compared with conventional therapy, CCBs and ACEIs offered similar overall cardiovascular protection, but CCBs provided more reduction in the risk of …