Placebo controls can enhance the value of two types of hypertension trials: measurement of the blood pressure-lowering efficacy of antihypertensive treatment and determination of whether therapeutic interventions can affect clinical endpoints. However, the possibility of adverse outcomes in hpertensive patients allocated to placebo therapy raises ethical concerns.
Placebo controls in efficacy studies are particularly helpful in thoroughly quantifying the effect of treatment. The hazard to patients can be minimized by exposing them to placebo for the least possible amount of time and, assuming that blood pressure is itself the primary variable, reducing the probability of cardiovascular events by excluding subjects with severe hypertension or major concomitant risk factors.
Endpoint studies present a more difficult challenge, for they are designed in anticipation of cardiovascular events and patients at high risk are often enrolled in order to more rapidly achieve the required number of endpoints for statistical analysis. In such circumstances, positive therapeutic controls, despite the complexities of analysis, must be preferred to placebo.
Important questions regarding the management of early-stage hypertension remain, and despite official treatment guidelines recommendations, currently based chiefly on extrapolation and judgement, many physicians routinely withhold therapy in mild hypertension, even when other risk factors are present. With appropriate safeguards, placebo-controlled trials may be necessary to examine potenial benefits of therapy in such patients. Indeed, resolving therapeutic uncertainty and creating well founded recommendations for the future management of the many patients with milder forms of hypertension can make placebo controls both ethical and appropriate.
1Department of Medicine, The Brookdale University Hospital and Medical Center Brooklyn, New York, USA.
2Correspondence and requests for reprints to Dr Michael A. Weber, Department of Medicine, The Brookdale University Hospital and Medical Center, 1 Brookdale Plaza, Brooklyn, New York, NY 11212-3198, USA Tel: +1 718 240 5652; fax: +1 718 240 6618.
Received 19 October 1998 Accepted 26 October 1998