Evaluation of endpoints in hypertension.

Cardiovascular mortality is the undisputed "hard endpoint" in hypertension intervention trials. Non-fatal myocardial infarction and stroke are frequently included in this category as well. For obvious reasons, such hard endpoints are not always realistic in relatively short-term (3-5 years) trials comprising patients with a relatively low absolute risk, such as mild hypertension. Nor are they directly applicable in the daily clinical routine care of hypertensive patients. In most situations intermediate endpoints are used as substitutes for the hard endpoints. These intermediate or substitute endpoints are sometimes referred to as surrogate endpoints. The most frequently used intermediate endpoint is blood pressure itself. It is also a most relevant substitute endpoint, being easy to measure and evaluate in routine clinical practice. Blood pressure is obviously a very strong predictor of cardiovascular risks, particularly as regards stroke. An ongoing large intervention trial in hypertension, the Hypertension Optimal Treatment (HOT) Study is specifically designed to evaluate the obtained level of treated blood pressure in relation to hard endpoints such as fatal and non-fatal stroke and myocardial infarction as well as other cardiovascular mortality. In view of the strong link between blood pressure and prognosis in hypertension, as demonstrated in several epidemiologic studies, it is disappointing to note that several recent reports show that only a minority of treated hypertensive patients are well controlled.