Legacy Effect in the Treatment of Hypertension: Persistent Cardiovascular Protection after Conclusion of Randomized Clinical Trials in Hypertension

Abstract

Recent findings: Essential hypertension is the main determinant of cardiovascular morbidity and mortality worldwide. During the last decades, several antihypertensive drug therapies have been introduced and tested in clinical trials, both as monotherapies and combination therapies. The current recommended therapeutic approaches effectively reduce the lifetime risk of experiencing major cardiovascular outcomes and disabling comorbidities, such as myocardial infarction, stroke, and congestive heart failure. On the basis of multiple proofs, antihypertensive therapy is currently recommended for improving event-free survival rate and quality of life in different clinical settings and conditions. At the same time, other cardiovascular drugs, including novel lipid-lowering, anti-platelet, and anti-coagulation agents, have been made available and also contribute to reduce the incidence of atherothrombotic diseases.

Purpose of review: Beyond the beneficial aspects obtained by pharmacological treatment of major cardiovascular risk factors and comorbidities, including hypertension, several aspects remain to be defined. One major limitation linked to randomized, controlled clinical trials is represented by the relatively short duration of the studies, which usually ranges between 1 and 5 years. Whether antihypertensive therapy should be maintained for a longer time (after 5 years) and whether this is supported by sufficient evidence of a persisting benefit is supported by limited post-trial observations but mostly by findings derived from large clinical registries. The so-called legacy effect in the treatment of hypertension, in which patients who are treated with a given antihypertensive therapy may derive a long-term benefit after discontinuation of therapy, has been recently proposed on the basis of accumulating evidence and, in particular, on the availability of long-term post-trial observations in randomized controlled clinical trials. In this review, we discuss the evidence witnessing a legacy effect of antihypertensive therapy and whether this supports sufficiently lifetime drug treatment of hypertension.

Keywords: Cardiovascular prevention; Hypertension; Legacy effect; Myocardial infarction; Randomized clinical trials; Stroke.