Physicians' Academy for Cardiovascular Education

Hypertension: Long-term CV benefits with intervention for BP and cholesterol

Long-term mortality after blood pressure-lowering and lipid-lowering treatment in patients with hypertension in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy study: 16-year follow-up results of a randomized factorial trial

Literature - Gupta A, Mackay J, Whitehouse A et al. - The Lancet 2018; published online ahead of print DOI:

Introduction and methods

Long-term cardiovascular (CV) benefits have been reported for hypertension trials comparing active drug treatment with placebo, in which substantial in-trial blood pressure (BP) differences were observed [1]. However, only few long-term CV event and mortality follow-up data are available from more recent trials with two active treatments [2]. Although long-term follow-up studies of placebo-controlled statin trials with persistent benefits have been reported [3-5], none involved patients with hypertension who were also assigned interventions with different antihypertensive strategies. This sub-analysis of the Anglo-Scandinavian Cardiac Outcomes (ASCOT) trial therefore evaluated the long-term effect of original BP-lowering (BPL) regimens and lipid-lowering (LL) treatment on all-cause and cause-specific mortality outcomes in hypertensive patients.

ASCOT Legacy involved long-term follow up of the 8,580 UK-based patients from the original ASCOT trial [6]. The ASCOT trial study was a multicenter randomized trial with a 2x2 factorial design comparing amlodipine-based (n=4,305) versus atenolol-based (n=4,275) BPL therapy in 8,580 hypertensive patients aged 40-79 year. Of these patients, those with total cholesterol levels of ≤6.5 mmol/L, no previous lipid treatment with statins or fibrates and at least three additional risk factors for CVD were further randomized to receive either atorvastatin-based LL therapy (n=2,317) or placebo (n=2,288). The remaining patients formed the non-LL (NLL) treatment arm. Subjects with history of coronary heart disease (CHD) events, currently treated angina, or a cerebrovascular event within three months of randomization were excluded.

The primary outcome was non-fatal myocardial infarction and fatal CHD, which was adjudicated independently by two physicians.

Main results


The legacy outcomes from the ASCOT trial show the long-term benefits of antihypertensive treatment with a calcium channel blocker-based regimen and cholesterol-lowering treatment with a statin for reducing CV mortality, 16 years after entry into the trial and more than 10 years after its closure. The fact that interventions for BP and cholesterol are associated with long-term benefits on CV outcomes is supported by these data.

Editorial comment

In an editorial comment [7], Suzanne Oparil, MD, and Richard H. Fu say a major limitation of the study is that when the trial ended the researchers no longer had access to nonfatal cardiovascular disease outcomes or to antihypertensive and lipid-lowering medications being taken by the participants. Therefore, it is hard to say for certain that the short period of being on the medications translated to legacy effects so many years later. They say the study raises the issue of the need for properly recording and allowing access to long-term data on patients enrolled in clinical trials. “With such information, legacy studies could gather more meaningful findings by studying patients categorized into distinct groups based on post-trial or pre-follow-up variables,” they write.


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