The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) Legacy Study is a UK based trial that reports long-term beneficial effects of antihypertensives and statins in terms of mortality and cardiovascular outcomes after 16 years of follow-up in patients with hypertension.
While previous hypertension trials comparing active drug treatment with placebo have reported substantial post-randomization blood pressure differences between the two groups, long-term post-trial follow-up data from trials comparing active treatments are scant. While there have been long-term follow-up studies showing the persistent benefit of previously assigned statin therapy, no prior long-term study has involved hypertensives who were assigned interventions with different antihypertensive strategies. Gupta et al. designed this UK-based, multicenter, randomized trial, with a 2 × 2 factorial design, conducted in hypertensives, with a follow up duration of a median of 15·7 years (IQR 9·7–16·4 years), which aimed to evaluate patients for all-cause and cardiovascular mortality to compare two antihypertensive treatment strategies and, using a factorial design, to also compare atorvastatin with placebo. The study was designed such that patients enrolled in the blood pressure-lowering arm (BPLA) of ASCOT were randomized to receive either amlodipine-based or atenolol-based blood pressure-lowering treatment. Moreover, those who had total cholesterol of ≤ 6·5 mmol/L and no previous lipid-lowering treatment were further randomized to receive either atorvastatin or placebo as part of the lipid-lowering arm (LLA) of ASCOT. The rest of the patients comprised the non-LLA group. All causes of death were independently adjudicated by a team of two physicians.
“To our knowledge, we report for the first time that the legacy benefit from the amlodipine-based regimen in terms of reducing the risk of stroke mortality seems to be independent of blood pressure levels achieved. Our data contribute to evidence to support the long-term benefits of statins for reducing cardiovascular mortality.”- Dr. Ajay Gupta, M.D.
In the study, Gupta et al. found that out of a total 8580 UK-based patients, 38·3% died, including 38·4% of 4275 and 38·1% of 4305 assigned to atenolol-based and amlodipine-based treatment respectively. In the LLA arm, the percentage of deaths was 39·5% and 37·3% of those assigned atorvastatin. An aggregate of 36·9% of all deaths was from cardiovascular-related causes. Patients in the BPLA arm had no overall difference in all-cause mortality between treatments (adjusted hazard ratio [HR] 0·90, 95% CI 0·81–1·01, p=0·0776]), however, significantly fewer deaths from stroke (adjusted HR 0·71, 0·53–0·97, p=0·0305) occurred in the amlodipine-based treatment group as compared to the atenolol-based treatment group. There was no interaction between treatment allocation in the BPLA and in the LLA. In the non-LLA group, however, fewer cardiovascular deaths (adjusted HR 0·79, 0·67–0·93, p=0·0046) occurred among those assigned to amlodipine-based treatment as compared with those on atenolol-based treatment (p=0·022). In the LLA arm, significantly fewer cardiovascular deaths (HR 0·85, 0·72–0·99, p=0·0395) occurred among patients assigned to statin than those assigned to placebo.
By demonstrating that patients on amlodipine-based treatment had fewer stroke deaths and patients on atorvastatin had fewer cardiovascular deaths over 10 years after trial closure, the ASCOT Legacy study supported the notion that interventions for blood pressure and cholesterol were associated with long-term benefits on cardiovascular outcomes. The authors stated, “To our knowledge, we report for the first time that the legacy benefit from the amlodipine-based regimen in terms of reducing the risk of stroke mortality seems to be independent of blood pressure levels achieved. Our data contribute to evidence to support the long-term benefits of statins for reducing cardiovascular mortality.”
Leave a Reply
You must be logged in to post a comment.