Antihypertensive therapy and the benefits of atorvastatin in the Anglo-Scandinavian Cardiac Outcomes Trial: lipid-lowering arm extension

Peter S Sever, Neil R Poulter, Bjorn Dahlof, Hans Wedel et al.
Journal of Hypertension 2009, 27 (5): 947-54

OBJECTIVE: To determine the cardiovascular benefits of atorvastatin stratified by blood pressure-lowering regimen, 2.2 years after closure of the lipid-lowering arm (LLA) of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-LLA).

METHODS: In ASCOT-LLA, 10,305 hypertensive patients randomized to amlodipine-based or atenolol-based therapy and with a total cholesterol 6.5 mmol/l or less were further randomized to atorvastatin or placebo. ASCOT-LLA was terminated after 3.3 years median follow-up. Cardiovascular outcomes in these patients were further evaluated 2.2 years later, at the end of the blood pressure-lowering arm (BPLA).

RESULTS: By the end of BPLA in both groups originally assigned statin or placebo, approximately 65% were receiving a statin, and lipid levels had equalized. The benefits of atorvastatin observed in LLA were sustained throughout BPLA. At the end of BPLA, in those assigned amlodipine-based therapy, atorvastatin reduced coronary heart disease deaths and nonfatal myocardial infarction (MI) by 46% [hazard ratio 0.54, confidence interval (CI) 0.40-0.72, P < 0.0001], stroke by 37% [hazard ratio 0.63, CI 0.46-0.87, P = 0.004] and total cardiovascular events and procedures by 27% [hazard ratio 0.73, CI 0.63-0.86, P < 0.0001]. In the atenolol-based group, atorvastatin reduced coronary heart disease death and nonfatal MI by 25% [hazard ratio 0.75, CI 0.57-0.97, P = 0.03], stroke by 10% [hazard ratio 0.90, CI 0.69-1.18, P = 0.43] and total cardiovascular events and procedures by 13% [hazard ratio 0.87, CI 0.76-1.0, P = 0.05]. P values for heterogeneity were low, but failed to achieve statistical significance (0.10, 0.10 and 0.11 for chronic heart disease, stroke and total cardiovascular events, respectively).

CONCLUSION: Although not statistically significant, the benefits of atorvastatin appeared greater among those on amlodipine-based compared with atenolol-based therapy. These data provide supporting evidence that coassignment to atorvastatin may have generated differential effects on coronary and other cardiovascular outcomes by amlodipine-based and atenolol-based treatment in ASCOT-BPLA.

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