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

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.