Long-term benefits of atorvastatin on the incidence of cardiovascular events: the ASCOT-Legacy 20-year follow-up.

Aims: Cardiovascular (CV) deaths were reduced by atorvastatin during a 16-year follow-up of participants in the Anglo-Scandinavian Cardiac Outcomes Trial-lipid-lowering arm. We now extend these observations over 20 years and report both non-fatal and fatal CV outcomes.

Methods: A cohort of 4605 UK hypertensive participants with total cholesterol <6.5 mmol/L (2317 atorvastatin vs 2288 placebo) was followed for up to 21 years (IQR 9.1-19.3). Cox proportional hazard models assessed HRs for non-fatal and fatal CV events. At the end of the original trial (3.3 years), all participants were offered atorvastatin. Lipid profiles were obtained from all subjects 2 years later and from subgroups approximately 9 years post-trial.

Results: Patients allocated to atorvastatin had a significant reduction in non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD) events (HR (95% CI) 0.81 (0.69 to 0.94, p=0.006)), total coronary events (0.88 (0.80 to 0.98, p=0.017)) and CV deaths (0.86 (0.74 to 0.99, p=0.048)). No significant reduction in heart failure (HF), strokes, total CV events and all-cause mortality was observed.In participants assigned atorvastatin in the trial, 3-year mean low-density lipoprotein-cholesterol was strongly associated with long-term CV outcomes. The HRs per 1 mmol/L decrease were for non-fatal MI and fatal CHD (0.69 (0.57 to 0.85, p<0.001)), total coronary events (0.70 (0.61 to 0.79, p<0.001)), non-fatal and fatal HF (0.68 (0.57 to 0.81, p<0.001)), non-fatal and fatal stroke (0.74 (0.59 to 0.92, p=0.006)), total CV events and procedures (0.74 (0.66 to 0.81, p<0.001)), CV mortality (0.66 (0.55 to 0.81, p<0.001)) and all-cause mortality (0.81 (0.71 to 0.90, p<0.001)).Two years after the trial, approximately two-thirds of subjects in each arm were taking atorvastatin. At this time point and approximately 9 years post-trial, lipid profiles were similar between those formerly assigned atorvastatin or placebo.

Conclusions: These observations provide further evidence for the long-term legacy effects of statins and have implications for the early introduction of statins to prevent CV events and mortality.