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

• Published in: Heart (British Cardiac Society) Vol. 111; no. 16; pp. 769 - 775
• Main Authors: Sever, Peter S, Rostamian, Somayeh, Whiteley, William, Ariti, Cono, Godec, Thomas, Gupta, Ajay, Mackay, Judith, Whitehouse, Andrew, Poulter, Neil R, Aldegather, Jehad, Collier, David, Delles, Christian, Dyker, Alexander, Eaton, Mike, Heller, Simon, Hildick-Smith, David, Kristinsson, Arni, Lip, Greg, MacGregor, Graham, MacDonald, Tom, Milward, Ann, O’Hare, Paul, Reckless, John, Shakespeare, Carl, Handrean, Soran, Stanley, Adrian, Stokes, Jacqueline, Thom, Simon, Webster, John
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd and British Cardiovascular Society 01.08.2025; BMJ Publishing Group LTD
• Subjects: Aged; Angina pectoris; Anticholesteremic Agents - therapeutic use; atherosclerosis; Atorvastatin; Blood pressure; Cardiac risk factors and prevention; Cardiovascular disease; cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - mortality; Cardiovascular Diseases - prevention & control; Cholesterol; Female; Follow-Up Studies; Heart attacks; Heart failure; Heptanoic Acids - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; hyperlipidemias; Hypertension; Hypertension - complications; Hypertension - drug therapy; Incidence; Lipids; Male; Middle Aged; Mortality; pharmacology, clinical; Public health; Pyrroles - therapeutic use; Statins; Stroke; Time Factors; Treatment Outcome; United Kingdom - epidemiology; United Kingdom; United Kingdom > UK; England; Scotland; atherosclerosis; pharmacology, clinical; cardiovascular diseases; hyperlipidemias
• ISSN: 1355-6037; 1468-201X
• DOI: 10.1136/heartjnl-2024-325104

AimsCardiovascular (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.MethodsA 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.ResultsPatients 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.ConclusionsThese 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.