Effect of combinations of drugs on all cause mortality in patients with ischaemic heart disease: Nested case-control analysis

Objective: To determine the effect of combinations of statins, aspirin, β blockers, and angiotensin converting enzyme inhibitors in the secondary prevention of all cause mortality in patients with ischaemic heart disease. Design: Open prospective cohort study with nested case-control analysis. Setting: 1.18 million patients registered with 89 general practices across 23 strategic health authority areas within the United Kingdom. Practices had longitudinal data for a minimum of eight years and were contributing to QRESEARCH, a new database. Patients: All patients with a first diagnosis of ischaemic heart disease between January 1996 and December 2003. Cases were patients with ischaemic heart disease who died. Controls were patients with ischaemic heart disease who were matched for age, sex, and year of diagnosis and were alive at the time their matched case died. Main outcome measures: Odds ratio with 95% confidence interval for risk of death in cases compared with controls. Exposure was current use of different combinations of statins, aspirin, β blockers, and angiotensin converting enzyme inhibitors before death in cases, or the equivalent date in controls. Results: 13 029 patients had a first diagnosis of ischaemic heart disease (incidence rate 338 per 100 000 person years). 2266 cases were matched to 9064 controls. Drug combinations associated with the greatest reduction in all cause mortality were statins, aspirin, and β blockers (83% reduction, 95% confidence interval 77% to 88%); statins, aspirin, β blockers, and angiotensin converting enzyme inhibitors (75% reduction, 65% to 82%); and statins, aspirin, and angiotensin converting enzyme inhibitors (71% reduction, 59% to 79%). Treatments associated with the smallest reduction in all cause mortality were β blockers alone (19% reduction, 37% reduction to 4% increase), angiotensin converting enzyme inhibitors alone (20% reduction, 1% to 35%), and combined statins and angiotensin converting enzyme inhibitors (31% reduction, 57% reduction to 12% increase). Conclusions: Combinations of statins, aspirins, and β blockers improve survival in high risk patients with cardiovascular disease, although the addition of an angiotensin converting enzyme inhibitor conferred no additional benefit despite the analysis being adjusted for congestive cardiac failure.