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, beta blockers, and angiotensin converting enzyme inhibitors in the secondary prevention of all cause mortality in patients with ischaemic heart disease.


METHODS
Open prospective cohort study with nested case-control analysis.


METHODS
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.


METHODS
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.


METHODS
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, beta 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 beta blockers (83% reduction, 95% confidence interval 77% to 88%); statins, aspirin, beta 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 beta 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 beta 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.
Hippisley-Cox
Julia
J
Division of Primary Care, School of Community Health Sciences, University Park, Nottingham NG2 7RD. julia.hippisley-cox@nottingham.ac.uk
Coupland
Carol
C
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000368:Aged; D000369:Aged, 80 and over; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004812:Epidemiologic Methods; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D017202:Myocardial Ischemia / Q000401:mortality / Q000517:prevention & control*; D006113:United Kingdom / Q000453:epidemiology
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D001241:Aspirin