Comparisons of outcomes between patients treated and untreated in observational studies may be biased due to differences in patient prognosis between groups, often because of unobserved treatment selection biases.

The objective of this study was to compare four analytic methods for removing the effects of selection bias in observation studies: multivariable model risk adjustment, propensity score risk adjustment, propensity-based matching, and instrumental variable analysis.

A national cohort of 122,124 patients who were elderly (aged 65-84 years), receiving Medicare, and hospitalized with acute myocardial infarction (AMI) in 1994-1995, and who were eligible for cardiac catheterization were assembled.  Baseline chart reviews were taken from the Cooperative Cardiovascular Project and linked to Medicare health administrative data to provide a rich set of prognostic variables.  Patients were followed for up to seven years through to December 31, 2001, to assess the association between long-term survival and cardiac catheterization within 30 days of hospital admission.  The main outcome measure was the risk-adjusted relative mortality rate using each of the analytic methods.

Patients who received cardiac catheterization (n=73,238) were younger and had lower AMI severity than those who did not.  After adjustment for prognostic factors by using standard statistical risk-adjustment methods, cardiac catheterization was associated with a 50% relative decrease in mortality (for multivariable model risk adjustment: adjusted relative risk [RR], 0.51; 95% confidence interval [CI], 0.50-0.52; for propensity score risk adjustment: adjusted RR, 0.54; 95% CI, 0.53-0.55; and for propensity-based matching: adjusted RR, 0.54; 95% CI, 0.52-0.56).  Using regional catheterization rates as an instrument, instrumental variable analysis showed a 16% relative decrease in mortality (adjusted RR, 0.84; 95% CI, 0.79-0.90).  The survival benefits of routine invasive care from randomized clinical trials are between 8% and 21%.

Estimates of the observational association of cardiac catheterization with long-term AMI mortality are highly sensitive to analytic method.  All standard risk-adjustment methods have the same limitations regarding removal of unmeasured treatment selection biases.  Compared with standard modeling, instrumental variable analysis may produce less biased estimates of treatment effects, but is more suited to answering policy questions than specific clinical questions.