Selective Prescribing Led to Overestimation of the Benefits of Lipid-lowering Drugs

Objective: Observational studies have found beneficial effects of lipid-lowering drugs on diverse outcomes, including venous thromboembolism, hip fracture, dementia, and all-cause mortality. Selective use of these drugs in frail people may confound these relationships.

Study Design And Setting: We measured 1-year mortality in two cohorts of New Jersey residents, aged 65-99 years, enrolled in state-sponsored drug benefits programs: 112,463 persons hospitalized during the years 1991-1994 and 106,838 nonhospitalized enrollees. Use of lipid-lowering drugs and other medications, as well as diagnoses, were evaluated before follow-up.

Results: In age- and sex-adjusted analyses, users of lipid-lowering drugs had a 43% reduced death rate relative to nonusers among hospitalized enrollees and a 56% reduction in the nonhospitalized sample. Available markers of frailty and comorbidity predicted decreased use of these drugs. Control for the propensity to use lipid-lowering drugs attenuated but did not eliminate these effects. After such adjustment, users had a 30% reduction in death rate (95% confidence interval [CI]: 25%-35%) among hospitalized enrollees and a 41% reduction (95% CI: 35%-47%) in the nonhospitalized sample. Unmeasured frailty associated with a 26%-33% reduced odds of receiving lipid-lowering therapy could explain this effect.

Conclusion: Frailty and comorbidity that influence use of preventive therapies can substantially confound apparent benefits of lipid-lowering drugs on outcomes.