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These four excluded conditions were all included as covariates.The study chronic conditions included atrial fibrillation,8 coronary artery disease,6 depression10 (defined by at least two claims for depression or by self reported depression), diabetes mellitus,7 heart failure,9 hyperlipidemia,21 and hypertension.11 Though thromboembolic disease (pulmonary embolism and venous thrombosis) was present in less than 10% of the population, it was included because of its high mortality risk.22 Though no drug class met the criteria for inclusion for chronic kidney disease, we included this common chronic condition because of its effect on use of several of the study drugs and its association with mortality.Of the 20 026 participants aged 65 years or more, 2682 were Medicare Advantage participants who lacked claims data.Of the 17 344 remaining, 6984 did not have multiple chronic conditions as defined by having at least two study chronic conditions.For example, the adjusted hazard ratio for β blockers was 0.59 (95% confidence interval 0.48 to 0.72) for people with atrial fibrillation and 0.68 (0.57 to 0.81) for those with heart failure.

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The study sample included Medicare Current Beneficiary Survey participants enrolled from 2005-09, with follow-up through 2011.19 The Medicare Current Beneficiary Survey is a representative sample of Medicare—the federal health insurance for older adults and people with disabilities—beneficiaries in the United States obtained using stratified multistage sampling from the Centers for Medicare and Medicaid Services enrollment file.19 We included all participants aged 65 years or more with at least two of nine chronic conditions, identified by at least one inpatient or two other kinds of claims (outpatient, physician, skilled nursing, home health) during the first two years of participation.Not only are the benefits of drugs uncertain, greater numbers of drugs reduce adherence, compound the burden of treatment, and increase the likelihood of adverse drug effects.13 14 15 16 Strategies to determine drug effects in those with multiple conditions are needed to minimize these potential harms and burdens and to guide prescribing decisions that maximize benefits.17 Evaluating the effect of drugs on universal health outcomes such as survival, function, and symptom burden that are affected by most conditions and are important to people could lay the foundation for an evidence based approach to drug decision making for people with multiple coexisting conditions.Though randomized clinical trials remain the ideal, they are not feasible for studying all possible combinations of conditions and drugs of potential benefit for people with multiple chronic conditions.Exposures Drugs included β blockers, calcium channel blockers, clopidogrel, metformin, renin-angiotensin system (RAS) blockers; selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs); statins; thiazides; and warfarin.Main outcome measure Adjusted hazard ratios for death among participants with a condition and taking a guideline recommended drug relative to participants with the condition not taking the drug and among participants with the most common combinations of four conditions.

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