Raisa Levin

BACKGROUND: Adherence to medications that are prescribed after myocardial infarction is poor. Eliminating out-of-pocket costs may increase adherence and improve outcomes. METHODS: We enrolled patients discharged after myocardial infarction and randomly assigned their insurance-plan sponsors to full prescription coverage (1494 plan sponsors with 2845 patients) or usual prescription coverage (1486 plan sponsors with 3010 patients) for all statins, beta-blockers, angiotensin-converting-enzyme inhibitors, or angiotensin-receptor blockers. The primary outcome was the first major vascular event or revascularization. Secondary outcomes were rates of medication adherence, total major vascular events or revascularization, the first major vascular event, and health expenditures. RESULTS: Rates of adherence ranged from 35.9 to 49.0% in the usual-coverage group and were 4 to 6 percentage points higher in the full-coverage group (P<0.001 for all comparisons). There was no significant between-group difference in the primary outcome (17.6 per 100 person-years in the full-coverage group vs. 18.8 in the usual-coverage group; hazard ratio, 0.93; 95% confidence interval [CI], 0.82 to 1.04; P=0.21). The rates of total major vascular events or revascularization were significantly reduced in the full-coverage group (21.5 vs. 23.3; hazard ratio, 0.89; 95% CI, 0.90 to 0.99; P=0.03), as was the rate of the first major vascular event (11.0 vs. 12.8; hazard ratio, 0.86; 95% CI, 0.74 to 0.99; P=0.03). The elimination of copayments did not increase total spending ($66,008 for the full-coverage group and $71,778 for the usual-coverage group; relative spending, 0.89; 95% CI, 0.50 to 1.56; P=0.68). Patient costs were reduced for drugs and other services (relative spending, 0.74; 95% CI, 0.68 to 0.80; P<0.001). CONCLUSIONS: The elimination of copayments for drugs prescribed after myocardial infarction did not significantly reduce rates of the trial's primary outcome. Enhanced prescription coverage improved medication adherence and rates of first major vascular events and decreased patient spending without increasing overall health costs. (Funded by Aetna and the Commonwealth Fund; MI FREEE ClinicalTrials.gov number, NCT00566774.).

BACKGROUND: Although cyclooxygenase-2 inhibitors (coxibs) were developed to cause less gastrointestinal hemorrhage than nonselective nonsteroidal antiinflammatory drugs (NSAIDs), there has been concern about their cardiovascular safety. We studied the relative risk of acute myocardial infarction (AMI) among users of celecoxib, rofecoxib, and NSAIDs in Medicare beneficiaries with a comprehensive drug benefit. METHODS AND RESULTS: We conducted a matched case-control study of 54 475 patients 65 years of age or older who received their medications through 2 state-sponsored pharmaceutical benefits programs in the United States. All healthcare use encounters were examined to identify hospitalizations for AMI. Each of the 10 895 cases of AMI was matched to 4 controls on the basis of age, gender, and the month of index date. We constructed matched logistic regression models including indicators for patient demographics, healthcare use, medication use, and cardiovascular risk factors to assess the relative risk of AMI in patients who used rofecoxib compared with persons taking no NSAID, taking celecoxib, or taking NSAIDs. Current use of rofecoxib was associated with an elevated relative risk of AMI compared with celecoxib (odds ratio [OR], 1.24; 95% CI, 1.05 to 1.46; P=0.011) and with no NSAID (OR, 1.14; 95% CI, 1.00 to 1.31; P=0.054). The adjusted relative risk of AMI was also elevated in dose-specific comparisons: rofecoxib < or =25 mg versus celecoxib < or =200 mg (OR, 1.21; 95% CI, 1.01 to 1.44; P=0.036) and rofecoxib >25 mg versus celecoxib >200 mg (OR, 1.70; 95% CI, 1.07 to 2.71; P=0.026). The adjusted relative risks of AMI associated with rofecoxib use of 1 to 30 days (OR, 1.40; 95% CI, 1.12 to 1.75; P=0.005) and 31 to 90 days (OR, 1.38; 95% CI, 1.11 to 1.72; P=0.003) were higher than >90 days (OR, 0.96; 95% CI, 0.72 to 1.25; P=0.8) compared with celecoxib use of similar duration. Celecoxib was not associated with an increased relative risk of AMI in these comparisons. CONCLUSIONS: In this study, current rofecoxib use was associated with an elevated relative risk of AMI compared with celecoxib use and no NSAID use. Dosages of rofecoxib >25 mg were associated with a higher risk than dosages < or =25 mg. The risk was elevated in the first 90 days of use but not thereafter.

BACKGROUND: Whether the use of selective serotonin-reuptake inhibitors (SSRIs) and other antidepressants during pregnancy is associated with an increased risk of congenital cardiac defects is uncertain. In particular, there are concerns about a possible association between paroxetine use and right ventricular outflow tract obstruction and between sertraline use and ventricular septal defects. METHODS: We performed a cohort study nested in the nationwide Medicaid Analytic eXtract for the period 2000 through 2007. The study included 949,504 pregnant women who were enrolled in Medicaid during the period from 3 months before the last menstrual period through 1 month after delivery and their liveborn infants. We compared the risk of major cardiac defects among infants born to women who took antidepressants during the first trimester with the risk among infants born to women who did not use antidepressants, with an unadjusted analysis and analyses that restricted the cohort to women with depression and that used propensity-score adjustment to control for depression severity and other potential confounders. RESULTS: A total of 64,389 women (6.8%) used antidepressants during the first trimester. Overall, 6403 infants who were not exposed to antidepressants were born with a cardiac defect (72.3 infants with a cardiac defect per 10,000 infants), as compared with 580 infants with exposure (90.1 per 10,000 infants). Associations between antidepressant use and cardiac defects were attenuated with increasing levels of adjustment for confounding. The relative risks of any cardiac defect with the use of SSRIs were 1.25 (95% confidence interval [CI], 1.13 to 1.38) in the unadjusted analysis, 1.12 (95% CI, 1.00 to 1.26) in the analysis restricted to women with depression, and 1.06 (95% CI, 0.93 to 1.22) in the fully adjusted analysis restricted to women with depression. We found no significant association between the use of paroxetine and right ventricular outflow tract obstruction (relative risk, 1.07; 95% CI, 0.59 to 1.93) or between the use of sertraline and ventricular septal defects (relative risk, 1.04; 95% CI, 0.76 to 1.41). CONCLUSIONS: The results of this large, population-based cohort study suggested no substantial increase in the risk of cardiac malformations attributable to antidepressant use during the first trimester. (Funded by the Agency for Healthcare Research and Quality and the National Institutes of Health.).

OBJECTIVES: To propose standardized methods for measuring concurrent adherence to multiple related medications and to apply these definitions to a cohort of patients with diabetes mellitus. STUDY DESIGN: Retrospective cohort study of 7567 subjects with diabetes prescribed 2 or more classes of oral hypoglycemic agents in 2005. METHODS: For each medication class, adherence for each patient was estimated using prescription-based and interval-based measures of proportion of days covered (PDC) from cohort entry until December 31, 2006. Concurrent adherence was calculated by applying these 2 measures in the following 3 ways: (1) the mean of each patient's average PDC, (2) the proportion of days during which patients had at least 1 of their medications available to them, and (3) the proportion of patients with a PDC of at least 80% for all medication classes. Because patients taking multiple related medications have distinct patterns of use, the analysis was repeated after classifying patients into mutually exclusive groups. RESULTS: Concurrent medication adherence ranged from 35% to 95% depending on the definition applied. Interval-based measures provide lower estimates than prescription-based techniques. Definitions that require the use of at least 1 drug class categorize virtually all patients as adherent. Requiring patients to have a PDC of at least 80% for each of their drugs results in only 30% to 40% of patients being defined as adherent. The variability in adherence is greatest for patients whose treatment regimen changed the most during follow-up. CONCLUSIONS: The variability in adherence estimates derived from different definitions may substantially impact qualitative conclusions about concurrent adherence to related medications. Because the measures we propose have different underlying assumptions, the choice of technique should depend on why adherence is being evaluated.