Raisa Levin

A Cohort Study of Thiazolidinediones and Fractures in Older Adults with Diabetes

CONTEXT Thiazolidenediones (TZDs) are selective ligands of peroxisome-proliferator-activated receptor-gamma and have been shown to reduce bone mineral density. Recent results from several randomized controlled trials find an increased risk of fracture with TZDs compared with other oral antidiabetic agents. OBJECTIVE The aim of the study was to determine the association between TZD use and fracture risk among older adults with diabetes. DESIGN We conducted a cohort study. PARTICIPANTS Medicare beneficiaries with at least one diagnosis of diabetes initiating monotherapy for an oral hypoglycemic agent participated in the study. MAIN OUTCOME We measured the incidence of fracture within the cohort. RESULTS Among the 20,964 patients with diabetes eligible for this study, 686 (3.3%) experienced a fracture during the median follow-up of approximately 10 months. Although not statistically significant, patients using only a TZD were more likely to experience a fracture than those using metformin (adjusted relative risk, 1.31; 95% confidence interval, 0.98-1.77; P = 0.071) or a sulfonylurea (adjusted relative risk, 1.21; 95% confidence interval, 0.94-1.55; P = 0.12). Each individual TZD was associated with an increased risk, with confidence intervals overlapping unity, compared with both metformin and sulfonylureas. The adjusted risk of any fracture associated with TZD use compared with metformin was elevated for non-insulin-using patients, women and men. If TZD use is associated with fractures, the number needed for one excess fracture when comparing TZD users to sulfonylurea users was 200, and the number was 111 when comparing TZDs with metformin. CONCLUSIONS As has been found with other analyses, our data suggest that TZDs may be associated with an increased risk of fractures compared with oral sulfonylureas and metformin.

Comparison of Cardiovascular Outcomes in Elderly Patients With Diabetes Who Initiated Rosiglitazone vs Pioglitazone Therapy

BACKGROUND Recent meta-analyses have raised the possibility that rosiglitazone maleate may increase the risk of ischemic cardiovascular events, whereas pioglitazone hydrochloride could not be linked to such a risk. We compared cardiovascular outcomes and mortality between patients initiating pioglitazone vs rosiglitazone therapy. METHODS We assembled an inception cohort of Medicare beneficiaries older than 65 years with state-sponsored prescription drug benefits who had diabetes mellitus and initiated treatment with rosiglitazone or pioglitazone between January 1, 2000, and December 31, 2005. The study outcomes included all-cause mortality, myocardial infarction, stroke, and hospitalization for congestive heart failure. RESULTS Of 28 361 patients selected, 50.3% initiated treatment with pioglitazone and 49.7% with rosiglitazone. Most baseline characteristics were similar between the groups. As preferred in drug safety research, we censored patients at crossover or at 60 days after discontinuation of therapy with their study drug; during 29 060 person-years of follow-up, 1869 patients died. After adjustment for a large number of patient characteristics, Cox regression models revealed 15% greater mortality among patients who initiated therapy with rosiglitazone compared with pioglitazone (95% confidence interval, 5%-26%). Use of rosiglitazone was also associated with a 13% greater risk of congestive heart failure (95% confidence interval, 1%-26%). No differences between the 2 drugs were found in their rates of myocardial infarction or stroke. CONCLUSIONS Our findings from a large population-based cohort of US seniors are compatible with an increased risk of all-cause mortality and congestive heart failure in patients initiating therapy with rosiglitazone compared with similar patients initiating therapy with pioglitazone. Limitations of this study include residual confounding due to its nonrandomized nature.

Relationship Between Selective Cyclooxygenase-2 Inhibitors and Acute Myocardial Infarction in Older Adults

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 ≤25 mg versus celecoxib ≤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 ≤25 mg. The risk was elevated in the first 90 days of use but not thereafter.

Full Coverage for Preventive Medications after Myocardial Infarction

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 (

A combined comorbidity score predicted mortality in elderly patients better than existing scores

66,008 for the full-coverage group and

The Comparative Safety of Analgesics in Older Adults With Arthritis

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 trials 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.).

The effects of initial drug choice and comorbidity on antihypertensive therapy compliance: results from a population-based study in the elderly.

OBJECTIVE To develop and validate a single numerical comorbidity score for predicting short- and long-term mortality, by combining conditions in the Charlson and Elixhauser measures. STUDY DESIGN AND SETTING In a cohort of 120,679 Pennsylvania Medicare enrollees with drug coverage through a pharmacy assistance program, we developed a single numerical comorbidity score for predicting 1-year mortality, by combining the conditions in the Charlson and Elixhauser measures. We externally validated the combined score in a cohort of New Jersey Medicare enrollees, by comparing its performance to that of both component scores in predicting 1-year mortality, as well as 180-, 90-, and 30-day mortality. RESULTS C-statistics from logistic regression models including the combined score were higher than corresponding c-statistics from models including either the Romano implementation of the Charlson Index or the single numerical version of the Elixhauser system; c-statistics were 0.860 (95% confidence interval [CI]: 0.854, 0.866), 0.839 (95% CI: 0.836, 0.849), and 0.836 (95% CI: 0.834, 0.847), respectively, for the 30-day mortality outcome. The combined comorbidity score also yielded positive values for two recently proposed measures of reclassification. CONCLUSION In similar populations and data settings, the combined score may offer improvements in comorbidity summarization over existing scores.

Compliance with antihypertensive therapy among elderly Medicaid enrollees: the roles of age, gender, and race.

BACKGROUND The safety of alternative analgesics is unclear. We examined the comparative safety of nonselective NSAIDs (nsNSAIDs), selective cyclooxygenase 2 inhibitors (coxibs), and opioids. METHODS Medicare beneficiaries from Pennsylvania and New Jersey who initiated therapy with an nsNSAID, a coxib, or an opioid from January 1, 1999, through December 31, 2005, were matched on propensity scores. We studied the risk of adverse events related to analgesics using incidence rates and adjusted hazard ratios (HRs) from Cox proportional hazards regression. RESULTS The mean age of participants was 80.0 years, and almost 85% were female. After propensity score matching, the 3 analgesic cohorts were well balanced on baseline covariates. Compared with nsNSAIDs, coxibs (HR, 1.28; 95% confidence interval [CI], 1.01-1.62) and opioids (1.77; 1.39-2.24) exhibited elevated relative risk for cardiovascular events. Gastrointestinal tract bleeding risk was reduced for coxib users (HR, 0.60; 95% CI, 0.35-1.00) but was similar for opioid users. Use of coxibs and nsNSAIDs resulted in a similar risk for fracture; however, fracture risk was elevated with opioid use (HR, 4.47; 95% CI, 3.12-6.41). Use of opioids (HR, 1.68; 95% CI, 1.37-2.07) but not coxibs was associated with an increased risk for safety events requiring hospitalization compared with use of nsNSAIDs. In addition, use of opioids (HR, 1.87; 95 CI, 1.39-2.53) but not coxibs raised the risk of all-cause mortality compared with use of nsNSAIDs. CONCLUSIONS The comparative safety of analgesics varies depending on the safety event studied. Opioid use exhibits an increased relative risk of many safety events compared with nsNSAIDs.

A Propensity Analysis of Late Versus Early Nephrologist Referral and Mortality on Dialysis

Approximately half of all elderly patients have elevated blood pressure, and proper treatment of this disorder leads to decreased cardiovascular morbidity in patients 65 and older. This study examined the effect of initial drug choice and comorbidity on medication compliance. We conducted a retrospective follow-up of 8643 outpatients aged 65 to 99 with newly prescribed antihypertensive therapy (AHT) from 1982 to 1988 in the New Jersey Medicaid and Medicare programs. Compliance was measured in terms of the number of days in which AHT was available to the patient during the 12 months following the initiation of therapy. Odds ratios (OR) and 95% confidence intervals (CI) for the outcome of good compliance (> or =80%) were calculated. In a logistic regression model, good compliance (> or =80%) was significantly associated with use of newer agents such as angiotensin converting enzyme inhibitors (OR 1.9, 95% CI 1.6 to 2.2) and calcium channel blockers (OR 1.7, 95% CI 1.5 to 2.1) as compared to thiazides, the presence of comorbid cardiac disease (OR 1.2, 95% CI 1.1 to 1.2), and multiple physician visits (OR 2.2, 95% CI 1.8 to 2.5). Good compliance was inversely associated with use of multiple pharmacies (OR 0.4, 95% CI 0.4 to 0.5) and number of medications prescribed overall (OR 0.8, 95% CI 0.7 to 0.9). Drug choice, comorbidity, and health services utilization were significantly associated with AHT compliance and represent important considerations in the management of high blood pressure. Noncompliance may be an important cause of treatment failure in elderly hypertensives.

Improvements in long-term mortality after myocardial infarction and increased use of cardiovascular drugs after discharge: a 10-year trend analysis.

OBJECTIVES This study measured compliance and related demographic factors in a retrospective cohort of 4068 elderly outpatients newly starting antihypertensive therapy from 1982 through 1988. METHODS Logistic regression modeling of data from the New Jersey Medicaid program was used. RESULTS These patients filled antihypertensive prescriptions covering an average of only 179 days in the 365-day follow-up period (49%) Good compliance (> or = 80%) was associated with advanced age (odds ratio [OR] = 2.12, for patients 85 or older) and White race (OR = 0.55 for Blacks). There was no relationship between compliance and gender. CONCLUSIONS Despite the efficacy of antihypertensive therapy in preventing cardiovascular morbidity, such high rates of noncompliance may contribute to suboptimal patient outcomes.