Abstract Background Hyperuricemia and gout are associated with an increased risk of cardiovascular disease (CVD). It is unknown whether treating hyperuricemia with xanthine oxidase inhibitors (XOIs), ...including allopurinol and febuxostat, modifies cardiovascular risks. Methods We used US insurance claims data to conduct a cohort study among gout patients, comparing XOI initiators with non-users with hyperuricemia defined as serum uric acid level ≥6.8 mg/dL. We calculated incidence rates of a composite nonfatal cardiovascular outcome that included myocardial infarction, coronary revascularization, stroke, and heart failure. Propensity score (PS)-matched Cox proportional hazards regression compared the risk of composite cardiovascular endpoint in XOI initiators vs those with untreated hyperuricemia, controlling for baseline confounders. In a subgroup of patients with uric acid levels available, PS-matched Cox regression further adjusted for baseline uric acid levels. Results There were 24,108 PS-matched pairs with a mean age of 51 years and 88% male. The incidence rate per 1000 person-years for composite CVD was 24.1 (95% confidence interval CI 22.6-26.0) in XOI initiators and 21.4 (95% CI, 19.8-23.2) in the untreated hyperuricemia group. The PS-matched hazard ratio for composite CVD was 1.16 (95% CI, 0.99-1.34) in XOI initiators vs those with untreated hyperuricemia. In subgroup analyses, the PS-matched hazard ratio for composite CVD adjusted for serum uric acid levels was 1.10 (95% CI, 0.74-1.64) among XOI initiators. Conclusions Among patients with gout, initiation of XOI was not associated with an increased or decreased cardiovascular risk compared with those with untreated hyperuricemia. Subgroup analyses adjusting for baseline uric acid levels also showed no association between XOI and cardiovascular risk.
Abstract Background The prevalence of vascular risk factors, cardiovascular disease, and restless legs syndrome increases with age. Prior studies analyzing the associations between vascular risk ...factors, cardiovascular disease, and restless legs syndrome found controversial results. We therefore aim to evaluate the associations between prevalent vascular risk factors, prevalent cardiovascular disease, and restless legs syndrome. Methods We conducted a cross-sectional study among 22,786 participants of the US Physicians' Health Studies I and II. Restless legs syndrome was classified according to the 4 minimal diagnostic criteria. Vascular risk factors and restless legs syndrome symptoms were self-reported. Prevalent cardiovascular disease events, including major cardiovascular disease, stroke, and myocardial infarction, were confirmed by medical record review. Age- and multivariable-adjusted logistic regression models were used to evaluate the association among vascular risk factors, prevalent cardiovascular disease events, and restless legs syndrome. Results The mean age of the cohort was 67.8 years. The prevalence of restless legs syndrome was 7.5% and increased significantly with age. Diabetes significantly increased the odds of restless legs syndrome (odds ratio OR, 1.41; 95% confidence interval CI, 1.21-1.65), whereas frequent exercise (OR, 0.78; 95% CI, 0.67-0.91) and alcohol consumption of 1 or more drinks per day (OR, 0.80; 95% CI, 0.69-0.92) significantly reduced the odds of restless legs syndrome in multivariable-adjusted models. Prevalent stroke showed an increased multivariable-adjusted OR of 1.40 (1.05-1.86), whereas men with prevalent myocardial infarction had a decreased OR of 0.73 (0.55-0.97) for restless legs syndrome. Conclusions The restless legs syndrome prevalence among US male physicians is similar to that of men of the same age group in other western countries. A history of diabetes is the most consistent risk factor associated with restless legs syndrome. Prevalent stroke and myocardial infarction are related to restless legs syndrome prevalence.
Abstract Objectives Recent research suggests that rheumatoid arthritis increases the risk of venous thromboembolism. This study compared the risk of venous thromboembolism in patients with newly ...diagnosed rheumatoid arthritis initiating a biologic disease-modifying antirheumatic drug (DMARD) with those initiating methotrexate or a nonbiologic DMARD. Methods We conducted a population-based cohort study using US insurance claims data (2001-2012). Three mutually exclusive, hierarchical DMARD groups were used: (1) a biologic DMARD with and without nonbiologic DMARDs; (2) methotrexate without a biologic DMARD; or (3) nonbiologic DMARDs without a biologic DMARD or methotrexate. We calculated the incidence rates of venous thromboembolism. Cox proportional hazard models stratified by propensity score (PS) deciles after asymmetric PS trimming were used for 3 pairwise comparisons, controlling for potential confounders at baseline. Results We identified 29,481 patients with rheumatoid arthritis with 39,647 treatment episodes. From the pairwise comparison after asymmetric PS trimming, the incidence rate of hospitalization for venous thromboembolism per 1000 person-years was 5.5 in biologic DMARD initiators versus 4.4 in nonbiologic DMARD initiators and 4.8 in biologic DMARD initiators versus 3.5 in methotrexate initiators. The PS decile-stratified hazard ratio of venous thromboembolism associated with biologic DMARDs was 1.83 (95% confidence interval CI, 0.91-3.66) versus nonbiologic DMARDs and 1.39 (95% CI, 0.73-2.63) versus methotrexate. The hazard ratio of venous thromboembolism in biologic DMARD initiators was the highest in the first 180 days versus nonbiologic DMARD initiators (2.48; 95% CI, 1.14-5.39) or methotrexate initiators (1.80; 95% CI, 0.90-3.62). Conclusions The absolute risk for venous thromboembolism was low in patients with newly diagnosed rheumatoid arthritis. Initiation of a biologic DMARD seems to be associated with an increased short-term risk of hospitalization for venous thromboembolism compared with initiation of a nonbiologic DMARD or methotrexate.
Abstract Background Previous studies evaluating the association of cardiovascular disease and vascular risk factors with restless legs syndrome showed inconsistent results, especially for the ...potential relation between various vascular risk factors and restless legs syndrome. We therefore aimed to analyze the relationships between vascular risk factors, prevalent cardiovascular disease, and restless legs syndrome. Methods This is a cross-sectional study of 30,262 female health professionals participating in the Women's Health Study (WHS). Restless legs syndrome was defined according to diagnostic criteria of the International Restless Legs Study Group. Information on vascular risk factors (diabetes, hypertension, hypercholesterolemia, body mass index BMI, alcohol, smoking, exercise, and family history of myocardial infarction) was self-reported. Cardiovascular disease events (coronary revascularization, myocardial infarction, and stroke) were confirmed by medical record review. Prevalent major cardiovascular disease was defined as nonfatal stroke or nonfatal myocardial infarction. Logistic regression models were used to evaluate the association between vascular risk factors, prevalent cardiovascular disease, and restless legs syndrome. Results Of the 30,262 participants (mean age: 63.6 years), 3624 (12.0%) reported restless legs syndrome. In multivariable-adjusted models, BMI (odds ratio OR for BMI ≥ 35 kg/m2 , 1.35; 95% confidence interval CI, 1.17-1.56), diabetes (OR, 1.19; 95% CI, 1.04-1.35), hypercholesterolemia (OR, 1.17; 95% CI, 1.09-1.26), smoking status (OR for ≥ 15 cigarettes/day, 1.41; 95% CI, 1.19-1.66), and exercise (OR for exercise ≥ 4 times/week, 0.84; 95% CI, 0.74-0.95) were associated with restless legs syndrome prevalence. We found no association between prevalent cardiovascular disease (major cardiovascular disease, myocardial infarction, and stroke) and restless legs syndrome prevalence. Women who underwent coronary revascularization had a multivariable-adjusted OR of 1.39 (1.10-1.77) for restless legs syndrome. Conclusions In this large cohort of female health professionals, various vascular risk factors are associated with the prevalence of restless legs syndrome. We could not confirm the results of previous reports indicating an association between prevalent cardiovascular disease and restless legs syndrome.
Improvements in Long-Term Mortality After Myocardial Infarction and Increased Use of Cardiovascular Drugs After Discharge: A 10-Year Trend Analysis Soko Setoguchi, Robert J. Glynn, Jerry Avorn, ...Murray A. Mittleman, Raisa Levin, Wolfgang C. Winkelmayer The use of recommended cardiovascular medications after myocardial infarction (MI) has increased during the past decade. Little is known whether the increasing use of drugs contributed to the improvements in MI prognosis. Using data from Medicare and pharmacy programs in 2 states, we assessed trends in the mortality and the contribution to increasing medication use after MI in multivariate models. Among 21,484 MI patients, mortality decreased significantly with a 3% reduction in each year (1995 to 2004). Adjusting for the use of cardiovascular medications completely eliminated the mortality trend, suggesting that the mortality improvement is mainly due to increased use of these medications.
Background Advances in heart failure (HF) treatments have prolonged survival, but more patients die of HF than of any type of cancer. Little is known about the current practice in end-of-life (EOL) ...care in HF. Methods Two EOL cohorts (HF and cancer) were identified using Medicare data linked with pharmacy and cancer registry data. We assessed use of hospice, opiates, and acute care services (hospitalizations, emergency department ED visits, intensive care unit ICU admissions, and death in acute care). Time trends and predictors of use were assessed using multivariate regression including demographics and cardiovascular and noncardiovasuclar comorbidities. Results Among 5,836 HF patients with median age of 85, 77% female and 4% black, 20% were referred to hospice compared to 51% of 7,565 cancer patients. A modest rise in hospice use over time was parallel in the 2 groups. Twenty-two percent of HF patients filled opiate prescriptions during 60 days before death compared to 46% of cancer patients. Use of acute care services in the 30 days before death was higher for HF (64% vs 39% for ED visits, 60% vs 45% for hospitalizations, and 19% vs 7% for ICU admission). More HF patients died during acute hospitalizations than cancer patients (39% vs 21%). Conclusion Patients dying of HF were less likely to be supported by hospice and opiates but more likely to die in hospitals than patients with cancer. Our study suggests that opportunities may exist to improve hospice and opiate use in HF patients.
Abstract Objective To explore the “healthy user” and “healthy adherer” effects—hypothetical sources of bias thought to arise when patients who initiate and adhere to preventive therapies are more ...likely to engage in healthy behaviors than are other subjects. Methods The authors examined the association between statin initiation and adherence, and the subsequent use of preventive health services and incidence of clinical outcomes unlikely to be associated with the need for, or use of, a statin among older enrollees in two state-sponsored drug benefit programs. Results After adjustment for demographic and clinical covariates, patients who initiated statin use were more likely to receive recommended preventive services than noninitiators matched on age, sex, and state (hazard ratio HR: 1.10, 1.06–1.14 for males, HR: 1.09, 1.07–1.11 for females) and appeared to have a lower risk of a range of adverse outcomes (HR: 0.87, 0.85–0.89) thought to be unrelated to statin use. Adherence to a statin regimen was also associated with increased rates of preventive service use and a decreased rate of adverse clinical outcomes (HR: 0.93, 0.88–0.99). Conclusions These results suggest that patients initiating and adhering to chronic preventive drug therapies are more likely to engage in other health-promoting behaviors. Failure to account for this relationship may introduce bias in any epidemiologic study evaluating the effect of a preventive therapy on clinical outcomes.
Objectives We sought to evaluate the cost-effectiveness of applying the JUPITER (Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial results into ...clinical practice. Background The JUPITER trial found that rosuvastatin reduces vascular events in apparently healthy subjects with elevated high-sensitivity C-reactive protein (hs-CRP) but normal low-density lipoprotein (LDL) cholesterol levels. The implications of expanding treatment recommendations based on these results have not been evaluated. Methods We constructed a cost-effectiveness model of men ≥50 years and women ≥60 years with LDL cholesterol levels of <130 mg/dl and no known cardiovascular disease. We compared: 1) hs-CRP testing followed by rosuvastatin treatment for patients with hs-CRP levels ≥2.0 mg/l; and 2) usual care (i.e., no testing and no treatment). Estimates of treatment effectiveness were based on the JUPITER trial and were varied in sensitivity analyses. Results Among patients with LDL <130 mg/dl and hs-CRP levels ≥2.0 mg/l, rosuvastatin had an incremental cost-effectiveness of $25,198 per quality-adjusted life year (QALY) gained compared to usual care. If the effectiveness of rosuvastatin were 50% of that observed in JUPITER, the incremental cost-effectiveness ratio would increase to $50,871 per QALY. Implementing this strategy only in patients with a Framingham risk score ≥10% yielded an incremental cost-effectiveness of $14,205 per QALY. Among such intermediate-risk patients, a JUPITER-based strategy becomes cost-saving at a rosuvastatin price of <$0.86 per day. Conclusions Rosuvastatin treatment for JUPITER-eligible patients appears to be cost-effective, particularly among those with a Framingham risk score ≥10%.
Objectives The aim of this study was to evaluate the effect of statin treatment in primary prevention of cardiovascular events in different race/ethnic groups. Background Clinical trial evidence ...about the efficacy of statins in the primary prevention of cardiovascular events among nonwhites is uncertain. Methods JUPITER trial, a randomized, double-blind, placebo-controlled evaluation of rosuvastatin 20 mg in the primary prevention of myocardial infarction (MI), stroke, arterial revascularization, hospitalization for unstable angina, and cardiovascular death included 12,683 whites and 5,117 nonwhites with low-density lipoprotein levels <130 mg/dL and high-sensitivity C-reactive protein levels ≥2.0 mg/L. Results Random allocation to rosuvastatin resulted in a 45% reduction in the primary end point among whites (hazard ratio HR 0.55, 95% CI 0.43-0.69) and a 37% reduction among nonwhites (HR 0.63, 95% CI 0.41-0.99). Blacks (HR 0.65, 95% CI 0.35-1.22) and Hispanics (HR 0.58, 95% CI 0.25-1.39) had similar risk reductions. Among nonwhites in the placebo group, the stroke rate exceeded the MI rate (0.44 vs 0.20 per 100 person-years); an opposite pattern was observed among whites (0.31 vs 0.42 per 100 person-years). Nonwhites had higher death rates than whites (2.25 vs 0.93 per 100 person-years); however, all-cause mortality was similar at 20% with rosuvastatin treatment in both participant groups. Conclusions When used in primary prevention among individuals with low-density lipoprotein <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L, rosuvastatin significantly reduced first MI, stroke, arterial revascularization, hospitalization for unstable angina, and cardiovascular death among whites and nonwhites.
Abstract Background: Rapid growth in prescription drug costs has compelled insurers to require increased patient cost-sharing. Objective: The aim of this study was to compare the effects of 2 recent ...cost-sharing policies on emergency hospitalizations due to chronic obstructive pulmonary disease, asthma, or emphysema (CAE), and on physician visits. Methods: We analyzed data from a large-scale natural experiment in British Columbia (BC), Canada. The cost-sharing policies were a fixed copayment policy ( fixed copay policy ) and an income-based deductible (IBD) policy with 25% coinsurance ( IBD policy ). Prescription, physician billing, and hospitalization records were obtained from the BC Ministry of Health. From the total population of BC residents ≥65 years of age, we extracted data from all patients dispensed an inhaled corticosteroid, β2 -agonist, or anticholinergic from June 30, 1997, to April 30, 2004. Poisson regression was used to evaluate the impact of the policies in a cohort of patients receiving long-term inhaler treatment. An identically defined historical control group unaffected by the policy changes was used for comparison. Results: The study population included 37,320 users of long-term inhaled medications from the BC population of 576,000 persons ≥65 years of age. During the IBD period but not the fixed copay period, emergency hospitalizations for CAE increased 41% (95% CI for adjusted rate ratio RR, 1.24–1.60) in patients ≥65 years of age. There was also a significant increase in physician visits of 3% (95% CI for adjusted RR, 1.01–1.05). No significant increases were observed during the fixed copay period. In a secondary analysis using a concurrent control group, we estimated a smaller but significant increase in emergency CAE hospitalizations of 29% (95% CI for adjusted RR, 1.09–1.52). This analysis also showed increases in physician visits (fixed copay period RR, 1.03 95% CI for adjusted RR, 1.01–1.05; IBD period RR, 1.07 95% CI for adjusted RR, 1.05–1.08). Conclusion: The results suggest that the IBD policy was likely associated with an increased risk for emergency hospitalization and physician visits in these users of inhaled medications who were aged ≥65 years.
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