BackgroundCardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA) patients. This study is the first to report the association of hydroxychloroquine (an antirheumatic medication that has been associated with decreased risk of diabetes, a less atherogenic lipid profile, and antithrombotic properties) with CVD in RA.Methods and ResultsA retrospective incident RA cohort from January 1, 2001, to October 31, 2013, excluding patients with CVD prior to RA diagnosis, was constructed. Patients were categorized as hydroxychloroquine users versus nonusers and were allowed to contribute time to either group according to hydroxychloroquine exposure. The primary outcome was adjudicated incident CVD defined as a composite of coronary artery disease, stroke, transient ischemic attack, sudden cardiac death, and peripheral artery disease with arterial revascularization procedure. The secondary outcome was a composite of incident coronary artery disease, stroke, and transient ischemic attack. Cox time‐varying regression models were used to estimate the association between hydroxychloroquine exposure and development of CVD, after adjusting for propensity score and relevant confounders, including demographics, CVD‐related comorbidities, RA severity, and activity indicators and medications. We included 1266 RA patients, 547 hydroxychloroquine users, and 719 nonusers. During the observation period, 102 CVD events occurred, 3 in hydroxychloroquine users and 99 in nonusers. The fully adjusted Cox model showed a hazard ratio of 0.28 (95% CI 0.12–0.63, P=0.002) for incident CVD and 0.30 (95% CI 0.13–0.68, P=0.004) for incident composite coronary artery disease, stroke, and transient ischemic attack for hydroxychloroquine users versus nonusers, respectively.ConclusionIn this hypothesis‐generating study, hydroxychloroquine use was associated with a 72% decrease in the risk of incident CVD in RA patients. If these preliminary results are confirmed in larger studies, our findings may be used as a rationale for a randomized study of hydroxychloroquine use for primary prevention of CVD in RA or nonrheumatic high‐risk patients.

Background Falls and resulting fractures are a leading cause of morbidity/mortality in the elderly. With the withdrawal of certain selective COX2 inhibitors in 2004, narcotic analgesics have increasingly been recommended as first-line therapy in guidelines for the treatment of chronic pain. Objectives To evaluate the changes in types of medications prescribed for pain pre- and post-withdrawal of certain selective COX2 inhibitors in 2004 and to determine if there was an association with fall events among elderly patients with a diagnosis of osteoarthritis. Design A nested case-control design using electronic medical records compiled between 2001–2009. Setting Electronic medical records for care provided in an integrated health system in rural Pennsylvania over a nine year period (2001–9), the midpoint of which rofecoxib (Vioxx) and valdecoxib (Bextra) were pulled from the market. Participants 13,354 patients, aged 65–89, with a diagnosis of osteoarthritis (OA). Measurements The incidence of falls/fractures was examined in relation to analgesics prescribed: narcotics, COX2 inhibitors, or nonsteroidal anti-inflammatory drugs (NSAIDs). The comparison sample of no fall patients was matched 3:1 to fall patients according to age, gender and comorbidity. Results Narcotic analgesic prescriptions were associated with a significantly increased risk of falls/fractures. The odds ratio of experiencing a fall/fracture was higher in patients prescribed narcotic analgesics than those prescribed a COX2 inhibitor (3.3, 2.5–4.3) or NSAID (4.1, 3.7–4.5). Conclusion The increased use of narcotic analgesics is associated with an increased risk of falls/fractures in elderly patients with osteoarthritis, an observation that suggests the current guidelines for the treatment of pain, which include first-line prescription of narcotics, should be re-evaluated.

Objective. To determine the association of tumor necrosis factor ␣ (TNF␣) inhibitors with risk for cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients. Methods. A retrospective cohort of 2,101 incident RA patients was established. Medication exposure was categorized into the following groups: TNF␣ inhibitors alone or in combination with methotrexate (MTX; aTNF group); MTX alone or in combination with other nonbiologic disease-modifying antirheumatic drugs (DMARDs; MTX group); and no MTX, nonbiologic DMARDs (reference group). Primary outcome was adjudicated incident coronary artery disease (CAD), defined as myocardial infarction, unstable angina, or coronary revascularization procedure. Secondary outcome was adjudicated incident CVD, defined as a composite of CAD, stroke, transient ischemic attack, abdominal aortic aneurysm, peripheral arterial disease, or arterial revascularization procedure. Cox regression models were used to calculate the hazard ratio for CAD and CVD for the aTNF and MTX groups compared to the reference group.

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BackgroundIn surveys, interviews, and focus groups, patients taking medications and offered Web portal access to their primary care physicians’ (PCPs) notes report improved adherence to their regimens. However, objective confirmation has yet to be reported.ObjectiveTo evaluate the association between patient Internet portal access to primary care physician visit notes and medication adherence.MethodsThis study is a retrospective comparative analysis at one site of the OpenNotes quasi-experimental trial. The setting includes primary care practices at the Geisinger Health System (GHS) in Danville, Pennsylvania. Participants include patients 18 years of age or older with electronic portal access, GHS primary care physicians, and Geisinger health plan insurance, and taking at least one antihypertensive or antihyperlipidemic agent from March 2009 to June 2011. Starting in March 2010, intervention patients were invited and reminded to read their PCPs' notes. Control patients also had Web portal access throughout, but their PCPs' notes were not available. From prescription claims, adherence was assessed by using the proportion of days covered (PDC). Patients with a PDC ≥.80 were considered adherent and were compared across groups using generalized linear models.ResultsA total of 2147 patients (756 intervention participants, 35.21%; 1391 controls, 64.79%) were included in the analysis. Compared to those without access, patients invited to review notes were more adherent to antihypertensive medications—adherence rate 79.7% for intervention versus 75.3% for control group; adjusted risk ratio, 1.06 (95% CI 1.00-1.12). Adherence was similar among patient groups taking antihyperlipidemic agents—adherence rate 77.6% for intervention versus 77.3% for control group; adjusted risk ratio, 1.01 (95% CI 0.95-1.07).ConclusionsAvailability of notes following PCP visits was associated with improved adherence by patients prescribed antihypertensive, but not antihyperlipidemic, medications. As the use of fully transparent records spreads, patients invited to read their clinicians’ notes may modify their behaviors in clinically valuable ways.

Associations between variability of glomerular filtration rate (GFR), death, and cardiovascular events have not been reported among patients with chronic kidney disease (CKD). In order to evaluate this, we retrospectively analyzed the risk of death and de novo heart failure as a function of variability in estimated GFR among a cohort of 3361 patients with stage 3 CKD. At baseline, patients with greater variability were younger, more likely to have diabetes, hypertension, and other comorbid conditions, and were more likely to have proteinuria and higher estimated GFR. In multivariate-adjusted Cox proportional hazard models over a median follow-up of 3.9 years, the risk of death associated with the highest relative to the lowest quartile of variability was 1.40 (95% confidence interval 1.05-1.87); there was no association with new-onset heart failure. The mortality association was independent of serum albumin, proteinuria, baseline estimated GFR, and the slope of the estimated GFR. Thus, variability in estimated GFR predicts death among patients with stage 3 CKD independent of previously reported risk factors. The prognostic utility of complementing existing risk stratification metrics with dynamic changes in GFR among patients with CKD warrants investigation.

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Previous case reports and small studies have suggested that 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (HMG-CoA-Is) may increase the risk of tendon rupture. We conducted a population-based retrospective cohort evaluation to better assess this relationship. From approximately 800,000 enrollees of a private insurance database, those who were aged ≤64 years with at least 1 year of continuous enrollment were selected. Exposure was defined as initiation of HMG-CoA-I after the beginning of the study period. Each exposed person was matched with 2 controls of similar age and gender. Baseline characteristics, including known risk factors for tendon rupture, were compared between exposed and control cohorts with fidelity to the study's matched design. After adjusting for differences in follow-up and baseline characteristics, incidence rate ratios for tendon rupture was assessed in HMG-CoA-I users and nonusers. A total of 34,749 exposed patients were matched with 69,498 controls. There was no difference in the occurrence of tendon ruptures in HMG-CoA-I users versus nonusers. The results remained unchanged after adjustment for age and gender. In conclusion, this population-based retrospective cohort evaluation suggests that use of HMG-CoA-Is as a group are not associated with tendon rupture.