Rivaroxaban Plus Aspirin in Obese and Overweight Patients With Vascular Disease in the COMPASS Trial

BackgroundDirect oral anticoagulants are administered in fixed doses irrespective of body weight, but guidelines recommend against their use in patients with extremes of body weight.ObjectivesThis study determined the effects of dual-pathway inhibition antithrombotic regimen (rivaroxaban 2.5 mg twice daily plus aspirin 100 mg/day) compared with aspirin Halone across a range of patient body mass indexes (BMIs) and body weights.MethodsThis was a secondary analysis of the COMPASS (Cardiovascular OutcoMes for People using Anticoagulation StrategieS) trial, which included patients with chronic coronary artery disease or peripheral artery disease. Efficacy and safety outcomes were studied in relation to BMI: (normal 18.5 ≤BMI <25 kg/m², overweight 25 ≤BMI <30 kg/m², obese ≥30 kg/m²) and body weight (≤70 kg, 70 < weight ≤90 kg, and >90 kg; as well as ≤120 kg vs. >120 kg).ResultsAmong 27,395 randomized patients, 6,459 (24%) had normal BMI, 12,047 (44%) were overweight, and 8,701 (32%) were obese. The combination of rivaroxaban and aspirin compared with aspirin produced a consistent reduction in the primary outcome of cardiovascular death, stroke, or myocardial infarction, irrespective of BMI or body weight. For 18.5 ≤BMI <25 kg/m²: 3.5% vs. 5.0%; hazard ratio (HR): 0.73 (95% credible interval [CrI]: 0.58 to 0.90); 25 ≤ BMI <30 kg/m²: 4.3% vs. 5.1%; HR: 0.80 (95% CrI: 0.66 to 0.96); BMI ≥30 kg/m²: 4.2% vs. 6.1%; HR: 0.71 (95% CrI: 0.57 to 0.86). For body weight ≤70 kg: 4.1% vs. 5.3%; HR: 0.75 (95% CrI: 0.62 to 0.91); 70 < weight ≤90 kg: 4.1% vs. 5.3%; HR: 0.76 (95% CrI: 0.65 to 0.89); >90 kg: 4.2% vs. 5.7%; HR: 0.74 (95% CrI: 0.61 to 0.90). Effects on bleeding, mortality, and net clinical benefit were consistent irrespective of BMI or bodyweight.ConclusionsThe effects of dual-pathway antithrombotic therapy are consistent irrespective of BMI or body weight, suggesting no need for dose adjustments in the ranges of weights and BMI of patients enrolled in the COMPASS trial. Further studies need to address this problem in relation to greater extremes of body weight. (Rivaroxaban for the Prevention of Major Cardiovascular Events in Coronary or Peripheral Artery Disease [COMPASS]; NCT01776424)     

Is Screening for Atrial Fibrillation in Canadian Family Practices Cost-Effective in Patients 65 Years and Older?

We present an economic evaluation of a recently completed cohort study in which 2054 seniors were screened for atrial fibrillation (AF) in 22 Canadian family practices. Using a Markov model, trial and literature data were used to project long-term outcomes and costs associated with 4 AF screening strategies for individuals aged 65 years or older: no screening, screen with 30-second radial manual pulse check (pulse check), screen with a blood pressure machine with AF detection (BP-AF), and screen with a single-lead electrocardiogram (SL-ECG). Costs and outcomes were discounted at 1.5% and the model used a lifetime horizon from a public payer perspective. Compared with no screening, screening for AF in Canadian family practice offices using pulse check or screen with a blood pressure machine with AF detection is the dominant strategy whereas screening with SL-ECG is a highly cost-effective strategy with an incremental cost per quality-adjusted life-year (QALY) gained of CAD$4788. When different screening strategies were compared, screening with pulse check had the lowest expected costs ($202) and screening with SL-ECG had the highest expected costs ($222). The no-screening arm resulted in the lowest number of QALYs (8.74195) whereas pulse check and SL-ECG resulted in the highest expected QALYs (8.74362). Probabilistic analysis confirmed that pulse check had the highest probability of being cost-effective (63%) assuming a willingness to pay of $50,000 per QALY gained. Screening for AF in seniors during routine appointments with Canadian family physicians is a cost-effective strategy compared with no screening. Screening with a pulse check is likely to be the most cost-effective strategy.     

Confidence interval construction for a difference between two dependent intraclass correlation coefficients

Inferences for the difference between two dependent intraclass correlation coefficients (ICCs) may arise in studies in which a sample of subjects are each assessed several times with a new device and a standard. The ICC estimates for the two devices may then be compared using a test of significance. However, a confidence interval for a difference between two ICCs is more informative since it combines point estimation and hypothesis testing into a single inference statement. We propose a procedure that uses confidence limits for a single ICC to recover variance estimates needed to set confidence limits for the difference. An advantage of this approach is that it provides a confidence interval that reflects the underlying sampling distribution. Simulation results show that this method performs very well in terms of overall coverage percentage and tail errors. Two data sets are used to illustrate this procedure. Copyright © 2009 John Wiley & Sons, Ltd.