Quality of anticoagulant control and patient experience associated with long-term warfarin in Canadian patients with non-valvular atrial fibrillation: A multicentre, prospective study.

BACKGROUND: Despite the fact that direct oral anticoagulants (DOACs) are favoured over warfarin for stroke prevention in patients with non-valvular atrial fibrillation (NVAF), physicians need to maintain competence in using and monitoring warfarin since many patients have contraindications or other barriers to using DOACs. Unlike DOACs, warfarin therapy requires regular blood testing to ensure that it is within a target range to ensure efficacy and safety. There is limited real-world data on the adequacy of warfarin control and the cost and burden of monitoring warfarin therapy in Canadian NVAF patients. OBJECTIVES: In a large cohort of Canadian patients with NVAF on warfarin we assessed time in therapeutic range (TTR), determinants of TTR, process of care, direct costs, health related quality of life and loss of work time and productivity related to warfarin therapy. METHODS: Five hundred and fifty one patients with NVAF, either newly initiated or stable on warfarin were prospectively enrolled across 9 Canadian provinces from primary care practices and anticoagulant clinics. Participating physicians provided baseline demographic and medical information. Patients completed diaries for 48 weeks, capturing information about International Normalized Ratio (INR) test results, test locations, process of INR monitoring, direct costs of travel, health-related quality of life and work productivity measures. TTR was estimated using linear interpolation of INR results and linear regression used to investigate associations between TTR and factors (defined a priori). RESULTS: Four hundred and eighty (87.1%) patients had complete follow-up with an overall TTR of 74.4% based on 7,175 physician-reported INR values from 501 patients. 88% of this cohort were monitored through routine medical care (RMC). The average number of INRs per patient during the 48-week period was 14.1 (standard deviation (SD) = 8.3) tests with a mean duration of 23.8 (SD = 11.1) days between tests. We did not find a relationship between TTR and age, sex, presence of major comorbidities, patient's province of residence or rural vs. urban residence. 12% of patients monitored through anticoagulant clinics had significantly better TTR than patients monitored through RMC (82% vs. 74%; 95% confidence interval: -13.8, -1.2; p = 0.02). Health related quality of life utility values were high and remained consistent throughout the study. The majority of patients reported no impact on either work productivity or impairment of regular activities due to being on long-term warfarin treatment. CONCLUSIONS: We showed excellent overall TTR in an observed Canadian cohort, with monitoring through a dedicated anticoagulant clinic being associated with a statistically and clinically significant improvement in TTR. The burden of warfarin therapy on patients' health related quality of life or daily work and activities was low.

A double-blind, randomized controlled trial of the prevention of clinically important venous thromboembolism after isolated lower leg fractures.

BACKGROUND: Among patients with isolated below-knee fractures, previous studies have detected asymptomatic deep vein thrombosis in 10%-40% using contrast venography. However, the clinical relevance of these thrombi is unknown; there is considerable uncertainty about the risk: benefit of routine thromboprophylaxis and clinical practice guidelines differ in their recommendations. METHODS: In this multicenter, double-blind trial, 265 patients with isolated lower leg fractures requiring surgery were randomized to subcutaneous dalteparin 5000 units or matching placebo once daily for 2 weeks with bilateral Doppler ultrasound (DUS) of the proximal leg veins on postoperative day 14±2 and 3-month follow-up. The primary effectiveness outcome was clinically important venous thromboembolism (CIVTE), defined as the composite of symptomatic venous thromboembolism within 3 months after surgery and asymptomatic proximal deep vein thrombosis on DUS. The primary safety outcome was major bleeding. RESULTS: Two hundred fifty-eight patients (97%) were included in the primary outcome analysis for effectiveness (130: dalteparin; 128: placebo). Incidence of CIVTE in the dalteparin and placebo groups was 1.5% and 2.3%, respectively (absolute risk reduction, 0.8%; 95% confidence interval, -2.0 to 3.0). There were no fatal pulmonary emboli or major bleeding. CONCLUSIONS: The overall incidence of CIVTE after surgically repaired, isolated tibia, fibula, and ankle fractures was low (1.9%; 95% confidence interval, 0.7-4.7), with no observed differences between dalteparin and placebo either for CIVTE or safety. Recruitment was stopped at the first interim analysis. This study also demonstrates the substantial discrepancy in venous thromboembolism rates between trials that use venographic outcomes compared with more clinically relevant outcomes. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Symptomatic venous thromboembolism uncommon without thromboprophylaxis after isolated lower-limb fracture: the knee-to-ankle fracture (KAF) cohort study.

BACKGROUND: The prevalence of deep vein thrombosis as demonstrated by routine venography in patients with distal lower-extremity injury requiring cast immobilization or surgery is 10% to 40%. These deep vein thromboses are usually asymptomatic and distal, and the need for thromboprophylaxis in these patients is not known. METHODS: We conducted a multicenter prospective cohort study to define the prevalence of symptomatic venous thromboembolism in patients with a tibial, fibular, or ankle fracture (treated nonoperatively) or a patellar or foot fracture (treated operatively or conservatively). Consecutive patients were enrolled at five Ontario, Canada, hospitals within ninety-six hours after injury, and they were followed with a telephone interview at two, six, and twelve weeks. Thromboprophylaxis was not allowed. Suspected venous thromboembolism was investigated in a standardized manner. RESULTS: From August 2002 to June 2005, 1200 patients were enrolled, and a three-month follow-up was completed for 98% of them. Eighty-two percent of the patients were treated with cast or splint immobilization for an average (and standard deviation) of 42 ± 32 days. Overall, seven patients (0.6%; 95% confidence interval [CI] = 0.2% to 1.2%) had symptomatic, objectively confirmed venous thromboembolism. Two of them had proximal deep vein thrombosis; three, calf deep vein thrombosis; and two, pulmonary embolism. There were no fatal pulmonary emboli. CONCLUSIONS: Symptomatic venous thromboembolism is an infrequent complication after fractures of the distal part of the lower limb requiring cast immobilization and managed without thromboprophylaxis. Given these estimates of symptomatic venous thromboembolism, the risk-benefit ratio and cost-effectiveness of routine anticoagulant prophylaxis are unlikely to be favorable for these patients. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.