Adjusted-dose Warfarin Research Articles

PMD10 Analysis of Costs of Complications for Stroke Prevention in Atrial Fibrillation Patients, Comparing Dose-Adjusted Warfarin to Left Atrial Appendage Closure

PMD10 Analysis of Costs of Complications for Stroke Prevention in Atrial Fibrillation Patients, Comparing Dose-Adjusted Warfarin to Left Atrial Appendage Closure

Dabigatran Compared With Warfarin for Stroke Prevention With Atrial Fibrillation: Experience in Hong Kong

Dabigatran is an oral direct thrombin inhibitor recently approved for stroke prevention in atrial fibrillation (AF) as an alternative to warfarin. The primary advantages of dabigatran are freedom from monitoring and less interaction with other drugs and food. It is ideal for patients who are unwilling to adhere to regular coagulation monitoring or whose therapeutic effect using warfarin is not optimal despite adequate monitoring and management. However, the impact of dabigatran on health-related quality of life (HRQoL) and drug compliance has been less evaluated. This study aimed to evaluate the clinical and humanistic outcomes of dabigatran use in Hong Kong. Dabigatran 110 mg twice daily was non-inferior in stroke prophylaxis in AF patients compared to adjusted-dose warfarin; while dabigatran 150 mg twice daily was superior to adjusted-dose warfarin in the real world data in Hong Kong. We retrospectively analyzed 244 patients with newly diagnosed AF and prescribed dabigatran (n = 122) or warfarin (n = 122) for stroke prophylaxis from the Prince of Wales Hospital between January 2010 to November 2011. Clinical outcomes including death, stroke, bleeding, and HRQoL using the EuroQol EQ-5D-5L were compared between patients on dabigatran and warfarin. The median duration of follow-up was 310 days. Stroke occurred in 2 patients (1.64%) in the dabigatran group and 4 in the warfarin group (3.28%) (adjusted hazard ratio [HR]: 0.53, P = 0.47). Bleeding of any degree occurred in 28 patients on dabigatran and 38 patients on warfarin (adjusted HR: 0.76, P = 0.28), with age over 70 years and renal impairment being significant positive predictors of bleeding (P = 0.01 and 0.02, respectively). Dyspepsia was the most common adverse event of dabigatran over warfarin (19.7% vs 8.2%, P = 0.01). Rate of discontinuation of dabigatran was 25.4%, with dyspepsia being the most common cause for discontinuation (6 patients, 4.92%). There was no significant difference in drug compliance or HRQoL at 1 year between the 2 groups (utility score 0.77 [dabigatran] vs 0.74 [warfarin], P = 0.28). In Hong Kong, the clinical efficacy and safety of dabigatran were comparable to that of warfarin, and drug compliance and HRQoL of using dabigatran and warfarin were similar after 1 year of use.

Cost-effectiveness of apixaban compared with warfarin for stroke prevention in atrial fibrillation.

BackgroundApixaban was shown to be superior to adjusted-dose warfarin in preventing stroke or systemic embolism in patients with atrial fibrillation (AF) and at least one additional risk factor for stroke, and associated with reduced rates of hemorrhage. We sought to determine the cost-effectiveness of using apixaban for stroke prevention.MethodsBased on the results from the Apixaban Versus Warfarin in Patients with Atrial Fibrillation (ARISTOTLE) trial and other published studies, we constructed a Markov model to evaluate the cost-effectiveness of apixaban versus warfarin from the Medicare perspective. The base-case analysis assumed a cohort of 65-year-old patients with a CHADS2 score of 2.1 and no contraindication to oral anticoagulation. We utilized a 2-week cycle length and a lifetime time horizon. Outcome measures included costs in 2012 US$, quality-adjusted life-years (QALYs), life years saved and incremental cost-effectiveness ratios.ResultsUnder base case conditions, quality adjusted life expectancy was 10.69 and 11.16 years for warfarin and apixaban, respectively. Total costs were $94,941 for warfarin and $86,007 for apixaban, demonstrating apixaban to be a dominant economic strategy. Upon one-way sensitivity analysis, these results were sensitive to variability in the drug cost of apixaban and various intracranial hemorrhage related variables. In Monte Carlo simulation, apixaban was a dominant strategy in 57% of 10,000 simulations and cost-effective in 98% at a willingness-to-pay threshold of $50,000 per QALY.ConclusionsIn patients with AF and at least one additional risk factor for stroke and a baseline risk of ICH risk of about 0.8%, treatment with apixaban may be a cost-effective alternative to warfarin.

COMPARISON OF ASPIRIN COMBINED NAOXINTONG VERSUS ADJUSTED-DOSE WARFARIN IN ELDERLY PATIENTS WITH HIGH-RISK NON-VALVULAR ATRIAL FIBRILLATION AND GENETIC VARIANTS OF VKORC1

ObjectivesAdjusted-dose warfarin and aspirin reduce stroke in patients with atrial fibrillation, and warfarin is substantially more efficacious than aspirin. But patients especially in Chinese population with genetic variants of vitamin...

Dabigatran Etexilate

This article provides an overview of the clinical profile of oral dabigatran etexilate (Pradaxa®, Pradax™) [hereafter referred to as dabigatran] when used for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF), followed by a review of cost-utility analyses of dabigatran in this patient population. Dabigatran (110 or 150 mg twice daily) demonstrated noninferiority versus adjusted-dose warfarin with regard to the prevention of stroke and systemic embolism (primary endpoint) in patients with AF in the RE-LY trial, and the 150 mg twice-daily dosage was significantly more effective than warfarin for this endpoint, as well as most other efficacy endpoints. The incidence of major bleeding was generally similar in patients receiving dabigatran 150 mg twice daily or warfarin, but was lower in patients receiving dabigatran 110 mg twice daily. With regard to other bleeding endpoints, dabigatran was generally associated with lower rates than warfarin, except for gastrointestinal major bleeding. Dabigatran (both dosages) was associated with a higher incidence of dyspepsia than warfarin. Results of modelled cost-utility analyses from several countries from the perspective of a healthcare payer over a lifetime (or 20-year) time horizon and primarily based on data from the RE-LY trial were generally consistent. All but one analysis demonstrated that twice-daily dabigatran 150 mg (or age-adjusted, sequential dosing) was cost effective with regard to the incremental cost per QALY gained relative to adjusted-dose warfarin in the prevention of stroke and systemic embolism in AF patients, as the results were below generally accepted cost-effectiveness thresholds. In contrast, the incremental cost per QALY gained for dabigatran 110 mg twice daily versus warfarin exceeded cost-effectiveness thresholds in all studies except one. Sensitivity analyses suggested that the cost utility of dabigatran versus warfarin was generally robust to variations in the majority of parameters. However, the incremental cost per QALY gained for dabigatran versus warfarin improved when levels of international normalized ratio control in warfarin recipients decreased and when the baseline level of risk of stroke increased.

Rivaroxaban for stroke prevention in atrial fibrillation: a critical review of the ROCKET AF trial

Oral anticoagulation is the mainstay of therapy for stroke prevention in patients with atrial fibrillation (AF). Vitamin K antagonists such as warfarin have many drawbacks that reduce their uptake, safety and effectiveness. The ROCKET AF trial compared rivaroxaban (20 mg/day; 15 mg/day in patients with creatinine clearance 30–49 ml/min) with dose-adjusted warfarin (international normalized ratio 2–3) in 14,264 patients with AF and a prior history of stroke or at least two other additional risk factors for stroke. The ROCKET AF trial demonstrated the noninferiority of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism, with a similar rate of major bleeding and a substantial reduction in intracranial hemorrhage. These results, in conjunction with its convenient once-daily dosing regimen, make rivaroxaban an attractive alternative to warfarin for stroke prevention in AF.

Low Risk of Thromboembolic Complications With Tranexamic Acid After Primary Total Hip and Knee Arthroplasty

The use of antifibrinolytic medications in hip and knee arthroplasty reduces intraoperative blood loss and decreases transfusion rates postoperatively. Tranexamic acid (TXA) specifically has not been associated with increased thromboembolic (TE) complications, but concerns remain about the risk of symptomatic TE events, particularly when less aggressive chemical prophylaxis methods such as aspirin alone are chosen. We determined whether the rate of symptomatic TE events differed among patients given intraoperative TXA when three different postoperative prophylactic regimens were used after primary THA and TKA. We retrospectively reviewed 2046 patients who underwent primary THA or TKA and received TXA from 2007 to 2009. The three chemical regimens included aspirin alone, warfarin (target international normalized ratio, 1.8-2.2), and dalteparin. Primary outcome measures were venous TE events, including symptomatic deep vein thrombosis (DVT) and pulmonary embolism (PE), and arterioocclusive events, including myocardial infarction and cerebrovascular accident. Patients judged to be at high risk for TE due to recent cardiac stent placement or strong personal/family history of TE disease were excluded. For aspirin, warfarin, and dalteparin, the rates of symptomatic DVT (0.35%, 0.15%, and 0.52%, respectively) and nonfatal PE were similar (0.17%, 0.43%, and 0.26%, respectively). There were no fatal PE. Among the three groups, we found no difference in the rates of symptomatic DVT or PE with or without stratification by ASA score. A low complication rate was seen when using TXA as a blood conservation modality during primary THA and TKA with less aggressive thromboprophylactic regimens such as aspirin alone and dose-adjusted warfarin.

Cost–Effectiveness of Rivaroxaban Compared to Warfarin for Stroke Prevention in Atrial Fibrillation

Rivaroxaban has been found to be noninferior to warfarin for preventing stroke or systemic embolism in patients with high-risk atrial fibrillation (AF) and is associated with a lower rate of intracranial hemorrhage. To assess the cost-effectiveness of rivaroxaban compared to adjusted-dose warfarin for the prevention of stroke in patients with AF, we built a Markov model using a United States payer/Medicare perspective and a lifetime time horizon. The base-case analysis assumed a cohort of patients with AF 65 years of age with a congestive heart failure, hypertension, age, diabetes, stroke (2 points) score of 3 and no contraindications to anticoagulation. Data sources included the Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) and other studies of anticoagulation. Outcome measurements included costs in 2011 United States dollars, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Patients with AF treated with rivaroxaban lived an average of 10.03 QALYs at a lifetime treatment cost of $94,456. Those receiving warfarin lived an average of 9.81 QALYs and incurred costs of $88,544. The ICER for rivaroxaban was $27,498 per QALY. These results were most sensitive to changes in the hazard decrease of intracranial hemorrhage and stroke with rivaroxaban, cost of rivaroxaban, and time horizon. Monte Carlo simulation demonstrated rivaroxaban was cost-effective in 80% and 91% of 10,000 iterations at willingness-to-pay thresholds of $50,000 and $100,000 per QALY, respectively. In conclusion, this Markov model suggests that rivaroxaban therapy may be a cost-effective alternative to adjusted-dose warfarin for stroke prevention in AF.

CATCH: A randomized trial comparing tinzaparin versus warfarin for treatment of acute venous thromboembolism (VTE) in cancer patients.

TPS9149^ Background: VTE is a major cause of morbidity and mortality in cancer patients. LMWHs have been shown to be superior to warfarin in one randomized study, but adequately powered confirmatory studies have not been conducted and warfarin continues to be widely used for treatment of cancer-associated VTE. Methods: We are conducting an open-label, randomized trial of tinzaparin versus warfarin in 900 patients with active cancer and symptomatic proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE). Tinzaparin is given at full treatment doses (175 IU/kg once daily) for 6 months in the experimental arm and initial tinzaparin treatment for 5-10 days followed by dose-adjusted warfarin (target INR 2.0-3.0) is given for 6 months in the control arm. The primary composite outcome is time to recurrent VTE event, including incidentally diagnosed VTE and fatal PE. Baseline characteristics will be analysed for their ability to predict the risk for recurrent VTE or bleeding. In particular, the parameters of the Khorana scale and Wells rule will be tested for their usefulness in predicting recurrent VTE. Predictive biomarkers will be tested including D-dimer and Tissue Factor. Assessment of post-thrombotic syndrome (PTS), quality of life and healthcare resource utilization will also be performed. The trial is recruiting in > 160 sites in >25 countries in 4 continents (NCT01130025). As of Jan 2012, 135 sites were activated for study enrolment and 228 patients have been enrolled. We anticipate completion of enrolment in Jan 2013. The results obtained from this study will add significantly to the knowledge on the efficacy, safety and cost-effectiveness of LMWH to prevent recurrent VTE. Important prospective data on the clinical significance of incidental VTE in patients with active cancer will be generated, and analyses of risk stratification parameters will add important information that may help to further tailor therapy. The study of PTS, which has not previously been done in this selected patient population, will add to the evidence that tinzaparin significantly reduces the incidence of PTS and leg ulcers (Hull et al, Am J Med 2009;122:762-9).

053 Factors affecting quality of warfarin anticoagulation in patients with atrial fibrillation: insights from affirm

IntroductionThe efficacy of warfarin anticoagulation in atrial fibrillation patients at risk for stroke is related to time in therapeutic range (TTR) with an INR 2.0–3.0. Factors predisposing to low TTR...

Intracranial Hemorrhage in Atrial Fibrillation Patients During Anticoagulation With Warfarin or Dabigatran

Intracranial hemorrhage is the most devastating complication of anticoagulation. Outcomes associated with different sites of intracranial bleeding occurring with warfarin versus dabigatran have not been defined. Analysis of 18 113 participants with atrial fibrillation in the Randomized Evaluation of Long-term anticoagulant therapY (RE-LY) trial assigned to adjusted-dose warfarin (target international normalized ratio, 2-3) or dabigatran (150 mg or 110 mg, both twice daily). During a mean of 2.0 years of follow-up, 154 intracranial hemorrhages occurred in 153 participants: 46% intracerebral (49% mortality), 45% subdural (24% mortality), and 8% subarachnoid (31% mortality). The rates of intracranial hemorrhage were 0.76%, 0.31%, and 0.23% per year among those assigned to warfarin, dabigatran 150 mg, and dabigatran 110 mg, respectively (P<0.001 for either dabigatran dose versus warfarin). Fewer fatal intracranial hemorrhages occurred among those assigned dabigatran 150 mg and 110 mg (n=13 and n=11, respectively) versus warfarin (n=32; P<0.01 for both). Fewer traumatic intracranial hemorrhages occurred among those assigned to dabigatran (11 patients with each dose) compared with warfarin (24 patients; P<0.05 for both dabigatran doses versus warfarin). Independent predictors of intracranial hemorrhage were assignment to warfarin (relative risk, 2.9; P<0.001), aspirin use (relative risk, 1.6; P=0.01), age (relative risk, 1.1 per year; P<0.001), and previous stroke/transient ischemic attack (relative risk, 1.8; P=0.001). The clinical spectrum of intracranial hemorrhage was similar for patients given warfarin and dabigatran. Absolute rates at all sites and both fatal and traumatic intracranial hemorrhages were lower with dabigatran than with warfarin. Concomitant aspirin use was the most important modifiable independent risk factor for intracranial hemorrhage.

New Oral Anticoagulants for Atrial Fibrillation: A Review of Clinical Trials

BackgroundWarfarin had been the only oral anticoagulant for stroke prevention in patients with atrial fibrillation (AF) for decades. Direct thrombin inhibitors and factor Xa inhibitors are new anticoagulants recently approved for prevention of stroke or systemic embolism in patients with AF. ObjectiveThe aim of this article was to provide a systematic review of recently published clinical data on the direct thrombin inhibitors and factor Xa inhibitors in the management of AF. MethodsA search of the ClinicalTrials.gov registry was conducted using the subject terms dabigatran, rivaroxaban, and apixaban. Each search was limited to clinical trials that included patients with AF. Completed studies with warfarin as the main comparator were identified. From the yielded results, the national clinical trial identifier was inputted in PubMed (1966–November 2011) for a search of published literature. ResultsThree Phase III clinical trials reported the efficacy of each agent in patients who have AF and risk factors for stroke or embolic complications. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study reported dabigatran 150 mg was associated with a lower rate of stroke and systemic embolism, whereas dabigatran 110 mg was associated with a similar rate for such events when compared with warfarin (relative risk = 0.66; 95% confidence interval [CI], 0.53–0.82; P < 0.001; and relative risk = 0.91; 95% CI, 0.74–1.11; P = 0.34, respectively). From the intention-to-treat analysis of the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, rivaroxaban was reported to be noninferior to warfarin in reducing stroke or systemic embolism (2.1% vs 2.4% per year; hazard ratio = 0.88; 95% CI, 0.75–1.03; P < 0.001). The Apixaban for Reduction in Stroke and Other Thrombotic Events in Atrial Fibrillation (ARISTOTLE) trial reported that apixaban reduced stroke or systemic embolic events by 21% when compared with warfarin (1.27% vs 1.60% per year, respectively; hazard ratio = 0.79; 95% CI, 0.66–0.95; P < 0.001). All 3 agents were associated with similar bleeding when compared with warfarin. ConclusionsPublished data suggest that all 3 agents are at least as efficacious as dose-adjusted warfarin, with similar major bleeding profiles. For patients who are unwilling to adhere to regular coagulation monitoring or whose therapeutic effect using warfarin is not optimal despite adequate monitoring and management, the inhibitors of direct thrombin or factor Xa may provide alternative choices in anticoagulation.

Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF

In ROCKET AF, rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation (AF). We aimed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack (TIA). In ROCKET AF, patients with AF who were at increased risk of stroke were randomly assigned (1:1) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin (international normalised ratio 2·0-3·0). Patients and investigators were masked to treatment allocation. Between Dec 18, 2006, and June 17, 2009, 14 264 patients from 1178 centres in 45 countries were randomly assigned. The primary endpoint was the composite of stroke or non-CNS systemic embolism. In this substudy we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA. Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population. ROCKET AF is registered with ClinicalTrials.gov, number NCT00403767. 7468 (52%) patients had a previous stroke (n=4907) or TIA (n=2561) and 6796 (48%) had no previous stroke or TIA. The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (2·79% rivaroxaban vs 2·96% warfarin; hazard ratio [HR] 0·94, 95% CI 0·77-1·16) and those without (1·44%vs 1·88%; 0·77, 0·58-1·01; interaction p=0·23). The number of major and non-major clinically relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA (13·31% rivaroxaban vs 13·87% warfarin; HR 0·96, 95% CI 0·87-1·07) and those without (16·69%vs 15·19%; 1·10, 0·99-1·21; interaction p=0·08). There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA. These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF. Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare.

Is Dabigatran Cost Effective Compared With Warfarin for Stroke Prevention in Atrial Fibrillation?

Warfarin has provided protection against cardioembolic stroke in the setting of nonvalvular atrial fibrillation (NVAF) for the past 60 years. Dabigatran, the first oral direct thrombin inhibitor to be approved in the United States, promises to provide the same or better stroke protection with reduced risk of intracranial hemorrhage. However, it remains to be seen whether grand-scale adoption of dabigatran will be cost effective. To critically assess current evidence regarding the cost effectiveness of dabigatran for preventing stroke in patients with NVAF compared with warfarin. The objective was addressed through the development of a critically appraised topic that included a clinical scenario, structured question, literature search strategy, critical appraisal, assessment of results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and content experts in the field of vascular neurology. A cost-effectiveness analysis (CEA) that followed a hypothetical cohort of NVAF patients 65 years of age or older and CHADS2≥1 over their lifetime comparing dabigatran with adjusted-dose warfarin was reviewed. Assuming a willingness to pay a threshold of $50,000 per quality-adjusted life year (QALY), base case results favored high-dose (150 mg bid) dabigatran as a cost-effective alternative to warfarin. Sensitivity analysis asserted that the cost effectiveness of dabigatran improved if it could be obtained for ≤$13/d or if it was used in populations with high risk of stroke or intracranial hemorrhage. Dabigatran 150 mg bid ($12,286 per QALY) is a cost-effective alternative to International Normalized Ratio-adjusted warfarin for the prevention of ischemic stroke in patients 65 years of age or older with NVAF.

For people with non-valvular atrial fibrillation rivaroxaban is non-inferior to warfarin for preventing stroke or embolism, with no difference in the risk of clinically relevant bleeding

Commentary on: Patel MR, Mahaffey KW, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883–91.[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] Atrial fibrillation (AF) significantly increases the...

Abstract 152: Predictors of Intracranial Hemorrhage Among Anticoagulated Patients with Atrial Fibrillation: Insights from the Rivaroxaban Once-daily oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)

Background: For patients with atrial fibrillation (AF) at moderate to high risk of stroke, oral anticoagulation reduces the risk of ischemic stroke but may increase hemorrhagic stroke and offset the intended benefits in certain individuals. Identifying individuals with AF at high risk of stroke who are likely to have an intracranial hemorrhage (ICH) if treated with anticoagulants remains a challenge. Methods: We investigated factors associated with ICH in 14,264 patients with nonvalvular AF randomized to rivaroxaban or dose-adjusted warfarin in ROCKET AF. The endpoint of interest was ICH in the entire intention-to-treat population. Cox proportional hazards modeling was used to identify factors associated with ICH. Results: Over a median follow-up of 1.94 years, 136 patients experienced ICH events (intracerebral hemorrhage [n=98], subarachnoid hemorrhage [n=5], subdural hemorrhage [n=32], extradural hemorrhage [n=1]). The average annual rate of ICH was 0.55 per 100 patient-years. The significant independent predictors of increased risk for ICH were increased age, history of prior stroke or TIA, black or Asian race, decreasing serum albumin, and decreased platelet count below 210 x 10 9 /l (Table, C-index=0.677). Creatinine clearance was not associated with the occurrence of ICH after accounting for other variables in the model (P=0.3181). Aspirin and thienopyridine use at baseline were associated with an increased risk of ICH whereas randomization to rivaroxaban (versus warfarin) was protective. Conclusions: Among patients with AF at moderate to high risk of stroke who were treated with anticoagulation, the average annual rate of ICH was 0.55 per 100 patient-years. Risk of ICH was increased among those who were non-white, older, had prior stroke or TIA, had low platelet counts, low serum albumin, and were taking antiplatelet therapy. Rivaroxaban was associated with a significantly lower risk of ICH compared with warfarin. The external validity of these findings requires testing in other AF populations.

Abstract 172: Cost-Effectiveness of Dabigatran Compared with Warfarin for Secondary Stroke Prevention in Patients with Atrial Fibrillation and Prior Stroke or Transient Ischemic Attack

Background: The cost-effectiveness of dabigatran for secondary stroke prevention in patients who present with atrial fibrillation (AF) and stroke or transient ischemic attack (TIA) has not been directly assessed. Methods: A Markov decision model was constructed (Figure 1) using data from a substudy of the Randomized Evaluation of Long-Term Therapy (RE-LY) trial, other trials of warfarin therapy for AF, and the published cost of dabigatran. We compared two treatment strategies: adjusted-dose warfarin therapy with an international normalized ratio (INR) target of 2 to 3, versus dabigatran 150 mg twice daily. The target population was a cohort of patients aged 70 years and older with non-valvular AF, prior stroke or TIA, and no contraindication to anticoagulation. The model outputs were costs in 2010 U.S. dollars and quality-adjusted life-years (QALYs). Results: In the base case, quality-adjusted life expectancy was 4.36 QALYs with dabigatran compared with 4.04 QALYs with warfarin. Dabigatran provided 0.34 additional QALYs at a cost of $9,500, yielding an incremental cost-effectiveness ratio of $28,000. In sensitivity analyses (Figure 2), the cost-effectiveness of dabigatran was influenced by patients’ age, the cost of dabigatran, the relative risk of stroke using dabigatran compared with warfarin, and the quality of INR control achieved with warfarin therapy. Conclusions: Dabigatran appears to be cost-effective relative to warfarin for stroke prevention in patients with AF and prior stroke or TIA. Our analysis is limited by its reliance on data from a substudy of a single randomized trial, and our results may not apply in settings with atypically good INR control using warfarin.

Abstract 148: Efficacy and Safety of Rivaroxaban Compared with Warfarin Among Elderly Patients with Nonvalvular Atrial Fibrillation in the ROCKET-AF Trial

Background: Nonvalvular atrial fibrillation (AF) affects 5-10% of people over 75 years of age, in whom the risk of thromboembolism is higher than in younger individuals. Although warfarin protects against ischemic stroke, many patients cannot sustain treatment because of bleeding, drug interactions and coagulation monitoring. The oral Factor Xa inhibitor, rivaroxaban, displayed noninferior efficacy and safety as an alternative anticoagulant in the ROCKET-AF trial (median age 73 years). This analysis compares these treatments in patients &gt;75 years. Methods: The ROCKET-AF trial (n=14,264) included 6,229 patients &gt;75 years of age with AF and at least 1 additional stroke risk factor randomized to adjusted-dose warfarin (target INR 2.0-3.0) or fixed-dose rivaroxaban (20 mg daily; 15 mg daily if baseline creatinine clearance &lt;50 ml/min), double-blind. The primary endpoint was all strokes (ischemic or hemorrhagic) and systemic embolism analyzed during the on-treatment period and according to intention-to-treat (ITT). Results: Compared to younger patients, those ≥75 years at baseline had a mean CHADS 2 score of 3.7 vs. 3.3, 46 vs. 35% were female, and 42 vs. 65% had prior stroke/TIA. During 9,247 patient-years exposure, 429 stroke or systemic embolic events occurred among patients &gt;75 years old. Long-term tolerability was similar between treatments; 59.4% of patients on warfarin (W) and 59.3% on rivaroxaban (R) completed the trial taking assigned treatment, compared with 69.9 and 68.7% in younger patients. The mean INR in the warfarin group (2.44, SD=0.86) was within target range for 56.9% (SD=21.6) of follow-up, compared to 53.9% (SD=20.9) in younger patients. The table compares annualized event rates for patients &lt;75 and &gt;75 years of age at entry. The on-treatment thromboembolism rates of 1.78 vs. 2.65%/year with rivaroxaban and warfarin, respectively (HR 0.67; 95% CI 0.51-0.89) were not much higher than in younger patients. Older patients had higher rates of (mostly non-major) clinically relevant bleeding (interaction p =0.009), but rates with warfarin and rivaroxaban were comparable. Conclusions: In elderly, high-risk patients with AF, once-daily oral rivaroxaban without coagulation monitoring or dose adjustment performed favorably compared to adjusted-dose warfarin as it did in the overall ROCKET-AF population. 1

Income poverty and cardiovascular disease

Schofield et al. presented a cross-sectional study on the association between working condition and health status, with special emphasis on cardiovascular disease (CVD), adjusted for sex, age and education [1]. Their studywas based on the 2003 Survey of Disability, Ageing and Carers (SDAC). The severity of CVD was not evaluated in their study, but it might be reasonable to speculate that the severity of CVD would be highest in patients with no job and lowest in full-time workers. They concluded that CVD in patients with no job was associated with the highest risk of living in poverty. The authors also reported the association between CVD and poverty using a three-dimensional model (low income, poor health and insufficient education) for poverty [2]. In this paper, the percentage of poor healthwas higher among thosewith heart and circulatory diseases than for other health conditions. By the way, they defined CVD as covering a broad spectrum of disorders including heart disease, angina, myocardial infarction, hypertension, stroke, and other heart/circulatory diseases, in Reference 1. Among the 8793 recorded subjects, those with chronic health conditions other than CVD were not used for their analysis. The numbers of full-time workers, part-timeworkers and persons with no job among the subjects with CVD were 349, 166 and 110, respectively, and the numbers of full-time workers, part-time workers and persons with no job among the healthy subjects were 2265, 783 and 625, respectively. They conducted logistic regression analysis to predict income poverty using working status among healthy subjects (Table 2 and Fig. 1 in Reference 1) and patients with CVD (Table 4 in Reference 1), while setting CVD patients with no job as the control group. To understand the association between income poverty and CVD, the combination of working pattern/status (full-time, part-time, and no job) and presence of CVD should be included as an independent variable for logistic regression analysis, in addition to sex, age and education. If full-time workers (n=2265) with no ill health were set as a control group, the risk of income poverty for other groups could be better estimated. In their study, the odds ratios and 95% confidence Fig. 1. Effects of the 3 new anticoagulants on all-cause mortality compared with dose-adjusted warfarin.

Efficacy and Safety of Periprocedural Dabigatran in Patients Undergoing Catheter Ablation of Atrial Fibrillation

Periprocedural anticoagulation using uninterrupted warfarin could reduce the risk of thromboembolic complications of atrial fibrillation (AF) ablation. Few studies, however, have evaluated the efficacy and safety of periprocedural dabigatran in AF ablation. A total of 211 consecutive patients who underwent AF ablation, including 110 patients who received 110mg dabigatran twice daily (group D) and 101 patients who received dose-adjusted warfarin (international normalized ratio, 2.0-3.0; group W), were evaluated. Dabigatran was discontinued on the morning of the procedure, and resumed on the next morning. Warfarin was continued throughout the procedure. During the procedure, heparin infusion was maintained to achieve an activated clotting time of >300s. Postprocedural cerebral magnetic resonance imaging (MRI) was performed in 60 patients (group D, n=31; group W, n=29). No periprocedural deaths or symptomatic thromboembolic complications were observed in either group. MRI indicated a silent cerebral infarction in 1 patient in each group. Five patients in group D and 11 in group W had minor bleeding (P=0.12). Cardiac tamponade occurred in 2 patients in group W, but in none in group D. Total bleeding complications occurred less frequently in group D (4.5%) than in group W (12.9%; P<0.05). Dabigatran at a dose of 110mg twice daily was safe for AF ablation in patients with a relatively low risk of thromboemboli, suggesting that it may become an alternative to warfarin in those patients.