Relative Risk Of Major Bleeding Research Articles

Efficacy and safety of oral anticoagulants according to kidney function among patients with atrial fibrillation.

Patients with severely reduced kidney function have been excluded from randomized controlled trials and data on the safety and efficacy of direct oral anticoagulants (DOACs) according to kidney function remain sparse. The aim was to evaluate the safety and efficacy of the DOACs across subgroups of kidney function. Using multiple Danish nationwide registers and laboratory databases, we included patients initiated on oral anticoagulants (OACs) with atrial fibrillation and available creatinine level and followed patients for 2 years to evaluate occurrence of stroke/thromboembolism (TE) and major bleeding. Among 26 686 included patients, 3667 (13.7%) had an estimated glomerular filtration rate (eGFR) of 30-49mL/min/1.73m2 and 596 (2.2%) had an eGFR below 30 mL/min/1.73m2. We found no evidence of differences regarding the risk of stroke/TE between the OACs (P-value interaction >0.05 for all). Apixaban was associated with a lower 2-year risk of major bleeding compared to vitamin K antagonists (VKA) [hazard ratio 0.79, 95% confidence interval (CI) 0.67-0.93], and the risk difference was significantly larger among patients with reduced kidney function (P-value interaction 0.018). Rivaroxaban was associated with a higher risk of bleeding compared to apixaban (hazard ratio 1.78, 95%CI 1.32-2.39) among patients with eGFR 30-49mL/min/1.73m2. Overall, we found no differences regarding the risk of stroke/TE, but apixaban was associated with a 21% lower relative risk of major bleeding compared to VKA. This risk reduction was even greater when comparing apixaban to VKA among patients with eGFR 15-30mL/min/1.73m2, and when comparing apixaban to dabigatran and rivaroxaban among patients with eGFR 30-49mL/min/1.73m2.

Effect of antiplatelet therapy after COVID-19 diagnosis: A systematic review with meta-analysis and trial sequential analysis.

Coronavirus disease 2019 (COVID-19) may predispose patients to thrombotic disease in the venous and arterial circulations. Based on the current debate on antiplatelet therapy in COVID-19 patients, we performed a systematic review and meta-analysis to investigate the effect of antiplatelet treatments. We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science on February 1, 2023, and only included Randomized clinical trials. The study followed PRISMA guidelines and used Random-effects models to estimate the pooled percentage and its 95% CI. Five unique eligible studies were included, covering 17,950 patients with COVID-19. The result showed no statistically significant difference in the relative risk of all-cause death in antiplatelet therapy versus non-antiplatelet therapy (RR 0.94, 95% CI, 0.83-1.05, P = 0.26, I2 = 32%). Compared to no antiplatelet therapy, patients who received antiplatelet therapy had a significantly increased relative risk of major bleeding (RR 1.81, 95%CI 1.09-3.00, P = 0.02, I2 = 16%). The sequential analysis suggests that more RCTs are needed to draw more accurate conclusions. This systematic review and meta-analysis revealed that the use of antiplatelet agents exhibited no significant benefit on all-cause death, and the upper bound of the confidence interval on all-cause death (RR 95% CI, 0.83-1.05) suggested that it was unlikely to be a substantiated harm risk associated with this treatment. However, evidence from all RCTs suggested a high risk of major bleeding in antiplatelet agent treatments. According to the results of our sequential analysis, there is not enough evidence available to support or negate the use of antiplatelet agents in COVID-19 cases. The results of ongoing and future well-designed, large, randomized clinical trials are needed.

Updated Meta-Analysis of Randomized Controlled Trials on Primary Outpatient Thromboprophylaxis (POTP) in Patients with Lung Cancer Receiving Chemotherapy

Introduction Lung cancer (LC) is the leading cause of cancer mortality in the USA. Thrombosis is the second leading cause of death in cancer patients and in recent years, several studies have been conducted to determine beneficial effect of POTP in reduction of VTE (venous thromboembolism) rate in solid cancer patients with the aim to improve the overall survival. We performed an updated meta- analysis of randomized control trials (RCTs) to determine the benefit and risk of POTP with low-molecular weight heparins (LMWHs) and direct oral anticoagulants (DOACs) in patients with LC receiving chemotherapy. Methods We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2023. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Fixed effects model was applied. Results A total of 5,434 patients with LC from five RCTs and subgroups of another five RCTs were included in our meta-analysis. The prophylactic doses of bemiparin, certoparin, dalteparin, nadroparin, semuloparin and tinzaparin, intermediate dose of enoxaparin and prophylactic dose of rivaroxaban and apixaban were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I 2 statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The VTE incidence was 114 (4.12%) in PATP group and 207 (7.8%) in control group with a RR of 0.53 (95% CI: 0.43 to 0.67, P < 0.00001). The absolute RD in VTE was -0.04 (95% CI: -0.05 to -0.02, P < 0.00001) with an estimate of the number needed to treat (NNT) of 25 to prevent one VTE event. In subgroup analysis of PATP trials treated with LMWHs in study arm, VTE events were reported in 112 (4.2%) in PATP group and 202 (7.9%) in control group with a RR of 0.54 (95% CI: 0.43 to 0.67, P < 0.00001). The absolute RD in VTE was -0.04 (95% CI: -0.05 to -0.02, P < 0.00001). In subgroup analysis of PATP trials treated with DOACs in study arm, VTE events were reported in 2 (2.2%) in PATP group and 5 (5%) in control group with a RR of 0.46 (95% CI: 0.09 to 2.31, P=0.35). The absolute RD in VTE was -0.03 (95% CI: -0.08 to -0.03, P=0.36). Major bleeding (MB) events were reported in 34 (1.6%) patients in POTP group compared to 17 (0.86%) in control group according to an analysis of 7 RCTs. The pooled relative risk for MB was statistically significant at 1.84 (95% CI: 1.06 to 3.22, P = 0.03). Conclusions Our analysis showed that the relative risk reduction is 47% with a NNT of 25 to prevent one VTE with statistically significant increase in MB events in ambulatory patients with LC by providing POTP. In our subgroup meta-analysis of POTP with DOACs, there was no statistically significant difference in reduction of VTE in LC patients with Khorana Score ≥2. Hence, the selection of appropriate patients who are high risk for VTE is crucial and further studies are required to define high risk subsets of LC patients receiving chemotherapy who may benefit from POTP.

Mortality and bleeding associated with the management of sub-massive pulmonary embolism: a systematic review and Bayesian network meta-analysis

Current guidelines recommend anticoagulation (AC) for low and intermediate-risk pulmonary embolism (PE) and systemic thrombolysis (tPA) for high risk (massive) PE. How these treatment options compare with other modalities of treatment such as catheter directed thrombolysis (CDT), ultrasound assisted catheter thrombolysis (USAT), and administering lower dose of thrombolytics (LDT) is unclear. There is no study that has compared all these treatment options. We conducted a systematic review and Bayesian network meta-analysis of randomized controlled trials in patients with submassive (intermediate risk) PE. Fourteen randomized controlled trials were included, comprising 2132 patients. On Bayesian network meta-analysis, a significant decrease in mortality was noted in tPA versus AC. There was no significant difference between USAT versus CDT. For risk of major bleeding, there was no significant difference in relative risk of major bleeding between tPA versus AC and USAT versus CDT. tPA was found to have a significantly higher risk of minor bleeding and a lower risk of recurrent PE compared to AC. Systemic thrombolysis is associated with a significant reduction in mortality and recurrent PE compared to anticoagulation but an increased risk of minor bleeding. There was no difference in risk of major bleeding. Our study also shows that while the newer modalities of treatment for pulmonary embolism are promising, there is lack of data to comment on the purported advantages.

The Number of Concomitant Drugs and the Safety of Direct Oral Anticoagulants in Routine Care Patients with Atrial Fibrillation.

Background The benefit of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) on major bleeding was less prominent among atrial fibrillation (AF) patients with polypharmacy in post-hoc randomized controlled trials analyses. Whether this phenomenon also exists in routine care is unknown. The aim of the study is to investigate whether the number of concomitant drugs prescribed modifies safety and effectiveness of DOACs compared with VKAs in AF patients treated in general practice. Study Design Adult, nonvalvular AF patients with a first DOAC or VKA prescription between January 2010 and July 2018 were included, using data from the United Kingdom Clinical Practice Research Datalink. Primary outcome was major bleeding, secondary outcomes included types of major bleeding, nonmajor bleeding, ischemic stroke, and all-cause mortality. Effect modification was assessed using Cox proportional hazard regression, stratified for the number of concomitant drugs into three strata (0–5, 6–8, ≥9 drugs), and by including the continuous variable in an interaction term with the exposure (DOAC vs. VKA). Results A total of 63,600 patients with 146,059 person-years of follow-up were analyzed (39,840 person-years of DOAC follow-up). The median age was 76 years in both groups, the median number of concomitant drugs prescribed was 7. Overall, the hazard of major bleeding was similar between VKA-users and DOAC-users (hazard ratio [HR] 0.98; 95% confidence interval [CI] 0.87–1.11), though for apixaban a reduction in major bleeding was observed (HR 0.81; 95% CI 0.68–0.98). Risk of stroke was comparable, while risk of nonmajor bleeding was lower in DOAC users compared with VKA users (HR 0.92; 95% CI 0.88–0.97). We did not observe any evidence for an impact of polypharmacy on the relative risk of major bleeding between VKA and DOAC across our predefined three strata of concomitant drug use ( p -value for interaction = 0.65). For mortality, however, risk of mortality was highest among DOAC users, increasing with polypharmacy and independent of the type of DOAC prescribed ( p -value for interaction <0.01). Conclusion In this large observational, population-wide study of AF patients, risk of bleeding, and ischemic stroke were comparable between DOACs and VKAs, irrespective of the number of concomitant drugs prescribed. In AF patients with increasing polypharmacy, our data appeared to suggest an unexplained yet increased risk of mortality in DOAC-treated patients, compared with VKA recipients.

Comparative efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation and chronic kidney disease

Aim To compare efficacy and safety of direct oral anticoagulants (DOACs) for prevention of stroke in patients with nonvalvular atrial fibrillation and reduced creatinine clearance.Material and methods Systematic search for literature and indirect comparison of DOACs were performed.Results The indirect comparison included five randomized clinical trials. The DOACs were comparable by the efficacy of preventing stroke and systemic embolism. The safety profiles had differences. Apixaban significantly decreased the relative risk of major bleeding compared to rivaroxaban by 27 % (relative risk (RR) 0.73; 95 % confidence interval (CI): 0.55-0.98). The apixaban advantage was even greater in the group of patients with a creatinine clearance &lt;50 ml/min: RR was reduced by 48 % compared to rivaroxaban (RR=0.52; 95 % CI: 0.32-0.84), by 50 % compared to dabigatran 300 mg/day (RR=0.50; 95 % CI: 0.31-0.81), and by 48 % compared to dabigatran 220 mg/day (RR=0.52; 95 % CI: 0.32-0.85)Conclusion The indirect comparison of DOACs showed that their efficacy was comparable. With respect of safety, apixaban is the preferrable DOAC for patients with atrial fibrillation and creatinine clearance below 50 ml/min.

Low Molecular Weight Heparin Vs Direct Oral Anticoagulants (Apixaban, Edoxaban and Rivaroxaban) for the Treatment of Cancer Associated Thrombosis: A Cost- Effective Analysis

Introduction: Cancer associated venous thromboembolism (CAT) is a major complication of cancer; results in more than 2-fold increased mortality in cancer patients compared to those without CAT. Approximately 20% of all venous thromboembolism is contributed to by patients with cancer, indicating a huge economic burden. While low molecular weight heparin (LMWH) has been the standard treatment for CAT, more recently several direct oral anticoagulants (DOACs) have been tested in randomized controlled trials and are now available for use (Table 1). However, these agents have not all been compared head-to-head and the decision to choose is often based on arbitrary factors such as patient comorbidities, scheduling ease, availability of agents, patient and physician preference, insurance coverage etc. The objective of our study was to examine the cost-effectiveness of DOACs when compared to the traditional LMWH. Methods: We constructed a 9-state Markov transition decision model to examine strategies of 1) LMWH, 2) Apixaban, 3) Edoxaban, and 4) Rivaroxaban for the treatment of CAT (Figure 1). Our hypothetical cohort consisted of cancer patients who entered the Markov model at almost 50 years of age. These patients were assumed to have a base case utility of 0.609 (adapted from the literature, specific for cancer patients with VTE with no distant metastasis residing in the US). Survival rates were based on 2011 life tables of the US population extracted from the Centers for Disease Control and Prevention database. Data sources included MEDLINE searches, bibliographies from relevant articles in English language. The Center for Medicare/Medicaid Services 2018 data was used to extract drug costs. Cycle length was one month and we used a lifelong time horizon with a healthcare system perspective. Outcomes measure included effectiveness measured in quality-adjusted life years (QALYs) and costs measured in 2019 U.S. dollars. We made some "simplifying" assumptions to run our model: 1) Effect of treatment and side effects of each medication were maintained through the life cycle and no crossover was allowed after failure 2) Cost and morbidity of major bleeding was considered temporary; (one cycle length i.e. one month), after which the patient would recover and his utility would be equivalent to that of base case. Anticoagulants would be discontinued for this patient population for the rest of their life time. 3) Patients whose anticoagulants were discontinued were assumed to not experience another bleeding event but they were still at risk for developing a recurrent VTE. 5) Due to the paucity of literature evaluating the utility value of anticoagulants in cancer population, we assumed that the all DOACs had the same utility (=1) as they are taken orally. Meanwhile, LMWH was assumed to have a lower utility of about 0.98 as it is administered as a subcutaneous injection. Results: Apixaban dominated all other strategies by being less costly and more effective than LMWH or the other DOACs. All relative risks and hazard ratios were compared with LMWH. One-way sensitivity analyses were conducted to examine the impact of uncertainty in selected parameter values (relative risks, hazard ratios, costs of different agents, age and utilities). 1) Apixaban remains cost-saving, unless the hazard ratio for recurrent VTE on Apixaban exceeds 3.8. It remains cost-effective with an incremental cost-effectiveness ratio (ICER) &amp;lt; $50,000/QALY up to a hazard ratio 4.08. 2) Apixaban remains cost saving till the relative risk for major bleeding exceeds 1.58 and it remains cost-effective (ICER &amp;lt; $50,000/ QALY) up to a relative risk of 1.61. However when the relative risk for major bleeding for Apixaban exceeds 1.7, the ICER exceeds $150,000/QALY. 3) Apixaban remains cost saving as long as its monthly cost is under $270. It is no longer cost-effective (ICER &amp;gt; $50,000/ QALY) when the monthly cost of Apixaban exceeds $299. Conclusion: Treatment of CAT with Apixaban is both more effective and less costly when compared to other modalities, including LMWH, Edoxaban and Rivaroxaban. Disclosures No relevant conflicts of interest to declare.

Updated Meta-Analysis of Randomized Controlled Trials on Primary Ambulatory Thromboprophylaxis (PATP) in Patients with Advanced Pancreatic Cancer (APC) Receiving Chemotherapy

Introduction: Thrombosis is the second leading cause of death in cancer patients and patients with APC are categorized as high-risk of developing venous thromboembolism (VTE). Many trials had failed to demonstrate improvement in survival with PATP. Despite decreasing VTE events, PATP in solid cancer patients is not routinely recommended. We conducted an updated meta- analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWH) and direct oral anticoagulants (DOAC) in patients with APC receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. The primary meta- analytic approach was a random effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Results: A total of 1,013 patients with APC from two RCTs and a subgroup of another three RCTs were included in our meta-analysis. The prophylactic, intermediate and therapeutic doses of LMWH and prophylactic dose of DOAC (rivaroxaban) were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2statistic for heterogeneity was 60, suggesting some heterogeneity among RCTs. The VTE incidence was 28 (5.43%) in PATP group and 60 (12.07%) in control group with a RR of 0.44 (95% CI: 0.20 to 0.99, P = 0.05) and RD of -0.06 (95% CI: -0.11 to -0.01, P = 0.01). In fixed effects model, the pooled RR was 0.45 (95% CI: 0.29 to 0.70, P = 0.0003) and the absolute RD in VTE was -0.07 (95% CI: -0.10 to -0.03, P = 0.0002) with an estimate of the number needed to treat (NNT) of 15 to prevent one VTE event. MB events were reported in 9 (4.11%) patients in PATP group compared to 7 (3.27%) in control group according to an analysis of 2 RCTs. The pooled relative risk for MB was statistically non-significant at 1.25 (95% CI: 0.47 to 3.31, P = 0.65). Conclusions: In our study, PATP in APC may statistically significantly decrease VTE events, approximately with relative risk reduction of 55% and a NNT of 15, without increasing MB events. Proper selection of patients who are high risk for VTE in outpatient setting is important. More RCTs are required to further define high risk subsets of APC patients receiving chemotherapy who may benefit from PATP. Disclosures Oo: Medical Education Speakers Network: Honoraria; Janssen and Janssen: Other: Research: site co-investigator .

Cost-Utility Analysis of Apixaban Compared to Usual Care for the Primary Thromboprophylaxis of Ambulatory Cancer Patients Initiating Chemotherapy

Introduction: Apixaban 2.5mg twice daily has been shown to significantly reduce the risk of venous thromboembolism (VTE) compared to placebo for the primary thromboprophylaxis of VTE in ambulatory cancer patients initiating chemotherapy, who are at intermediate-high risk of VTE, with a Khorana score of ≥2 (hazard ratio, 0.41; 95% confidence interval, 0.26 to 0.65; P&amp;lt;0.001). In this study, we estimated whether the health benefit gained from apixaban justified its costs. Method: We conducted a cost-utility analysis of apixaban (2.5mg twice daily) compared to usual care, whereby no apixaban is prescribed, from the perspective of Canada's healthcare system. Our target population was ambulatory cancer patients starting chemotherapy with an intermediate-high risk of VTE. We developed a Markov model with a cycle length of 1-week to simulate costs and quality-adjusted life years (QALYs) for patients receiving either apixaban or usual care over 6 months (Figure 1). To estimate the baseline time varying risk of VTE among ambulatory cancer patients undergoing chemotherapy, we created pseudo patient-level data from survival curves reported for patients in the placebo arm of the AVERT trial using 'WebPlotDigitizer'. We fitted parametric survival models to the patient-level data points to extrapolate VTE risk beyond the trial follow-up period (median follow-up 183 days). The best model was selected based on a visual inspection and the Akaike Information Criterion. The relative risk of VTE, clinically relevant non-major bleeding, and major bleeding (using the International Society of Thrombosis and Haemostasis criteria) as a result of apixaban was obtained from the AVERT trial using the on-treatment analysis. We conducted a targeted literature search to obtain the risk of complications among cancer patients receiving low-molecular-weight heparin for the initial treatment and secondary prevention of VTE using a meta-analysis technique. Hazard ratio for increased risk of death due to cancer was estimated as a weighted average of the age-standardized mortality rate by tumor type, based on the proportion of patients with each tumor type in the AVERT trial. Costs were obtained from published Canadian sources. Baseline health utility values for patients on chemotherapy and in remission were calculated as a weighted average of utility values by tumour type, also based on the proportion of patients with each tumour type in the AVERT trial. Utility values for chemotherapy and remission for each tumour type, as well as event specific disutility values, were obtained from the published literature. Both costs and QALYs were discounted using an annual rate of 1.5%, as recommended by the Canadian Agency for Drugs and Technologies in Health. We conducted deterministic and probabilistic sensitivity analyses to assess robustness of study findings. Results: Over a 6-month period, apixaban was associated with a lower health system cost (C$25,987 vs C$26,268) and a slight increase in QALYs (0.3339 vs 0.3337) compared to usual care (Table 1). The probability that apixaban was cost-saving compared to usual care was 90%; however, this probability decreased with the greater willingness to pay (WTP) values partly due to the high uncertainty in the difference in QALYs. At a WTP threshold of C$50,000/QALY, the probability of apixaban being cost effective was 57% (Figure 2). Over 1 year, apixaban reduced health care system costs by C$1,113 and improved QALYs by 0.0005 units compared to usual care. At a WTP threshold of C$50,000/QALY, the probability of apixaban being cost effective increased to 70%. Our results were robust to the change in time horizon; however, they were more sensitive to the relative risk of VTE, the relative risk of major bleeding, the costs amassed in the post-VTE period, and the treatment cost of acute VTE. Probabilistic sensitivity analysis indicated a high-level uncertainty around cost effectiveness estimates, which may be driven by the wide confidence intervals around estimates for relative risk of complications in patients receiving thromboprophylaxis with apixaban. Conclusion: From a publicly funded health system's perspective apixaban is a cost saving option for thromboprophylaxis among ambulatory cancer patients initiating chemotherapy. Disclosures Wells: BMS/Pfizer: Honoraria, Research Funding; Bayer: Honoraria; Sanofi: Honoraria; Daiichi Sankyo: Honoraria. Carrier:Servier: Honoraria; Bayer: Honoraria; Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Leo Pharma: Honoraria, Research Funding. OffLabel Disclosure: Apixaban can be used as postoperative prophylaxis of DVT/PE and for treatment of DVT/PE. We performed a cost-utility analysis of apixaban 2.5mg BID for the primary thromboprophylaxis of ambulatory cancer patients initiating chemotherapy, at intermediate-high risk of venous thromboembolism.

Meta-Analysis and Cost-Effectiveness Analysis of Low-Dose Direct Oral Anticoagulant for the Prevention of Cancer Associated Thrombosis

Introduction: Randomized controlled trials (RCTs) have shown similar yet conflicting primary outcomes for the use of low-dose direct oral anticoagulant (DOAC), including rivaroxaban and apixaban, in the prevention of cancer-associated thrombosis (CAT). It remains unclear if this preventive strategy is consistent, robust, and cost-effective across different trial populations. Methods: We performed a systematic review of RCTs that compared DOAC vs. placebo for CAT prevention using EMBASE, MEDLINE, and CENTRAL. Two authors screened/reviewed articles and abstracted the data. Primary efficacy, sensitivity efficacy, and safety outcomes were uniformly defined and extracted from the studies. Meta-analysis was performed using random-effects model. Subgroup analysis was performed for patients with intermediate- and high-risk Khorana Score. Using inputs from the meta-analysis and relevant epidemiology and outcomes studies, we performed a cost-utility analysis using a Markov state-transition model over life time in a hypothetical cohort of 60-year-old high-risk patients with a similar distribution of cancers as the pooled RCTs. We calculated the differences in cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) and performed one-way and probabilistic sensitivity analyses to test the robustness of the results. Results: A total of 202 records were identified and 28 full-text articles were assessed. Two studies with 1415 participants were eligible to be included for meta-analysis (Table 1). For DOAC vs. placebo, the relative risk (RR) for overall VTE incidence by six months was 0.56 (0.35-0.89). The RR for major bleeding (MB) on-treatment was 1.96 (0.80-4.82). Patients with high-risk Khorana score (3+) derived the largest absolute risk reduction of VTE. Based on a Markov model, in patients at intermediate-to-high risk for VTE (Khorana Score 2+), prophylaxis with low-dose DOAC thromboprophylaxis for 6 months, compared to placebo, was associated with 32 per 1000 fewer CAT events and 11 per 1000 more MB over life-time. Prophylaxis was associated with an incremental cost increase of $1,445 and an incremental QALY increase of 0.12, resulting in an ICER of $11,947 per QALY gained (Figure 1). Key drivers of ICER variation included the relative risks of VTE and major bleeding as well as the cost of drug. Based on the cost-effectiveness acceptability curve, this preventive strategy was 94% cost effective at the threshold of $50,000. In a scenario sensitivity analysis, patients with the highest risk of VTE (Khorana Score 3+) derived the most benefit from low-dose DOAC thromboprophylaxis. Conclusion: Low-dose DOAC (rivaroxaban or apixaban) thromboprophylaxis for 6 months reduces the rate of overall VTE in higher-risk cancer patients starting systemic chemotherapy and may increase the likelihood of bleeding. It appears to be a cost-effective strategy for the prevention of CAT in intermediate-to-high risk ambulatory patients based on our analyses; however, the differential impact on QALY is small over lifetime. Future research should focus on a better understanding of the significance of these adverse events on longer term quality of life and their impact on delays in anti-cancer treatment. Disclosures Kuderer: Celldex: Consultancy; Halozyme: Consultancy; Coherus Biosciences: Consultancy, Other: Travel, Accommodations, Expenses; Mylan: Consultancy, Other: Travel, Accommodations, Expenses; Pfizer: Consultancy; Myriad Genetics: Consultancy; Janssen Scientific Affairs, LLC: Consultancy, Other: Travel, Accommodations, Expenses. Khorana:Janssen: Consultancy; Bayer: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy. Carrier:Leo Pharma: Honoraria, Research Funding; Servier: Honoraria; Bayer: Honoraria; Pfizer: Honoraria, Research Funding; BMS: Honoraria, Research Funding. Lyman:G1 Therapeutics, Halozyme Therapeutics, Partners Healthcare, Hexal, Bristol-Myers Squibb, Helsinn Therapeutics, Amgen Inc., Pfizer, Agendia, Genomic Health, Inc.: Consultancy; Amgen Inc.: Other: Research support, Research Funding; Generex Biotechnology: Membership on an entity's Board of Directors or advisory committees; Janssen Scientific Affairs, LLC: Research Funding.

Updated Meta-Analysis of Randomized Controlled Trials on Primary Ambulatory Thromboprophylaxis (PATP) in Patients with Locally Advanced or Metastatic Lung Cancer Receiving Chemotherapy

Introduction: Lung cancer (LC) is the second most common cancer in both sexes and is the leading cause of cancer mortality in the United States. Thrombosis is the second leading cause of death in cancer patients and PATP in solid cancer patients were performed in research trials to decrease venous thromboembolism (VTE) rates with ultimate aim to improve survival. We undertook an updated meta- analysis of RCTs to determine the benefit and risk of PATP with low-molecular weight heparins (LMWHs) and direct oral anticoagulants (DOAC) in patients with locally advanced or metastatic LC receiving chemotherapy. Methods: We performed a comprehensive literature search using MEDLINE and EMBASE databases through June 30, 2019. The references of all potential studies were also reviewed for any additional relevant studies. The RCTs with reduction in VTE as a primary or secondary endpoint and the major bleeding (MB) as a safety outcome were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran's Q- statistic. Fixed effects model was applied. Results: A total of 5,375 patients with LC from five RCTs and a subgroup of another four RCTs were included in our meta-analysis. The prophylactic doses of bemiparin, certoparin, dalteparin, nadroparin, semuloparin and tinzaparin, intermediate dose of enoxaparin and prophylactic dose of rivaroxaban were used in the studies. The duration of LMWH and DOAC ranged from 3 to 6 months. The randomization ratio was 2 to 1 in PROTECHT study and 1 to 1 in all other studies. The I2statistic for heterogeneity was 0, suggesting homogeneity among RCTs. The VTE incidence was 114 (4.16%) in PATP group and 207 (7.85%) in control group with a RR of 0.53 (95% CI: 0.43 to 0.67, P &lt; 0.001). The absolute RD in VTE was -0.04 (95% CI: -0.05 to -0.02, P &lt; 0.001) with an estimate of the number needed to treat (NNT) of 28 to prevent one VTE event. MB events were reported in 26 (1.37%) patients in PATP group compared to 15 (0.84%) in control group according to an analysis of 6 RCTs. The pooled relative risk for MB was statistically non-significant at 1.57 (95% CI: 0.85 to 2.88, P = 0.15). Conclusions: Our analysis showed that the relative risk reduction is 46% with a NNT of 28 to prevent one VTE without increasing MB events in ambulatory patients with locally advanced or metastatic LC. Selection of appropriate patients who are high risk for VTE is crucial and further studies are required to define high risk subsets of LC patients receiving chemotherapy who may benefit from PATP. Disclosures Oo: Janssen and Janssen: Other: Research: site co-investigator ; Medical Education Speakers Network: Honoraria.

Meta-analysis of safety and efficacy of oral anticoagulants in patients requiring catheter ablation for atrial fibrillation.

The ideal oral anticoagulant agent during catheter ablation (CA) for atrial fibrillation (AF) remained unclear. Novel oral anticoagulants (NOACs) are safer and effective compared to uninterrupted vitamin K antagonists (U-VKA) among patients requiring CA for AF. Four randomized controlled trials (RCTs) and 9 observational studies (OS) were selected using PubMed/Medline, EMBASE and the CENTRAL data bases (Inception-December-2017). Estimates were reported as random effects risk ratio (RR) with 95% confidence interval (CI). The primary safety outcome was major bleeding and main efficacy endpoint was thromboembolism. In RCTs restricted analysis, NOACs significantly reduced the relative risk of major bleeding by 72% compared to U-VKA (RR, 0.28, 95% CI, 0.14-0.58, P < 0.001). This significant effect was not achieved in OS based analysis (RR, 0.86, 95% CI, 0.42-1.78, P = 0.68). In terms of thromboembolism, both anticoagulation strategies were equally effective in analysis of RCTs (RR, 0.28, 95% CI, 0.05-1.70, P = 0.17) or OS (RR, 1.43, 95% CI, 0.46-4.39, P = 0.54). In sensitivity analysis, there was no difference among uninterrupted NOACs (U-NOACs) and U-VKA in terms of major bleeding [(RCTs: RR, 0.33, 95% CI, 0.10-1.06, P = 0.06); (OS: RR, 0.70, 95% CI, 0.28-1.78, P = 0.46)] or thromboembolism [(RCTs: RR, 0.25, 95% CI, 0.03-2.29, P = 0.22); (OS: RR, 0.68, 95% CI, 0.08-5.53, P = 0.72)]. NOACs, either interrupted or un-interrupted, are safer and equally effective drugs compared to U-VKA in AF patients requiring CA.

An Individual Participant Data Meta-Analysis of 13 Randomized Trials to Evaluate the Impact of Prophylactic Use of Heparin in Oncological Patients

Background: Parenteral anticoagulants may improve outcomes in patients with cancer by reducing the risk of venous thromboembolism (VTE) and through a direct anti-tumour effect. Study-level meta-analysis indicates a reduction in VTE and provide moderate certainty that a small survival benefit exists; it is unclear if patients with specific cancers benefit more or less. Utilizing data from randomized controlled trials (RCT), this individual participant data meta-analysis examines the impact of heparin on survival, VTE and major bleeding in oncological patients randomized to low-molecular weight heparin (LMWH) or no LMWH.Methods: We performed a comprehensive systematic search for all RCTS (last search date March 2017) and contacted authors and sponsors to obtain individual participant data of patients with solid cancers and no other indication for prophylactic or therapeutic anticoagulation. We utilized the GRADE approach to evaluate the certainty of evidence and produce an evidence profile. All analyses followed the intention-to-treat principle. We calculated the impact on mortality through multivariable hierarchical models with patient-level variables as fixed effects and a categorical trial variable as a random effect. We adjusted the analysis for age, cancer type and metastasis status. To investigate whether intervention effects vary by predefined subgroups, including type of cancer, we tested interaction terms in the statistical model.Results: A total of 18 RCTs (n=10,041 participants) were eligible for inclusion and we obtained data from 82.4% of the participants (13 RCTs, n=8,278; n=4,139 for LMWH and n=4,139 for no LMWH). The meta-analysis revealed an adjusted relative risk of mortality within one year of 0.99 (95% CI: 0.95, 1.03) and a hazard ratio of 0.97 (95% CI: 0.82, 1.14) after one year. The relative risk for VTE was 0.58 (95% CI: 0.48, 0.71), 0.57 (95% CI: 0.44, 0.74) for symptomatic deep vein thrombosis and 0.58 (95%CI: 0.44, 0.77) for symptomatic pulmonary embolism, separately. For every 1,000 patients treated, approximately 16 fewer would experience symptomatic DVT and 16 fewer would experience any PE. The adjusted relative risk for major bleeding throughout trial duration was 1.24 (95% CI: 0.91, 1.69; P=0.17). Subgroup analysis, by cancer type, of VTE occurrence throughout trial duration identified lung cancer OR=0.52 (95% CI: 0.39, 0.68; P<0.001) and pancreatic cancer OR=0.55 (95% CI: 0.35, 0.88; P=0.01) patients as experiencing the greatest benefit from LMWH treatment. The certainty of the evidence for the outcomes was moderate to high.Conclusion: LMWH reduces risk of VTE without increasing risk of bleeding but does not improve survival across all patients.Funding: Canadian Institutes of Health Research knowledge synthesis grant, KRS 126594Registration: International Prospective Register for Systematic Reviews (PROSPERO), CRD42013003526. DisclosuresSchünemann:Canadian Institutes of Health Research: Research Funding. Crowther:Alexion: Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Boehringer Ingelheim: Speakers Bureau; Leo Pharma: Research Funding; Pfizer: Honoraria; Portola: Consultancy; Shinogi: Consultancy. Macbeth:Pfizer: Other: Provision of Dalteparin for FRAGMATIC trial; Cancer Research UK: Research Funding. Griffiths:Pfizer: Consultancy, Other: Comment: I run an academic clinical trials unit, have received educational/investigator intiated research grants from companies that make these heparin agents. As consultant > 3 years ago, advised Pfizer on clinical trial designs unrelated to this study., Research Funding. Van Es:Pfizer: Employment, Other: Comment: Dr. van Es reports personal fees from Pfizer as a member of their advisory board. These fees are unrelated to this project.. Streiff:Roche: Research Funding; Portola: Research Funding; Janssen Scientific Affairs, LLC: Consultancy, Research Funding; CSL Behring: Consultancy, Research Funding. Ageno:BMS-Pfizer: Consultancy, Honoraria; Bayer AG: Consultancy, Honoraria, Research Funding; Boehringer Ingelheim: Consultancy, Honoraria; Daiichi Sankyo: Consultancy, Honoraria. Bozas:PharmaMar: Honoraria. McBane:Bristol Myers Squibb: Other: Research grant for cancer associated VTE. Maraveyas:Bayer: Other: Personal fees and conference attendance; Bristol-Myers Squibb: Other: Grants and personal fees; Leo Pharma: Other: Grants, personal fees and conference attendance; Pfizer: Other: Personal fees. Loprinzi:Bristol Myers: Other: Grant - unrelated to this project; Janssen: Other: Grant - unrelated to this project.

Assessing Bleeding Risk in Patients With Intentional Overdoses of Novel Antiplatelet and Anticoagulant Medications

In recent years, the use of novel anticoagulants and antiplatelet agents has become widespread. Little is known about the toxicity and bleeding risk of these agents after acute overdose. The primary objective of this study is to evaluate the relative risk of all bleeding and major bleeding in patients with acute overdose of novel antiplatelet and anticoagulant medications. This study is a retrospective study of acute ingestion of apixaban, clopidogrel, ticlopidine, dabigatran, edoxaban, prasugrel, rivaroxaban, and ticagrelor reported to 7 poison control centers in 4 states during a 10-year span. The prevalence of bleeding for each agent was calculated, and hemorrhage was classified as trivial, minor, or major. A total of 322 acute overdoses were identified, with the majority of cases involving clopidogrel (260; 80.7%). Hemorrhage occurred in 16 cases (4.9%), including 7 cases of clopidogrel, 6 cases of rivaroxaban, 2 cases of dabigatran, and 1 case of apixaban. Most cases of hemorrhage were classified as major (n=9). Comparing the novel anticoagulants with the P2Y12 receptor inhibitors, the relative risk for any bleeding with novel anticoagulant was 6.68 (95% confidence interval 2.63 to 17.1); the relative risk of major bleeding was 18.1 (95% confidence interval 3.85 to 85.0). Acute overdose of novel anticoagulants or antiplatelet agents is associated with a small risk of significant hemorrhage. The risk is greater with the factor Xa inhibitors and direct thrombin inhibitors than with the P2Y12 receptor antagonists.

Low- Molecular Weight Heparins (LMWH) Versus Vitamin K Antagonists (VKAs) in the Treatment and Secondary Prevention of Cancer-Associated Venous Thromboembolism (VTE): A Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs)

▪Introduction: Cancer-associated thrombosis accounts for about 20% of all cases of VTE. VTE increases not only mortality but also morbidity in cancer patients. LMWH is currently recommended over VKAs by major consensus guidelines and it is primarily based on a single, large RCT (CLOT trial) and some smaller studies. However, recently published CATCH trial, which enrolled 900 cancer patients with acute VTE, did not detect a statistically significant reduction in recurrent VTE between tinzaparin and warfarin groups. Hereby, we conducted a systematic review and meta-analysis of RCTs to determine the efficacy and safety of LMWH versus VKA in the treatment and secondary prevention of cancer-associated VTE.Methods: MEDLINE and EMBASE databases were searched through June 30, 2016. All potential studies and their references were evaluated for any additional relevant studies. The RCTs which compare LMWH vs VKA in the treatment of VTE were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR), and risk difference (RD) with 95% confidence interval (CI). Fixed effects model was applied.Results: A total of 2196 cancer patients with acute VTE from 6 RCTs and a subgroup of another 2 RCTs were eligible for analysis. Enoxaparin, dalteparin, tinzaparin and nadroparin were used on LMWH group and warfarin or acenocoumarol were used on VKA group. The treatment duration was from 3 to 6 months. The VTE incidence was 77 (6.832%) in LMWH group vs 128 (11.973%) in VKA group with a RR of 0.572 (95% CI: 0.436 to 0.750, P < 0.001). The absolute RD in VTE was -0.051 (95% CI: -0.076 to -0.027, P < 0.001). Major bleeding (MB) events were reported in 49 (4.757%) patients in LMWH group vs 45 (4.473%) in VKA group according to the analysis of 6 RCTs. The pooled relative risk for MB was statistically non-significant at 1.049 (95% CI: 0.705 to 1.562, P = 0.812). Composite clinically relevant non-major (CRNM) and minor bleeding events were noted in 143 (13.883%) patients in LMWH group and in 163 (16.203%) in VKA group according to the analysis of 6 RCTs. The RR for composite CRNM and minor bleeding was statistically significant at 0.773 (95% CI: 0.630 to 0.948, P 0.014), favoring LMWHs over VKAs.Conclusions: Our meta-analysis confirms that LMWHs significantly decrease recurrent VTE events compared to VKAs without increasing MB in patients with cancer-associated VTE. LMWH therapy appears to have less CRNM and minor bleeding events compared to VKAs. [Display omitted] [Display omitted] [Display omitted] DisclosuresOo:Daiichi Sankyo: Research Funding.

Major Bleeding and Hemorrhagic Stroke With Direct Oral Anticoagulants in Patients With Renal Failure: Systematic Review and Meta-Analysis of Randomized Trials

Direct oral anticoagulants (DOACs) are used as an alternative for traditional antithrombotic therapy. However, the safety profile of DOACs in patients with renal failure (RF) has not been determined. A systematic review was performed assessing the reported safety of DOACs compared with vitamin K antagonists (VKAs) in patients with RF and estimated creatinine clearance (eCrCL)< 50mL/min and eCrCL 50 to 80mL/min. MEDLINE, EMBASE, Cochrane, and the Clinical Trials Registry (ClinicalTrials.gov) were searched for randomized clinical trials up to November 2015. The data were pooled by using both traditional frequentist and Bayesian random effects models. Nine trials met the inclusion criteria. Among 94,897 participants, 54,667 (58%) had RF. Compared with VKAs, DOACs were associated with a significantly decreased risk formajor bleeding in patients with eCrCL 50 to 80mL/min (risk ratio, 0.87 [95%CI, 0.81-0.93]) and a nonsignificant decrease in the risk for major bleeding in patients with eCrCL< 50mL/min (risk ratio, 0.83 [95%CI, 0.68-1.02]); there was evidence of significant heterogeneity. Indirect comparisons, using Bayesian network analysis, indicated that apixaban was associated with a decreased rate of major bleeding compared with other DOACs inpatients with eCrCL <50mL/min. DOACs were associated with a significant decrease in the risk for hemorrhagic stroke compared with VKAs in patients with eCrCL< 50mL/min and 50 to 80mL/min. As a class, DOACs are associated with a reduced risk for hemorrhagic stroke compared with VKAs in patients with RF. However, DOACs may differ from each other in their relative risk for major bleeding in patients with eCrCL< 50mL/min. PROSPERO registry; No.: CRD42014013730; URL: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014013730.

Benefit and Risk of Primary Thromboprophylaxis in Ambulatory Patients with Advanced Pancreatic Cancer Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: Vascular thromboembolism (VTE) is the second leading cause of death in patients with cancer. Despite the fact that mortality is increased in cancer patients who developed VTE compared to those without VTE, empirical prophylaxis against VTE in ambulatory patients with cancer remains controversial. The risk of VTE is higher for certain types of cancer such as pancreatic and hematologic malignancies, in patients with advanced cancer, and in those who are undergoing chemotherapy or radiotherapy. We carried out a systematic review and meta-analysis of randomized controlled trials (RCT) to investigate the benefit and risk of primary thromboprophylaxis (PTP) with low-molecular weight heparins (LMWH) in ambulatory patients with advanced pancreatic cancer receiving chemotherapy.Methods: We undertook an extensive literature search using MEDLINE and EMBASE databases through July 13, 2014. References of the potential studies were also reviewed for any additional relevant studies. RCTs with reduction in symptomatic VTE as a primary endpoint were included. Mantel-Haenszel method was used to estimate the pooled event-based risk ratio (RR) as well as the pooled absolute risk difference (RD) with 95% confidence interval (CI). Fixed effects model was applied because there was homogeneity among the included studies (I2 = 0.00).Results: Two RCTs and a subgroup of another two RCTs, comprising a total of 738 patients with advanced pancreatic cancer, were eligible for analysis. Antithrombotics used in these trials were nadroparin (prophylactic dose), semuloparin (prophylactic dose), enoxaparin (semi-therapeutic dose), and dalteparin (therapeutic dose). The duration of PTP lasted from three to six months. The crude incidence of VTE was 5.51% and 15.12% in those receiving anticoagulants and in control patients, respectively, with a risk ratio of 0.36 (CI: 0.22 – 0.59, p < 0.0001). The absolute risk difference in VTE was 9.5% (CI: 5.3 – 13.8 %, p < 0.0001), with an estimate of the number needed to treat (NNT) of 10.5 to prevent one symptomatic VTE event. Major bleeding events were reported in 5.48% of patients on thromboprophylaxis compared to 7.94% in control patients according to an analysis of two RCTs. The pooled relative risk for major bleeding was statistically nonsignificant at 0.68 (CI: 0.33 – 1.39, p = 0.29).Conclusions: A previous meta-analysis reported that approximately 60 patients were required to be treated with LMWH to prevent one symptomatic VTE among unselected cancer patients receiving chemotherapy. Our meta-analysis revealed that thromboprophylaxis resulted in a significant reduction in symptomatic VTE events with NNT of 10.5 without an increase in major bleeding events, indicating that PTP with anticoagulants in advanced pancreatic cancer patients receiving chemotherapy may be beneficial. Further large randomized phase III studies are recommended to evaluate the effects of such targeted thromboprophylaxis on morbidity, mortality and the costs of care. [Display omitted] [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Influence of sex on risk of bleeding in anticoagulated patients: a systematic review and meta‐analysis

The risk of bleeding on anticoagulation varies between patients. It is uncertain whether sex influences this risk. To determine if the risk of major bleeding differs between men and women receiving anticoagulation for atrial fibrillation or venous thromboembolism(VTE). We searched MEDLINE, EMBASE, and Cochrane databases, and relevant conference proceedings, until February 2013. We included randomized controlled trials and prospective cohort studies of patients on therapeutic anticoagulation for atrial fibrillation or VTE. Two reviewers independently extracted data. The relative risk of bleeding in men compared to women was pooled using a random-effects model. Forty-two studies including 94 293 patients were eligible; 78 044 patients (83%) had atrial fibrillation; 16 156 patients (17%) had VTE; 37 250 patients were women (40%); and there were 4147 major bleeds. The relative risk of major bleeding for men vs. women was 1.02(95% CI 0.95–1.10; P = 0.27 for heterogeniety). The relative risk was 1.02 (95% CI 0.95–1.09) in patients with atrial fibrillation and 0.80 (95% CI 0.65–0.98) in patients with VTE (P = 0.03 for subgroup effect). Type of anticoagulant,intensity of anticoagulation, and whether patients began or were already established on anticoagulants at enrollment did not influence the relative risk of major bleeding in men compared to women. The risk of major bleeding on anticoagulation appears to be the same in men and women, particularly if patients have atrial fibrillation. This finding is less certain for patients with VTE, in whom the risk of bleeding may be marginally lower in men compared to in women.

Consistency of safety profile of new oral anticoagulants in patients with renal failure

The use of new oral anticoagulants (NOACs) in patients with impaired renal function has raised major concerns, in particular the possibility of an increased risk of bleeding due to accumulation. The aims of this work were to assess the safety of NOACs in patients with renal failure and describe the relationship between clinical events and drug renal excretion magnitude. All phase III trials comparing NOACs with vitamin K antagonists (VKAs) in patients with estimated glomerular filtration (eGFR) rate <50mLmin(-1) were eligible. The main safety and efficacy outcomes were major bleeding and thrombosis. A meta-regression was performed to estimate the correlation between the treatment effect estimate and the percentage of renal excretion. Nine studies (12272 patients) were included. A significantly greater relative reduction in major bleeding was seen for NOACs with renal excretion <50% (RR, 0.61; CI, 0.51-0.74) than for those with high renal excretion (RR, 0.96; CI, 0.85-1.07) (interaction test, P<0.0001). A linear relationship between the relative risk of major bleeding and the magnitude of renal excretion was found by meta-regression (R(2) =0.66, P=0.03). For thrombosis, a greater treatment effect of NOA vs. INR-adjusted VKA was observed in patients with eGFR <50mLmin(-1) (RR 0.78, CI 0.67-0.92), but no correlation between treatment effect and renal excretion was found. New oral anticoagulants were at least as effective as VKAs, with reduced risks of major bleeding and thrombosis in patients with eGFR <50mLmin(-1) . The renal excretion of these new drugs seemed to modify the safety profile, contrary to the efficacy.

Trifecta or Triple Threat? The Challenge of Post-PCI Management in Patients Receiving Chronic Oral Anticoagulant Therapy

We are fortunate to practice in an era of medicine which has many proven therapies. However, we are increasingly faced with coadministration of therapies whose combined effects have not been fully evaluated. Perhaps the most common and difficult of these scenarios is the use of dual antiplatelet therapy in patients who require chronic oral anticoagulation. Although each of these treatments has clear benefits, there is concern about bleeding risk when they are used together. Physicians are forced to choose between risking a thromboembolic or a bleeding complication. To best serve our patients, we must consider not only our initial reaction to do no harm, but go through the slower process of calculating the risk and severity of all possible adverse effects. However, for this process to succeed, we need robust data on which to base these calculations. This issue of the Canadian Journal of Cardiology (CJC) contains 2 articles which provide much-needed data. In the first, Ho and colleagues study the most common group of patients requiring chronic anticoagulation—individuals with atrial fibrillation. Their single-centre Canadian study included 602 patients with atrial fibrillation as their only indication for anticoagulation who underwent percutaneous coronary intervention (PCI) between 2008 and 2009. All were treated with dual antiplatelet therapy using aspirin and clopidogrel. The study was not randomized; however, physicians elected to treat 382 patients with triple therapy (ie, continued warfarin along with dual antiplatelet therapy), and 220 patients received dual antiplatelet therapy alone. Physicians clearly favoured triple therapy among patients with a higher risk of stroke, as patients receiving triple therapy were older (72.9 vs 70.5 years, P 0.039), were more likely to have suffered a previous stroke (14.4% vs 6.4%, P 0.01) and had a higher Congestive Heart Failure, Hypertension, Age, Diabetes, Stroke/Transient Ischemic Attack CHADS2 score (2.6 vs 2.1; P 0.001). 6