Restarting Anticoagulation and Outcomes After Major Gastrointestinal Bleeding in Atrial Fibrillation
2013; Elsevier BV; Volume: 113; Issue: 4 Linguagem: Inglês
10.1016/j.amjcard.2013.10.044
ISSN1879-1913
AutoresWaqas Qureshi, Chetan Mittal, Iani Patsias, Kiran Garikapati, Aishwarya Kuchipudi, Gagandeep Cheema, Mohammad Elbatta, Zaid Alirhayim, Fatimah Khalid,
Tópico(s)Venous Thromboembolism Diagnosis and Management
ResumoData regarding the outcomes of restarting anticoagulation in patients who develop gastrointestinal bleeding (GIB) while anticoagulated are sparse. We hypothesized that restarting anticoagulation in these patients is associated with better outcomes. This is a retrospective cohort study that enrolled subjects who developed GIB while on anticoagulation from 2005 to 2010. Atrial fibrillation was defined by history and electrocardiography on presentation. GIB was defined as a decrease in hemoglobin by 2 g, visible bleeding, or positive endoscopic evaluation. Time-to-event adjusted analyses were performed to find an association of restarting warfarin and recurrent GIB, arterial thromboembolism, and mortality. Stratified analysis by duration of interruption of warfarin was also performed. Overall, 1,329 patients (mean age 76 years, women 45%) developed major GIB. Warfarin was restarted in 653 cases (49.1%). Restarting warfarin was associated with decreased thromboembolism (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.54 to 0.93, p = 0.01) and reduced mortality (HR 0.67, 95% CI 0.56 to 0.81, p <0.0001) but not recurrent GIB (HR 1.18, 95% CI 0.94 to 1.10, p = 0.47). When the outcomes were stratified by duration of warfarin interruption, restarting warfarin after 7 days was not associated with increased risk of GIB but was associated with decreased risk of mortality and thromboembolism compared with resuming after 30 days of interruption. Decision to restart warfarin after an episode of major GIB is associated with improved survival and decreased thromboembolism without increased risk of GIB after 7 days of interruption. Data regarding the outcomes of restarting anticoagulation in patients who develop gastrointestinal bleeding (GIB) while anticoagulated are sparse. We hypothesized that restarting anticoagulation in these patients is associated with better outcomes. This is a retrospective cohort study that enrolled subjects who developed GIB while on anticoagulation from 2005 to 2010. Atrial fibrillation was defined by history and electrocardiography on presentation. GIB was defined as a decrease in hemoglobin by 2 g, visible bleeding, or positive endoscopic evaluation. Time-to-event adjusted analyses were performed to find an association of restarting warfarin and recurrent GIB, arterial thromboembolism, and mortality. Stratified analysis by duration of interruption of warfarin was also performed. Overall, 1,329 patients (mean age 76 years, women 45%) developed major GIB. Warfarin was restarted in 653 cases (49.1%). Restarting warfarin was associated with decreased thromboembolism (hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.54 to 0.93, p = 0.01) and reduced mortality (HR 0.67, 95% CI 0.56 to 0.81, p <0.0001) but not recurrent GIB (HR 1.18, 95% CI 0.94 to 1.10, p = 0.47). When the outcomes were stratified by duration of warfarin interruption, restarting warfarin after 7 days was not associated with increased risk of GIB but was associated with decreased risk of mortality and thromboembolism compared with resuming after 30 days of interruption. Decision to restart warfarin after an episode of major GIB is associated with improved survival and decreased thromboembolism without increased risk of GIB after 7 days of interruption. In patients with nonvalvular atrial fibrillation (AF), warfarin has been the anticoagulant agent of choice for the last 3 decades.1Mant J.W. Pro: 'Warfarin should be the drug of choice for thromboprophylaxis in elderly patients with atrial fibrillation'. Why warfarin should really be the drug of choice for stroke prevention in elderly patients with atrial fibrillation.Thromb Haemost. 2008; 100: 14-15PubMed Google Scholar Elderly patients appear to have a greater propensity for complications of therapy such as GIB on one end or cerebrovascular events on the other end of the therapeutic spectrum.2Suehiro T. Yakeishi Y. Sakai F. Matsuzaki K. Sanefuji K. Toyokawa T. Shioshita K. Sugie Y. Okudaira Y. Kano T. Mine H. Suetsugu K. Suetsugu F. Suehiro N. Suhiro K. Gastrointestinal bleeding and blood transfusion in the elderly in Japan.Hepatogastroenterology. 2012; 59: 1480-1483PubMed Google Scholar GIB occurs in 5% to 15% of patients on long-term anticoagulation.3Lee J.K. Kang H.W. Kim S.G. Kim J.S. Jung H.C. Risks related with withholding and resuming anticoagulation in patients with non-variceal upper gastrointestinal bleeding while on warfarin therapy.Int J Clin Pract. 2012; 66: 64-68Crossref PubMed Scopus (30) Google Scholar, 4Fihn S.D. McDonell M. Martin D. Henikoff J. Vermes D. Kent D. White R.H. Risk factors for complications of chronic anticoagulation. A multicenter study. Warfarin Optimized Outpatient Follow-up Study Group.Ann Intern Med. 1993; 118: 511-520Crossref PubMed Scopus (682) Google Scholar, 5Landefeld C.S. Beyth R.J. Anticoagulant-related bleeding: clinical epidemiology, prediction, and prevention.Am J Med. 1993; 95: 315-328Abstract Full Text PDF PubMed Scopus (788) Google Scholar Literature is scarce about the various outcomes in this specific population and controversy exists regarding various outcomes based on durations of interruption of warfarin. Short-term interruption has been shown to increase mortality and thromboembolism.6Raunso J. Selmer C. Olesen J.B. Charlot M.G. Olsen A.M. Bretler D.M. Nielsen J.D. Dominguez H. Gadsboll N. Kober L. Gislason G.H. Torp-Pedersen C. Hansen M.L. Increased short-term risk of thrombo-embolism or death after interruption of warfarin treatment in patients with atrial fibrillation.Eur Heart J. 2012; 33: 1886-1892Crossref PubMed Scopus (62) Google Scholar It is important to understand the risks of development of recurrent gastrointestinal hemorrhage, mortality, and thromboembolism in the context of resuming warfarin in this particular group. Warfarin has shown to not only improve cardiovascular mortality but also quality of life.7Smith P. Long-term anticoagulant treatment after acute myocardial infarction. The Warfarin Re-Infarction Study.Ann Epidemiol. 1992; 2: 549-552Abstract Full Text PDF PubMed Scopus (8) Google Scholar, 8Das A.K. Willcoxson P.D. Corrado O.J. West R.M. The impact of long-term warfarin on the quality of life of elderly people with atrial fibrillation.Age Ageing. 2007; 36: 95-97Crossref PubMed Scopus (15) Google Scholar We hypothesized that warfarin treatment prevents thromboembolism and has mortality benefit over the subjects who are not restarted on warfarin. Also, we investigated the various durations of interruption and the risk of GIB, thromboembolism, and mortality. This is a retrospective cohort study that evaluated the patients enrolled at the anticoagulation clinic of Henry Ford Health System with a large catchment area serving all socioeconomic strata, covering majority of Southeast Michigan, United States. Patients who developed major GIB (defined in the following) while taking warfarin and then had evidence of resolution of major GIB (defined as stability of hemoglobin levels with 2 g of hemoglobin decrease from the last known hemoglobin level warranting hospitalization, (2) need for blood transfusion of at least 2 units, and (3) visible bleeding by health personnel or endoscopic evidence of stigmata of recent bleeding in the form of visible bleeding or clot. We decided to analyze GIB within 90 days, as propensity for recurrent GIB should be short term. Also, 12% of the patients developed recurrent GIB and we only considered the index GIB. Thromboembolism was defined as venous thromboembolism (pulmonary embolism and deep venous thrombosis), arterial thromboembolism, or stroke or transient ischemic attack. Stroke or transient ischemic attack was defined as any of the following: (1) recent stroke on brain computed tomogram, (2) on brain magnetic resonance image, and (3) diagnosis of stroke or transient ischemic attack by a neurologist. This outcome was obtained over 1-year duration and only the first episode of thromboembolism was considered as an outcome. Mortality data were updated from the Social Security Death Index, death certificates, or hospital notes. Outcomes were evaluated by 2 blind reviewers (FK and ZA). These were then rechecked and conflicts resolved by consensus. Descriptive statistics were used to summarize the data. Continuous variables are expressed as mean ± SD and categorical variables are mentioned in percentages. They were analyzed using t test for continuous variables and Fisher's exact test or chi-square test for categorical variables, as appropriate. Univariate analyses and adjusted Cox proportional analyses were conducted to enunciate the association between restarting warfarin therapy and outcomes. These analyses were adjusted for age, gender, race, Charlson co-morbidity index, number of blood product transfusions, international normalized ratio on admission, and CHADS2 and HAS-BLED scores. Cumulative incidences were evaluated using Kaplan-Meier method. Time of interruption of warfarin along with restarting warfarin status was added as an interaction term in the Cox proportional hazards model to investigate the association of time in development of thromboembolism, mortality, and recurrent GIB. Because the interaction was significant, we divided the time of interruption of warfarin into 5 groups ( 30 days). Incidences were calculated by the formula: incidence per 100 person-years. Incidence rate ratios were calculated by the formula: incidence rate per 100 person-years of/incidence rate per 100 person-years in patients who interrupted warfarin for >30 days. Kaplan-Meier curves were produced to evaluate the differences in the cumulative incidences of recurrent GIB, mortality, and thromboembolism stratified by time duration of interruption of warfarin and cessation of warfarin use. All analyses were performed using PASW, version 18.0 (SPSS Inc., Chicago, Illinois), and JMP Pro 10.0 (SAS Institute, Cary, North Carolina). The study was analyzed on the basis of the initial group assigned to the patient (similar to intention-to-treat analysis) and p value of <0.05 was considered significant. Overall, 1,329 patients (mean age 75 ± 11 years, women 47%) developed GIB during January 2005 to December 2010. There were 653 patients (49%) who were restarted on warfarin after a median duration of 50 days (interquartile range 21 to 78). The median CHADS2 and HAS-BLED scores were 3. Endoscopic evaluation was performed in 883 cases (66.4%). Chronic AF was present in 751 (52.6%), persistent AF in 345 (25.9%), and paroxysmal AF in 233 patients (17.5%). Caucasians, patients with concomitant upper and lower sources for GIB, diabetics, patients with renal disease, history of coronary artery disease, and history of falls were less likely to be restarted on warfarin (p 200 mg/dl or lipid-lowering medication use; anemia defined as hemoglobin 200 mg/dl or lipid-lowering medication use; anemia defined as hemoglobin <10 mg/dl after resolution of gastrointestinal bleed. CHADS2 = Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, Stroke; HAS-BLED = Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile INR, Elderly (age ≥65 years), Drugs/alcohol; INR = international normalized ratio (detailed definitions are in the Supplementary material); TTR = time within therapeutic range. In total, 463 deaths occurred over a period of 2 years. Restarting warfarin was independently associated with decreased mortality (adjusted hazard ratio 0.66, 95% confidence interval 0.55 to 0.80, p <0.0001) compared with warfarin cessation group. The survival analysis is shown in Figure 1. There were 4 thromboembolism-related deaths all in the patients in whom warfarin was stopped, whereas, there was only 1 death attributable to massive gastrointestinal hemorrhage in the patients who resumed warfarin. There was no significant difference in survival by the duration of interruption of warfarin <30 days; however, as the interruption duration became longer, the survival approached toward the group that did not resume warfarin (Figure 2).Figure 2(A) Kaplan-Meier survival analysis showing 1-year mortality stratified by duration of interruption of warfarin. (B) Time-to-event analysis showing 90-day cumulative incidence of recurrent GIB stratified by duration of interruption of warfarin. (C) Time-to-event analysis showing 1-year cumulative incidence of thromboembolism stratified by duration of interruption of warfarin.View Large Image Figure ViewerDownload Hi-res image Download (PPT) There were 90 patients who developed recurrent major GIB within 90 days of index GIB (Table 2). The freedom from 90-day recurrent GIB is shown in Figure 1. Cumulative incidences of GIB based on duration of interruption of warfarin are given in Figure 2, which shows that the group that restarted warfarin within the first 7 days has greater risk of recurrent GIB; however, the cumulative incidences of the rest of the groups are very similar to the group that restarted warfarin after 30 days. Table 3 demonstrates the incidences of patients stratified by days of interruption of warfarin. It also shows the incidence rate ratios compared with the group that was restarted on warfarin after 30 days of interruption of warfarin. The incidence rate ratios of 7- to 15-day, 15- to 21-day, and 21- to 30-day groups are not significantly different for recurrent GIB from the incidence rate ratio of patients who restarted warfarin after 30 days of interruption (Table 3).Table 2Unadjusted and adjusted hazard ratios for restarting warfarin versus not restarting warfarinOutcomeUnadjusted Hazard Ratio (95% CI)p ValueAdjusted Hazard Ratio (95% CI)p ValueThromboembolism0.75 (0.58–0.98)0.030.71 (0.54–0.93)0.01Recurrent gastrointestinal bleed1.20 (0.78–1.86)0.401.18 (0.94–1.10)0.47Mortality0.72 (0.60–0.86)<0.00010.67 (0.56–0.81)<0.0001CI = confidence interval. Open table in a new tab Table 3Adjusted hazard ratios stratified by time duration of interruption of warfarin for various outcomesOutcomeWarfarin RestartedYesNo (n = 676) 30 Days (n = 429)Thromboembolism Events97111251131 Incidence11.6 (8.3–16.2)12.0 (8.2–17.5)18.1 (13.4–24.5)20.7 (15.5–27.7)20.4 (17.8–23.5)19.8 (18.1–21.6) IRR, p value0.57 (0.28–1.15), 0.110.59 (0.27–1.29), 0.180.89 (0.46–1.70), 0.731.01 (0.54–1.90), 0.97ReferenceNA HR (95% CI), p value0.76 (0.37–1.59), 0.470.48 (0.20–1.15), 0.090.60 (0.30–1.19), 0.141.00 (0.52–1.94), >0.99Reference1.35 (0.97–1.89), 0.07Recurrent GIB Events167762529 Incidence19.3 (14.6–25.5)10.8 (7.2–16.3)10.9 (7.2–16.4)9.9 (6.3–15.5)9.9 (8.0–12.3)5.4 (4.5–6.6) IRR, p value1.95 (0.98–3.89), 0.061.09 (0.44–2.71), 0.851.09 (0.44–2.72), 0.851.00 (0.38–2.65), >0.99ReferenceNA HR (95% CI), p value3.27 (1.82–5.91), 0.0021.03 (0.45–2.35), 0.931.42 (0.65–3.11), 0.371.50 (0.55–4.04), 0.42Reference1.27 (0.75–2.13), 0.37Mortality Events17162021113276 HR (95% CI), p value0.56 (0.33–0.93), 0.030.56 (0.33–0.98), 0.040.56 (0.34–0.90), 0.020.84 (0.52–1.35), 0.46Reference1.26 (1.01–1.57), 0.04CI = confidence interval; HR = hazard ratio; IRR = incidence rate ratio; NA = not applicable. Open table in a new tab CI = confidence interval. CI = confidence interval; HR = hazard ratio; IRR = incidence rate ratio; NA = not applicable. There were 221 patients (16.6%) who developed a thromboembolic episode within 1 year of interruption of warfarin. The risk was reduced in patients who were restarted on warfarin (hazard ratio 0.71, 95% confidence interval 0.54 to 0.93, p = 0.01; Table 2). The freedom from 1-year thromboembolism is shown in Figure 1. Cumulative incidences of thromboembolic events based on duration of interruption of warfarin are given in Figure 2, which shows that there is a trend in decrease in the risk of thromboembolic events if anticoagulation was started earlier. Table 3 demonstrates the incidences of patients stratified by days of interruption of warfarin. It also lists the incidence rate ratios compared with the group that was restarted on warfarin after 30 days of interruption of warfarin. There is a trend toward reduced incidence the earlier the warfarin therapy is reinstituted (Table 3). This study provides incidences of thromboembolism, mortality, and recurrent GIB in patients who developed GIB while on anticoagulation for nonvalvular AF. The study also demonstrated that lower risks of thromboembolism and mortality were associated with resuming anticoagulation. There were also no significant differences in risk of GIB between resuming warfarin after 1 week of interruption of warfarin compared with restarting warfarin after 1 month; however, risk of recurrent GIB was significantly greater if warfarin was resumed within the first week of major GIB. We found that as many as 1/2 of the patients that interrupt warfarin during a major GIB did not resume taking warfarin. The study is not large enough to be generalizable to the rest of the country; however, the cohort had adequate diversity to provide an idea of this practice gap. Moreover, we also found that majority of the deaths and thromboembolic events occurred in the patients who did not restart warfarin within a month. Interrupting warfarin may lead to an increase in short-term risk of thromboembolism.6Raunso J. Selmer C. Olesen J.B. Charlot M.G. Olsen A.M. Bretler D.M. Nielsen J.D. Dominguez H. Gadsboll N. Kober L. Gislason G.H. Torp-Pedersen C. Hansen M.L. Increased short-term risk of thrombo-embolism or death after interruption of warfarin treatment in patients with atrial fibrillation.Eur Heart J. 2012; 33: 1886-1892Crossref PubMed Scopus (62) Google Scholar This may have clinical implications especially if further research shows that early resumption of warfarin leads to better outcomes. For the purpose of our study, we equated the term cessation with interruption of >6 months and did not analyze them by causes. However, we noticed that majority of the cessation occurred due to inability to follow up with anticoagulation clinic or physician refusal of continuing anticoagulation due to the documentation of previous GIB (37%). These findings were markedly different from the findings of the Atrial Fibrillation Follow-up Investigation of Rhythm Management trial, in which physician refusal to continue warfarin and patient's refusal accounted for 19% of the cases.9Sherman D.G. Kim S.G. Boop B.S. Corley S.D. Dimarco J.P. Hart R.G. Haywood L.J. Hoyte K. Kaufman E.S. Kim M.H. Nasco E. Waldo A.L. Occurrence and characteristics of stroke events in the Atrial Fibrillation Follow-up Investigation of Sinus Rhythm Management (AFFIRM) study.Arch Intern Med. 2005; 165: 1185-1191Crossref PubMed Scopus (187) Google Scholar Several previous studies have evaluated the treatment interruptions in surgical patients but are limited by the small number of events.10Garcia D.A. Regan S. Henault L.E. Upadhyay A. Baker J. Othman M. Hylek E.M. Risk of thromboembolism with short-term interruption of warfarin therapy.Arch Intern Med. 2008; 168: 63-69Crossref PubMed Scopus (280) Google Scholar, 11Jamula E. Lloyd N.S. Schwalm J.D. Airaksinen K.E. Douketis J.D. Safety of uninterrupted anticoagulation in patients requiring elective coronary angiography with or without percutaneous coronary intervention: a systematic review and metaanalysis.Chest. 2010; 138: 840-847Crossref PubMed Scopus (46) Google Scholar, 12Ghanbari H. Feldman D. Schmidt M. Ottino J. Machado C. Akoum N. Wall T.S. Daccarett M. Cardiac resynchronization therapy device implantation in patients with therapeutic international normalized ratios.Pacing Clin Electrophysiol. 2010; 33: 400-406Crossref PubMed Scopus (56) Google Scholar, 13Tompkins C. Cheng A. Dalal D. Brinker J.A. Leng C.T. Marine J.E. Nazarian S. Spragg D.D. Sinha S. Halperin H. Tomaselli G.F. Berger R.D. Calkins H. Henrikson C.A. Dual antiplatelet therapy and heparin "bridging" significantly increase the risk of bleeding complications after pacemaker or implantable cardioverter-defibrillator device implantation.J Am Coll Cardiol. 2010; 55: 2376-2382Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar, 14Jaffer A.K. Brotman D.J. Bash L.D. Mahmood S.K. Lott B. White R.H. Variations in perioperative warfarin management: outcomes and practice patterns at nine hospitals.Am J Med. 2010; 123: 141-150Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar We had comparable sample size but found that our cohort experienced greater number of events. This is perhaps due to the higher co-morbidity burden in our patients. Patients who are at a greater risk of GIB are also at greater risk of thromboembolic events as the risk scores such as HAS-BLED and CHADS2 share many common variables. Another interesting finding was that, there, the incidence of thromboembolic events and deaths within the first 90 days of interruption of warfarin was greater than the incidences afterward. However, the risks for these events stayed higher in the group that did not restart warfarin suggesting that there might be other factors that might be playing a role in these events. Whether this occurred because of "rebound hypercoagulability" or "catch up" of events is not clear and is a matter of controversy.15Michaels L. Beamish R.E. Relapses of thromboembolic disease after discontinued anticoagulant therapy. A comparison of the incidence after abrupt and after gradual termination of treatment.Am J Cardiol. 1967; 20: 670-673Abstract Full Text PDF PubMed Scopus (27) Google Scholar, 16Harenberg J. Haas R. Zimmermann R. Plasma hypercoagulability after termination of oral anticoagulants.Thromb Res. 1983; 29: 627-633Abstract Full Text PDF PubMed Scopus (27) Google Scholar, 17Genewein U. Haeberli A. Straub P.W. Beer J.H. Rebound after cessation of oral anticoagulant therapy: the biochemical evidence.Br J Haematol. 1996; 92: 479-485Crossref PubMed Scopus (132) Google Scholar, 18Palareti G. Legnani C. Warfarin withdrawal. Pharmacokinetic-pharmacodynamic considerations.Clin Pharmacokinet. 1996; 30: 300-313Crossref PubMed Scopus (137) Google Scholar Our finding of decreased mortality may be explained by the anticoagulation effects of warfarin.19Rothberg M.B. Celestin C. Fiore L.D. Lawler E. Cook J.R. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit.Ann Intern Med. 2005; 143: 241-250Crossref PubMed Scopus (288) Google Scholar To investigate the optimal duration of restarting warfarin after an episode of major GIB, we attempted to evaluate the different durations of interruption of warfarin with respect to the reference group of patients who resumed taking warfarin after 1 month. We found that patients who resumed taking warfarin in the first week were at a greater risk of recurrent GIB; however, the rest of the groups did not show significant differences. In contrast, lower risk of mortality and thromboembolism was associated with earlier re-initiation of warfarin. Although there are many other variables that physicians take into account while making a decision of resuming warfarin in these patients, we have provided the risks versus benefits of these treatment decisions that might have clinical implications. Our study faces the limitations that any study based on insurance claims and retrospective data does. Although we tried to narrow down our exposure variable, there was some crossover that occurred. However, we used an analysis similar to intention-to-treat analysis to minimize the confounding. We also were not able to enunciate all the factors that affect the clinical decision making. However, confirmation of thromboembolism, recurrent GIB, and mortality by way of medical chart review strengthens the validity of our data. The study is also susceptible to detection bias and may have underestimated the events of thromboembolism in the group that did not resume warfarin as there was less health-care contact. Also, patients who were perceived at greatest risk of GIB were probably not restarted on warfarin, and hence, the association of resuming warfarin with GIB might be underestimated. There might be also a component of survivorship bias as we only used the data for patients who were alive for at least 2 days after index major GIB. However, we wanted to avoid making conclusions about patients who were so ill that they did not survive their first 48 hours, which might have led to further underestimation of our results, as many of them did not resume taking warfarin. Also, as apparent in the baseline characteristics of the cohort, the patients restarted on warfarin had fewer co-morbidities, which might have led to improved outcomes. We performed various methods to adjust for this in the analysis; however, there was still a difference in mortality that was unexplained by just selection bias. The authors have no conflicts of interest to disclose. Download .docx (.03 MB) Help with docx files Supplementary Figure 1 and Supplementary Table 1 Erratum for Qureshi et al. "Restarting Anticoagulation and Outcomes After Major Gastrointestinal Bleeding in Atrial Fibrillation" Am J Cardiol 2014;113:662–668American Journal of CardiologyVol. 116Issue 1PreviewIn the abstract and Table 2, the adjusted hazard ratio is not correct. The correct adjusted hazard ratio is 1.18 (95% CI 0.75 to 1.84), p = 0.47. Full-Text PDF Restarting Anticoagulation After Major Gastrointestinal BleedingAmerican Journal of CardiologyVol. 113Issue 10PreviewWe read the recent report of Qureshi et al1 reporting the outcomes of restarting anticoagulation after gastrointestinal bleeding (GIB) in patients with atrial fibrillation. The investigators found that patients who resumed taking warfarin in the first week were at a higher risk of recurrent GIB (incidence ratio of 19.3%), whereas a lower risk of thromboembolism and mortality was associated with this early reinitiation of warfarin. Because their findings are important to both current practice and future research, several limitations of this study deserve attention. Full-Text PDF
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