The Impact of Clinical Pharmacy Services on Direct Oral Anticoagulant Medication Selection and Dosing in the Ambulatory Care Setting.

Background: Off-label dosing of direct oral anticoagulants (DOACs) is both common and associated with adverse patient outcomes. Evidence describing best practices to support optimal direct oral anticoagulant (DOAC) dosing is limited. Objective: To describe the impact of clinical pharmacist intervention on DOAC prescribing. Methods: This retrospective study was a descriptive analysis conducted within an integrated healthcare system with a centralized, pharmacist-led Anticoagulation Management Service (AMS). Patients prescribed a DOAC between January 1, 2020 and December 31, 2020 were included. Pharmacy dispensing reports were generated for pharmacist review and anticoagulant drug therapy changes were recommended to physicians where appropriate. The primary objective was to describe the number and type of recommendations made. Secondary objectives were to determine the provider acceptance rate based on the intervention type and on clinical vs formulary recommendations. Results: Clinical pharmacists made 147 recommendations for 2331 unique patients included in the analysis. Twenty-three recommendations (16%) were to decrease the dose, 46 (31%) were to increase the dose, 14 (10%) were to change the medication due to clinical scenario, 62 (42%) were to change the medication due to cost, and 2 (1%) were another issue. One hundred twenty-three (84%) recommendations were accepted. The provider acceptance rate was similar for clinical and formulary recommendations (85% and 82% respectively). Conclusion: Implementation of report-driven clinical pharmacist intervention led to an improvement in appropriate DOAC medication selection and dosing.

Clinical outcomes of dabigatran use in patients with non-valvular atrial fibrillation and weight >120 kg.

BACKGROUND: Patients with obesity were underrepresented in studies evaluating the safety and effectiveness of direct oral anticoagulants (DOAC) in patients with non-valvular atrial fibrillation (NVAF). This study compared clinical outcomes in patients with NVAF and weighing >120 kg and ≤120 kg who were receiving dabigatran. MATERIALS AND METHODS: This retrospective, matched, longitudinal cohort study included patients from three integrated healthcare delivery systems. Patients ≥18 years of age with NVAF were included if between September 1, 2016 and June 30, 2019 they received dabigatran. Patients >120 kg and ≤120 kg were matched up to 1:6 on age, sex, and CHA2DS2-VASc score. Data were extracted from administrative databases. The primary outcome was a composite of ischemic stroke, clinically-relevant bleeding, systemic embolism, and all-cause mortality. Multivariable regression analyses were performed. RESULTS: 777 and 3522 patients >120 kg and ≤120 kg, respectively, were matched. The >120 kg group tended to be younger with a higher burden of chronic disease. There was no difference between groups in the composite outcome (adjusted hazard ratio [AHR] 1.10, 95% confidence interval 0.89-1.37) or individual components of the composite. A subanalysis of clinically-relevant bleeding identified that patients >120 kg were at a greater risk of gastrointestinal bleeding (AHR 1.44, 95% CI 1.01-2.05). CONCLUSIONS: In patients with NVAF and >120 kg, dabigatran use was associated with a small increased risk of gastrointestinal bleeding but no differences in stroke, mortality or clinically-relevant bleeding. These findings suggest that dabigatran use is reasonable in patients with NVAF and weight >120 kg.

Temporal trends in first-line outpatient anticoagulation treatment for cancer-associated venous thromboembolism.

BACKGROUND: First-line treatment and secondary prevention of venous thromboembolism (VTE) in patients with cancer consisted, historically, of unfractionated heparin or low-molecular weight heparin (LMWH). With recent clinical trials of direct oral anticoagulants (DOAC) showing similar efficacy as LMWH, little is known about anticoagulant prescribing patterns in patients with cancer and a VTE. This study characterized the temporal trends in first-line outpatient anticoagulation therapy for cancer-associated VTE. MATERIALS AND METHODS: This retrospective cohort study of patients who were hospitalized for a cancer-associated venous thromboembolism (VTE) between 01/01/2000 and 10/31/2017 identified patients from the cancer registries at two regions of an integrated healthcare delivery system. The primary outcome was the trend in age- and sex-adjusted rates of first-line anticoagulant therapy during the 30 days post-hospital discharge. Therapies were categorized as 1) injectable LMWH monotherapy, 2) warfarin ± injectable, 3) injectable fondaparinux monotherapy, or 4) DOAC ± injectable. RESULTS: Overall, 9816 patients were included with a mean age of 66 ± 13 years and 54% were female. From 2000 to 2003, warfarin ± injectable was used in ≈90% of cases. After 2003, there was a steady decline in warfarin use (25% in 2017) corresponding with increased LMWH use: 11% in 2003 to 55% in 2017. The DOAC ± injectable use has rapidly increased from <1% in 2014 to 20% in 2017. CONCLUSIONS: From 2000 to 2017, first-line anticoagulant therapy for cancer-associated VTE has experienced a substantial increase in LMWH and DOAC use with a resultant decline in warfarin use.

Vitamin K versus warfarin interruption alone in patients without bleeding and an international normalized ratio > 10.

BACKGROUND: Reversal of an international normalized ratio (INR) > 10 with vitamin K is recommended in patients experiencing bleeding; however, information on outcomes with reversal using vitamin K in non-bleeding patients is lacking. OBJECTIVE: To compare clinical and safety outcomes between non-bleeding patients receiving warfarin with an INR > 10 who did and did not receive a prescription for vitamin K. PATIENTS/METHODS: This was a retrospective cohort study conducted in an integrated health-care delivery system. Adult patients receiving warfarin therapy who experienced an INR > 10 without bleeding between 01/01/2006 and 06/30/2018 were included. Patients were assessed for an outpatient dispensing or in-office administration of vitamin K on the day of or the day after an INR > 10 and then clinically relevant bleeding, thromboembolism, all-cause mortality, and time to INR < 4 within the next 30 days. RESULTS: A total of 809 patients was included with 332 and 477 who were and were not dispensed vitamin K, respectively. Overall, mean patient age was 71.7 years, 60.1% were female and the mean INR was 10.4 at presentation. There were no differences between groups in 30-day rates of bleeding or thromboembolism (both P > .05). Patients dispensed vitamin K had a higher likelihood of mortality (15.1% versus 10.1%, P = .032, adjusted odds ratio = 1.63, 95% confidence interval 1.03 to 2.57). Overall, time to an INR < 4 was similar between groups. CONCLUSION: Vitamin K administration was not associated with improved clinical outcomes in asymptomatic patients with an INR > 10.

Pharmacy Technician Management of Stable, In-Range INRs Within a Clinical Pharmacy Anticoagulation Service.

BACKGROUND: There is increasing demand on pharmacist time within clinical pharmacy services, and pharmacy technicians are a crucial resource for expanding pharmacy practice. OBJECTIVE: To assess the safety and effectiveness of pharmacy technician management of stable, in-range international normalized ratio (INR) results compared with usual care. METHODS: This retrospective, longitudinal, noninferiority cohort study was conducted at an integrated health care delivery system with a centralized anticoagulation service. Adult patients receiving chronic warfarin therapy with therapeutic INR results over a 3-month period (i.e., 100% time in therapeutic range [TTR] during the 3 months before the index date) were eligible for referral to technician warfarin management between March 1, 2015, and December 31, 2015. Patients with similar INR control during the same period but not referred to technician management were included as comparators in the usual care group. A one-sided noninferiority margin for the technician management group was set to -2.5% for mean TTR. Propensity scoring was used in regression modeling via inverse probability of treatment weights to compare between-group differences to account for covariates that may have influenced assignment to the technician group. Finally, bleeding, thromboembolic, and mortality outcomes were compared. RESULTS: 1,840 and 1,116 patients were included in the technician and usual care groups, respectively. The mean age of included patients was 73.1 years, and the majority (77.9%) had received warfarin for > 3 years. TTR during follow-up was 83.3% and 77.7% in the technician and usual care groups, respectively (mean difference = 5.7%; 95% CI = 4.1%-7.2%). The risk of thromboembolism was similar between the technician and usual care groups (HR = 0.84; 95% CI = 0.17-4.22; P = 0.832); however, bleeding (HR = 0.60; 95% CI = 0.39-0.94; P = 0.026) and all-cause mortality (HR = 0.44; 95% CI = 0.25-0.77; P = 0.004) were lower in the technician group during follow-up. CONCLUSIONS: Technician management of stable patients receiving chronic warfarin therapy within an integrated health care delivery system's centralized anticoagulation service was associated with noninferior TTR results compared with usual care pharmacist management. DISCLOSURES: This study was internally funded by the Kaiser Permanente Pharmacy Department. The study sponsor had no role in the study design, analysis, or interpretation. The authors have no relevant financial conflicts of interest to disclose.

Effect of increased time in the therapeutic range on atrial fibrillation outcomes within a centralized anticoagulation service.

BACKGROUND: Clinical pharmacy anticoagulation services have improved the quality of anticoagulant therapy and are associated with lower rates of bleeding and thromboembolism compared to usual care. Several studies have found that higher time-in-therapeutic range (TTR) during warfarin therapy is associated with better warfarin outcomes. However, whether increasing TTR over time within an established anticoagulation service is associated with further reduction in bleeding and thromboembolic outcomes is unknown. METHODS: This was a retrospective cohort study of patients with atrial fibrillation conducted at an integrated healthcare delivery system with a centralized, pharmacist-managed anticoagulation service. Clinical outcomes (clinically-relevant bleeding, ischemic stroke or systemic embolism, and all-cause mortality) and TTR were compared between two distinct time periods: 1/1/2006 through 12/31/2007 (control group) and 1/1/2012 through 12/31/2013 (observation group) with regression modeling to adjustment for potential confounders. RESULTS: There were 3641 and 4764 patients in the control and observation groups, respectively. The mean age was 74.3 years and 54.4% of the cohort was female. Mean TTR was higher in the observation group (70.5% vs. 63.4%, p < 0.001). The composite outcome of clinically-relevant bleeding, thromboembolism and all-cause mortality occurred in 4.6% and 3.6% of the control and observation groups, respectively (adjusted odds ratio = 0.69; 95% confidence interval 0.54-0.87). Individual rates of stroke/systemic embolism and all-cause mortality were each lower in the observation group (both p < 0.05) while clinically-relevant bleeding was not significantly different (p = 0.256). CONCLUSION: Increased TTR within a clinical pharmacy anticoagulation management service was associated with a lower risk of the composite outcomes of bleeding, thromboembolism and death in a large atrial fibrillation population receiving warfarin.

The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) Study for Patients on a Direct Oral Anticoagulant Who Need an Elective Surgery or Procedure: Design and Rationale.

Background The perioperative management of patients who take a direct oral anticoagulant (DOAC) for atrial fibrillation and require treatment interruption for an elective surgery/procedure is a common clinical scenario for which best practices are uncertain. The Perioperative Anticoagulant Use for Surgery Evaluation (PAUSE) study is designed to address this unmet clinical need. We discuss the rationale for the PAUSE design and analysis plan as well as the rationale supporting the perioperative DOAC protocol. Methods PAUSE is a prospective study with three parallel cohorts, one for each DOAC, to assess a standardized but patient-specific perioperative management protocol for DOAC-treated patients with atrial fibrillation. The perioperative protocol accounts for DOAC type, patient's renal function and surgery/procedure-related bleeding risk. The primary study aim is to demonstrate the safety of the PAUSE protocol for the perioperative management of each DOAC. The secondary aim is to determine the effect of the pre-procedure interruption on residual anticoagulation when measured by the dilute thrombin time for dabigatran and anti-factor Xa levels for rivaroxaban and apixaban. The study hypothesis is that the perioperative management protocol for each DOAC is safe for patient care, defined by expected risks for major bleeding of 1% (80% power to exclude 2%), and for arterial thromboembolism of 0.5% (80% power to exclude 1.5%) in each DOAC group. Conclusion The PAUSE study has the potential to establish a standard-of-care approach for the perioperative management of DOAC-treated patients. The PAUSE management protocol is designed to be easily applied in clinical practice, as it is standardized and also patient specific.

Assessment of the coding accuracy of warfarin-related bleeding events.

INTRODUCTION: Using International Classification of Diseases, 9th edition (ICD-9) diagnosis codes to identify potential warfarin-related bleeding events from administrative datasets is highly efficient but may be prone to identifying non-events. The objective of this study was to evaluate the ability of bleeding-related ICD-9 codes to identify true bleeding events in patients who were receiving warfarin therapy at the time of hospitalization. METHODS: This was a cross-sectional study conducted in an integrated healthcare delivery system. Anticoagulated patients aged ≥18years and hospitalized between January 1, 2014 and March 31, 2014 were identified using administrative data queries. All hospitalizations were manually chart reviewed by a trained abstractor blinded to hospitalization diagnoses to assess for true bleeding events. Identification of the presence or lack of bleeding-related ICD-9 diagnosis code(s) for each hospitalization was then performed. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for each ICD-9 code present. RESULTS: There were 486 hospitalizations in 468 anticoagulated patients with 57 true bleeding events identified. Patients had a mean age of 73.4years and 50% were female. For codes in the principal position, sensitivity, specificity, PPV, and NPV were 7.0%, 99.8%, 80.0%, and 89.0%, respectively. For codes in any position, sensitivity, specificity, PPV, and NPV were 94.7%, 90.9%, 58.1%, and 99.2%, respectively. For major bleeding, sensitivity, specificity, PPV, and NPV were 100%, 83.1%, 14.0%, and 100%, respectively. CONCLUSIONS: While the absence of a bleeding ICD-9 code reliably ruled-out hospitalization for warfarin-related bleeding, bleeding ICD-9 codes in the principal position were rarely used and undesirable false positive rates were identified when ICD-9 codes when recorded in any position and for major bleeding. Manual chart review is recommended to validate bleeding events from administrative data.

Bridge Therapy Outcomes in Patients With Mechanical Heart Valves.

BACKGROUND: Bridge therapy is associated with an increased risk of major bleeding in patients with atrial fibrillation and venous thromboembolism (TE) without a corresponding reduction in TE. The benefits of bridge therapy in patients with mechanical heart valve (MHV) prostheses interrupting warfarin for invasive procedures are not well described. METHODS AND RESULTS: A retrospective cohort study was conducted at an integrated health-care delivery system. Anticoagulated patients with MHV interrupting warfarin for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified. Patients were categorized according to exposure to bridge therapy during the periprocedural period and TE risk (low, medium, and high). Outcomes validated via manual chart review included clinically relevant bleeding, TE, and all-cause mortality in the 30 days following the procedure. There were 547 procedures in 355 patients meeting inclusion criteria. Mean cohort age was 65.2 years, and 38% were female. Bridge therapy was utilized in 466 (85.2%) procedures (95.2%, 77.3%, and 65.8% of high, medium, and low TE risk category procedures, respectively). The 30-day rate of clinically relevant bleeding was numerically higher in bridged (5.8%; 95% confidence interval [CI], 3.9%-8.3%) versus not bridged procedures (1.2%; 95% CI, <0.1%-6.7%; P = .102). No TEs or deaths were identified. CONCLUSION: The use of bridge therapy is common among patients with MHV and may be associated with increased bleeding risk. Further research is needed to determine whether bridge therapy reduces TE in patients with MHV interrupting warfarin for invasive procedures.

Risk of thromboembolism, recurrent hemorrhage, and death after warfarin therapy interruption for intracranial hemorrhage.

BACKGROUND: Whether and when to resume oral anticoagulant therapy for patients who survive warfarin-related intracranial hemorrhage (ICH) remains a dilemma lacking consensus recommendations and high-quality evidence to guide clinical decision making. OBJECTIVE: To determine the incidences of recurrent ICH, thrombosis, and death in relation to resumption or non-resumption of warfarin therapy during the 365 days after incident ICH. METHODS: We conducted a retrospective cohort study of adult patients in an integrated healthcare delivery system who were receiving warfarin therapy at the time of incident (index) ICH between 1/1/2000 and 12/31/2007 and survived to hospital discharge. The primary outcomes were recurrent ICH, thrombosis (stroke, systemic embolism, and venous thromboembolism), and all-cause mortality during the 365 days following index ICH. Patients were assigned to one of two groups defined by warfarin therapy resumption after the index ICH. RESULTS: There were 160 patients discharged from the hospital following warfarin-related index ICH; of these 54 (33.8%) resumed warfarin therapy and 106 (66.2%) did not. Recurrent ICH occurred in a numerically greater, but statistically non-significant, proportion of patients who did not resume warfarin therapy (7.6% vs. 3.7%, p=0.497). Similarly, patients who did not resume warfarin had a three-fold higher (12.3% vs. 3.7%, p=0.092) and approximately two-fold higher (31.1% vs. 18.5%, p=0.089) rates of thrombosis and all-cause mortality, respectively, during follow up. CONCLUSION: Resumption of warfarin therapy following warfarin-associated ICH appeared not to be associated with increased risk of recurrent ICH but trended toward reduced thrombosis and all-cause mortality.

Bleeding, Recurrent Venous Thromboembolism, and Mortality Risks During Warfarin Interruption for Invasive Procedures.

IMPORTANCE: The risk of bleeding and recurrent venous thromboembolism (VTE) among patients receiving long-term warfarin sodium therapy for secondary VTE prevention who require temporary interruption of anticoagulant therapy for surgery or invasive diagnostic procedures has not been adequately described. OBJECTIVE: To describe the rates of clinically relevant bleeding and recurrent VTE among patients in whom warfarin therapy is interrupted for invasive procedures and compare these rates among patients who did and did not receive bridge therapy. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted at Kaiser Permanente Colorado, an integrated health care delivery system. Patients in whom warfarin therapy was interrupted for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified via queries of administrative data sets. A total of 1812 procedures in 1178 patients met inclusion criteria. Data on outcomes and exposures were collected between June 1, 2005, and April 30, 2012. EXPOSURES: Use of bridge therapy vs no bridge therapy during warfarin interruption. MAIN OUTCOMES AND MEASURES: Thirty-day clinically relevant bleeding, recurrent VTE, and all-cause mortality. Outcomes were verified via manual review of medical records. RESULTS: Among the 1178 patients, the mean (SD) age was 66.1 (12.7) years, 830 procedures (45.8%) were in men, and the most common indication for warfarin therapy was deep vein thrombosis (56.3%). Most patients were considered to be at low risk for VTE recurrence at the time of warfarin interruption (1431 procedures [79.0%]) according to the consensus guidelines of the American College of Chest Physicians. Clinically relevant bleeding within 30 days after the procedure in the bridge therapy and non-bridge therapy groups occurred in 15 patients (2.7%) and 2 patients (0.2%), respectively (hazard ratio, 17.2; 95% CI, 3.9-75.1). There was no significant difference in the rate of recurrent VTE between the bridge and non-bridge therapy groups (0 vs 3; P = .56). No deaths occurred in either group. CONCLUSIONS AND RELEVANCE: Bridge therapy was associated with an increased risk of bleeding during warfarin therapy interruption for invasive procedures in patients receiving treatment for a history of VTE and is likely unnecessary for most of these patients. Further research is needed to identify patient- and procedure-related characteristics associated with a high risk of perioperative VTE recurrence during warfarin therapy interruption.

Warfarin interactions with antibiotics in the ambulatory care setting.

IMPORTANCE: The effect of antibiotic coadministration on the international normalized ratio (INR) in a relatively stable, real-world warfarin population has not been adequately described. Case reports and studies of healthy volunteers do not account for the potential contribution of acute illness to INR variability. OBJECTIVE: To compare the risk of excessive anticoagulation among patients with stable warfarin therapy purchasing an antibiotic (antibiotic group) with the risk in patients purchasing a warfarin refill (stable controls) and patients with upper respiratory tract infection but not receiving an antibiotic (sick controls). DESIGN, SETTING, AND PARTICIPANTS: A retrospective, longitudinal cohort study evaluated patients receiving warfarin between January 1, 2005, and March 31, 2011, at Kaiser Permanente Colorado, an integrated health care delivery system. Continuous data were expressed as mean (SD) or median (interquartile range). Multivariable logistic regression analysis was used to identify factors independently associated with a follow-up INR of 5.0 or more. A total of 5857 (48.8%), 5579 (46.5%), and 570 (4.7%) patients were included in the antibiotic, stable control, and sick control groups, respectively. Mean age was 68.3 years, and atrial fibrillation was the most common (44.4%) indication for anticoagulation. EXPOSURES: Warfarin therapy with a medical visit for upper respiratory tract infection or coadministration of antibiotics. MAIN OUTCOMES AND MEASURES: Primary outcomes were the proportion of patients experiencing a follow-up INR of 5.0 or more and change between the last INR measured before the index date and the follow-up INR. RESULTS: The proportion of patients experiencing an INR of 5.0 or more was 3.2%, 2.6%, and 1.2% for the antibiotic, sick, and stable groups, respectively (P < .001, antibiotic vs stable control group; P < .017, sick vs stable control group; P = .44, antibiotic vs sick control group). Cancer diagnosis, elevated baseline INR, and female sex predicted a follow-up INR of 5.0 or more. Among antibiotics, those interfering with warfarin metabolism posed the greatest risk for an INR of 5.0 or more. CONCLUSIONS AND RELEVANCE: Acute upper respiratory tract infection increases the risk of excessive anticoagulation independent of antibiotic use. Antibiotics also increase the risk; however, most patients with previously stable warfarin therapy will not experience clinically relevant increases in INR following antibiotic exposure or acute upper respiratory tract infection.

Unfractionated heparin dose requirements targeting intermediate intensity antifactor Xa concentration during pregnancy.

STUDY OBJECTIVE: To describe unfractionated heparin (UFH) dosing requirements and monitoring parameters to achieve target antifactor Xa concentrations in pregnant women receiving intermediate-dose UFH therapy. DESIGN: Retrospective cohort analysis. SETTING: Centralized anticoagulation service in an integrated health care delivery system. PATIENTS: Twenty-five pregnant women (who had 27 pregnancies) who received intermediate-dose UFH between January 1, 1998, and March 31, 2005. MEASUREMENTS AND MAIN RESULTS: Demographic and clinical data were retrieved by using an integrated electronic medical, pharmacy, and laboratory records system. The primary outcome was the required UFH dose at the time of first target antifactor Xa level achieved. Antifactor Xa levels were measured at the mid-dosing interval for UFH. An antifactor Xa assay concentration of 0.1-0.3 unit/ml was used as the target range for intermediate-dose UFH for antithrombotic management of pregnant women as described in the American College of Chest Physicians clinical practice guidelines. The mean UFH dose required to achieve this target antifactor Xa range was 236.9 units/kg/day. The UFH doses required to achieve target antifactor Xa levels correlated significantly with patient weight (r = 0.682, p<0.001). The final UFH dose/kg required at the end of pregnancy was similar to that at the first target level (p>0.05) when adjusted for weight. However, the total daily amount of UFH did increase by the end of pregnancy (21,889 vs 19,320 units, p=0.02). There was an average of 7.9 antifactor Xa determinations and 3.1 dosage modifications during the mean of 19 weeks of antenatal UFH therapy. Most (62%) antifactor Xa levels were within the target range. No thromboembolic events, heparin-induced thrombocytopenia, or osteopenic fracture occurred. There was one hemorrhagic complication that resolved with temporary withdrawal of UFH. CONCLUSIONS: Pregnant women required a mean UFH dose of 236.9 units/kg/day to achieve the targeted antifactor Xa level of 0.1-0.3 unit/ml. The required UFH doses correlated with patient weight, and most antifactor Xa levels were within the desired target range. These findings may assist clinicians in more precisely initiating and monitoring intermediate-dose UFH in pregnant patients.

Thromboembolic consequences of subtherapeutic anticoagulation in patients stabilized on warfarin therapy: the low INR study.

STUDY OBJECTIVE: To quantify the absolute risk of thromboembolism associated with a significant subtherapeutic international normalized ratio (INR) in patients with previously stable anticoagulation while receiving warfarin. DESIGN: Retrospective, matched cohort analysis. SETTING: Centralized anticoagulation service in an integrated health care delivery system. PATIENTS: A total of 2597 adult patients receiving warfarin from January 1998-December 2005; 1080 patients were in the low INR cohort and were matched to 1517 patients in the therapeutic INR cohort based on index INR date, indication for warfarin, and age. MEASUREMENTS AND MAIN RESULTS: Stable, therapeutic anticoagulation was defined as two INR values, measured at least 2 weeks apart, within or above the therapeutic range. The low INR cohort included patients with a third INR value of 0.5 or more units below their therapeutic range. The therapeutic INR cohort included patients with a third therapeutic INR value and no INR value 0.2 or more units below their target INR range in the ensuing 90 days. The primary outcome was anticoagulation-related thromboembolism during the 90 days after the index INR. Secondary outcomes were times to the first occurrence of anticoagulation-related complications (bleeding, thromboembolism, or death) in the 90 days after the index INR. Four thromboembolic events (0.4%) occurred in the low INR cohort and one event (0.1%) in the therapeutic INR cohort (p=0.214). The differences in the proportions of thromboembolism, bleeding, or death were not significant between the cohorts (p>0.05). No significant differences were noted in the hazard of thromboembolism, bleeding, or death between the cohorts (p>0.05). CONCLUSION: Patients with stable INRs while receiving warfarin who experience a significant subtherapeutic INR value have a low risk of thromboembolism in the ensuing 90 days. The risk was similar to that observed in a matched control population in whom therapeutic anticoagulation was maintained. These findings do not support the practice of anticoagulant bridge therapy for patients stabilized on warfarin therapy to reduce their risk for thromboembolism during isolated periods of subtherapeutic anticoagulation.