Strategies to reduce out-of-pocket medication costs for Canadians with peripheral arterial disease.

BACKGROUND: Given that peripheral arterial disease (PAD) disproportionately affects people of lower socioeconomic status, out-of-pocket expenses for preventive medications are a major barrier to their use. We carried out a cost comparison of drug therapies for PAD to identify prescribing strategies that minimize out-of-pocket expenses for these medications. METHODS: Between March and June 2019, we contacted outpatient pharmacies in Hamilton, Ontario, Canada, to assess pricing of pharmacologic therapies at dosages included in the 2016 American College of Cardiology/American Heart Association guideline for management of lower extremity PAD. We also gathered pricing information for supplementary charges, including delivery, pill splitting and blister packaging. We calculated prescription prices with and without dispensing fees for 30-day brand-name and generic prescriptions, and 90-day generic prescriptions. RESULTS: Twenty-four pharmacies, including hospital-based, independent and chain, were included in our sample. In the most extreme scenario, total 90-day medication costs could differ by up to $1377.26. Costs were affected by choice of agent within a drug class, generic versus brand-name drug, quantity dispensed, dispensing fee and delivery cost, if any. CONCLUSION: By opting for prescriptions for 90 days or as long as possible, selecting the lowest-cost generic drugs available in each drug class, and identifying dispensing locations with lower fees, prescribers can minimize out-of-pocket patient medication expenses. This may help improve adherence to guideline-recommended therapies for the secondary prevention of vascular events in patients with PAD.

Periprocedural Management of Patients With Atrial Fibrillation Receiving a Direct Oral Anticoagulant Undergoing a Digestive Endoscopy.

INTRODUCTION: The periprocedural management of patients with atrial fibrillation (AF) using a direct oral anticoagulant (DOAC) undergoing elective gastrointestinal (GI) endoscopic procedure remains uncertain. We investigated the safety of a standardized periprocedural DOAC management strategy. METHODS: The Periprocedural Anticoagulation Use for Surgery Evaluation cohort study enrolled adult patients receiving a DOAC (apixaban, rivaroxaban, or dabigatran) for AF scheduled for an elective procedure or surgery. This analysis addresses patients undergoing digestive endoscopy. Standardized periprocedural management consisted of DOAC interruption 1 day preendoscopy with resumption 1 day after procedure at low-moderate risk of bleeding or 2 days in case of a high bleeding risk. Thirty-day outcomes included GI bleeding, thromboembolic events, and mortality. RESULTS: Of 556 patients on a DOAC (mean [SD] age of 72.5 [8.6] years; 37.4% female; mean CHADS 2 score 1.7 [1.0]), 8.6% were also on American Society of Anesthesiology (ASA) and 0.7% on clopidogrel. Most of the patients underwent colonoscopies (63.3%) or gastroscopies (14.0%), with 18.9% having both on the same procedural day. The mean total duration of DOAC interruption was 3.9 ± 1.6 days. Four patients experienced an arterial thromboembolic event (0.7%, 0.3%-1.8%) within 24.2 ± 5.9 days of DOAC interruption. GI bleeding events occurred in 2.5% (1.4%-4.2%) within 11.1 ± 8.1 days (range: 0.6; 25.5 days) of endoscopy, with major GI bleeding in 0.9% (0.4%-2.1%). Three patients died (0.5%; 0.2%-1.6%) 15.6-22.3 days after the endoscopy. DISCUSSION: After a contemporary standardized periprocedural management strategy, patients with AF undergoing DOAC therapy interruption for elective digestive endoscopy experienced low rates of arterial thromboembolism and major bleeding.

Effectiveness and safety of the direct oral anticoagulants in non-triple positive antiphospholipid syndrome without prior arterial thromboembolism.

Thrombotic antiphospholipid syndrome (TAPS) is an autoimmune disorder that manifests with venous thromboembolism (VTE) and/or arterial thromboembolism (ATE) in the presence of persistent antiphospholipid antibodies (aPLs). Recent trials have failed to demonstrate non-inferiority of the direct oral anticoagulants (DOACs) compared to vitamin K antagonists as anticoagulation in TAPS, but there is a subgroup of non-triple positive patients without prior ATE in who only limited data exists. The objective of this study was to assess the effectiveness and safety of DOACs in non-triple positive TAPS without prior ATE. We conducted a retrospective review of all non-triple positive TAPS patients without prior ATE who were anticoagulated with a DOAC at two tertiary care hospitals from January 2010 to July 2020. We assessed outcomes of VTE, ATE, major bleeding, and clinically relevant non-major bleeding (CRNMB). 50 patients were included in the analysis, encompassing 157.2 years of patient follow-up. There were no recurrent VTE, but one patient had a possible arterial thrombosis (0.64 events per 100 patient-years [95% confidence interval (CI 0.16-35.49)] as a transient ischemic attack (TIA) which occurred on reduced dose DOAC. There were no major bleeding events, but two patients had CRNMB (1.27 events per 100 patient-years [95% CI 1.5-46.0]), both as menorrhagia. DOACs were effective and safe as anticoagulation in non-triple positive TAPS patients without prior ATE with a low rate of recurrent thrombosis and bleeding. Larger, prospective controlled studies are required to confirm these findings prior to routine use of DOACs in this subgroup.

Prevention and Management of Urgent/Emergent Limb Ischemia.

PURPOSE OF REVIEW: Patients who require urgent or emergent peripheral revascularization represent one of the highest risk subgroups of PAD patients. They suffer unacceptably high complication rates including recurrent ALI, vascular amputation, and death. In this article, we examine (1) the burden of cardiovascular complications according to PAD severity, (2) discuss medical optimization to improve vascular outcomes in symptomatic LE-PAD patients, and (3) review the evidence for management of patients following urgent/emergent limb ischemia. RECENT FINDINGS: The VOYAGER trial recently demonstrated that rivaroxaban 2.5 mg BID + ASA daily significantly reduces major adverse cardiac and limb events in patients following lower extremity revascularization. A recent Canadian survey also demonstrated that significant heterogeneity exists in antithrombotic prescribing practices following urgent/emergent revascularization. COMPASS and VOYAGER have demonstrated the efficacy of aspirin 81 mg daily and rivaroxaban 2.5 mg twice daily at reducing MACE and MALE events in stable PAD patients and those undergoing elective revascularization. Patients who require urgent or emergent peripheral revascularization remain the highest thrombotic risk subgroup of PAD patients, in whom there is insufficient evidence to guide antithrombotic therapy. Despite clear evidence that multi-modal medical therapy (including statins, antihypertensive agents and smoking cessation) benefits patients with atherosclerosis, their use remains unacceptably low in PAD, and greater efforts are needed to understand and address patient, health provider, and system issues that prevent their optimal implementation in practice.

Antithrombotics in stable peripheral artery disease.

Patients with peripheral artery disease (PAD) are at high risk for ischemic cardiovascular complications. While single antiplatelet therapy (SAPT), predominantly aspirin, has long been the standard antithrombotic treatment in stable PAD, there have now been greater than 40,000 PAD patients randomized to varying antiplatelet and/or anticoagulant regimens. In this review, we provide a summary of the current evidence for antithrombotics in stable PAD, focusing on the rates of major adverse cardiovascular events (MACE), major adverse limb events (MALE), and major bleeding. SAPT has a limited role in the treatment of asymptomatic PAD, particularly in the absence of concomitant coronary artery disease. In symptomatic PAD, SAPT is effective in preventing MACE, though treatment with a thienopyridine appears marginally superior to aspirin. Dual antiplatelet therapy (DAPT) suggests benefit over SAPT in reducing MACE and MALE, though studies to date are not conclusive and/or are associated with excess major bleeding. Combining moderate to high intensity vitamin K antagonists with antiplatelet therapy does not reduce MACE or MALE and increases life-threatening bleeding. Rivaroxaban 2.5 mg BID in addition to aspirin reduces the incidence of both MACE and MALE as compared to aspirin alone, without increasing life-threatening bleeding. This regimen is associated with a reduced severity of MALE when it does occur. Comparisons across antithrombotic trials in PAD are challenging given the heterogeneity of patient populations and the differing assessment of outcomes. The vascular medicine practitioner can reduce ischemic cardiac and limb events, as well as minimize life-threatening bleeding, by choosing the optimal antithrombotic regimen in their PAD patients.

Rivaroxaban and Aspirin in Peripheral Vascular Disease: a Review of Implementation Strategies and Management of Common Clinical Scenarios.

PURPOSE OF REVIEW: Peripheral artery disease (PAD) affects an estimated 200 million people worldwide and is associated with significant cardiovascular morbidity and mortality. Cardiovascular risk is further increased among individuals with polyvascular disease, where either cerebrovascular or coronary artery disease is present in addition to PAD. In this review, we present common clinical scenarios encountered when managing patients with PAD and provide an evidence-based approach to prescribing optimal antithrombotics in this population. RECENT FINDINGS: The COMPASS trial recently demonstrated that rivaroxaban 2.5 mg BID + ASA daily significantly reduces major adverse cardiac and limb events in patients with PAD. Despite these advances, morbidity following MALE events remains high. With widespread approval by federal health regulators, the COMPASS regimen should be strongly considered in PAD patients who do not have a high bleeding risk. Implementing the COMPASS regimen in patients with PAD, along with other vascular risk reduction strategies, will have a substantial impact on reducing atherothromboembolic risk in patients with established vascular disease.

Examining postpartum anticoagulation practices: An international survey of healthcare providers.

BACKGROUND: The risk of venous thromboembolism (VTE) is 15 to 35-fold higher in the postpartum period compared to non-pregnant individuals. Clinical practice guidelines recommend the use of postpartum thromboprophylaxis with low molecular weight heparin (LMWH) for 6 weeks in individuals at high risk of developing VTE. However, a marked reduction in the risk of VTE risk occurs beyond the third week of the postpartum period. OBJECTIVE: We sought to characterize practice patterns of clinicians who manage postpartum individuals at high risk of VTE. METHODS: We conducted a cross-sectional study using a self-administered electronic questionnaire. The survey explored the use of postpartum thromboprophylaxis in high-risk individuals. Descriptive statistics were used to summarize survey responses. RESULTS: Of the 113 participants that responded to the initial invitation, 78 completed the survey (Europe (53.9 %); North America (23.2 %); Australia and New Zealand (19.0 %)). For individuals with a prior unprovoked or provoked deep venous thrombosis or pulmonary embolism, cerebral vein thrombosis and splanchnic vein thrombosis, 97.4 %, 93.5 %, 91.0 % and 88.5 % of the respondents recommended six weeks of postpartum thromboprophylaxis using LMWH, respectively. The recommendation for 6 weeks of thromboprophylaxis in patients with sickle cell disease and obstetric APS was comparatively lower (70.5 and 78.2 % respectively). Respondents with higher practice volumes and more years of experience in clinical practice were more likely to recommend a shorter duration of thromboprophylaxis. CONCLUSION: Our study highlights the variability in clinician recommendations and the acceptability of treatment durations for postpartum thromboprophylaxis in high-risk conditions. Prospective studies are needed to determine optimal duration and establish evidence-based management.

Antithrombotic Therapy in Peripheral Artery Disease: Risk Stratification and Clinical Decision Making.

Patients with peripheral artery disease (PAD) are an underrecognised group with significant thrombotic risk. This risk is modifiable with the use of aggressive secondary preventative efforts, including optimisation of antithrombotic therapy. Appropriate antithrombotic selection for patients with PAD requires appropriate assessment of thrombotic and bleeding risk. Recent Canadian guidelines have recommended dual pathway therapy initiation for stable PAD and post-revascularisation patients. However, there is ongoing discussion about how to identify PAD patients who stand to benefit most from these therapies while trying to minimise harm from bleeding. Clinical equipoise also persists around questions such as the utility of dual antiplatelet therapy in conjunction with rivaroxaban after high-risk endovascular interventions and the optimal therapy for patients experiencing acute limb ischemia. In patients with chronic PAD and high-risk comorbidities or limb features, or in patients after revascularisation, dual pathway therapy with low-dose rivaroxaban and aspirin has emerged as the only regimen to reduce major adverse cardiovascular and limb events while maintaining an acceptable bleeding profile. After endovascular revascularisation, limited-duration (< 30 days) clopidogrel may be added to rivaroxaban and aspirin in selected high-risk patients at the provider's discretion. After acute limb ischemia, the risk of another vascular event is exceptionally high, but there is no high-quality evidence to guide decision making for intensified antithrombotic therapy. Randomised investigations addressing this question are urgently needed to better serve this high-risk and vulnerable population.

Canadian Cardiovascular Society 2022 Guidelines for Peripheral Arterial Disease.

Patients with widespread atherosclerosis such as peripheral artery disease (PAD) have a high risk of cardiovascular and limb symptoms and complications, which affects their quality of life and longevity. Over the past 2 decades there have been substantial advances in diagnostics, pharmacotherapy, and interventions including endovascular and open surgical to aid in the management of PAD patients. To summarize the evidence regarding approaches to diagnosis, risk stratification, medical and intervention treatments for patients with PAD, guided by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework, evidence was synthesized, and assessed for quality, and recommendations provided-categorized as weak or strong for each prespecified research question. Fifty-six recommendations were made, with 27% (15/56) graded as strong recommendations with high-quality evidence, 14% (8/56) were designated as strong recommendations with moderate-quality evidence, and 20% (11/56) were strong recommendations with low quality of evidence. Conversely 39% (22/56) were classified as weak recommendations. For PAD patients, strong recommendations on the basis of high-quality evidence, include smoking cessation interventions, structured exercise programs for claudication, lipid-modifying therapy, antithrombotic therapy with a single antiplatelet agent or dual pathway inhibition with low-dose rivaroxaban and aspirin; treatment of hypertension with an angiotensin converting enzyme or angiotensin receptor blocker; and for those with diabetes, a sodium-glucose cotransporter 2 inhibitor should be considered. Furthermore, autogenous grafts are more effective than prosthetic grafts for surgical bypasses for claudication or chronic limb-threatening ischemia involving the popliteal or distal arteries. Other recommendations indicated that new endovascular techniques and hybrid procedures be considered in patients with favourable anatomy and patient factors, and finally, the evidence for perioperative risk stratification for PAD patients who undergo surgery remains weak.

Medical Therapy Following Urgent/Emergent Revascularization in Peripheral Artery Disease Patients (Canadian Acute Limb Ischemia Registry [CANALISE I]).

BACKGROUND: Following severe limb ischemia requiring urgent/emergent revascularization, peripheral arterial disease patients suffer a high risk of recurrent atherothrombosis. METHODS: Patients discharged from Hamilton General Hospital (Hamilton, Ontario) between April 2016 and September 2017 following severe limb ischemia requiring urgent/emergent revascularization were identified via the Local Health Integration Network CorHealth database, with supplemental information from chart review. RESULTS: A total of 158 patients admitted for urgent/emergent revascularization were identified (148 alive at discharge). Among patients without a pre-existing indication for anticoagulation, 38.8% (n = 47) were discharged on single-antiplatelet therapy, 27.3% (n = 33) on dual-antiplatelet therapy, 19.8% (n = 24) on anticoagulants plus antiplatelet therapy, 6.6% (n = 8) on anticoagulants alone, and 2.6% (n = 3) on unknown therapy. Patients who received angioplasty with stenting were more likely be discharged on dual-antiplatelet therapy (hazard ratio [HR]: 7.14; 95% confidence interval [CI]: 2.87-17.76; P < 0.01); patients who received an embolectomy/thrombectomy were more likely be discharged on an anticoagulant alone (HR: 2.61; 95% CI: 1.00-6.81; P = 0.049); and patients who received peripheral bypass grafting were more likely be discharged on single-antiplatelet therapy (HR: 2.28; 95% CI: 1.11-4.69; P = 0.024). Neither statins (60.8% vs 56.3%; P = 0.23) nor renin-angiotensin-aldosterone system inhibitors (48.7% vs 50.6%; P = 0.58) were prescribed at higher rates at discharge, compared with the rate at admission. CONCLUSIONS: Substantial heterogeneity exists in antithrombotic prescription following urgent/emergent revascularization. No intensification of non-antithrombotic vascular protective medications occurred during hospitalization. Clinical trials and health system interventions to optimize medical therapy in peripheral arterial disease patients are urgently needed.

INTRODUCTION: Après une ischémie grave d'un membre ayant nécessité une revascularisation urgente/nouvelle revascularisation, les patients atteints d'une maladie artérielle périphérique ont un risque élevé de récidive d'athérothrombose. MÉTHODES: Nous avons recensé les patients qui ont obtenu leur sortie de la Hamilton General Hospital (Hamilton, Ontario) entre avril 2016 et septembre 2017 à la suite d'une ischémie grave d'un membre ayant nécessité une revascularisation urgente/nouvelle revascularisation via la base de données Local Health Integration Network CorHealth et grâce aux renseignements complémentaires issus de la revue des dossiers. RÉSULTATS: Nous avons recensé un total de 158 patients admis pour une revascularisation urgente/nouvelle revascularisation (148 patients en vie à la sortie de l'hôpital). Parmi les patients chez lesquels l'anticoagulation n'avait pas antérieurement été indiquée, 38,8 % (n = 47) avaient reçu à leur sortie de l'hôpital un simple traitement antiplaquettaire; 27,3 % (n = 33), une bithérapie antiplaquettaire; 19,8 % (n = 24), des anticoagulants plus un traitement antiplaquettaire; 6,6 % (n = 8), des anticoagulants seuls; 2,6 % (n = 3), un traitement inconnu. Les patients qui avaient subi une angioplastie et une pose d'endoprothèse étaient plus susceptibles d'obtenir à leur sortie de l'hôpital une bithérapie antiplaquettaire (rapport de risque [RR] : 7,14; intervalle de confiance [IC] à 95 % : 2,87-17,76; P < 0,01); les patients qui avaient subi une embolectomie, ou thrombectomie, étaient plus susceptibles d'obtenir à leur sortie de l'hôpital un anticoagulant seul (RR : 2,61; IC à 95 % : 1,00-6,81; P = 0,049); les patients qui avaient subi un pontage périphérique étaient plus susceptibles d'obtenir à leur congé de l'hôpital un simple traitement antiplaquettaire (RR : 2,28; IC à 95 % : 1,11-4,69; P = 0,024). Comparativement à l'admission, ni les statines (60,8 % vs 56,3 %; P = 0,23) ni les inhibiteurs du système rénine­angiotensine­aldostérone (48,7 % vs 50,6 %; P = 0,58) n'avaient été prescrits à des taux plus élevés à la sortie de l'hôpital. CONCLUSIONS: Nous observons une hétérogénéité substantielle de l'ordonnance des antithrombotiques après la revascularisation urgente/nouvelle revascularisation. L'hospitalisation n'a donné lieu à aucune augmentation des médicaments de protection vasculaire non antithrombotiques. Des essais cliniques et des interventions du système de santé qui permettent d'optimiser le traitement médical des patients atteints d'une maladie artérielle sont d'une urgente nécessité.

A National Canadian Survey of Antithrombotic Therapy After Urgent and Emergent Limb Revascularization.

Patients with peripheral artery disease who undergo urgent or emergent lower extremity revascularization have the highest risk of major adverse cardiac and limb events. Although available evidence suggests that antithrombotic therapy reduces this risk, optimal antithrombotic therapy is unclear. In this report, we aim to describe current practice patterns for use of antithrombotic therapies after urgent/emergent peripheral artery revascularization. A self-administered online survey was distributed to all active vascular surgeons registered through the Canadian Society of Vascular Surgery (n = 149) between March 19 and April 29, 2019. The overall response rate was 53% (79/149). More than half of the respondents use a medical specialist service in aiding decision-making (52% (95% confidence interval [CI], 40.9%-63.0%). When concerned for high rethrombosis risk, respondents most commonly favoured initiation of either aspirin plus full dose anticoagulation (60% [95% CI, 49.2%-70.8%]) or dual antiplatelet therapy (58% (95% CI, 47.1%-68.9%]). Intraoperative findings and patient characteristics prompting concern for high rethrombosis risk include residual proximal/distal occlusive disease (75% [95% CI, 65.5%-84.5%]), poor-quality venous conduit (76% [95% CI, 66.6%-85.4%]), distal/infrapopliteal synthetic conduit (77% [95% CI, 67.7%-86.3%]), and history of multiple previous failed vascular interventions (98% [95% CI, 94.9%-100%]). More than 90% of respondents believe significant uncertainty exists in antithrombotic decision-making after urgent/emergent peripheral revascularization. Substantial uncertainty exists regarding antithrombotic therapy after urgent/emergent revascularization. In patients at high perceived rethrombosis risk, vascular surgeons preferentially choose aspirin with full-dose anticoagulation or dual antiplatelet therapy. Because of the clinical uncertainty in this domain, trials to determine optimal antithrombotic therapy in this high-risk population are required.

Rivaroxaban and Aspirin in Patients With Symptomatic Lower Extremity Peripheral Artery Disease: A Subanalysis of the COMPASS Randomized Clinical Trial.

Importance: Patients with symptomatic lower extremity peripheral artery disease (LE-PAD) experience an increased risk of major vascular events. There is limited information on what clinical features of symptomatic LE-PAD prognosticate major vascular events and whether patients at high risk have a greater absolute benefit from low-dose rivaroxaban and aspirin. Objective: To quantify the risk of major vascular events and investigate the response to treatment with low-dose rivaroxaban and aspirin among patients with symptomatic LE-PAD based on clinical presentation and comorbidities. Design, Setting, and Participants: This is a subanalysis of a previously reported subgroup of patients with symptomatic LE-PAD who were enrolled in a large, double-blind, placebo-controlled randomized clinical trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies [COMPASS]) in 602 centers in 33 countries from March 2013 to January 2020. Data analysis was completed from May 2016 to June 2020. Interventions: A combination of low-dose rivaroxaban and aspirin compared with aspirin alone. Main Outcomes and Measures: Thirty-month incidence risk of myocardial infarction, stroke and cardiovascular death (MACE), major adverse limb events (MALE) including major vascular amputation, and bleeding. Results: The COMPASS trial enrolled 4129 patients with symptomatic LE-PAD (mean [SD] age, 66.8 [8.8] years; 2932 men [71.0%]). The 30-month Kaplan-Meier incidence risk of MACE or MALE, including major amputation, was 22.6% in those with prior amputation (this outcome was observed in 54 patients), 17.6% (n = 15) in those with Fontaine III or IV symptoms, and 11.8% (n = 142) in those with previous peripheral artery revascularization, classifying these features as high-risk limb presentations. The 30-month incidence risk of MACE or MALE, including major amputation, was 14.1% (n = 118) in those with kidney dysfunction, 13.5% (n = 67) in those with heart failure, 13.4% (n = 199) in those with diabetes, and 12.8% (n = 222) in those with polyvascular disease, classifying these features as high-risk comorbidities. Among patients with either high-risk limb presentations or high-risk comorbidities, treatment with rivaroxaban and aspirin compared with aspirin alone was associated with an estimated 4.2% (95% CI, 1.9%-6.2%) absolute risk reduction for MACE or MALE, including major amputation, at 30 months. Although the estimated absolute risk increase of major bleeding was higher with rivaroxaban and aspirin in combination than aspirin alone (2.0% [95% CI, 0.5%-3.9%]) for patients with either high-risk limb presentation or high-risk comorbidity, the estimated absolute risk increase of fatal or critical organ bleeding was low in this high-risk group (0.4% [95% CI, 0.2%-1.8%]), such that the net clinical benefit was estimated to be 3.2% (95% CI, 0.6%-5.3%). Conclusions and Relevance: Patients with LE-PAD with high-risk limb presentations or high-risk comorbidities had a high incidence of major vascular events. For these patients, treatment with rivaroxaban and aspirin in combination compared with aspirin alone led to a large absolute reduction in vascular risk.

Periprocedural Management of Oral Anticoagulation.

Decisions surrounding periprocedural anticoagulation management must balance thromboembolic and procedural bleed risk. The interruption of both warfarin and DOACs requires consideration of anticoagulant pharmacokinetics, procedural bleed risk and patient characteristics. There is a diminishing role for periprocedural bridging LMWH overall and no role for bridging LMWH for the procedural interruption of DOACs. A clinical approach to perioperative DOAC management based on operative bleeding risk and renal function is safe and effective, and at present, is preferred over preprocedural DOAC levels testing. Clear communication of the anticoagulation interruption plan to both the patient and the patient's care team is essential.

Thrombolysis in Pulmonary Embolism: An Evidence-Based Approach to Treating Life-Threatening Pulmonary Emboli.

Acute pulmonary embolism (PE) is associated with high in-hospital morbidity and mortality, both via cardiorespiratory decompensation and the bleeding complications of treatment. Thrombolytic therapy can be life-saving in those with high-risk PE, but requires careful patient selection. Patients with PE and systemic arterial hypotension ("massive PE") should receive thrombolytic therapy unless severe contraindications are present. Patients with PE and right ventricular dysfunction/injury, but without hypotension ("submassive PE"), should be considered for thrombolysis on a case-by-case basis, considering bleeding risk, cardiac biomarkers, echocardiography, and most importantly, clinical status.

Predictors of Bleeding in the Perioperative Anticoagulant Use for Surgery Evaluation Study.

Background In the PAUSE (Perioperative Anticoagulant Use for Surgery Evaluation) Study, a simple, standardized, perioperative interruption strategy was provided for patients with nonvalvular atrial fibrillation taking direct oral anticoagulants (DOACs). Our objective was to define the factors associated with perioperative bleeding. Methods and Results We analyzed bleeding as the composite of major and clinically relevant nonmajor bleeding. Putative predictors of bleeding, and preoperative DOAC level were prospectively collected during recruitment. We used stratified logistic regression models for analysis. All statistical analyses were performed in R version 3.6.0. There were 3007 patients requiring perioperative DOAC interruption. More than one third of the included patients underwent a high bleeding risk procedure. The 30-day rates of major and clinically relevant nonmajor bleeding were 3.02% in apixaban (n=1257), 2.84% in dabigatran (n=668), and 4.16% for rivaroxaban (n=1082). Multivariate analysis stratified by region found more bleeding for hypertension (odds ratio [OR], 1.79; 95% CI 1.07-2.99; P=0.027), and prior bleeding (OR, 1.71; 95% CI, 1.08-2.71; P=0.021). Surgical bleed risk classification (high- versus low-risk) as a predictor of bleeding was only significant in the univariate analysis. The prediction model for major and clinically relevant nonmajor bleeding had an area under the curve of 0.71, and the preoperative DOAC level did not improve the area under the curve of the model. Conclusions In patients treated with DOACs who required an elective surgery/procedure and were managed with standardized DOAC interruption and resumption, there we did not find reversible risk factors for bleeding, suggesting that adjustment of the PAUSE management protocol to mitigate against bleeding is not needed.

Treatment in the dental practice of the patient receiving anticoagulation therapy.

BACKGROUND: The use of anticoagulants is ubiquitous in outpatient medical practice, with anticoagulants now among the most common classes of medications prescribed in the United States. Despite its safety, anticoagulation around minimally invasive dental procedures remains a source of discomfort for dental practitioners and a common reason for referral to specialist anticoagulation clinics. The introduction of new anticoagulant options, as well as the changing practice pattern in anticoagulant prescription, somewhat contributes to this situation. Reviewing the commonly used anticoagulants in outpatient medical practice, as well as their implications in dental practice, is integral to providing safe oral health care. CONCLUSIONS: Direct oral anticoagulants are now the preferred agents for most patients receiving anticoagulation therapy. With patients receiving any type of therapeutic anticoagulation, clinicians usually can perform dental procedures such as restorations, limited dental extractions, endodontic procedures, soft-tissue biopsies, and scalings safely without anticoagulation therapy interruption. Although local hemostatic maneuvers are often sufficient during dental procedures, antifibrinolytic medications, as well as local sponges and glues, can be used to ensure adequate hemostasis. Different classes of anticoagulants interact with commonly prescribed medications in unique ways and may require differing management and monitoring. PRACTICAL IMPLICATIONS: Clinicians can perform most dental procedures safely despite patients' receiving therapeutic anticoagulation. Recognizing common classes of anticoagulants, incorporating strategies to minimize bleeding, and understanding how commonly prescribed medications in dentistry interact with anticoagulants are essential to practicing safe, comprehensive care.

Cost-Efficient Medical Education: An Innovative Approach to Creating Educational Products.

BACKGROUND: Cost is a barrier to creating educational resources, and new educational initiatives are often limited in distribution. Medical training programs must develop strategies to create and implement cost-effective educational programming. OBJECTIVE: We developed high-quality medical programming in procedural instruction with efficient economics, reaching the most trainees at the lowest cost. METHODS: The Just-In-Time online procedural program was developed at the University of Toronto in Canada, aiming to teach thoracentesis, paracentesis, and lumbar puncture skills to internal medicine trainees. Commercial vendors quoted between CAD $50,000 and $100,000 to create 3 comprehensive e-learning procedural modules-a cost that was prohibitive. Modules were therefore developed internally, utilizing 4 principles aimed at decreasing costs while creating efficiencies: targeting talent, finding value abroad, open source expansion, and extrapolating efficiency. RESULTS: Procedural modules for thoracentesis, paracentesis, and lumbar puncture were created for a total cost of CAD $1,200, less than 3% of the anticipated cost in utilizing traditional commercial vendors. From November 2016 until October 2018, 1800 online instructional sessions have occurred, with over 3600 pageviews of content utilized. While half of the instructional sessions occurred within the city of Toronto, utilization was documented in 10 other cities across Canada. CONCLUSIONS: The Just-in-Time online instructional program successfully created 3 procedural modules at a fraction of the anticipated cost and appeared acceptable to residents based on website utilization.

Sex Differences in Dose Escalation and Overdose Death during Chronic Opioid Therapy: A Population-Based Cohort Study.

BACKGROUND: The use of opioids for noncancer pain is widespread, and more than 16,000 die of opioid-related causes in the United States annually. The patients at greatest risk of death are those receiving high doses of opioids. Whether sex influences the risk of dose escalation or opioid-related mortality is unknown. METHODS AND FINDINGS: We conducted a cohort study using healthcare records of 32,499 individuals aged 15 to 64 who commenced chronic opioid therapy for noncancer pain between April 1, 1997 and December 31, 2010 in Ontario, Canada. Patients were followed from their first opioid prescription until discontinuation of therapy, death from any cause or the end of the study period. Among patients receiving chronic opioid therapy, 589 (1.8%) escalated to high dose therapy and n = 59 (0.2%) died of opioid-related causes while on treatment. After multivariable adjustment, men were more likely than women to escalate to high-dose opioid therapy (adjusted hazard ratio 1.44; 95% confidence interval 1.21 to 1.70) and twice as likely to die of opioid-related causes (adjusted hazard ratio 2.04; 95% confidence interval 1.18 to 3.53). These associations were maintained in a secondary analysis of 285,520 individuals receiving any opioid regardless of the duration of therapy. CONCLUSIONS: Men are at higher risk than women for escalation to high-dose opioid therapy and death from opioid-related causes. Both outcomes were more common than anticipated.