Antithrombotics in heart failure with reduced ejection fraction and normal sinus rhythm: an evidence appraisal.

OBJECTIVE: To review the thromboembolic risk, pathophysiology associated with the risk, and literature investigating the use of antithrombotics in patients with heart failure with reduced ejection fraction and normal sinus rhythm (HFrEF-NSR). DATA SOURCES: An English language literature search was performed with MEDLINE/PubMed and Embase from January 1950 to October 2013 using the search terms heart failure, HFrEF, systolic heart failure, cardiomyopathy, left ventricular dysfunction, sinus rhythm, thromboembolism, deep vein thrombosis, pulmonary embolism, myocardial infarction, acute coronary syndrome, acute coronary events, coronary artery disease, stroke, and cerebrovascular events to identify relevant articles. References in the retrieved articles were also assessed to identify other important articles. STUDY SELECTION AND DATA ABSTRACTION: All pertinent original studies, reviews, consensus documents, and guidelines were evaluated for inclusion. DATA SYNTHESIS: Patients with HFrEF-NSR may be predisposed to developing thromboembolic events. Studies that have examined the role of antithrombotics (warfarin and/or antiplatelet therapy) for reducing thromboembolic risk have been inconclusive. The WASH and HELAS pilot trials--the only studies with a no-antithrombotics or placebo comparator group--did not find a benefit with antithrombotic therapy but found an increased risk of bleeding with warfarin and of hospitalizations with aspirin. Although the clinical outcome studies (WATCH and WARCEF) suggested that warfarin may reduce stroke risk compared with antiplatelet therapy, the lack of a placebo group and lower-than-projected enrollment prevents definitive conclusions from being made. CONCLUSIONS: Current evidence does not support the routine use of antithrombotics for preventing thromboembolic events in patients with HFrEF-NSR without compelling indications.

Successful alteplase bolus administration for a presumed massive pulmonary embolism during cardiopulmonary resuscitation.

OBJECTIVE: To describe the case of a patient successfully resuscitated with bolus alteplase for a presumed massive pulmonary embolism (PE) with associated cardiac arrest. CASE SUMMARY: A 54-year-old man presented to the emergency department for evaluation of syncope following recent open reduction and internal fixation of his ankle. On arrival, his condition rapidly deteriorated and progressed to cardiopulmonary arrest. Because of noncompliance with postoperative thromboprophylaxis, there was high suspicion for PE. Following 40 minutes of advanced cardiac life support, empirical alteplase 50 mg was administered intravenously over 2 minutes with return of spontaneous circulation (ROSC) observed 6 minutes later. The diagnosis of PE using computed tomographic angiography was confirmed after fibrinolytic therapy. Although his hospital course was complicated by a gastrointestinal bleed requiring transfusion, he was discharged neurologically intact. DISCUSSION: Clinical guidelines recommend fibrinolytic therapy for patients with PE and cardiac arrest. Data from retrospective analyses, case series, and case reports suggest that various fibrinolytic regimens may facilitate ROSC and improve neurologically intact survival without an increased risk of fatal hemorrhage. CONCLUSION: The choice of fibrinolytic therapy should be based on hospital availability, with prompt initiation of treatment and incorporation of an intravenous bolus. A reasonable treatment regimen is alteplase 0.6 mg/kg (maximum of 50 mg) or fixed dose of alteplase 50 mg given over 2 to 15 minutes. Resuscitation should be continued for at least 30 minutes, or until ROSC, after fibrinolytic initiation to allow time for the medication to work.

Acute pulmonary emboli in a patient on long-term dabigatran therapy.

OBJECTIVE: To describe the case of a patient who developed acute pulmonary emboli (PE) despite long-term anticoagulation with dabigatran. CASE SUMMARY: A 69-year-old obese woman was hospitalized for worsening shortness of breath, dyspnea on exertion, and left pleuritic chest pain. On admission, a computed tomography angiogram revealed acute bilateral PE, despite use of dabigatran for atrial fibrillation for approximately 5 years prior to admission. Dabigatran was stopped and therapeutic enoxaparin was initiated concomitantly with warfarin. An investigation into possible causes for the development of the PE, including hypercoagulability, was unrevealing. Since dabigatran should have protected against PE, the patient was questioned regarding adherence to her regimen. She stated that she was adherent but reported using a pillbox. The patient was discharged home on warfarin with an enoxaparin bridge until her international normalized ratio was at least 2.0. DISCUSSION: The underlying cause for the patient's acute PE is unknown but could possibly be attributed to obesity and reduced mobility. Although dabigatran should have prevented PE, the presence of interacting drugs, patient-specific pharmacokinetics, suboptimal medication storage, and laboratory abnormalities may have resulted in reduced dabigatran exposure and protection. This is a reasonable hypothesis; however, the patient did not develop a stroke while receiving dabigatran. CONCLUSIONS: Our patient developed acute bilateral PE despite receiving long-term anticoagulation with dabigatran. While it is possible that patient-specific factors resulted in reduced dabigatran exposure and efficacy, conclusions cannot be made.

The role of apixaban for venous and arterial thromboembolic disease.

OBJECTIVE: To provide a comprehensive review of the pharmacology, pharmacokinetics, pharmacodynamics, clinical trial data, adverse effects, and drug interactions of apixaban. DATA SOURCES: An English-language literature search was performed with MEDLINE/PubMed from January 2007 to August 2011 using the search terms apixaban, factor Xa inhibitors, FXa inhibitors, BMS-562247-01, venous thromboembolism, deep vein thrombosis, pulmonary embolism, myocardial infarction, acute coronary syndrome, ACS, atrial fibrillation, atrial arrhythmias, total hip replacement or arthroplasty, total knee replacement or arthroplasty, and orthopedic surgery to identify relevant articles. The references of the retrieved articles, professional society meeting abstracts, and the Web site www.clinicaltrials.gov were reviewed to identify other pertinent articles. STUDY SELECTION AND DATA ABSTRACTION: Pertinent original studies involving apixaban's pharmacology, pharmacokinetics, drug interactions, and clinical efficacy and safety data were included. DATA SYNTHESIS: Results of 2 large Phase 3 trials suggest that apixaban is superior for stroke and systemic embolism prevention compared to both aspirin and warfarin in patients with atrial fibrillation (AF); rates of major bleeding and intracranial hemorrhage were similar to those of aspirin but significantly reduced compared to warfarin. Completed trials in orthopedic surgery found apixaban to be superior to enoxaparin in total hip replacement (THR) surgery but inferior in total knee replacement (TKR) surgery, with similar rates of major bleeding. A Phase 3 trial of apixaban in acute coronary syndrome was stopped early because of excess bleeding. Future Phase 3 trials will help to determine apixaban's role for treatment of deep vein thrombosis and pulmonary embolism. Currently, apixaban is approved only in Europe for prophylaxis of venous thromboembolism in adults who have undergone elective THR or TKR. CONCLUSIONS: A Phase 3 trial in patients with AF revealed apixaban to be superior to warfarin for stroke and systemic embolism prophylaxis, with lower rates of major bleeding. Further studies will help to confirm the role of apixaban for other indications.