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Drug Info Challenge: Antithrombotic Therapy in Chronic Heart Failure

Antithrombotic Therapy in Chronic Heart Failure

The ability to answer drug information (DI) questions is a critical skill for pharmacists in all practice areas. Student pharmacists are frequently asked to answer DI questions that may not have been covered in the standard pharmacy curriculum. Often, these responses require in-depth research and they always require good writing skills.

OPA’s first student Drug Information Challenge was initiated in 2013 to highlight high quality DI responses by publishing them in the Ohio Pharmacist journal and on OPA’s website. Students from four of the seven colleges submitted questions from physicians, educators, patients and preceptors. Submissions were blinded to name, school, and graduation year before grading. Judges scored submissions on grammar and punctuation, completeness of response, strength of references and clarity of recommendation.

This year’s winner was Joy Hoffman, PharmD candidate 2016, from Ohio Northern University. Her article, Effervescent Alendronate Bioavailability, was published in the April 2013 issue of Ohio Pharmacist

The following article, Antithrombotic Therapy in Chronic Heart Failure, was submitted by Ashley Neltner and Jordan Staley, PharmD candidates 2013 from Ohio Northern University and received honorable mention.

Should antithrombotic therapy be used in clinical practice for all heart failure patients, specifically those patients enrolled in hospice?

Response: Heart failure is a condition, often chronic, in which the heart cannot pump enough blood to the rest of the body. As the heart's pumping becomes less effective, blood may back up and pool in other areas of the body which often decreases the ejection fraction. This decrease causes a high mortality and morbidity due to the risk of venous thromboembolism (VTE), cardioembolic stroke, and sudden death from a new thrombotic occlusion or an arrhythmic event.1 While these complications have a thrombosis-related pathophysiological basis, there remains debate over the benefit of using antithrombotic therapy in clinical practice for all heart failure patients. For this reason, the Heart Failure Association of the European Society of Cardiology and the Working Group on Thrombosis created a task force to review the published evidence and propose a ‘best practice’ consensus on thromboembolic risk and antithrombotic therapy for heart failure patients in sinus rhythm. These published trials on this topic are described below and in the linked table:  Table 1 Antithrombotic Therapy in Chronic Heart Failure.

The SOLVD trial found the use of warfarin was independently associated with a significant reduction in all-cause mortality and in the risk of death or hospital admission for heart failure.2 Yet patients included taking warfarin at baseline had more frequent diagnoses of atrial fibrillation and overall there was no reduction in deaths due to stroke, pulmonary embolism or other vascular causes when comparing the warfarin users to the non-warfarin users.

Additionally, four randomized clinical trials have been conducted since 2004 that have tested the efficacy of antithrombotic therapy in patients with heart failure in sinus rhythm. These include the WASH study, HELAS trial, WATCH trial, and WARCEF study. In the WASH study, patients were randomized to receive warfarin, aspirin, or no antithrombotic therapy and the rate of all-cause death, non-fatal MI, and cerebrovascular accident were compared.3 There was no difference in the primary endpoints amongst the three treatment groups. The HELAS trial randomized patients to receive aspirin, warfarin or placebo and no difference in the primary endpoints of non-fatal stroke, VTE, MI, re-hospitalization, exacerbation of heart failure or death from any cause was observed.4 Additionally, major hemorrhage was seen among the warfarin groups but not in other group at a rate of 4.6 per 100 patient years. The WATCH trial assessed the rate of death, non-fatal stroke, and non-fatal MI in patients receiving aspirin, clopidogrel, or warfarin. Again, there was no difference in the primary endpoints among treatment groups although the use of warfarin appeared to reduce the incidence of stroke compared with aspirin or clopidogrel.5 Yet, major bleeding was higher with warfarin than with clopidogrel or aspirin. Lastly, the WARCEF study compared the efficacy of aspirin to warfarin with the primary outcome of time to first occurrence in a composite endpoint of death, ischemic stroke, or intracerebral hemorrhage.6 Overall, there was no significant difference seen in the primary endpoint between the warfarin and aspirin groups, however, there was a significant reduction in ischemic stroke among those on warfarin versus aspirin.

Final Recommendation: With no overall benefit of warfarin on rates of death and stroke, and with an increase in major bleeding despite the potential for a reduction in ischemic stroke, there is currently no compelling reason to use warfarin routinely for all heart failure patients in sinus rhythm.1 This aligns with the ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults that anticoagulation in heart failure should only be initiated as treatment in the hospital (IV or subcutaneous) and in patients with heart failure who have concomitant disorders such as supraventricular arrhythmias.7 For this reason, the risk of bleeding outweighs the benefit of anticoagulation in the palliative care setting, making discontinuation of anticoagulants appropriate in CHF patients without a compelling indication, such as history of MI, CVA, VTE, or atrial fibrillation.

References:

  1. Lip GYH, Ponikowski P, Andreotti F, Anker SD, Filippatos G et al. Thrombo-embolism and antithrombotic therapy for heart failure in sinus rhythm: a joint consensus document from the ESC heart failure association and the ESC working group on thrombosis. Eur J Heart Fail2012;14:681–695.
  1. Al-Khadra AS, Salem DN, Rand WM, Udelson JE, Smith JJ et al. Warfarin anticoagulation and survival: A cohort analysis from the studies of left ventricular dysfunction. J Am Coll Cardiol 1998;31:749-753.
  2. Cleland JGF, Findlay I, Jafri S, Sutton G, Falk R et al. The Warfarin/Aspirin Study in Heart failure (WASH): A randomized trial comparing antithrombotic strategies for patients with heart failure. Am Heart J 2004;148:157-164.
  3. Cokkinos DV, Haralabopoulos GC, Kostis JB, Toutouzas PK. Efficacy of antithrombotic therapy in chronic heart failure: The HELAS study. Eur J Heart Fail 2006;8:428-432.
  4. Massie BM, Collins JF, Ammom SE, Armstrong PW, Cleland JGF et al. Randomized Trial of Warfarin, Aspirin, and Clopidogrel in Patients With Chronic Heart Failure: The Warfarin and Antiplatelet Therapy in Chronic Heart Failure (WATCH) Trial. Circulation 2009;119:1616-1624.
  5. Homma S, Thompson JL, Pullicino PM, Levin B, Freudenberger RS et al. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med 2012;366(20):1859-69.
  6. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS et al. 2009 focused update: ACCF/AHA guidelines for the diagnosis and management of heart failure in adults: a report of the american college of cardiology foundation/american heart association task force on practice guidelines. Circulation 2009;119:1977-2016.

 


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