Is Anticoagulation Treatment Needed in Heart Failure Patients?
LH is a 60-year-old white male with a 10-year history of longstanding hypertension as well as systolic heart failure (sys-HF) with a reduced ejection fraction (EF) of 20%. He was just discharged from the local hospital for a HF exacerbation. He received intravenous diuresis for 2 days and was discharged home without any medication changes.
His current medications include carvedilol immediate-release (IR) 25 mg twice daily, lisinopril 20 mg daily, spironolactone 25 mg daily, bumetanide 1 mg daily, and aspirin 81 mg daily.
He presents today (5 days post-discharge) for a follow-up appointment and is stable from a HF standpoint: weight and blood pressure are stable, lungs clear to auscultation bilaterally, no pitting edema, or jugular venous pressure. He has no shortness of breath, and he left the hospital in good electrolyte balance.
One of the cardiologists who saw him in the hospital mentioned that anticoagulation might be a consideration, so he came in to follow up. It seems like a big step to him. Is it really necessary?
To Start Anticoagulation Or Not
It is believed that a sys-HF contributes to a hypercoagulable state for a variety of reasons. Most notably, a reduced cardiac output and abnormal (or reduced) blood flow may lead to thrombus formation as blood is more static and likely to clot. Furthermore, the low cardiac output, combined with reduced exercise (eg, sedentary lifestyle) and peripheral edema, also increase the risk for venous thromboembolism.
Finally, there is some evidence that platelet reactivity and coagulation factors activity is increased in patients with HF, further contributing to increased risk for thromboembolism. Reduced EF also increases the risk for the formation of a left ventricular thrombus, although how the risk for systemic venous embolism correlates with the formation of a left ventricular thrombus—arterial since the left ventricular serves the arterial segment of the circulation—is not clear at this time.
These pathophysiologic changes seen in sys-HF appear to confer a higher risk for stroke (1.2% to 1.8% per year) and systemic embolism (1.5% to 2.7% per year).1 By comparison, epidemiological data demonstrates an incidence of venous thromboembolism in 0.1% in the general population.2 Those with sys-HF have an increased risk for stroke and systemic embolism. These rates, however, should be interpreted with caution as many HF patients have comorbidities that independently increase the risk for such events (eg, underlying cardiovascular disease and atrial fibrillation), making it difficult to determine the exact contribution of the sys-HF towards the thromboembolic risk compared to the comorbidities.
Less data is available for those HF patients with a preserved ejection fraction (ie, diastolic dysfunction [dia-HF]), but it appears as if the risk for stroke is the same as those with sys-HF. One study did not show that EF was correlated with the risk for thromboembolism potentially suggesting those with preserved or reduced-EF heart failure are at a similar risk for stroke or thromboembolism.3 However, this study only included 197 patients and the results should be interpreted cautiously.
Although it appears as if patients with sys-HF are at an increased risk for stroke and systemic embolism, the role of antiplatelet or anticoagulation therapy is not clear. Two randomized controlled trials compared antiplatelet therapy (aspirin in both, clopidogrel in one) to warfarin in patients with an EF ≤35%. The WATCH study4 (goal international normalized ratio [INR] 2.5 to 3, 74% with coronary artery disease) did not show a difference in the rate of death, nonfatal MI, or nonfatal stroke between the treatment groups. The WARCEF study5 (goal INR 2 to 3.5, 43% with coronary artery disease) also showed no difference between groups with respect to the primary outcome of ischemic stroke, intracerebral hemorrhage, or all-cause mortality.
Clinical Application
Based on the available evidence, sys-HF appears to increase the risk for thromboembolic events. However, whether or not this risk is high enough to justify antithrombotic therapy is debatable. The estimated risk of thromboembolism in sys-HF (1.5% to 2.7% per year) is roughly equivalent to the level of risk incurred by patients with atrial fibrillation and a CHADS2 score of 0 to 1 (1.9% to 2.8% per year).
At the lower end of that risk stratification (CHADS score = 0), no antithrombotic therapy is indicated; at the upper end of that risk stratification (CHADS2 score = 1) antithrombotic therapy is indicated.2 Risk from sys-HF falls somewhere in between.
Although most of our data about successful risk reduction for thromboembolism comes from the atrial fibrillation literature, it is likely that there are sufficient between-disease state commonalities that some of the principles learned in atrial fibrillation are applicable to sys-HF. If anything, one would anticipate that the remarkable risk reduction attained by anticoagulant therapy in atrial fibrillation may not be as dramatic in HF, since the physiologic derangements are quite different. Hence, we do not feel that we can share enthusiasm for routine anticoagulation simply on the basis of increased risk associated with sys-HF; the choice to initiate antiplatelet or anticoagulation therapy in a patient with sys-HF is more likely to be guided by additional risk factors and comorbidities independent of the presence or absence of sys-HF.
Guidelines
National guidelines are generally concordant with our philosophy. The most recent CHEST AT9 Guidelines2 suggest against using aspirin or warfarin in patients with sys-HF, except for patients with an established coronary artery disease (for whom aspirin is indicated) or a left ventricular thrombus (for whom 3 months of warfarin is indicated). If a patient has comorbid atrial fibrillation, the decision to initiate antiplatelet or anticoagulation therapy should be guided by the CHADS2 or CHA2DS2-VASc score. The presence of sys-HF is already incorporated into CHADS/CHADSVASC since the “C” in both of these is for congestive HF. The Heart Failure Society of America guidelines and the American College of Cardiology/American Heart Association both have similar recommendations regarding the use of antiplatelet or anticoagulation therapy.
Outcome of the Case
LH has sys-HF and therefore, does have an increased risk for stroke and thromboembolism. However, in the absence of another comorbidity that mandates antithrombotic treatment, sys-HF alone does not rise to the level of mandating anticoagulation. In the absence of established CAD, it is uncertain whether even ASA will provide risk reduction and hence is optional.
LH should be counseled that although he does have a modestly elevated risk for thromboembolism, given his lack of additional risk factors, the benefits of anticoagulation therapy do not outweigh the potential risks and therefore he does not require treatment.
It is important to convey to the patient that this treatment decision would be in agreement with numerous national guidelines, such CHEST and heart failure-specific guidelines. The potential risks and benefits of aspirin therapy should be discussed given the patient’s lack of coronary artery disease or other significant cardiovascular risk factor. Finally, reinforce that the patient should continue to maintain good BP control, since that is the primary modifiable risk factor that can potentially alter the course of HF.
In our case, LH was quite relieved to learn that another complicated medication would not have to be added to his regimen, and left the office satisfied that neither antiplatelet treatment nor antithrombotic therapy was necessary at this stage.
The Take-Away
• Patients with a reduced EF (sys-HF) appear to be at a greater risk for stroke and systemic embolism compared to those with a normal or preserved EF (dia-HF).
• Antiplatelet or anticoagulant therapy has not been shown to be beneficial in reducing the risk for stroke or thromboembolism in patients without comorbidities that independently increase the risk for such events.
• The choice to initiate antiplatelet or anticoagulation therapy in a patient with sys-HF should be guided by the presence of comorbidities. Guideline recommendations for the specific comorbidity should be followed accordingly.
Eric A. Dietrich, PharmD, BCPS, graduated from UF College of Pharmacy in 2011 and completed a 2-year fellowship in family medicine where he was in charge of a coumadin clinic. He now works for the UF Colleges of Pharmacy and Medicine.
Louis Kuritzky, MD, is a family physician affiliated with the University of Florida Family Medicine Residency Program, where he commonly co-manages warfarin cases with his colleagues.
References:
1.Colluci WS, Lip GYH. Antithrombotic therapy in patients with heart failure. Wolters Kluwer Health. www.uptodate.com/contents/antithrombotic-therapy-in-patients-with-heart-failure. Accessed September 20, 2014.
2.Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: CHEST Evidence-Based Clinical Practice Guidelines. 2012;141(2 Suppl).
3.Massie BM, Collins JF, Ammon SE, 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.
4.Cokkinos DV, Haralabopoulos GC, Kostis JB, Toutouzas PK; HELAS investigators. Efficacy of antithrombotic therapy in chronic heart failure: the HELAS study. Eur J Heart Fail. 2006;8(4):428-432.
5.Homma S, Thompson JL, Pullicino PM, et al; WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012;366(20):1859-1869.