Antiplatelet and Anticoagulant Agents in Heart Failure: Current Status and Future Perspectives

Perspective:

The following are 10 points to remember about this article, which reviews the current indications for antiplatelet and anticoagulant therapy in patients with systolic heart failure (HF).

1. HF is a stable of hypercoagulability (e.g., increased expression of tissue factor, protein C activation, etc.) and increased inflammation (increased tumor necrosis factor and interleukin-1), and this state of hypercoagulability is believed to be further increased in the setting of acute myocardial infarction (MI).

2. Venous thromboembolism (VTE): VTE risk in HF is 1.5-2.9 higher than in patients without HF. VTE occurs in HF due to reduced patient mobility, prothombotic factor activation, and elevated ventricular filling pressures and a low flow state within venous walls. Low cardiac output also reduces clearance of activation coagulation factors, and VTE risks are higher in those with lower left ventricular ejection fraction.

3. Stroke: Atrial fibrillation accounts for 15% of strokes and HF accounts for 9% of all strokes. HF patients have a 1-3.5% annual risk of stroke, and the increased risk in HF is independent of atrial fibrillation.

4. Acute HF exacerbation, acute MI, older age, and prior history of transient ischemic attack (TIA)/cerebrovascular accident (CVA) increases stroke risk. Patients have a fivefold increased risk of ischemic stroke after incident HF diagnosis. Risk then decreases to 1.96 six months following index HF admission. Following acute MI, annual stroke rate in the SAVE trial was 1.5%; risk of CVA is higher after an acute ischemic event.

5. There have been no randomized trials examining the impact of aspirin alone versus placebo in stroke reduction in HF.

6. Systolic HF and sinus rhythm: The randomized trials WASH (n = 279 patients) and WARCEF (n = 2,305 patients) compared 300-325 mg/day aspirin to warfarin (international normalized ratio [INR], 2.5-3.0) in patients with systolic HF. Neither study showed primary endpoint risk reduction (both including stroke and death) with warfarin. The WATCH trial compared aspirin plus clopidogrel versus warfarin (INR, 2.5-3) in patients (n = 1,587) with New York Heart Association class III/IV systolic HF. Again, no difference in mortality was noted. Both WARCEF and WATCH demonstrated reduced ischemic stroke risk at the expense of increased bleeding. Subanalysis of WARCEF suggested mortality benefit in patients <60 years.

7. A meta-analysis of the major stroke trials comparing warfarin with aspirin in systolic HF largely shows no difference in mortality and lower ischemic stroke risks (hazard ratio [HR], 0.48), but higher risks for bleeding (HR, 2.0).

8. New oral anticoagulants (OACs) in HF: To date, published randomized studies of new OAC efficacy are lacking in systolic HF. The RE-LY trial compared dabigatran with warfarin in atrial fibrillation. The 150 mg dabigatran dosing regimen demonstrated reduced stroke and similar bleeding risk compared with warfarin, and the 100 mg dabigatran dosing showed equivalent stroke risk and lower bleeding risk. In the 4,900 patients with symptomatic HF, there was no treatment effect with dabigatran. Similar findings of stroke risk equivalence and lack of treatment effect in HF were noted in the ARISTOTLE and ROCKET AF studies, comparing apixaban and rivaroxaban with warfarin, respectively.

9. Heart Failure Society of America (HFSA) Guidelines: The HFSA recommends chronic anticoagulation with warfarin (INR, 2-3) in all patients with HF and documented paroxysmal or persistent/permanent atrial fibrillation, history of embolism (deep-venous thrombosis, pulmonary embolism, CVA/TIA), or documented LV thrombus (evidence level C). It recommends anticoagulation for 3 months in the setting of recent large anterior MI or recent MI with documented thrombus (evidence level B). Routine use of aspirin in systolic HF patients without vascular disease is not recommended. No recommendations have been made on new OACs.

10. European Society of Cardiology (ESC) Consensus Statement: The ESC does not recommend routine use of aspirin or warfarin in patients with HF without a specific indication. Anticoagulation may be considered with patients with systolic HF with previous thromboembolism, new intracardiac thrombus, and right HF with pulmonary hypertension, but more research is needed to ascertain risk/benefit ratio. It also does not provide recommendations on new OACs.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Pulmonary Hypertension and Venous Thromboembolism, Vascular Medicine, Novel Agents, Acute Heart Failure, Chronic Heart Failure, Pulmonary Hypertension

Keywords: Myocardial Infarction, Stroke, Morpholines, Pulmonary Embolism, Warfarin, Pyrazoles, New York, Heart Failure, Systolic, Interleukin-1, Benzimidazoles, Hypertension, Pulmonary, Venous Thrombosis, Pyridones


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