Table 1.
An overview of clinical trials on stroke prevention in heart failure.
| Year | Clinical Trial | No. of Patients | Type of HF | Mean LVEF, % | Heart Rhythm | Mean FU, Months | Results |
|---|---|---|---|---|---|---|---|
| 2004 | WASH (Warfarin/Aspirin Study in Heart Failure) [84] | 279 | HFrEF | ≤35 | SR | 27 | No difference in PO (death, nonfatal myocardial infarction, or nonfatal stroke) between warfarin vs. aspirin vs. no antithrombotic treatment |
| 2006 | HELAS (Heart Failure Long-term Antithrombotic Study) [85] | 197 | HFrEF | <35 | SR | 22 | No difference in PO (nonfatal stroke, peripheral or pulmonary embolism, myocardial re-infarction, re-hospitalization, exacerbation of heart failure, or death from any causes) between aspirin vs. anticoagulant therapy |
| 2009 | PROTECT AF (WATCHMAN left Atrial Appendage System for Embolic Protection in Patients with Atrial Fibrillation) [104] | 707 | Chronic HF | ≥30 | AF | 48 | No difference in PO (stroke, systemic embolism, or cardiovascular/unexplained death) between LAA closure vs. warfarin |
| 2009 | WATCH (Warfarin and Antiplatelet Therapy in Chronic Heart Failure) [83] | 1587 | HFrEF | <35 | SR/AF | 21 | No difference in PO (all-cause mortality, nonfatal myocardial infarction, nonfatal stroke) between warfarin vs. aspirin vs. clopidogrel. Reduction in strokes but more hemorrhage in warfarin treatment |
| 2012 | WARCEF (Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction) [86] | 2305 | HFrEF | 25 | SR | 72 | No difference in PO (death, ischemic stroke, or intracerebral hemorrhage) between aspirin vs. warfarin. Prevention of ischemic strokes but more major hemorrhage |
| 2014 | PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) [105] | 407 | Chronic HF | ≥30–<35 | AF | 48 | No difference in PO (stroke, systemic embolism, or cardiovascular/unexplained death) between the LAA closure vs. warfarin |
| 2015 | ACTIVE (Atrial Fibrillation Clopidogrel Trial With Irbesartan for Prevention of Vascular Events) [81] | 3487 | HFrEF HFpEF |
<45 | AF | 43 | No difference in PO (stroke, transient attack and systemic embolism) between HFrEF vs. HFpEF |
| 2017 | COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) [92] | 27,395 | HFrEF | NA | AF | 23 | Improved cardiovascular outcome (cardiovascular death, stroke, myocardial infarction) but more major bleedings in patients with rivaroxaban and aspirin |
| 2018 | COMMANDER HF (Rivaroxaban in Patients with Heart Failure, Sinus Rhythm, and Coronary Disease) [89] | 5022 | HFrEF | <40 | SR | 20 | No difference in PO (death from any cause, myocardial infarction, or stroke) between treatment with antiplatelet agents and rivaroxaban in addition to antiplatelet agents. |
| 2020 | EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) [103] | 2789 | HFrEF | NA | AFF | 61 | The prevention of stroke by rhythm-control therapy in patients with AF and cardiovascular conditions |
| 2020 | LAARGE (Left-Atrium-Appendage occlude Register-Germany registry) [101] | 619 | HFpEF HFmrEF HFrEF |
>55 36–55 ≤35 |
AF | 12 | The efficacy of LAA closure in the prevention of stroke in patients with AF |
| 2020 | PRAGUE-17 (Left Atrial Appendage Closure vs. Novel Anticoagulation Agents in Atrial Fibrillation) [100] | 402 | Chronic HF | NA | AF | 21 | No difference in occurrence of stroke and increased risk of bleeding between LAA closure and therapy with direct oral anticoagulant |
AFF, atrial fibrillation or flutter; CHF, chronic heart failure; CV, cardiovascular; DOAC, direct oral anticoagulant; HFmrEF, heart failure with mid-range ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LAA, left atrial appendage; LVEF, left ventricular ejection fraction; PO, primary outcome; SR, sinus rhythm; TIA, transient ischemic attack.