Quality of Anticoagulation Control in Preventing Adverse Events in Patients With Heart Failure in Sinus Rhythm

Abstract

Background The aim of this study is to examine the relationship between time in therapeutic range (TTR) and clinical outcomes in heart failure (HF) patients in sinus rhythm (SR) treated with warfarin. Methods and Results We used data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death); with death alone; ischemic stroke alone; major hemorrhage alone; and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin patients, with TTR being treated as a time-dependent covariate. 2,217 patients were included in the analyses, among whom 1,067 were randomized to warfarin and 1,150 were randomized to aspirin. The median (IQR) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted p<0.001), death alone (adjusted p=0.001), and improved net clinical benefit (adjusted p<0.001). A similar trend was observed for the other two outcomes but significance was not reached (adjusted p=0.082 for ischemic stroke, adjusted p=0.109 for major hemorrhage). Conclusions In HF patients in SR, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938.

Stroke Risk Factors, Genetics, and Prevention

“…A secondary analysis showed that increasing the time that patients are in the therapeutic range with warfarin was significantly associated with better outcomes and improved net clinical benefit. 281 Based on a meta-analysis that included 3,663 patients, there is no clear evidence at this time to recommend the use of anti-coagulation in this subgroup of patients. 282 With the availability of newer oral anticoagulants with a more favorable risk profile, however, it is possible that future trials could demonstrate a benefit.…”

Management of Cardiac Involvement Associated With Neuromuscular Diseases: A Scientific Statement From the American Heart Association

“…[277][278][279] Studies of adults in sinus rhythm with HF and systolic LV dysfunction have not shown a clear difference in the incidence of stroke when warfarin and aspirin were compared to warfarin alone. [280][281][282][283] There are no similar prospective data available in children with systolic ventricular dysfunction, and the true risk of thromboembolism is unknown, regardless of NMD status. [284][285][286][287][288][289][290][291] It is well established that thrombosis prevention is indicated in adults with AF/atrial flutter in the absence of ventricular dysfunction, and extremely detailed riskbased guidelines for anticoagulation in AF/atrial flutter exist 205 ; however, data in children and those with NMDs are lacking.…”

Heart Failure Severity and Quality of Warfarin Anticoagulation Control (From the WARCEF Trial)

“…Assessment of TTR in WARCEF participants was described previously 6,7 . Briefly, we assumed that any change between two consecutive INR measurements takes place linearly over a 5-day period.…”

“…4,5 Previously using the data of patients with HF with reduced ejection fraction (HFrEF) and sinus rhythm from the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction (WARCEF) trial 6 , we have demonstrated that patients on warfarin with high TTR is associated with improved net clinical benefit compared both with patients on warfarin with low TTR and patients on aspirin only. 7 Unlike patients with AF, however, knowledge who tend to have a better anticoagulation among HFrEF patients is limited despite of high incidence of thrombosis among this population. We therefore undertook the present analysis of HFrEF patients enrolled in the WARCEF trial 6 to investigate the association between HF severity and TTR.…”