Effect of warfarin on survival in patients with concomitant left ventricular systolic dysfunction and pulmonary hypertension: a population cohort study

BACKGROUND: The use of oral anticoagulation in patients with heart failure in sinus rhythm remains controversial as previous large randomized controlled trials (RCTs) have not shown a survival benefit. However, heterogeneity exists among heart failure patients and it is possible that high-risk subgroups may benefit from anticoagulation (warfarin). We hypothesize that one such subgroup are patients with heart failure and pulmonary hypertension (PH), conditions associated with coagulation abnormalities.

METHODS: We conducted a retrospective, population-based, longitudinal cohort study in patients with left ventricular systolic dysfunction (LVSD) and PH [defined as a right ventricular systolic pressure (RVSP) >35 mmHg] identified from echocardiograms performed between January 1994 to May 2011. This data was linked using a unique patient-specific identifier to community-dispensed prescriptions, hospital admissions, and mortality data. For comparison, we included patients with LVSD and no PH.

RESULTS: A total of 2619 subjects with LVSD and a measurable RVSP were identified (mean ± SD age of 73 ± 12 years); 1606 out of 2619 had PH and 1013 out of 2619 had no PH. The overall mean follow-up period was 2.56 ± 3.0 years. In patients with LVSD and PH, the use of warfarin was associated with an improved survival [hazard ratio (HR) = 0.72 95% confidence interval (CI) 0.58-0.90, P = 0.0003], fewer non-cardiovascular disease-related deaths (HR = 0.65, 95%CI 0.49-0.87, P = 0.0033 and showed a trend towards reduced cardiovascular disease-associated mortality (HR = 0.72, 95%CI 0.51-1.02). Warfarin did not improve survival in those with LVSD with no PH.

CONCLUSIONS: In patients with both LVSD and PH, the use of warfarin is associated with a 28% reduction in mortality. Further prospective trials are required to confirm our findings.