Benefits of Anticoagulant Use in PAH Largely Unknown and in Need of Study, Researchers Say

Anticoagulant use in pulmonary arterial hypertension (PAH) is surrounded by scientific disagreement. A perspective attempted to analyze the differences between the two largest studies investigating the issue, but concluded that differences in study populations made comparisons meaningless. Randomized clinical or registry studies are needed to determine whether anticoagulant medication offers benefits, or risks, to PAH patients.

Despite the frequent use of anticoagulation drugs by PAH patients, surprisingly few studies have explored their potential benefit. Along with two large registry studies — the U.S.-based REVEAL and the European COMPERA — only nine cohort studies have compared patient survival rates with and without such treatment.

Two reviews and analyses of previously published data showed the treatment to be associated with a 31 percent reduction in mortality, but noted that these studies likely suffered from what is known as publication bias — a tendency to only report on positive findings.

And the two registry studies came to different conclusions. In the REVEAL registry, patients with idiopathic PAH treated with anticoagulant drugs had no survival benefit over those who went without treatment. Furthermore, treated patients with PAH secondary to systemic sclerosis had a tendency toward increased mortality.

The COMPERA trial, studying a mostly German population, also reported no benefit and possibly even decreased survival in patients with systemic sclerosis-associated PAH. Idiopathic PAH patients, however, showed an increased three-year survival of up to 12 percent.

The perspective, “Where do we go from here? Reappraising the data on anticoagulation in pulmonary arterial hypertension,“ written by two University of Utah researchers, scrutinized these studies, trying to explain the different results.

Their analysis, published in the Journal of Thoracic Disease, showed that patients in the COMPERA study were on average 20 years older than in the REVEAL study. They were also sicker and the study had a larger proportion of males. The authors argued that this difference in characteristics might reflect a patient group with unidentified heart problems or other issues that explain the outcomes reported.

Other differences also distinguished the trials. In the REVEAL study, a larger proportion of patients received other treatments that might increase the risk of bleeding, and the researchers hypothesized that an increased bleeding risk might counter any potential benefits of anticoagulation.

Also, the time of treatment with the anticoagulant medication warfarin differed between the studies, suggesting that the shorter treatment duration in the REVEAL trial was not enough to provide a benefit.

As a result of these differences, a direct comparison between the two studies cannot provide any meaningful interpretations. The authors suggest that trials designed to address this issue are needed to offer guidance on treatment practices for patients and clinicians alike.