The results of the GALILEO trial were presented by Dr. George Dangas at the American Heart Association 2019 meeting. The trial, which was stopped early, showed that in patients with a successful transcatheter aortic valve replacement (TAVR), a rivaroxaban-based strategy was associated with excessive ischemic and bleeding events.
Transcatheter aortic valve replacement has been increasing in popularity in patients with severe symptomatic aortic valve stenosis. Thromboembolic complications, which occur in both TAVR and surgical aortic valve replacement, have been observed both acutely and late after TAVR. Subclinical leaflet thrombosis has been associated with an increased risk of cerebrovascular events in some studies. In order to help reduce the risk of thromboembolic events, the current guidelines recommend the use of dual antiplatelet therapy (DAPT). However, this recommendation is not based on a solid body of evidence. Rivaroxaban, a factor Xa inhibitor, may be effective in reducing the risk of thromboembolic events in TAVR.
[perfectpullquote align=”full” bordertop=”false” cite=”” link=”” color=”” class=”” size=””]“It was interesting to say that in a study that had only 42% events, they were still able to have a statistically significant difference in all-cause mortality primarily driven by non-cardiac mortality.” – Dr. George Dangas, M.D., Ph.D.[/perfectpullquote]
GALILEO was an open-label randomized trial that compared a rivaroxaban-based strategy to an antiplatelet based strategy in patients with a successful TAVR. Patients were randomized in a 1:1 ratio to either rivaroxaban (10mg once daily) and aspirin (75-100mg once daily) or clopidogrel (75mg once daily) and aspirin (75-100mg once daily). In the rivaroxaban group, aspirin was stopped after 90 days and patients were continued on rivaroxaban. In the antiplatelet group, clopidogrel was dropped after 90 days and patients were continued on aspirin. Patients who had atrial fibrillation, an absolute indication for DAPT, a stroke within the last 3 months or bleeding diathesis were excluded. The primary efficacy endpoint for this study was a composite of death, stroke, myocardial infarction, systemic thromboembolism, symptomatic valve thrombosis, or deep venous thrombosis or pulmonary embolism. The primary safety outcome was Vascular Academic Research Consortium (VARC)-2 major, disabling, or life-threatening bleeding.
The trial was terminated early due to safety issues. At the time that the study was terminated, the primary efficacy endpoint occurred in 105 patients (9.8%) in the rivaroxaban group and 78 patients (7.2%) in the antiplatelet group (HR 1.35, 95% CI 1.01-1.81, p = 0.04). Additionally, the primary safety endpoint occurred in 46 patients (4.3%) in the rivaroxaban group and 31 patients (2.8%) in the antiplatelet group (HR 1.5, 95% CI 0.95-2.37, p = 0.08). Finally, all-cause mortality was higher in the rivaroxaban group (HR 1.69, 95% CI 1.13-2.53, p = 0.009). In an interview with Dr. C. Michael Gibson, Dr. Dangas discussed the results of the trial. He stated, “it was interesting to say that in a study that had only 42% events, they were still able to have a statistically significant difference in all-cause mortality primarily driven by non-cardiac mortality.” Dr. Dangas and his team assessed this difference in mortality in even more detail. The results of this analysis were published in the appendix of the paper. They found that the “vast majority of the deaths, maybe three quarters, did not have any preceding non-fatal ischemic or major bleeding event. Of those who had some, the majority were not within thirty days. We are talking about mortality that is not associated in an obvious way with any preceding event.” The mechanism that could potentially explain the disparity in mortality between the two groups is unclear.
It is important to note that this study does have its limitations. This was an open-label study and therefore, ascertainment bias cannot be excluded. Additionally, considering the fact that the study was terminated early, treatment effects and confidence intervals need to be interpreted with caution. Finally, the findings of this study do not apply to patients with an indication for anticoagulation.