Although the differences between groups were not statistically significant, combined findings have shown a risk reduced by close to half.
Scott E. Kasner, MD, MSCE, the Ruth M. and Tristram C. Colket, Jr. Presidents Distinguished Professor and chief of the Division of Vascular Neurology at the University of Pennsylvania
Scott E. Kasner, MD, MSCE
Patients with embolic stroke of undetermined source (ESUS) with patent foramen ovale (PFO) can have their risk of recurrent stroke reduced by roughly half with anticoagulation, though there are remaining imprecision issues.
New study data from the NAVIGATE ESUS trial comparing antiplatelet therapy with anticoagulation—specifically aspirin compared to rivaroxaban—combined with previous literature from the PICSS and CLOSE studies has shown that using anticoagulation yielded a summary odds ratio of 0.48 (95% CI, 0.24 to 0.96; P = .04) for ischemic stroke, with no evidence of heterogeneity.
NAVIGATE ESUS was a double-blind, randomized, phase III trial that included 459 sites in 31 countries, with a total of more than 7000 patients. PFO was present in 7.4% (n = 534) of patients on the basis of either transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE).
“The role of anticoagulants vs. antiplatelet agents in patients with PFO and stroke has been an open question for a long time,” lead author Scott E. Kasner, MD, MSCE, told NeurologyLive. “We know from clinical trials that PFO closure is better than antiplatelet therapy, but the risks and benefits of anticoagulation compared with antiplatelet therapy are not well established.”
Kasner, a professor and chief of the Division of Vascular Neurology at the University of Pennsylvania, explained that he and his colleagues observed numerically fewer strokes among patients treated with rivaroxaban (n = 259) compared to aspirin (n = 275). Specifically, they report a recurrent ischemic stroke rate of 2.6 events per 100 person-years on rivaroxaban compared to 4.8 events per 100 person-years for those treated with aspirin. Although, Kasner added, this fell short, statistically, from drawing any definite conclusions.
“However, when combined with prior studies, we found that anticoagulation appeared to reduce the risk of stroke by about half compared to antiplatelet therapy—mainly aspirin,” he said. A meta-analysis indicated that anticoagulation was superior to antiplatelet therapy (HR, 0.48; 95%CI: 0.24 to 0.96, P = .04).
Ultimately, the hazard ratio (HR) for recurrent ischemic stroke for patients with known PFO in NAVIGATE was 0.54 (95% CI, 0.22 to 1.36). The risk was similar for those without known PFO (HR, 1.06; 95% CI, 0.84 to 1.33; P­­interaction = .18). The risk for major bleeding for patients on rivaroxaban compared to aspirin for those with known PFO (HR, 2.05; 95% CI, 0.51 to 8.18) and without known PFO (HR, 2.82; 95% CI, 1.69 to 4.70; P­­interaction = .068).
“At this point, these results should not change practice,” Kasner said. “However, there are many patients in practice with PFO and stroke who either cannot get closure because of access, availability, and/or insurance, especially those over age 60 years who were not included in the closure trials; or do not want closure because of fear of invasive procedures and devices. If a future study comes along to further compare anticoagulation with antiplatelet therapy, then these patients may be interested in participating.”
Kasner and his colleagues noted that trials dedicated to comparing anticoagulation to antiplatelet therapy or PFO closure, or both, are warranted given these findings. Kasner added that, depending on the stance one has regarding the use of antiplatelet therapy compared to anticoagulation in these scenarios, the results may come as a surprise.
“Some will say, ‘strokes related to PFO are due to paradoxical embolism from the veins, so I knew that anticoagulation would be better,’ and others will say, ‘that seems very surprising, and I generally gave all these patients aspirin because I thought that was good enough,’” he said. “I have to admit that I was surprised.”
Kasner SE, Swaminathan B, Lavados P, et al. Rivaroxaban or aspirin for patent foramen ovale and embolic stroke of undetermined source: a prespecified subgroup analysis from the NAVIGATE ESUS trial. Lancet Neurol. Epub September 28, 2018. doi: 10.1016/S1474-4422(18)30319-3.