Vitamin K antagonists (VKA) are recommended by guidelines for stroke prevention in patients with rheumatic heart disease (RHD) and atrial fibrillation (AF).1 Regular INR monitoring may be difficult in low- and low-middle income countries and it was hypothesised that the use of direct oral anticoagulants could fulfil a major unmet need.
In a Hot Line session yesterday, Professor Ganesan Karthikeyan (All India Institute of Medical Sciences [AIIMS] - New Delhi, India) presented data from the INVICTUS trial – the largest randomised trial in RHD – which compared rivaroxaban with VKA for the prevention of CV events in patients with RHD and AF.
The open-label, parallel-group, non-inferiority INVICTUS trial analysed 4,531 patients from 24 countries in Africa, Asia and South America. Patients with echocardiographically documented RHD and AF were eligible if they had an elevated risk of stroke (mitral stenosis with valve area ≤2.0 cm², left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2-VASc score ≥2). Patients were randomised 1:1 to receive adjusted-dose VKA or rivaroxaban 20 mg once daily. The primary efficacy outcome was a composite of all-cause stroke, systemic embolism, myocardial infarction or death from vascular or unknown causes. The primary safety outcome was International Society on Thrombosis and Haemostasis (ISTH) major bleeding.
At a median follow up of 3.1 years, primary efficacy outcome events occurred at a rate of 8.26% per year for rivaroxaban and 6.46% per year for VKA.
The restricted mean survival time (RMST) for the primary outcome was 1,576 days in the rivaroxaban group and 1,652 days in the VKA group (difference −75 days; 95% CI −117 to −34; p<0.001). The risk of death was also significantly lower with VKA, with an RMST for death of 1,587 days in the rivaroxaban arm and 1,660 days in the VKA arm (difference −73 days, 95% CI −114 to −32). In terms of safety, ISTH major bleeding was not significantly different between the rivaroxaban (0.67% per year) and VKA (0.83% per year) groups.
Prof. Karthikeyan comments: “INVICTUS is the first trial to assess anticoagulant therapy for stroke prevention in patients with RHD and atrial AF. The results indicate that adjusted-dose VKA should remain the standard of care for this patient population.”