Barcelona, Spain – 28 Aug 2022: The largest trial in patients with rheumatic heart disease has found that in those with atrial fibrillation, vitamin K antagonists reduce cardiovascular events and mortality, without increasing major bleeding, compared to rivaroxaban. The late breaking research is presented in a Hot Line session today at ESC Congress 2022.1
Rheumatic heart disease is a chronic condition resulting from heart valve damage caused by rheumatic fever, an autoimmune inflammatory reaction to infection with streptococcal bacteria. It is estimated that more than 40 million people worldwide have rheumatic heart disease.2 One in five patients with symptomatic valve disease have atrial fibrillation3 and a concomitant risk of stroke and systemic embolism ranging from 0.4% to 4.2% per year.4,5
Professor Ganesan Karthikeyan of the All India Institute of Medical Sciences (AIIMS), New Delhi, India said: “Guidelines recommend vitamin K antagonists (VKA) for stroke prevention in patients with rheumatic heart disease and atrial fibrillation6 but until now there were no randomised controlled trials. Rheumatic heart disease largely occurs in low- and low-middle income countries7 where maintenance of the international normalised ratio, required for the effective use of VKA, is poor.8 Direct oral anticoagulants (DOACs) do not require monitoring and we reasoned that, if safe and effective, they would fulfil a major unmet need in these patients.”
INVICTUS was a randomised, open-label, non-inferiority trial comparing the DOAC rivaroxaban to VKA in patients with echocardiographically documented rheumatic heart disease, atrial fibrillation and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo contrast or thrombus, or CHA2DS2VASc score ≥2).9,10 The trial randomly allocated 4,565 patients from 138 sites in 24 countries in Africa, Asia and South America to rivaroxaban 20 mg once daily or adjusted dose VKA.
The primary efficacy outcome was a composite of 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.
A total of 4,531 patients were included in the final analysis. At a median follow up of 3.1 years, 559 out of 2,275 patients receiving rivaroxaban (8.26% per year) had a primary efficacy outcome event compared to 442 out of 2,258 patients receiving VKA (6.46% per year). 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 (RMST difference -75 days; 95% confidence interval [CI] -117 to -34; p<0.001).
The risk of death was also significantly lower among patients on VKA. The RMST for death was 1,587 days in the rivaroxaban arm and 1,660 days in the VKA arm (RMST difference -73 days, 95% CI -114 to -32).
There was no significant difference between the groups for the primary safety outcome, major bleeding, which occurred in 40 out of 2,266 patients (0.67% per year) in the rivaroxaban group and 56 out of 2,253 patients (0.83% per year) in the VKA group.
Professor Karthikeyan said: “INVICTUS is the first trial to assess anticoagulant therapy for stroke prevention in patients with rheumatic heart disease and atrial fibrillation. The results indicate that adjusted dose vitamin K antagonists should remain the standard of care for this patient population.”