The largest trial in patients with rheumatic heart disease (RHD) has found that in those patients with atrial fibrillation (AF), vitamin K antagonists (VKA) reduced cardiovascular events and mortality, without increasing major bleeding, compared to rivaroxaban.

INVICTUS was simultaneously published today in the NEJM (currently as full text) and presented at ESC Congress 2022 by the study’s national leader for India, Ganesan Karthikeyan. (Download Karthikeyan’s slides.)

Led by PHRI Senior Scientist Stuart Connolly, INVICTUS tested rivaroxaban against VKA, randomizing 4565 patients in 24 low- to middle-income countries (LMICs) including India, Mexico and countries in Africa, South America and Asia.

The results supported current guidelines: adjusted dose VKA as the standard of care for patients with RHD and AF.

RHD is a major public health problem in LMICs, where it remains an important cause of AF. As Karthikeyan noted:

“INVICTUS is a blueprint for future trials of understudied diseases in underrepresented populations to generate clinically relevant results.”

‘Unexpected results’

“This effect appears to be independent of AF-related stroke prevention, and suggests a direct effect on the disease process of RHD,” says Connolly. “The patients in our trial were much younger (average age of 51) and more likely to be female (72%) than in recent trials including only non-RHD patients. And there was a lower burden of hypertension (23%) than in previous trials.”

“Nevertheless, our study’s results were unexpected,” said Connolly.

The study was dedicated by the study team to the late Bongani Mayosi, of the University of Cape Town; as the initial principal investigator of INVICTUS, Mayosi played a pivotal role in the design and initiation of the study.

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