Rheumatic heart disease-associated AF: standard-of-care holds ground

Among patients with rheumatic heart disease–associated atrial fibrillation (AF), vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding.

The current standard of care for rheumatic heart disease-associated AF is vitamin K antagonist therapy; however, it can be difficult to administer because of many dietary and pharmacologic interactions, and requires regular blood sampling to monitor anticoagulation status. Prof. Ganesan Karthikeyan (All India Institute of Medical Sciences, India) presented the findings of the phase 3 INVICTUS trial (NCT02832544), which compared cardiovascular outcomes in patients with rheumatic heart disease and documented AF or atrial flutter at any time. In addition, at least 1 of the following criteria was also required: a CHA2DS2VASc score of at least 2, mitral stenosis with a mitral-valve area of no more than 2 cm², or echocardiographic evidence of either left atrial spontaneous echo contrast or left atrial thrombus. Key exclusion criteria were the presence of a mechanical heart valve or the likelihood of receiving one within the next 6 months, the use of dual antiplatelet therapy, treatment with dual strong inhibitors of CYP3A4 and P-glycoprotein, and renal insufficiency with an estimated glomerular filtration rate, <15 mL per minute. Participants were randomised to either receive treatment with factor Xa inhibitor rivaroxaban or with a standard vitamin K antagonist as an open-label design. The primary efficacy endpoint was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or non-cardiac) or unknown causes. The primary safety endpoint was major bleeding according to the ISTH.

Of the 4,531 patients included in the final analysis, with average follow-up of 3.1 years (mean age 50.5 years, 72.3% women), the primary endpoint analysis favoured treatment with vitamin K antagonist over rivaroxaban (HR 1.25; 95% CI 1.10–1.41; P<0.001), and as such, the proportional hazards assumption was not met. More patients in the rivaroxaban group than in the vitamin K antagonist group had a stroke (90 vs 65 patients, respectively), which was almost entirely attributable to a higher rate of ischaemic stroke in the rivaroxaban group (74 vs 48, respectively). Furthermore, a higher incidence of death was reported in the rivaroxaban arm than in the vitamin K antagonist arm (difference -72 days; 95% CI -117 to -28). The rate of major bleeding was similar in both arms. The mechanism for differences in mortality in the context of similar bleeding remains an open question.

1. Karthikeyan G, et al. INVICTUS - Rivaroxaban versus VKA for rheumatic atrial fibrillation. Hot Line Session 5, ESC Congress 2022, Barcelona, Spain, 26–29 August.
2. Connolly SJ, et al. N Engl J Med 2022;387:978-988.

 

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Posted on 27 October, 202224 January, 2023