‘No’ to routine use of rivaroxaban in outpatients with COVID-19

In non-hospitalised patients with symptomatic COVID-19 and an increased risk for thrombosis, rivaroxaban did not outperform placebo in reducing the risk for a composite outcome of venous and arterial thrombotic events, hospitalisation, and death in the PREVENT-HD trial.

“Outpatients with COVID-19 may have an increased risk for venous and arterial thrombotic events, especially if they carry one or more risk factors,” explained Dr Gregory Piazza (Brigham and Women’s Hospital, MA, USA). “Moreover, evidence suggests that lung deterioration leading to hospitalisation may be partially explained by in situ pulmonary artery thrombosis [1,2].” Dr Piazza and colleagues designed the PREVENT-HD trial (NCT04508023) to assess whether early initiation of thromboprophylactic dosing of rivaroxaban in outpatients with COVID-19 results in improved health outcomes [3].

The study randomised 1,284 participants with symptomatic COVID-19 and at least 1 risk factor 1:1 to rivaroxaban (10 mg, once daily) plus standard-of-care or placebo plus standard-of-care. The primary efficacy outcome was the time-to-first-occurrence of a composite endpoint of symptomatic venous thromboembolism (VTE), ischaemic stroke, acute limb ischaemia, non-central nervous system systemic embolisation, all-cause hospitalisation, and all-cause death up to day 35. Dr Piazza mentioned that enrolment ended early because the blinded pooled event rates were lower than expected, the COVID-related death and hospitalisation rates were falling nationwide, and there was a very low likelihood to reach the number of events that was required.

There was no significant difference between the intervention arm and the control arm in the rate of the primary efficacy endpoint (3.4% vs 3.0%; HR 1.16; P=0.626; see Figure). Dr Piazza noted that a post-hoc exploratory analysis did suggest a significant difference in the rate of symptomatic VTE and arterial thrombotic events in favour of the rivaroxaban arm (P=0.025). Non-major clinically relevant bleeding (1.5% vs 0.2%; P=0.01) and trivial bleeding (2.8% vs 0.8%; P=0.01) were more common in the rivaroxaban than in the placebo arm, while no differences were observed in International Society on Thrombosis and Haemostasis (ISTH) major bleeding (0.2% vs 0%) or fatal and critical site bleeding (0% in both arms).

Figure: Percentage of participants with respective outcome events at day 35 [1]



VTE, venous thromboembolism.

“Data from the PREVENT-HD trial do not support routine antithrombotic prophylaxis in non-hospitalised patients with symptomatic COVID-19,” concluded Dr Piazza. Prof. Renato Lopes (Duke University Medical Center, NC, USA) added that the results of the randomised controlled trials investigating the use of anticoagulants in COVID-19 are in contrast to the observational data that has been gathered on this topic, illustrating the critical importance of randomised controlled trials as a foundation for medical guidance in clinical practice.

 

1. 
   
   1. Ackermann M, et al. N Engl J Med 2020;383:120–128.
   2. Piazza G & Morrow DA. JAMA. 2020;324(24):2548–2549.
   3. Piazza G, et al. Rivaroxaban to reduce the risk of major venous and arterial thrombotic events, hospitalization, and death in medically ill outpatients with COVID-19: Primary results of the PREVENT-HD randomized clinical trial. LBS.07, AHA Scientific Sessions 2022, 05–07 November Chicago, USA.

 

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Posted on 11 January 2023