Extended-duration DOAC reduces fatal and major thromboembolic events in medically ill patients
Treatment with 10 mg rivaroxaban reduces fatal and major thromboembolic events without significantly increasing major bleeding in medically ill patients after discharge, compared to placebo.
Post-Discharge Prophylaxis With Rivaroxaban Reduces Fatal and Major Thromboembolic Events in Medically Ill PatientsLiterature - Spyropoulos AC, Ageno W, Albers GW et al., - J Am Coll Cardiol. 2020. doi: 10.1016/j.jacc.2020.04.071.
Introduction and methods
Many acute medically ill patients are at risk for venous thromboembolism (VTE) [1]. Hospitalization is an important risk factor for developing VTE and this risk continues after discharge [2,3]. The MARINER trial (a study of rivaroxaban on the venous thromboembolic risk in post-hospital discharge patients) previously randomized medically ill patients with additional risk factors for VTE to rivaroxaban (10 mg once daily in patients with creatinine clearance [CrCl] ≥50 ml/min or 7.5 mg daily for those with CrCl 30 to <50 ml/min at baseline) or placebo for 45 days after discharge [4]. The trial did not demonstrate a reduction in the primary endpoint of symptomatic VTE and VTE-related death. However, secondary efficacy endpoints showed a 56% reduction in symptomatic VTE and a 27% reduction in symptomatic VTE and all-cause mortality. Furthermore, the rivaroxaban dose of 7.5 mg was found to be ineffective. The current exploratory analysis evaluated whether rivaroxaban could reduce the incidence of symptomatic VTE, MI, nonhemorrhagic stroke and CV death in the stratum of patients treated with 10 mg rivaroxaban, compared to placebo.
MARINER was a prospective, multicenter, randomized, double-blind, placebo-controlled trial and included patients who were ≥40 years, were hospitalized for at least 3 and no more than 10 days prior to randomization for an acute medical illness, and had other risk factors for VTE (demonstrated by a total modified IMPROVE VTE risk score of ≥4 or VTE risk score of 2 or 3 with D-dimer >2× the upper limit of normal). During index hospitalization, patients received thromboprophylaxis with low-molecular-weight heparin or unfractionated heparin. Patients with increased bleeding risk were excluded. The population studied in the current analysis consisted of 4,909 patients who received rivaroxaban 10 mg and 4,913 patients who received placebo for 45 days post-discharge. The mean age was 67.8 years, 55.5% were men and 96.5% were white.
The efficacy outcome of the current exploratory analysis is the pre-specified composite of symptomatic VTE, MI, nonhemorrhagic stroke and CV death. The principal safety outcome was major bleeding.
Main results
- The pre-specified composite efficacy endpoint of symptomatic VTE (DVT and nonfatal PE), MI, nonhemorrhagic stroke, and CV death occurred in 1.28% of patients in the rivaroxaban group and in 1.77% of patients in the placebo group (HR 0.72, 95%CI 0.52-1.00, P=0.049).
- A tendency towards greater risk reductions with rivaroxaban compared to placebo was seen for symptomatic lower extremity DVT (HR 0.20, 95%CI 0.04-0.91) and symptomatic nonfatal PE (HR 0.36, 95%CI 0.12-1.14)
- Major bleeding occurred in 0.27% of patients in the rivaroxaban group and 0.18% of patients in the placebo group (HR 1.44, 95%CI 0.62-3.37, P=0.398).
- When looking at the type of major bleeding, 0.22% of patients in the rivaroxaban group and 0.12% of patients in the placebo group had major bleeding events with a fall in hemoglobin of ≥2 g/dl. 0.16% Of patients in the rivaroxaban group and 0.06% of patients in the placebo group received transfusion of >2U of packed red blood cells (or whole blood). There were 2 fatal bleeding events in the rivaroxaban group and 2 critical site bleeds in each group.
Conclusion
This exploratory analysis suggests that use of 10 mg rivaroxaban post-discharge leads to a risk reduction of the composite outcome of symptomatic VTE, MI, nonhemorrhagic stroke and CV death, without a significant increase in major bleeding, compared to placebo in medically ill patients with risk factors for VTE.
References
1. Piazza G, Fanikos J, Zayaruzny M, Goldhaber SZ. Venous thromboembolic events in hospitalized medical patients. Thromb Haemost 2009;102:505–10.
2. Office of the Surgeon General, National Heart, Lung, and Blood Institute. Publications and reports of the Surgeon General. In: The Surgeon General’s Call to Action to Prevent Deep Vein Thrombosis and Pulmonary Embolism. Rockville, MD: Office of the Surgeon General, 2008.
3. Amin AN, Varker H, Princic N, Lin J, Thompson S, Johnston S. Duration of venous thromboembolism risk across a continuum in medically ill hospitalized patients. J Hosp Med 2012;7:231–8.
4. Spyropoulos AC, Ageno W, Albers GW, et al. Rivaroxaban for thromboprophylaxis after hospitalization for medical illness. N Engl J Med 2018;379:1118–27.