Assessing Full Benefit of Rivaroxaban Prophylaxis in High-Risk Ambulatory Patients with Cancer: Thromboembolic Events in the Randomized CASSINI Trial.

Ajay K Kakkar,Gerald A Soff,Alok A Khorana,Hanno Riess,Peter Wildgoose,Simrati Kaul,Michael B Streiff,Mairéad G Mcnamara,Ujjwala Vijapurkar

doi:10.1055/s-0040-1712143

Abstract

Introduction In the CASSINI study, rivaroxaban thromboprophylaxis significantly reduced primary venous thromboembolism (VTE) endpoints during the intervention period, but several thromboembolic events designated as secondary efficacy endpoints were not included in the primary analysis. This study was aimed to evaluate the full impact of rivaroxaban thromboprophylaxis on all prespecified thromboembolic endpoints occurring on study. Methods CASSINI was a double-blind, randomized, placebo-controlled study in adult ambulatory patients with cancer at risk for VTE (Khorana score ≥2). Patients were screened at baseline for deep-vein thrombosis (DVT) and randomized if none was found. The primary efficacy endpoint was a composite of lower extremity proximal DVT, symptomatic upper extremity, or lower extremity distal DVT, any pulmonary embolism, and VTE-related death. This analysis evaluated all prespecified thromboembolic endpoints occurring on study to determine the full benefit of rivaroxaban prophylaxis. All endpoints were independently adjudicated. Results Total thromboembolic events occurred in fewer patients randomized to rivaroxaban during the full study period (29/420 [6.9%] and 49/421 [11.6%] patients in rivaroxaban and placebo groups, respectively [hazard ratio (HR) = 0.57; 95% confidence interval (CI): 0.36–0.90; p = 0.01]; number needed to treat [NNT] = 21). Similarly, fewer patients randomized to rivaroxaban experienced thromboembolism during the intervention period (13/420 [3.1%] patients) versus placebo (38/421 [9.0%] patients; HR = 0.33; 95% CI: 0.18–0.62; p < 0.001; NNT = 17). Conclusion Our findings confirm the substantial benefit of rivaroxaban thromboprophylaxis when considering all prespecified thromboembolic events, even after excluding baseline screen-detected DVT. The low NNT, coupled with prior data demonstrating a high number needed to harm, should assist clinicians in determining the risk/benefit of thromboprophylaxis in high-risk patients with cancer.

Highlights

In the CASSINI study, rivaroxaban thromboprophylaxis significantly reduced primary venous thromboembolism (VTE) endpoints during the intervention period, but several thromboembolic events designated as secondary efficacy endpoints were not included in the primary analysis
Total thromboembolic events occurred in fewer patients randomized to rivaroxaban during the full study period (29/420 [6.9%] and 49/421 [11.6%] patients in rivaroxaban and placebo groups, respectively [hazard ratio (HR) 1⁄4 0.57; 95% confidence interval (CI): 0.36–0.90; p 1⁄4 0.01]; number needed to treat [NNT] 1⁄4 21)
E108 Full Benefit of Rivaroxaban Prophylaxis Khorana et al Conclusion Our findings confirm the substantial benefit of rivaroxaban thromboprophylaxis when considering all prespecified thromboembolic events, even after excluding baseline screen-detected deep-vein thrombosis (DVT)

Summary

Introduction

In the CASSINI study, rivaroxaban thromboprophylaxis significantly reduced primary venous thromboembolism (VTE) endpoints during the intervention period, but several thromboembolic events designated as secondary efficacy endpoints were not included in the primary analysis. The primary efficacy endpoint was a composite of lower extremity proximal DVT, symptomatic upper extremity, or lower extremity distal DVT, any pulmonary embolism, and VTE-related death This analysis evaluated all prespecified thromboembolic endpoints occurring on study to determine the full benefit of rivaroxaban prophylaxis. We have previously reported the primary analysis results of one such randomized trial of outpatient thromboprophylaxis with daily rivaroxaban in ambulatory patients with cancer at higher risk for venous thromboembolism (VTE), based on a Khorana score of 2 or higher.[5] In this analysis of 841 randomized patients, the primary endpoint was a composite of any objectively confirmed symptomatic or asymptomatic lower extremity proximal deep-vein thrombosis (DVT), symptomatic upper extremity DVT, symptomatic lower extremity distal DVT, any pulmonary embolism (PE), or VTE-related death. The totality of benefit of rivaroxaban thromboprophylaxis can be clarified by evaluating its impact on all of these thromboembolic events, in addition to the primary endpoint events

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