Abstract
The Pulmonary Embolism Severity Index (PESI) has been validated in the setting of standard treatment of pulmonary embolism with initial low molecular weight heparin followed by vitamin K antagonists. We evaluated the proposed simplified PESI in a large, phase III randomized trial involving patients with symptomatic pulmonary embolism with or without deep vein thrombosis, who were treated with rivaroxaban or standard therapy.
The EINSTEIN PE study was an open-label, randomized, phase III study that compared oral rivaroxaban alone (15 mg twice daily for 3 weeks, followed by 20 mg once daily) with subcutaneous enoxaparin overlapping with and followed by a vitamin K antagonist (warfarin or acenocoumarol, target international normalized ratio 2.0–3.0) for 3, 6, or 12 months in patients with acute, symptomatic pulmonary embolism. At baseline, the simplified PESI score was assessed, with 1 point each assigned for age >80 years, history of cancer, chronic cardiopulmonary disease, heart beat ≥110 beats per minute, systolic blood pressure <100 mm Hg, and arterial oxyhemoglobin saturation <90%. Recurrent venous thromboembolism, fatal pulmonary embolism, all-cause mortality, and major bleeding at 7 days, 14 days, 30 days, 90 days, and at the end of the full intended treatment period were related to the simplified PESI score.
It was possible to calculate the simplified PESI score in 4831 of the 4832 included patients, of whom 2589 (53.6%) had a PESI score of 0; 1775 (36.7%) had a score of 1; and 467 (9.7%) had a score of 2 or 3. No patient had a simplified PESI score greater than 3. Incidences of outcomes in relation to time period, simplified PESI score and treatment are presented in the following table.
Incidences of outcomes in relation to time period, simplified PESI score, and treatment
| Outcome/time period . | Treatment . | Up to day 7 . | Up to day 14 . | Up to day 30 . | Up to day 90 . | Full period . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PESI score . | – . | 0 . | 1 . | ≥2 . | 0 . | 1 . | ≥2 . | 0 . | 1 . | ≥2 . | 0 . | 1 . | ≥2 . | 0 . | 1 . | ≥2 . |
| Recurrent VTE, % | Rivaroxaban | 0.4 | 0.2 | 1.6 | 0.6 | 0.7 | 1.6 | 0.8 | 1.0 | 1.6 | 1.4 | 1.4 | 2.5 | 1.9 | 1.8 | 3.7 |
| Standard | 0.3 | 0.4 | 1.3 | 0.5 | 0.7 | 2.2 | 0.7 | 1.1 | 3.6 | 1.1 | 1.4 | 4.5 | 1.4 | 1.8 | 4.9 | |
| Fatal PE, % | Rivaroxaban | 0 | 0 | 0.4 | 0 | 0.1 | 0.4 | 0 | 0.2 | 0.4 | 0.2 | 0.2 | 1.2 | 0.2 | 0.3 | 2.0 |
| Standard | <0.1 | 0.1 | 0.9 | 0.2 | 0.1 | 0.9 | 0.2 | 0.2 | 0.9 | 0.2 | 0.2 | 0.9 | 0.2 | 0.2 | 1.3 | |
| All-cause mortality, % | Rivaroxaban | 0 | 0.1 | 1.2 | 0 | 0.1 | 0.6 | 0 | 0.8 | 4.1 | 0.5 | 1.4 | 5.7 | 0.6 | 2.8 | 9.8 |
| Standard | <0.1 | 0.1 | 1.8 | 0.2 | 0.2 | 2.2 | 0.2 | 0.8 | 3.1 | 0.3 | 1.3 | 6.3 | 0.5 | 2.2 | 10.8 | |
| Major bleeding, % | Rivaroxaban | 0.3 | 0 | 0.8 | 0.5 | 0.1 | 0.8 | 0.5 | 0.3 | 0.8 | 0.7 | 0.7 | 1.2 | 0.9 | 1.1 | 2.1 |
| Standard | 0.2 | 0.6 | 1.4 | 0.5 | 0.9 | 1.8 | 0.7 | 1.1 | 3.2 | 0.8 | 1.8 | 3.6 | 1.2 | 2.8 | 5.4 | |
| Outcome/time period . | Treatment . | Up to day 7 . | Up to day 14 . | Up to day 30 . | Up to day 90 . | Full period . | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| PESI score . | – . | 0 . | 1 . | ≥2 . | 0 . | 1 . | ≥2 . | 0 . | 1 . | ≥2 . | 0 . | 1 . | ≥2 . | 0 . | 1 . | ≥2 . |
| Recurrent VTE, % | Rivaroxaban | 0.4 | 0.2 | 1.6 | 0.6 | 0.7 | 1.6 | 0.8 | 1.0 | 1.6 | 1.4 | 1.4 | 2.5 | 1.9 | 1.8 | 3.7 |
| Standard | 0.3 | 0.4 | 1.3 | 0.5 | 0.7 | 2.2 | 0.7 | 1.1 | 3.6 | 1.1 | 1.4 | 4.5 | 1.4 | 1.8 | 4.9 | |
| Fatal PE, % | Rivaroxaban | 0 | 0 | 0.4 | 0 | 0.1 | 0.4 | 0 | 0.2 | 0.4 | 0.2 | 0.2 | 1.2 | 0.2 | 0.3 | 2.0 |
| Standard | <0.1 | 0.1 | 0.9 | 0.2 | 0.1 | 0.9 | 0.2 | 0.2 | 0.9 | 0.2 | 0.2 | 0.9 | 0.2 | 0.2 | 1.3 | |
| All-cause mortality, % | Rivaroxaban | 0 | 0.1 | 1.2 | 0 | 0.1 | 0.6 | 0 | 0.8 | 4.1 | 0.5 | 1.4 | 5.7 | 0.6 | 2.8 | 9.8 |
| Standard | <0.1 | 0.1 | 1.8 | 0.2 | 0.2 | 2.2 | 0.2 | 0.8 | 3.1 | 0.3 | 1.3 | 6.3 | 0.5 | 2.2 | 10.8 | |
| Major bleeding, % | Rivaroxaban | 0.3 | 0 | 0.8 | 0.5 | 0.1 | 0.8 | 0.5 | 0.3 | 0.8 | 0.7 | 0.7 | 1.2 | 0.9 | 1.1 | 2.1 |
| Standard | 0.2 | 0.6 | 1.4 | 0.5 | 0.9 | 1.8 | 0.7 | 1.1 | 3.2 | 0.8 | 1.8 | 3.6 | 1.2 | 2.8 | 5.4 | |
PE, pulmonary embolism; VTE, venous thromboembolism.
Among patients with a simplified PESI score of 0 or 1, major clinical outcome events were rare during the first 30 days of treatment and were similar in patients treated with rivaroxaban or standard therapy. Patients with a simplified PESI score of 2 or more in both treatment groups had more frequent adverse outcomes both initially and in the long term.
Fermann:Novartis: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Radiometer: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Cubist: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Cardiorentis: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Prins:Bayer HealthCare: Consultancy; Sanofi-aventis: Consultancy; Boehringer Ingelheim: Consultancy; GlaxoSmithKline: Consultancy; Daiichi Sankyo: Consultancy; Leo Pharma: Consultancy; Thrombogenics: Consultancy; Pfizer: Consultancy. Wells:BMS/Pfizer: Research Funding; Pfizer: Honoraria; Bayer Schering Pharma: Honoraria; Boehringer Ingelheim: Honoraria; Bayer HealthCare Pharmaceuticals: Honoraria; Biomerieux: Honoraria. Pap:Bayer Pharma AG: Employment. Lensing:Bayer Pharma AG: Employment.
Author notes
Asterisk with author names denotes non-ASH members.
