In the Journals

Rivaroxaban appears safe, effective in routine clinical practice

Oral rivaroxaban appeared safe and effective compared with standard anticoagulation therapy for the treatment of symptomatic deep vein thrombosis, according to the results of an international prospective study.

Major bleeding and recurrent venous thromboembolism rates remained low in patients treated with rivaroxaban (Xarelto, Janssen Pharmaceuticals) and appeared consistent with previous findings, the researchers reported.

Phase 3 trial data demonstrated the safety and efficacy of rivaroxaban for the treatment and prevention of DVT and pulmonary embolism. However, limited data exist on the use of rivaroxaban in routine clinical practice, according to study background.

Walter Ageno, MD, professor in the department of clinical and experimental medicine at University of Insubria in Varese, Italy, and colleagues conducted a multicenter, international, prospective nonintervention study of patients with symptomatic DVT to compare oral rivaroxaban with standard anticoagulation therapy.

Standard anticoagulation therapy consisted of initial treatment with unfractionated heparin, low–molecular-weight heparin or fondaparinux (Arixtra, Mylan Ireland Ltd.), usually overlapping with and followed by a vitamin K antagonist.

Patients were assigned to treatment with rivaroxaban or standard therapy for at least 3 months for DVT. Following approval of rivaroxaban for PE, patients with DVT and concomitant PE became eligible; however, the researchers excluded patients with isolated PE.

Type, dose and treatment duration remained at the physician discretion.

Key safety and efficacy outcomes included major bleeding, recurrent VTE and all-cause mortality. The researchers conducted propensity score-adjusted analyses to account for potential imbalances between treatment groups.

The safety population included 4,768 patients (rivaroxaban, n = 2,619; standard therapy, n = 2,149). According to the researchers, patients in the rivaroxaban group tended to be younger (median age, 59 years vs. 66 years; P < .0001). They also were less likely to have active cancer or concomitant PE.

In the propensity score-adjusted analysis, 19 patients (0.8%) in the rivaroxaban group experienced major bleeding, compared with 43 patients (2.1%) on standard anticoagulation therapy (adjusted HR = 0.77; 95% CI, 0.4-1.5).

Researchers reported reduced frequency of recurrent VTE (1.4% vs. 2.3%; adjusted HR = 0.91; 95% CI, 0.54-1.54) and all-cause mortality (0.4% vs. 3.4%; adjusted HR = 0.51; 95% CI, 0.24-1.07) in the rivaroxaban group.

The researchers observed similar incidence of treatment-emergent adverse events between the two groups (rivaroxaban, n = 944 [36%]; standard therapy, n = 805 [37.5%]).

However, the researchers observed fewer major bleeding events in the safety population among patients assigned rivaroxaban (rates of any major bleeding, 0.7% [n = 19] vs. 2.3% [n = 48]).

No patients in the rivaroxaban group experienced a fatal bleeding event, whereas two occurred in the standard therapy group.

Further, rivaroxaban appeared to confer lower rates of recurrent VTE (1.4% vs. 2.6%) and all-cause mortality (0.5% vs. 4.1%).

Ageno and colleagues reported a lower rate of hospitalization (29% vs. 46%) and shorter mean duration of hospital stay (5 days vs. 7.7 days; P < .001) in the rivaroxaban group.

The researchers acknowledged the potential for selection bias in treatment allocation; however, they said their use of propensity score-adjusted analyses minimized potential confounding.

“Rivaroxaban, as a single-drug therapy, showed low rates of major bleeding and recurrent VTE in a broad range of patients,” Ageno and colleagues wrote. “Moreover, because it was associated with shorter hospital stays compared with standard anticoagulation therapy, rivaroxaban could also offer economic benefits and simplify patient management.”

In an accompanying editorial, Gregory Y.H. Lip, MD, FRCP, professor of cardiovascular medicine and director of the hemostasis, thrombosis and vascular biology unit at University of Birmingham Institute of Cardiovascular Science, identified other potential limitations of these findings.

“Inappropriate use of low-dose regimens might lead to under-dosing, and uptake of direct oral anticoagulants remain suboptimum in some health care systems, with the insistence of a trial of vitamin K antagonist treatment being done before a direct oral anticoagulant can be considered,” Lip wrote. “Notwithstanding these continued issues, the direct oral anticoagulants have clearly changed the landscape of thromboprophylaxis in VTE and stroke prevention in atrial fibrillation. … However, it is important to use the direct oral anticoagulants correctly — according to the prescribing label and guidelines — for the appropriate patient to ensure the best possible outcomes in real-world clinical practice.” – by Cameron Kelsall

Disclosure: Bayer HealthCare Pharmaceuticals and Janssen Research & Development LLC funded this study. Ageno reports research funding or honoraria from, or advisory board positions with Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures. Lip reports consultant and speaker roles with Bayer and several other pharmaceutical companies.

Oral rivaroxaban appeared safe and effective compared with standard anticoagulation therapy for the treatment of symptomatic deep vein thrombosis, according to the results of an international prospective study.

Major bleeding and recurrent venous thromboembolism rates remained low in patients treated with rivaroxaban (Xarelto, Janssen Pharmaceuticals) and appeared consistent with previous findings, the researchers reported.

Phase 3 trial data demonstrated the safety and efficacy of rivaroxaban for the treatment and prevention of DVT and pulmonary embolism. However, limited data exist on the use of rivaroxaban in routine clinical practice, according to study background.

Walter Ageno, MD, professor in the department of clinical and experimental medicine at University of Insubria in Varese, Italy, and colleagues conducted a multicenter, international, prospective nonintervention study of patients with symptomatic DVT to compare oral rivaroxaban with standard anticoagulation therapy.

Standard anticoagulation therapy consisted of initial treatment with unfractionated heparin, low–molecular-weight heparin or fondaparinux (Arixtra, Mylan Ireland Ltd.), usually overlapping with and followed by a vitamin K antagonist.

Patients were assigned to treatment with rivaroxaban or standard therapy for at least 3 months for DVT. Following approval of rivaroxaban for PE, patients with DVT and concomitant PE became eligible; however, the researchers excluded patients with isolated PE.

Type, dose and treatment duration remained at the physician discretion.

Key safety and efficacy outcomes included major bleeding, recurrent VTE and all-cause mortality. The researchers conducted propensity score-adjusted analyses to account for potential imbalances between treatment groups.

The safety population included 4,768 patients (rivaroxaban, n = 2,619; standard therapy, n = 2,149). According to the researchers, patients in the rivaroxaban group tended to be younger (median age, 59 years vs. 66 years; P < .0001). They also were less likely to have active cancer or concomitant PE.

In the propensity score-adjusted analysis, 19 patients (0.8%) in the rivaroxaban group experienced major bleeding, compared with 43 patients (2.1%) on standard anticoagulation therapy (adjusted HR = 0.77; 95% CI, 0.4-1.5).

Researchers reported reduced frequency of recurrent VTE (1.4% vs. 2.3%; adjusted HR = 0.91; 95% CI, 0.54-1.54) and all-cause mortality (0.4% vs. 3.4%; adjusted HR = 0.51; 95% CI, 0.24-1.07) in the rivaroxaban group.

The researchers observed similar incidence of treatment-emergent adverse events between the two groups (rivaroxaban, n = 944 [36%]; standard therapy, n = 805 [37.5%]).

However, the researchers observed fewer major bleeding events in the safety population among patients assigned rivaroxaban (rates of any major bleeding, 0.7% [n = 19] vs. 2.3% [n = 48]).

No patients in the rivaroxaban group experienced a fatal bleeding event, whereas two occurred in the standard therapy group.

Further, rivaroxaban appeared to confer lower rates of recurrent VTE (1.4% vs. 2.6%) and all-cause mortality (0.5% vs. 4.1%).

Ageno and colleagues reported a lower rate of hospitalization (29% vs. 46%) and shorter mean duration of hospital stay (5 days vs. 7.7 days; P < .001) in the rivaroxaban group.

The researchers acknowledged the potential for selection bias in treatment allocation; however, they said their use of propensity score-adjusted analyses minimized potential confounding.

“Rivaroxaban, as a single-drug therapy, showed low rates of major bleeding and recurrent VTE in a broad range of patients,” Ageno and colleagues wrote. “Moreover, because it was associated with shorter hospital stays compared with standard anticoagulation therapy, rivaroxaban could also offer economic benefits and simplify patient management.”

In an accompanying editorial, Gregory Y.H. Lip, MD, FRCP, professor of cardiovascular medicine and director of the hemostasis, thrombosis and vascular biology unit at University of Birmingham Institute of Cardiovascular Science, identified other potential limitations of these findings.

“Inappropriate use of low-dose regimens might lead to under-dosing, and uptake of direct oral anticoagulants remain suboptimum in some health care systems, with the insistence of a trial of vitamin K antagonist treatment being done before a direct oral anticoagulant can be considered,” Lip wrote. “Notwithstanding these continued issues, the direct oral anticoagulants have clearly changed the landscape of thromboprophylaxis in VTE and stroke prevention in atrial fibrillation. … However, it is important to use the direct oral anticoagulants correctly — according to the prescribing label and guidelines — for the appropriate patient to ensure the best possible outcomes in real-world clinical practice.” – by Cameron Kelsall

Disclosure: Bayer HealthCare Pharmaceuticals and Janssen Research & Development LLC funded this study. Ageno reports research funding or honoraria from, or advisory board positions with Bayer HealthCare Pharmaceuticals, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures. Lip reports consultant and speaker roles with Bayer and several other pharmaceutical companies.

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