Real-World Evaluation of the Safety and Effectiveness of Apixaban & Rivaroxaban Lead-in Dosing Compared to Parenteral Lead-in Dosing in the Treatment of Venous Thromboembolism: A Multi-Center Retrospective Cohort Study

Abstract

Ghazwa B Korayem,1,* Omar A Alshaya,2– 4,* Nirvana Alnajjar,1 Ahad Alawad,1 Rand Alotaibi,1 Nader Bin Sheraim,5 Fatemah M Hakami,6 Ohud S Alsudyyes,6 Rahaf H Alsoghayer,6 Lina M Alhushan,6 Asma H Qudayr,6,7 Majed S Al Yami,2– 4 Omar A Almohammed6,8 1Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, Riyadh, 11671, Saudi Arabia; 2Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3Pharmaceutical Care Department, King Abdulaziz Medical City, Riyadh, Saudi Arabia; 4King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 5Pharmaceutical Care Division, King Abdullah bin Abdulaziz University Hospital, Riyadh, Saudi Arabia; 6Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 7Department of Clinical Pharmacy, College of Pharmacy, Taif University, Taif, Saudi Arabia; 8Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia*These authors contributed equally to this workCorrespondence: Ghazwa B Korayem, Department of Pharmacy Practice, College of Pharmacy, Princess Nourah bint Abdulrahman University, P.O.Box 84428, Riyadh, 11671, Saudi Arabia, Tel [phone], Email [email protected] Omar A Almohammed, Department of Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia, Tel [phone], Email [email protected]: Although parenteral anticoagulation lead-in is not recommended with apixaban and rivaroxaban, parenteral anticoagulation is often used to replace apixaban or rivaroxaban lead-in doses for the initial phase treatment of VTE. Thus, our study compares the safety and effectiveness of lead-in parenteral anticoagulation to lead-in apixaban or rivaroxaban in patients who received apixaban or rivaroxaban for VTE treatment.Methods: A multi-center retrospective cohort study included adult patients (aged ≥ 18 years) admitted to the hospital with acute VTE and treated with either apixaban or rivaroxaban. Patients were grouped depending on the lead-in anticoagulation received for initial VTE treatment into the “Direct oral anticoagulation (DOAC) lead-in” group if patients received an appropriate lead-in dose of apixaban and rivaroxaban and patients who received parenteral lead-in the “parenteral lead-in” group.Results: A total of 389 patients were included; the DOAC lead-in group included 296 patients, whereas 93 patients were in the parenteral lead-in group. VTE recurrence (rVTE) during hospitalization and within 30 days was numerically higher in the parenteral lead-in group compared to the DOAC lead-in group (3.3% vs 0.6%; p=0.09 and 1.1% vs 0.7%; p=0.560), with a significantly higher number of patients with rVTE at 90 days (5.4% vs 1.4%; p=0.039). However, none of the patient’s characteristics were significantly associated with the incidence of rVTE. In addition, the major bleeding rate during hospitalization was significantly higher among the parenteral lead-in group than in the DOAC lead-in group (14.0% vs 3.7%; p< 0.001).Conclusion: Parenteral anticoagulation lead-in before starting maintenance of apixaban and rivaroxaban showed a significantly higher risk of bleeding and a trend toward higher VTE recurrence than the DOAC lead-in. This study adds to the evidence supporting the utilization of the DOAC lead-in regimen in treating patients with VTE. Still, larger studies with robust designs are needed to confirm these findings.Keywords: rivaroxaban, apixaban, lead-in, parenteral anticoagulation, venous thromboembolism, recurrence

Keywords

• rivaroxaban
• apixaban
• lead-in
• parenteral anticoagulation
• venous thromboembolism
• recurrence