Comparison of four-factor fixed-dose versus four-factor weight-based–dose prothrombin complex concentrate for emergent warfarin reversal: a systematic review and meta-analysis

Mohammed Alrashed; Norah Alabdulkarim; Jana Alaskah; Shrooq Alsoket; Renad Almotairi; Majed Al Yami; Shmeylan Al Harbi; Abdulkareem M. Albekairy; Abdulrahman Alshaya; Tariq Alqahtani; Abdulmajeed Alshehri; Abdullah Alshammari; Mohammed A. Alnuhait; Ahmed Aljabri

doi:10.15441/ceem.24.265

Systematic Review

doi: https://doi.org/10.15441/ceem.24.265 [Accepted]

Comparison of four-factor fixed-dose versus four-factor weight-based–dose prothrombin complex concentrate for emergent warfarin reversal: a systematic review and meta-analysis

Mohammed Alrashed^1,2

, Norah Alabdulkarim³, Jana Alaskah³, Shrooq Alsoket³, Renad Almotairi³, Majed Al Yami^1,2

, Shmeylan Al Harbi^1,2

, Abdulkareem M. Albekairy^1,2, Abdulrahman Alshaya^1,2

, Tariq Alqahtani^3,4,5, Abdulmajeed Alshehri^1,2, Abdullah Alshammari⁶

, Mohammed A. Alnuhait⁶

, Ahmed Aljabri⁷

¹Department of Pharmacy Practice, College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
²Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Riyadh, Saudi Arabia
³College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
⁴Department of Pharmaceutical Care Services, King Abdulaziz Medical City, Riyadh, Saudi Arabia
⁵King Abdullah International Medical Research Center, Riyadh, Saudi Arabia
⁶Department of Pharmaceutical Practices, College of Pharmacy, Umm Al Qura University, Makkah, Saudi Arabia
⁷Department of Pharmacy Practice, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia

Correspondence Mohammed Alrashed Tel: 0560096096, Email: rxedmo@gmail.com

Received: June 5, 2024. Revised: September 14, 2024. Accepted: September 14, 2024. Published online: January 14, 2025.

ABSTRACT

Objective
The objective of this systematic review and meta-analysis is to evaluate the efficacy, safety, time to international normalized ratio (INR) reversal, and total volume of four-factor prothrombin complex concentrate (4-PCC) administered using fixed-dose versus weight-based dosing strategies in patients requiring urgent warfarin reversal, with specific focus on clinical outcomes of hemostatic efficacy, thromboembolic events, and mortality rates.
Methods
A comprehensive systematic review was conducted using the PubMed, Embase, and Cochrane databases from inception through October 2023. We searched for randomized clinical trials or observational studies that compared efficacy or safety outcomes of fixed versus variable 4-PCC dose in adult patients.
Result
s: In the 14 included studies, the overall use of fixed-dose 4-PCC was associated with a lower likelihood of reaching the INR goal (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.80–0.89) compared to the variable-dose group. In addition, a significantly larger proportion of patients (169 of 651, 26%) required an additional dose of 4-PCC. The rates of mortality (RR, 0.85; 95% CI, 0.70–1.03) and thromboembolic events (RR, 1.27; 95% CI, 0.65–2.45) were similar between the two treatment groups.
Conclusion
This systematic review and meta-analysis showed that variable dosing of 4-PCC more successfully achieves the target INR for warfarin reversal compared to fixed dosing. However, the dosing strategies have similar mortality and thromboembolic rates. While fixed dosing offers a simpler approach, it may require additional administration. Future studies should focus on optimizing dosing strategies to balance efficacy, safety, and practicality in various clinical scenarios

Keywords: Blood coagulation factors; Factor Xa inhibitors; Meta-analysis; Prothrombin complex concentrate; Systematic review