ABSTRACT
BACKGROUND: Patients requiring emergent warfarin reversal (EWR) have been prescribed three-factor prothrombin complex concentrate (PCC3) and four-factor prothrombin complex concentrate (PCC4) to reverse the anticoagulant effects of warfarin. There is no existing systematic review and meta-analysis of studies directly comparing PCC3 and PCC4. METHODS: The primary objective of this systematic review and meta-analysis was to determine the effectiveness of achieving study defined target INR goal after PCC3 or PCC4 administration. Secondary objectives were to determine the difference in safety endpoints, thromboembolic events (TE), and survival during the patients' hospital stay. Random-effects meta-analysis models were used to estimate the odds ratios (OR), and heterogeneity associated with the outcomes. The Newcastle-Ottawa Scale was used to assess study quality, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. RESULTS: Ten full-text manuscripts and five abstracts provided data for the primary and secondary outcomes. Patients requiring EWR had more than three times the odds of reversal to goal INR when they were given PCC4 compared to PCC3 (OR = 3.61, 95% CI: 1.97-6.60, p < 0.001). There was no meaningful clinical association or statistically significant result between PCC4 and PCC3 groups in TE (OR = 1.56, 95% CI: 0.83-2.91, p = 0.17), or survival during hospital stay (OR = 1.34, 95% CI: 0.81-2.23, p = 0.25). CONCLUSION: PCC4 is more effective than PCC3 in meeting specific predefined INR goals and has similar safety profiles in patients requiring emergent reversal of the anticoagulant effects of warfarin.
Subject(s)
Anticoagulants , Warfarin , Anticoagulants/adverse effects , Blood Coagulation Factors , Hemorrhage , Humans , International Normalized Ratio , Retrospective Studies , Warfarin/adverse effectsABSTRACT
BACKGROUND: Prothrombin Complex Concentrates (PCC) are prescribed for emergent warfarin reversal (EWR). The comparative effectiveness and safety among PCC products are not fully understood. METHODS: Patients in an academic level one trauma center who received PCC3 or PCC4 for EWR were identified. Patient characteristics, PCC dose and time of dose, pre- and post-INR and time of measurement, fresh frozen plasma and vitamin K doses, and patient outcomes were collected. Patients whose pre-PCC International Normalized Ratio (INR) was > 6 h before PCC dose or the pre-post PCC INR was > 12 h were excluded. The primary outcome was achieving an INR ≤ 1.5 post PCC. Secondary outcomes were the change in INR over time, post PCC INR, thromboembolic events (TE), and death during hospital stay. Logistic regression modelled the primary outcome with and without a propensity score adjustment accounting for age, sex, actual body weight, dose, initial INR value, and time between INR measurements. Data are reported as median (IQR) or n (%) with p < 0.05 considered significant. RESULTS: Eighty patients were included (PCC3 = 57, PCC4 = 23). More PCC4 patients achieved goal INR (87.0% vs. 31.6%, odds ratio (OR) = 14.4, 95% CI: 3.80-54.93, p < 0.001). This result remained true after adjusting for possible confounders (AOR = 10.7, 95% CI: 2.17-51.24, p < 0.001). The post-PCC INR was lower in the PCC4 group (1.3 (1.3-1.5) vs. 1.7 (1.5-2.0)). The INR change was greater for PCC4 (2.3 (1.3-3.3) vs. 1.1 (0.6-2.0), p = 0.003). Death during hospital stay (p = 0.52) and TE (p = 1.00) were not significantly different. CONCLUSIONS: PCC4 was associated with a higher achievement of goal INR than PCC3. This relationship was observed in the unadjusted and propensity score adjusted results.