11-7 Meta-analysis Worksheet 1

Title: Comparing Direct Oral Anticoagulants (DOACs) vs Warfarin in Morbidly Obese Patients with Atrial Fibrillation
Authors: Kazuhiko Kido, Mikiko Shimizu, Tsuyoshi Shiga, Masayuki Hashiguchi
Objective: To compare the effectiveness and safety of DOACs versus warfarin in morbidly obese patients with atrial fibrillation (AF).
Recommendation by International Society of Thrombosis and Haemostasis: Prefer warfarin for patients with BMI > 40 kg/m2 or weight > 120 kg due to limited data on morbidly obese patients.

Literature Search: MEDLINE, Embase, Google Scholar, Web of Science, Cochrane Library (up to December 23, 2019).
Inclusion Criteria: Studies involving patients > 18 years with BMI > 40 kg/m2 or weight > 120 kg receiving warfarin, apixaban, dabigatran, edoxaban, or rivaroxaban.
Exclusion Criteria: Mechanical heart valve recipients, pregnant patients, those on dialysis, non-English articles, case series/control studies, and meeting abstracts.
Analysis Parameters: 5 studies included for stroke/systemic embolism, 4 studies for major bleeding.
Statistical Assessment: Pooled odds ratios (OR), 95% confidence intervals (CI). Significance at p < 0.05 with heterogeneity assessed using I2 statistics.

Finding: No significant difference in stroke or SE event rate between DOACs and warfarin.
- Odds Ratio: 0.85 (95% CI: 0.60, 1.19; p = 0.35; I2 = 0%).
Subgroup Analysis: Similar findings for apixaban or rivaroxaban versus warfarin.

Finding: DOACs associated with significantly lower major bleeding rates compared to warfarin.
- Odds Ratio: 0.63 (95% CI: 0.43, 0.94; p = 0.02; I2 = 30%).
Subgroup Analysis: No significant differences in major bleeding rates between specific DOACs and warfarin.

Assessment: Egger’s regression test showed no substantial publication bias. I2 statistics indicated low heterogeneity.

Conclusion: Generally, no difference in stroke or SE event rates between DOACs and warfarin; DOACs have lower major bleeding rates.
Obesity Paradox: Some studies suggest obese patients experience lower or comparable stroke rates; DOAC efficacy maintained irrespective of obesity status.
Future Research: A randomized controlled trial (RCT) comparing DOACs with warfarin in morbidly obese AF patients is recommended to confirm findings.

Study Quality: Most studies were retrospective; only one was a post hoc investigation of an RCT.
Uncertainty of Efficacy for Other DOACs: Majority of studies focused on apixaban and rivaroxaban, casting doubt on results for dabigatran or edoxaban.
Missing Data: Inability to report systemic embolism in three studies leads to potential underestimation of composite event rates.

A comprehensive list of studies referenced later in the document, aiding in detailed understanding and future reading.