This was an exploratory retrospective cohort study retrieving adult patients’ data from the electronic health records of King Abdulaziz Medical City (Riyadh) between January 01st, 2016 and December 31st, 2019. We included adult patients aged 18 years or above diagnosed with non-valvular AF and who received apixaban for stroke prevention regardless of their CHA2DS2-VASc score. Patients were excluded if they are known to have liver cirrhosis Child C, mechanical valve, serum creatinine > 1.5 mg/dL, follow up < 3 months, or using apixaban with a dose of ≤5 or > 10 mg/day. Included patients were then categorized into two groups based on the body mass index (BMI) (BMI ≥ 40 vs. BMI < 40) at the time of apixaban initiation. Patients' data were then followed for at least one year after apixaban initiation. The Institutional review board at King Abdullah International Medical Research Center (KAIMRC) approved the study in November 2021 (Ref.# NRC21R/482/11). Informed consent from the study patients was waived due to the retrospective observational nature of the study.
This study was conducted in King Abdulaziz Medical City (Riyadh). It is a tertiary-care academic referral hospital with 1601 beds in Riyadh, Saudi Arabia. King Abdulaziz Medical City includes cardiac and liver centers, intensive care units (ICUs), dental, ambulatory care centers, long-term care/ rehabilitation, emergency care, trauma centers, surgical and medical wards, obstetrics and gynecology, pediatrics, operating rooms, and home health care program.This center provides all types of care to all national guard soldiers and their families, including primary health care and specialized tertiary care.
Each patients’ data were collected and retrieved from the hospital system (Best Care); data were collected in an excel sheet. We collected patients’ demographic data, comorbidities, vital signs and laboratory tests, CHA2DS2-VASc score, and HAS-BLED scores at the time of apixaban initiation. Moreover, laboratory tests including coagulation profile, liver, and renal profile, complete blood count (hemoglobin and platelets), concomitant antiplatelets use, and concomitant use of gastrointestinal (GI) prophylaxis were collected. Moreover, we collect the following variables: confirmed stroke occurrence (ischemic or hemorrhagic), pulmonary embolism (PE), deep vein thrombosis (DVT), upper or lower GI bleeding (confirmed by documentation or using upper endoscopy or colonoscopy), the occurrence of left ventricular thrombus (confirmed by echocardiogram) while on apixaban.
This exploratory study aims to compare the effectiveness and safety of apixaban in patients with non-valvular AF who are morbidly obese (BMI ≥ 40) to non-morbidly obese patients (BMI < 40). The primary efficacy outcome was thrombotic events. Thrombotic events were identified using the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD10-CM) code (i.e., stroke, pulmonary embolism, deep vein thrombosis), chart review documentation and/or radiology findings. In contrast, the secondary outcomes were major and minor bleeding after apixaban initiation. Major bleeding was defined according to the ISTH as clinically overt bleeding associated with a fall in hemoglobin by ≥20 g/L, transfusion of ≥2 U packed red blood cells (PRBCs) or whole blood, retroperitoneal or intracranial bleeding, or fatal bleeding . In comparison, minor bleeding was defined according to the ISTH definition as any sign or symptom of bleeding that does not fit the criteria for the ISTH definition of major bleeding , but does meet at least one of the following criteria: requiring medical intervention by a healthcare professional, bleeding leading to hospitalization or increased level of care or prompting a face to face evaluation .
We presented continuous variables as mean with standard deviation (SD), or median with lower and upper quartile (Q1, Q3) as appropriate and categorical variables as number (percentage). The normality assumptions were assessed for all numerical variables using a statistical test (i.e., Shapiro–Wilk test) and graphical representation (i.e., histograms and Q-Q plots).
Baseline characteristics and outcome variables were compared between the two study groups. For categorical variables, we used the Chi-square or Fisher’s exact test. We compared the normally distributed continuous variables using the student t-test and non-normally distributed variables with the Mann-Whitney U test. Multivariable regression analysis and negative binomial regression were used for the outcomes considered in this study as appropriate. Regression analysis was done by considering PS score as one of the covariates in the model. The odds ratios (OR) or estimates with the 95% confidence intervals (CI) were reported as appropriate. No imputation was made for missing data as the cohort of patients in our study was not derived from random selection. We considered a P value of < 0.05 statistically significant and used SAS version 9.4 for all statistical analyses.
Propensity score matching procedure (Proc PS match) (SAS, Cary, NC) was used to match patients with BMI ≥ 40 (active group) to patients with BMI<40 (control group) who received Apixaban therapy based on patient’s age, gender, and HAS-BLED score at the time of Apixaban initiation. A greedy nearest neighbor matching method was used in which one patient with BMI ≥ 40 (active) group matched with one patient with BMI<40 (control), which eventually produced the smallest within-pair difference among all available pairs with treated patients. Patients were matched only if the difference in the logits of the propensity scores for pairs of patients from the two groups was less than or equal to 0.5 times the pooled estimate of the standard deviation.