Table 2.

Characteristics of the included articles that used inverse probability of treatment weighting as primary analyses (n=8)

Author and country	Setting and study period	Study population	Patient characteristics (range between NOACs)	Primary outcome definition	IPWT details	Sample size	Result/conclusion as reported in the article
Adeboyeje et al,17 USA	HealthCore Integrated Research Environment 1 November 2009–31 January 2016	NVAF patients newly prescribed OAC (no prescriptions for any anticoagulant in the 6-month period preceding their index dates)	Age (mean): 66–69 Male: 59.1%–65.5% CHA2DS2-VASc: 2.7–3.2 Comorbidity index: NR	Hospitalisation for major bleeding (ICD-9 CM codes; whether primary and secondary codes were used is not described	Extreme weights: not reported. Balanced if the absolute value of the STD was ≤10%.	Dabigatran: n=8539 Rivaroxaban: n=8398 Apixaban: n=3689	Apixaban and dabigatran were associated with lower major bleeding risk compared with rivaroxaban; however, apixaban had a lower risk of major gastrointestinal bleeding than dabigatran
Chan et al,46 Taiwan	Taiwan National Health Insurance Research 1 June 2012–31 December 2016	NVAF patients with their first prescription of OAC	Age: 75±10–76±10 Male: 55%–60% CHA2DS2-VASc: 3.7–3.9 Comorbidity index: NR	Hospitalisation for ischaemic stroke/systemic embolism, intracranial haemorrhage, major gastrointestinal bleeding, acute myocardial infarction, all major bleeding events and all-cause mortality. ICD-9 and 10 codes, whether primary and secondary codes were used is not described.	Extreme weights: not reported. Balanced if the absolute value of the STD was ≤10%.	Rivaroxaban: n=27 777 Dabigatran: n=20 079 Apixaban: n=5843	Three low-dose NOACs showed similar performance as without subgrouping
Charlton et al,22 USA	HealthCore Integrated Research Environment database 1 November 2010–31 March 2014	NVAF patients hospitalised for bleeding after starting OAC (AF diagnosis 6 months before starting one of the index drugs)	Age: 68.0±12.5–69.6±12.6 Male: 61.8–62.9 CHA2DS2-VASc: 3.8–3.8 CDI: 2.0–2.3	Total length of hospital stay, proportion of patients admitted to the ICU, mean length of ICU stay, and all-cause 30-day and 90-day mortality, ICD-9 codes, whether primary and secondary codes were used is not described	Extreme weights: not reported. Balance was tested using ANOVAs for significant differences.	Dabigatran: n=442 Rivaroxaban n=256	There were no significant differences in relative risk of all-cause 30 or 90 days
Graham et al,25 USA	Medicare 4 November 2011–30 June 2014	NVAF patients, at least 65 years old, initiating OAC at standard doses (first treatment, received no NOAC treatment for other indications in the last 6 months before the index date)	Age: 65–74 years: 50%–51% Age: 75–84: 40%–40% Age≥85: 9%–10% Male: 53%–53% CHADS2 ≥2: 66%–67% Comorbidity index: NR	Thromboembolic stroke, ICH, major extracranial bleeding events and mortality (as the first study outcome or within 30 days after hospitalisation for another primary outcome event), ICD-9 codes, whether primary and secondary codes were used is not described.	Extreme weights: not reported. Balanced if the absolute value of the STD was ≤10%.	Rivaroxaban: n=66 651 Dabigatran: n=52 240 Weighted cohorts Rivaroxaban: n=66 630 Dabigatran: n=52 264	Treatment with rivaroxaban was associated with statistically significant increases in intracranial bleeding and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran
Graham et al,24 USA	Fee-for-service Medicare Part A (hospitalisation), Part B (office-based care), and Part D (prescription drug coverage) October 2010–September 2015	NVAF patients of ≥65 years old (first initiation of treatment)	Age (mean): 74.9–75.5 Male: 52.2%–59.3% CHA2DS2-VASc≥2: 96.6%–97.4% Comorbidity index: NR	Hospitalised due to thromboembolic stroke, intracranial haemorrhage, major extracranial bleeding and all-cause mortality. ICD codes from the first hospital discharge diagnosis position.	Not described how weighted cohort was composed. Balanced if the absolute value of the STD was ≤10%.	Rivaroxaban: n=106 389 Dabigatran: n=86 198 Apixaban: n=73 039 Weighted cohort Rivaroxaban: n=106 369 Dabigatran: n=86 293 Apixaban: n=72 921	Dabigatran and apixaban were associated with a more favourable benefit−harm profile than rivaroxaban
Hernandez et al,27 USA	Medicare 4 November 2011–31 December 2013	NVAF patients (at any time before the index date; no NOAC treatment at least 3 months before the index date)	High dose: Age: <65: 5.0%–6.3% Age: 65–74: 38.4%–39.3% Age: ≥75: 55.3–55.7 Male: 45.9–49.5 CHADS2: 3.3–3.3 Comorbidity index: NR	Ischaemic stroke (inpatient, emergency room, or outpatient claim with primary or secondary, ICD-9 codes), other thromboembolic events, and all-cause mortality; ICD-9 codes, whether primary and secondary codes were used is not described. Any bleeding event and major bleeding; intracranial haemorrhage and gastrointestinal bleeding, not further described.	Extreme weights: not reported. Balanced if the absolute value of the STD was ≤10%.	Dabigatran n=9138 Rivaroxaban n=8367	There was no difference in stroke prevention between rivaroxaban and dabigatran; however, rivaroxaban was associated with a higher risk of thromboembolic events other than stroke, death and bleeding.
Larsen et al,43 Denmark	Danish National Prescription Registry, Danish National Patient Register, Danish Civil Registration System August 2011–October 2015	NVAF patients who were naïve to oral anticoagulants (no use of oral anticoagulant within 1 year)	Age (median, IQR): 67.6 (62.0–72.4)−71.8 (65.7–78.9) Male: 56.9%–66.1% CHA2DS2-VASc: 2.2–2.8 Comorbidity index: NR	Ischaemic stroke or systemic embolism, ICD-10 codes whether primary and secondary codes were used is not described	Extreme weights: not reported. Balanced if the absolute value of the STD was ≤10%.	Dabigatran: n=12 701 Rivaroxaban: n=7192 Apixaban: n=6349	Apixaban and dabigatran were associated with a significantly lower risk of death compared with rivaroxaban. Risk of any bleeding or major bleeding were significantly lower for apixaban and dabigatran than for rivaroxaban.
Meng et al,48 Taiwan	National Health Insurance claims database 1 June 2012–31 May 2015	All NVAF patients aged ≥20 years who initiated NOACs during study period	Age <65: 11.8%–13.5% Age 65–74: 29.7%–32.7% Age ≥75: 53.8%–58.4% Male: 54.6%–56.2% CHA2DS2-VASc: 3.2–3.3 Comorbidity index: NR	All-cause death, ischaemic stroke, intracranial haemorrhage, gastrointestinal haemorrhage needing transfusion, ICD-10 codes, whether primary and secondary codes were used is not described	Extreme weights: not reported. Balanced if the absolute value of the STD was ≤10%.	Dabigatran: n=13 505 Rivaroxaban: n=6551 Weighted pseudo-cohort Dabigatran: n=13 508; Rivaroxaban: n=6547	Rivaroxaban seemed to be associated with an increased risk of all-cause death compared with dabigatran

ANOVAs, analyses of variance; CHA2DS2-VASc, Congestive heart failure, Hypertension, Age ≥75 years, Diabetes Mellitus, Prior Stroke or TIA or thromboembolism, Vascular disease, Age 65–74 years, Sex; NOACs, non-vitamin K antagonist oral anticoagulants; NVAF, non-valvular atrial fibrillation.