Real-world effectiveness and safety of oral anticoagulation strategies in atrial fibrillation: a cohort study based on a German claims dataset

Figures & data

Figure 1 Defined patient samples.

Notes: ^aNo possible assignment to 1 of the 2 defined cohorts because of prescription of 2 different agents at index date, death at index date, prescription of an OAC agent 6 month before index date but no follow-up prescription after index date, or no OAC therapy at all.
Abbreviations: AF, atrial fibrillation; NOAC, non-vitamin K antagonist oral anticoagulants; OAC, oral anticoagulation; PS, propensity score; VKA, vitamin-K-antagonist.

Table 1 Characteristics of observed AF patient samples

Characteristics	All observed AF-patients	Unmatched			PS-matched
		Cohort 1 (NOAC)	Cohort 2 (VKA)	Cohort 1 versus 2 (p-value)	Cohort 1 (NOAC)	Cohort 2 (VKA)	Cohort 1 versus 2 (p-value)
N	483,149	51,155	128,274	–	37,439	37,439	–
Mean follow-up time since index date (SD); median	–	341.2 days (245.29); 290	393.1 days (311.30); 239	p<0.001	348.5 days (247.57); 299	365.5 days (290.74); 197	p>0.100
Mean age in years (SD)	76.24 (13.33)	78.21 (8.56)	76.61 (8.34)	p<0.001	78.21 (7.40)	78.16 (7.37)	p>0.100
Gender; Female N (%)	253,750 (52.52)	26,519 (51.84)	66,112 (51.54)	p>0.100	19,659 (52.51)	19,622 (52.41)	p>0.100
Mean CCI without age factor (SD)	3.56 (2.79)	5.09 (2.74)	4.45 (2.46)	p<0.001	4.78 (2.60)	4.80 (2.55)	P<0.500
Mean CHA2DS2 VASc score (SD)	2.47 (1.54)	3.09 (1.09)	2.88 (1.00)	p<0.001	2.96 (1.04)	2.95 (1.03)	p>0.100
Prescribed DDDs of study medicationa	NA	1.21 (1.97)	0.81 (1.67)	–	1.19 (1.87)	0.82 (1.80)	–
Prescribed DDDs of Heparins or Clopidogrelb	NA	3.27 (21.20)	3.32 (13.12)	p<0.001	3.16 (22.22)	3.67 (16.66)	p<0.001

Notes: The table lists sociodemographic characteristics for the different observed AF patient samples. These data refer to patient-specific index dates for age/gender and to the 12-month baseline period before index date. The date of the first prescription of a NOAC/VKA agent in the inclusion period was used as the index date.

a (NOAC/VKA) per observed patient day during follow-up period;

b Per observed patient month. CHA2DSs Vasc (congestive heart failure, hypertension, age, diabetes, previous stroke/transient ischemic attack, and Vascular disease). “–” indicates not calculated.

Abbreviations: CCI, Charlson comorbidity index; DDD, defined daily dosage; NA, not applicable; NOAC, non-vitamin K antagonist oral anticoagulants; PS, propensity score; VKA, vitamin-K-antagonist.

Table 2 Event rates, IRRs and HRs (time to first event) in compared PSM-AF patient cohorts; PSM NOAC versus VKA

	Observed outcome (events per 100 patient years)a			Observed outcome (time-to-first event)b
	PSM cohort 1 (NOAC) N=37,439 patients	PSM cohort 2 (VKA) N=37,439 patients	IRR (95% CI; p-value) cohort 1 versus 2	PSM-HR (95% CI; p-value) cohort 1 versus 2
a: Death	11.28	9.23	1.22 (1.17–1.28; p<0.001)	1.22 (1.17–1.28; p<0.001)
b: IS	2.18	1.15	1.90 (1.69–2.15; p<0.001)	1.92 (1.69–2.19; p<0.001)
c: Non-specified stroke	0.11	0.05	2.04 (1.16–3.70; p<0.010)	1.93 (1.13–3.32; p<0.050)
d: TIA	0.99	0.65	1.52 (1.29–1.79; p<0.001)	1.44 (1.21–1.70; p<0.001)
e: MI	1.33	1.06	1.26 (1.10–1.45; p<0.001)	1.31 (1.13–1.52; p<0.001)
f: AE	0.39	0.22	1.75 (1.32–2.32; p<0.001)	1.81 (1.36–2.34; p<0.001)
g: Hemorrhagic stroke	0.47	0.50	0.94 (0.76–1.17; p=0.573)	0.95 (0.76–1.21; p=0.695)
h: Severe bleeding	2.47	1.29	1.92 (1.71–2.15; p<0.001)	1.95 (1.74–2.20; p<0.001)
CO1 (a–f)	16.28	12.36	1.32 (1.27–1.37; p<0.001)	1.31 (1.26–1.36; p<0.001)
CO2 (g and h)	2.94	1.78	1.65 (1.49–1.82; p<0.001)	1.70 (1.53–1.88; p<0.001)
CO3 (a–h)	19.22	14.15	1.36 (1.31–1.41; p<0.001)	1.35 (1.30–1.41; p<0.001)
Sum observed patient years	35,746.97	37,486.99	–	–

Notes:

a The table lists results of the event rate analyses based on PSM cohorts. Results are reported as IRRs for events per 100 observed patient years;

b The table lists the results of Cox regression analyses based on PSM cohorts. Results are reported as HRs for time-to-first event. “–” indicates not calculated. a. All-cause death; b. Ischemic stroke (I63.x); c. Non-specified stroke (I64.x); d. Transient ischemic attack (G45.x); e. Myocardial infarction (I21.x/I22.x); f. Arterial embolism (H34.x/I26.x/K55.0); g. Hemorrhagic stroke (I60.x/I61.x/I62.x); h. Severe bleeding (ICD-10 codes: K92.2, K62.5, K55.22, R04.x, K25.0, K25.2, K25.4, K25.6, K26.0, K26.2, K26.4, K26.6, K27.0, K27.2, K27.4, K27.6, K28.0, K28.2, K28.4 or K28.6).

Abbreviations: AE, arterial embolism; AF, atrial fibrillation; CO1, effectiveness composite outcome 1; CO2, safety composite outcome 2; CO3, general composite outcome 3; HR, hazard ratio; IRR, incidence rate ratio; IS, ischemic stroke; MI, myocardial infarction; NOAC, non-vitamin K antagonist oral anticoagulants; PSM, propensity score-matched; TIA, transient ischemic attack; VKA, vitamin-K-antagonist.

Figure 2 Kaplan–Meier curves (time to event: CO1, CO2, CO3) for PSM-matched Cohorts 1 and 2.

Abbreviations: CO1: effectiveness composite outcome 1; CO2: safety composite outcome 2; CO3: general composite outcome 3; NOAC, non-vitamin K antagonist oral anticoagulants; PSM, propensity score matching; VKA, vitamin-K-antagonist.

Table 3 IRRs, HRs in PSM cohorts and aHRs for patients assigned to cohort 1 (NOAC) versus cohort 2 (VKA) compared with HRs reported in clinical trials

Events	Own analysis				Known major clinical trials
	PSM-IRRs (95% CI; p-value)	PSM-HRs (95% CI; p-value)	aHRs (95% CI; p-value)	PSM-HRs (95% CI; p-value) for therapy-naive patients	HRs (95% CI; p-value) – RE-LY^Citation8	HRs (95% CI; p-value) – ROCKET AF^Citation9	HRs (95% CI; p-value) – ARISTOTLE^Citation15
Death	1.22**** (1.17–1.28; p<0.001)	1.22**** (1.17–1.28; p<0.001)	1.10**** (1.06–1.15; p<0.001)	1.11** (1.03–1.20; p<0.010)	0.88 (0.77–0.00; NSR)	0.85 (0.70–1.02; NSR)	0.89* (0.80–1.00; p<0.050)
IS	1.90**** (1.69–2.15; p<0.001)	1.92**** (1.69–2.19; p<0.001)	1.52**** (1.37–1.69; p<0.001)	1.175**** (1.42–2.17; p<0.001)	0.76* (0.60–0.98; p<0.050)	0.94 (0.75–1.17; NSR)	0.92 (0.74–1.13; NSR)
Hemorrhagic stroke	0.94 (0.76–1.17; NSR)	0.95 (0.76–1.21; NSR)	0.68**** (0.56-0.82; p<0.001)	0.76 (0.52–1.11; NSR)	0.26**** (0.14–0.49; p<0.001)	0.59* (0.37–0.93; p<0.050)	0.51**** (0.35–0.75; p<0.001)
Severe bleedings	1.92**** (1.71–2.15; p<0.001)	1.95**** (1.74–2.20; p<0.001)	1.57**** (1.43–1.73; p<0.001)	1.58 (1.30–1.92; NSR)	0.93 (0.81–1.07; NSR)	1.03 (0.90–1.18; NSR)	0.71**** (0.61–0.81; p<0.001)

Notes: aHR is based on a multivariable Cox regression analysis; PSM-HR represents hazard ratio based on Cox regression analysis of time-to-first event with regard to PSM cohorts; PSM-IRR represents incidence rate ratio based on comparison of PSM cohorts.

* p<0.050;

** p< 0.010;

**** p<0.001.

Abbreviations: AF, atrial fibrillation; aHR, adjusted hazard ratio; HR, hazard ratio; IS, ischemic stroke; NOAC, non-vitamin K antagonist oral anticoagulants; IRR, incidence rate ratio; NSR: non-significant results; PSM, propensity score matching; VKA, vitamin-K-antagonist.

ConnollySJEzekowitzMDYusufSEikelboomJRE-LY Steering Committee and InvestigatorsDabigatran versus Warfarin in patients with atrial fibrillationN Engl J Med20093611139115119717844

 PubMed Web of Science ®Google Scholar

PatelMRMahaffeyKWGargJROCKET AF InvestigatorsRivaroxaban versus Warfarin in nonvalvular atrial fibrillationN Engl J Med201136588389121830957

 PubMed Web of Science ®Google Scholar

GrangerCBAlexanderJHMcMurrayJJApixaban versus Warfarin in patients with atrial fibrillationN Engl J Med201136598199221870978

 PubMed Web of Science ®Google Scholar