Table 1. Baseline characteristics of OAC-naïve AF patients with and without polypharmacy at baseline (≥5 and <5 concomitantly used drugs, respectively).
| Patient characteristics | No polypharmacy (<5 drugs) ( n = 86,631) |
Polypharmacy (≥5 drugs) | SMD a | |||
|---|---|---|---|---|---|---|
| Overall (≥5 drugs) ( n = 167,847) |
VKA ( n = 40,127) |
NOAC ( n = 127,720) |
Before IPTW | After IPTW | ||
| Age (y) | 72.5+/−11.6 | 76.3+/−10.2 | 72.8+/−11.5 | 77.4+/−9.6 | 0.43 | 0.016 |
| Female | 37,312 (43.1%) | 83,462 (49.7%) | 19,200 (47.8%) | 64,262 (50.3%) | 0.049 | 0.008 |
| Follow-up (y) | 1.3+/−1.5 | 1.3+/−1.5 | 0.9+/−1.3 | 1.4+/−1.5 | NA | NA |
| Comorbidities | ||||||
| Hypertension | 35,282 (40.7%) | 129,594 (77.2%) | 29,915 (74.5%) | 99,679 (78.0%) | 0.084 | 0.001 |
| Coronary artery disease | 7,211 (8.3%) | 40,632 (24.2%) | 12,068 (30.1%) | 28,564 (22.4%) | 0.172 | 0.002 |
| Congestive heart failure | 6,196 (7.2%) | 33,697 (20.1%) | 8,508 (21.2%) | 25,189 (19.7%) | 0.033 | 0.014 |
| Valvular heart disease | 7,457 (8.6%) | 28,705 (17.1%) | 9,706 (24.2%) | 18,998 (14.9%) | 0.241 | 0.013 |
| Peripheral artery disease | 2,740 (3.2%) | 18,196 (10.8%) | 5,906 (14.7%) | 12,290 (9.6%) | 0.144 | 0.003 |
| Dyslipidemia | 32,085 (37.0%) | 111,830 (66.6%) | 27,026 (67.4%) | 84,804 (66.4%) | 0.02 | 0.006 |
| Chronic kidney disease | 3,218 (3.7%) | 26,277 (15.7%) | 7,795 (19.4%) | 18,482 (14.5%) | 0.121 | 0.002 |
| Chronic liver disease | 1,265 (1.5%) | 7,192 (4.3%) | 2,204 (5.5%) | 4,988 (3.9%) | 0.065 | 0.005 |
| Chronic lung disease | 3,833 (4.4%) | 28,212 (16.8%) | 7,423 (18.5%) | 20,789 (16.3%) | 0.048 | 0.010 |
| Obstructive sleep apnea | 1,712 (2.0%) | 7,061 (4.2%) | 1,875 (4.7%) | 5,186 (4.1%) | 0.023 | 0.014 |
| Cancer | 4,678 (5.4%) | 20,509 (12.2%) | 4,882 (12.2%) | 15,627 (12.2%) | 0.01 | 0.017 |
| Upper GI tract disorder b | 2,681 (3.1%) | 16,497 (9.8%) | 4,470 (11.1%) | 12,027 (9.4%) | 0.047 | 0.005 |
| Lower GI tract disorder b | 3,840 (4.4%) | 13,817 (8.2%) | 3,290 (8.2%) | 10,527 (8.2%) | 0.014 | 0.004 |
| Diabetes mellitus | 11,062 (12.8%) | 71,641 (42.7%) | 19,083 (47.6%) | 52,558 (41.2%) | 0.126 | 0.047 |
| Anemia | 2,227 (2.6%) | 18,886 (11.3%) | 5,777 (14.4%) | 13,109 (10.3%) | 0.112 | 0.013 |
| Thyroid disease | 6,596 (7.6%) | 30,313 (18.1%) | 7,333 (18.3%) | 22,980 (18.0%) | 0.004 | 0.011 |
| Depression | 8,983 (10.4%) | 48,253 (28.7%) | 12,359 (30.8%) | 35,894 (28.1%) | 0.059 | 0.012 |
| Dementia | 2,485 (2.9%) | 11,077 (6.6%) | 2,301 (5.7%) | 8,776 (6.9%) | 0.055 | 0.014 |
| Parkinson's disease | 1,030 (1.2%) | 6,526 (3.9%) | 1,363 (3.4%) | 5,163 (4.0%) | 0.034 | 0.001 |
| History of falling | 2,986 (3.4%) | 17,187 (10.2%) | 3,418 (8.5%) | 13,769 (10.8%) | 0.089 | 0.049 |
| Frailty | 14,002 (16.2%) | 58,483 (34.8%) | 11,398 (28.4%) | 47,085 (36.9%) | 0.187 | 0.017 |
| Prior stroke/SE | 7,691 (8.9%) | 27,704 (16.5%) | 6,986 (17.4%) | 20,718 (16.2%) | 0.019 | 0.006 |
| Prior MB/CRNMB | 2,030 (2.3%) | 12,249 (7.3%) | 3,463 (8.6%) | 8,786 (6.9%) | 0.051 | 0.015 |
| Medication history | ||||||
| Number of concomitant drugs | 2.7+/−1.2 | 8.7+/−3.7 | 9.1+/−4.0 | 8.6+/−3.6 | 0.127 | 0.013 |
| Cardioselective beta blockers | 38,894 (44.9%) | 112,923 (67.3%) | 24,887 (62.0%) | 88,036 (68.9%) | 0.146 | 0.012 |
| Verapamil, diltiazem | 1,647 (1.9%) | 8,256 (4.9%) | 1,852 (4.6%) | 6,404 (5.0%) | 0.019 | 0.016 |
| Digoxin | 4,358 (5.0%) | 18,173 (10.8%) | 3,060 (7.6%) | 15,113 (11.8%) | 0.142 | 0.011 |
| Class I AAD | 6,912 (8.0%) | 16,389 (9.8%) | 2,552 (6.4%) | 13,837 (10.8%) | 0.160 | 0.005 |
| Class III AAD | 13,061 (15.1%) | 48,390 (28.8%) | 9,602 (23.9%) | 38,788 (30.4%) | 0.145 | 0.024 |
| Acetylsalicylic acid | 17,728 (20.5%) | 82,253 (49.0%) | 18,378 (45.8%) | 63,875 (50.0%) | 0.084 | 0.003 |
| P2Y12 inhibitor | 1,028 (1.2%) | 13,653 (8.1%) | 3,212 (8.0%) | 10,441 (8.2%) | 0.006 | 0.015 |
| Proton pump inhibitor | 16,244 (18.8%) | 86,004 (51.2%) | 21,468 (53.5%) | 64,536 (50.5%) | 0.059 | 0.030 |
| NSAID | 15,692 (18.1%) | 47,290 (28.2%) | 12,032 (30.0%) | 35,258 (27.6%) | 0.053 | 0.001 |
| Oral corticosteroids | 8,196 (9.5%) | 43,943 (26.2%) | 11,553 (28.8%) | 32,390 (25.4%) | 0.077 | 0.006 |
| SSRI/SNRI | 3,912 (4.5%) | 27,415 (16.3%) | 7,056 (17.6%) | 20,359 (15.9%) | 0.044 | 0.012 |
| Clinical risk score | ||||||
| CHA 2 DS 2 -VASc score | 2.5+/−1.6 | 4.0+/−1.7 | 3.8+/−1.9 | 4.0+/−1.7 | 0.122 | 0.001 |
| HAS-BLED score | 1.7+/−1.0 | 2.9+/−1.2 | 2.8+/−1.4 | 2.9+/−1.1 | 0.106 | 0.005 |
| Charlson Comorbidity Index | 3.3+/−1.8 | 4.8+/−2.3 | 4.7+/−2.5 | 4.9+/−2.3 | 0.117 | 0.012 |
Abbreviations: AAD, antiarrhythmic drug; AF, atrial fibrillation; CRNMB, clinically relevant nonmajor bleeding; GI, gastrointestinal; MB, major bleeding; NA, not applicable; NOAC, non-vitamin K antagonist oral anticoagulant; NSAID, nonsteroidal anti-inflammatory drug; OAC, oral anticoagulant; SE, systemic embolism; SMD, standardized mean difference; SNRI, serotonin and norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; VKA, vitamin K antagonist.
Note: Data shown as mean +/− standard deviation or counts and percentages. NOAC users without polypharmacy (30.0% reduced dose) included 10,167 dabigatran, 25,581 rivaroxaban, 20,894 apixaban, and 8,710 edoxaban users; NOAC users with polypharmacy (40.9% reduced dose) included 17,977 dabigatran, 48,840 rivaroxaban, 46,031 apixaban, and 14,872 edoxaban users. VKA users without polypharmacy included 9,170 acenocoumarol, 6,798 warfarin, and 5,311 phenprocoumon users; VKA users with polypharmacy included 20,480 acenocoumarol, 10,061 warfarin, and 9,586 phenprocoumon users.
Absolute SMDs illustrated for comparison of NOACs versus VKAs in patients with polypharmacy before and after stabilized inverse probability of treatment weighting.
Upper and lower gastrointestinal tract disorders were defined as gastroesophageal reflux disease or peptic ulcer disease; and diverticulosis, angiodysplasia, colorectal polyposis, or hemorrhoids, respectively.