Table 3.
Characteristics of study participants by outcome of interest
| Outcome | |||
|---|---|---|---|
| Serious bleedinga | Gastrointestinal bleeding | Non-traumatic intracranial hemorrhage | |
| Persons, person-days, and outcome occurrence | |||
| Number of persons | 6,463 | 5,832 | 684 |
| Person-days of observation time | 1,433,447 | 1,303,047 | 141,179 |
| During precipitant-exposed timeb | 740,318 | 666,694 | 80,453 |
| During precipitant-unexposed timec | 693,129 | 636,353 | 60,726 |
| Observation time per person in days, median (Q1; Q3) | 114 (48; 268) | 115 (49; 268) | 106 (45; 266) |
| Number of outcome occurrences during observation time | 7,388 | 6,419 | 996 |
| During precipitant-exposed time | 3,585 | 3,065 | 534 |
| During precipitant-unexposed time | 3,803 | 3,354 | 462 |
| Rate of outcome occurrence per 1,000 person-days during observation time | 5.2 | 4.9 | 7.1 |
| Demographic characteristics, number of persons (%), unless otherwise noted | |||
| Age in years at start of observation time, median (Q1; Q3) | 73.1 (64.9; 80.3) | 73.3 (65.1; 80.4) | 72.3 (63.5; 79.4) |
| Sex, female | 4,301 (66.5%) | 3,893 (66.8%) | 446 (65.2%) |
| Race/ethnicity | |||
| White | 3,307 (51.2%) | 3,063 (52.5%) | 262 (38.3%) |
| Black | 1,145 (17.7%) | 1,043 (17.9%) | 112 (16.4%) |
| Hispanic/Latino | 908 (14.0%) | 795 (13.6%) | 126 (18.4%) |
| Other/unknown | 1,103 (17.1%) | 931 (16.0%) | 184 (26.9%) |
| State of residence | |||
| California | 2,201 (34.1%) | 1,909 (32.7%) | 314 (45.9%) |
| Florida | 944 (14.6%) | 861 (14.8%) | 92 (13.5%) |
| New York | 1,669 (25.8%) | 1,525 (26.1%) | 156 (22.8%) |
| Ohio | 865 (13.4%) | 808 (13.9%) | 65 (9.5%) |
| Pennsylvania | 784 (12.1%) | 729 (12.5%) | 57 (8.3%) |
| Calendar year at start of observation time | |||
| 1999 | 210 (3.2%) | 190 (3.3%) | 21 (3.1%) |
| 2000 | 413 (6.4%) | 372 (6.4%) | 48 (7.0%) |
| 2001 | 456 (7.1%) | 419 (7.2%) | 44 (6.4%) |
| 2002 | 451 (7.0%) | 411 (7.0%) | 44 (6.4%) |
| 2003 | 458 (7.1%) | 408 (7.0%) | 54 (7.9%) |
| 2004 | 475 (7.3%) | 430 (7.4%) | 50 (7.3%) |
| 2005 | 521 (8.1%) | 474 (8.1%) | 49 (7.2%) |
| 2006 | 718 (11.1%) | 645 (11.1%) | 76 (11.1%) |
| 2007 | 541 (8.4%) | 478 (8.2%) | 70 (10.2%) |
| 2008 | 578 (8.9%) | 527 (9.0%) | 54 (7.9%) |
| 2009 | 672 (10.4%) | 601 (10.3%) | 75 (11.0%) |
| 2010 | 574 (8.9%) | 520 (8.9%) | 57 (8.3%) |
| 2011 | 396 (6.1%) | 357 (6.1%) | 42 (6.1%) |
| Medicare dual-enrollment, anytime during baseline period | 5,462 (84.5%) | 4,956 (85.0%) | 550 (80.4%) |
| Precipitant drugsd, number of person-days during precipitant-exposed time (%)e | |||
| glimepiride | 101,700 (7.1%) | 92,882 (7.1%) | 9,457 (6.7%) |
| glipizide | 259,066 (18.1%) | 236,553 (18.2%) | 25,667 (18.2%) |
| glyburide | 183,101 (12.8%) | 162,723 (12.5%) | 22,488 (15.9%) |
| metformin | 385,586 (26.9%) | 343,808 (26.4%) | 43,526 (30.8%) |
| Time-varying covariatesf, number of person-days (%), unless otherwise noted | |||
| Acute infection | 214,885 (15.0%) | 198,882 (15.3%) | 17,434 (12.3%) |
| Antiplatelet agents | 224,404 (15.7%) | 203,391 (15.6%) | 22,379 (15.9%) |
| CYP2C9 inhibitors | 114,769 (8.0%) | 108,115 (8.3%) | 8,406 (6.0%) |
| CYP1A2 inhibitors | 7,274 (0.5%) | 6,823 (0.5%) | 451 (0.3%) |
| CYP3A4 inhibitors | 577,352 (40.3%) | 527,600 (40.5%) | 54,396 (38.5%) |
| Drugs that can cause protein displacement | 30,917 (2.2%) | 27,580 (2.1%) | 3,443 (2.4%) |
| Drugs with unknown mechanism | 322,795 (22.5%) | 299,682 (23.0%) | 24,452 (17.3%) |
| Inducers of drug metabolism | 14,746 (1.0%) | 12,631 (1.0%) | 2,198 (1.6%) |
| NSAIDs | 120,204 (8.4%) | 110,194 (8.5%) | 10,165 (7.2%) |
| SNRIs | 46,348 (3.2%) | 42,773 (3.3%) | 3,677 (2.6%) |
| SSRIs | 280,375 (19.6%) | 256,594 (19.7%) | 25,815 (18.3%) |
| Thyroid hormones | 203,894 (14.2%) | 189,372 (14.5%) | 15,375 (10.9%) |
| Average daily dose of warfarin, in milligrams (Q1; Q3)g | 4.0 (2.5; 5.0) | 4.0 (2.5; 5.0) | 4.0 (2.5; 5.0) |
| Therapeutic drug monitoring for warfaring | 419,475 (29.3%) | 385,002 (29.5%) | 38,048 (27.0%) |
CYP: cytochrome P450. NSAID: nonsteroidal anti-inflammatory drug. Q1: First quartile. Q3: Third quartile. SNRI: serotonin and norepinephrine reuptake inhibitor, SSRI: selective serotonin reuptake inhibitors.
Composite outcome: occurrence of gastrointestinal bleeding or non-traumatic intracranial hemorrhage or both.
Precipitant-exposed time: time exposed to a precipitant drug.
Precipitant-unexposed time: time unexposed to a precipitant drug.
Exposure to precipitant drugs: indicator of the exposure status.
% of person-days: % of person-days for “yes” of the variable.
Time-varying covariates: indicator of the exposure status, measured in prior 31 days on the person-day level except for acute infection which were measured in prior 15 days. Detailed information on diagnosis codes used to identify acute infections is presented in Table S1.
Average daily dose of warfarin and therapeutic drug monitoring for warfarin were adjusted for in sensitivity analyses.