Table 1.

Summary table of studies reporting gastrointestinal bleeding and general bleeding for warfarin alone and warfarin combined with NSAID or selective COX-2 inhibitor

First author, publication year, country	Study design	Age (±SD or range) in years Warfarin indicationa	Outcome considered	No. cases	Concurrent therapy	Time with concomitant use	Reported multivariate odds ratio (95% CI)	Potential confounding variables
Shorr et al, 1993, United States14	Retrospective cohort	Over 65	GI bleeding	8	NSAID	30 d	2.66 (1.12–6.27)	Adjusted for history of ulcer disease, aspirin use, cigarette smoking, and heavy alcohol use
Johnsen et al, 2001, Denmark15	Retrospective cohort	Over 16	GI bleeding	269	NSAID	90 d	3.38 (1.21–10.17)	Adjusted for concomitant drugs
Battistella et al, 2005, Canada7	Case–control	79.8 ± 6.9	GI bleeding	24 22	NSAID COX-2	90 d	1.90 (1.16–3.11) 1.90 (1.40–2.40)	Adjusted by age, gender, potential interaction with other medications, prior GI bleeding, comorbidities, use of other gastrotoxic medications, and antiulcer agents (e.g., glucocorticoids)
Chung et al, 2005, United States20	Case–control	Average: 61.6	GB	123	COX-2	30 d	1.34 (0.70–2.57)	Adjusted for age and concomitant medications
Zhang et al, 2006, United States19	Retrospective cohort	64.29 ± 14.6	GB	700	NSAID	At least 7 d	1.88 (1.69–2.11)	Adjusted for age, gender, average dose of warfarin, and physician specialty
Hauta-Aho et al, 2009, Finland16	Case–control	NSAID: 68 (17–97) COX-2: 68 (24–92)	GI bleeding GB GI bleeding GB	8 44 2 12	NSAID COX-2	At least 7 d	2.79 (0.88–8.91) 2.57 (1.56–4.23) 2.91 (0.33–25.79) 3.10 (1.44–6.67)	Adjusted for age, sex, ward, proton-pump inhibitor, and oral glucocorticoid medications
Cheetham et al, 2009, United States13	Case–control	NSAID: 66.2 ± 12.8 Coxib: 67.9 ± 11.9 Coronary artery disease Congestive heart failure	GI bleeding	44 6	NSAID COX-2	NSAID + warfarin: 71 d COX-2 + warfarin: 113 d	3.58 (2.3–5.5) 1.71 (0.6–4.8)	Adjusted for medication used (warfarin and selective COX-2), baseline diseases, and prior GI bleeding
Wallerstedt et al, 2009, Sweden22	Case–control	Over 55 Atrial fibrillation	GB	2	NSAID	14 d	1.97 (0.44–8.74)	Adjusted for age, sex, and concomitant medications
Schelleman et al, 2011, United States17	Case–control	Over 18	GI bleeding	721	NSAID	30 d	1.68 (1.55–1.81)	Adjusted for index date, date, and state. Eligible controls consisted of warfarin users who had not been hospitalized with diagnosis of gastrointestinal bleeding
Vitry et al, 2011, Australia21	Retrospective cohort	Over 65	GB	69 27	NSAID COX-2	28 d	1.19 (0.90–1.59) 1.07 (0.69–1.68)	Adjusted for age, gender, socioeconomic index, number of comorbidities, number of prescribers, previous 1-y bleeding before first warfarin prescription, other medications
Mosholder et al, 2013, United States18	Retrospective cohort	Over 18 Heart failure Ischemic stroke	GI bleeding GB	NS NS	NSAID	14 d	1.39 (1.14–1.66) 1.24 (1.08–1.43)	Adjusted for age, gender, geographical region, income, hospitalization, emergency room visit, other medications

Abbreviations: CI, confidence interval; COX-2, selective cyclooxygenase-2 inhibitors; GB, general bleeding; GI, gastrointestinal; NS, nonspecified; NSAID, nonsteroidal anti-inflammatory drug; SD, standard deviation.

^aWarfarin indication reported when available.