Observational study of upper gastrointestinal tract bleeding events in patients taking duloxetine and nonsteroidal anti-inflammatory drugs: a case-control analysis

Figures & data

Figure 1 Selection of study population.

Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; SNRI, serotonin norepinephrine reuptake inhibitor; SSRI, selective serotonin reuptake inhibitor; THAM, Truven Health Analytics MarketScan; UGI, upper gastrointestinal.

Table 1 Baseline demographics, comorbidity index, and concomitant drug prescriptions

Variable	Cases N=33,571	Controls N=335,710	P-value
Age, years, mean (SD)	63.1 (17.2)	63.1 (17.2)	1.00
Female, n (%)	18,418 (54.9)	184,180 (54.9)	1.00
Males, n (%)	15,153 (45.1)	151,530 (45.1)	1.00
Charlson Comorbidity	1.81 (1.4)	0.91 (1.3)	<0.0001
Index score, mean (SD)
Concomitant drug therapy, n (%)
Proton pump inhibitors	14,228 (42.4)	45,388 (13.5)	<0.0001
Glucocorticoids	2,920 (8.7)	33,887 (10.1)	<0.0001
Antiplatelet drugs	2,558 (7.6)	28,612 (8.5)	<0.001
Anticoagulants	1,779 (5.3)	35,487 (10.6)	<0.001
Estrogen/progestin	978 (2.9)	12,600 (3.8)	<0.0001
H2 inhibitors	876 (2.6)	6,662 (2.0)	<0.0001

Abbreviations: SD, standard deviation; N, total number of patients; n, subgroup number of patients.

Table 2 Study groups based on current exposure to prescription duloxetine, NSAIDs, or aspirin

Study group	Medication exposure	Cases N=33,571 n (%)	Controls N=335,710 n (%)
1	None	25,688 (76.5)	262,627 (78.2)
2	Duloxetine only	320 (1.0)	3,604 (1.1)
3	NSAIDs or aspirin only	3,752 (13.1)	32,506 (9.7)
4	Duloxetine plus NSAIDs or aspirin	156 (0.5)	1,272 (0.4)

Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; N, total number of patients; n, subgroup number of patients.

Table 3 Doses of duloxetine prescribed across cases and controls

Duloxetine dose mg/day#	Cases N=33,571 n (%)	Controls N=335,710 n (%)
<60	86 (26.9)	1,008 (28.0)
60	188 (58.8)	2,041 (56.6)
>60	46 (14.4)	555 (15.4)

Notes:

# There was no significant difference between cases and controls in prescription rates across doses. (P=0.76).

Abbreviations: N, total number of patients; n, subgroup number of patients.

Table 4 UGI events across all cases and each dose of duloxetine in the duloxetine‐only exposure group

UGI event	All cases# N=33,571 n (%)	Duloxetine <60 mg/day N=86 n (%)	Duloxetine 60 mg/day N=188 n (%)	Duloxetine >60 mg/day N=46 n (%)	P-value (3×2 chi-square)	P-value trend analysis
UGI surgical procedure	18,257 (54.4)	36 (41.7)	93 (49.5)	25 (54.4)	0.33	0.14
Blood transfusion	4,962 (14.8)	6 (7.0)	23 (12.2)	6 (13.0)	0.38	0.21
Endoscopy	3,343 (10.0)	6 (7.0)	13 (6.9)	1 (2.2)	0.46	0.36
Hospital stay in days, mean (SD)	4.46 (5.6)	4.38 (5.7)	3.95 (3.4)	3.26 (2.1)	0.32	0.45
Readmission for UGI bleed within 30 days of discharge	1,295 (3.9)	36 (41.9)	93 (49.5)	25 (54.4)	0.33	0.21

Note:

# There was no significant difference between cases and controls across dosage groups.

Abbreviations: UGI, upper gastrointestinal; SD, standard deviation; N, total number of patients; n, subgroup number of patients.

Figure 2 Adjusted OR and 95% CI for concomitant exposure to duloxetine, NSAIDs, and aspirin was not associated with an increased risk for UGI bleeding as compared with the risk from exposure to duloxetine only.

Abbreviations: OR, odds ratio; CI, confidence interval; NSAIDs, nonsteroidal anti-inflammatory drugs; UGI, upper gastrointestinal; vs, versus.

Figure 3 Adjusted OR (95% CI) for the risk of UGI in patients across medication exposure groups.

Note: An OR of 1 is equal to the risk of UGI bleeding in patients who had no exposure to these medications.
Abbreviations: OR, odds ratio; CI, confidence interval; UGI, upper gastrointestinal; NSAIDs, nonsteroidal anti-inflammatory drugs.