Table 4.

Studies Reporting Safety Concerns

Study Population	Study Type Total N Comparison Quality	Harm(s) (Length of Follow‐up)	Results Reported by Authors
Belch et al4 POPADAD study Patients with diabetes mellitus and asymptomatic PAD	RCT Total N: 636 ASA vs placebo Good	GI bleeding, GI symptoms, arrhythmia, rash (6.7 y)	GI bleeding: ASA 13 (4%), placebo 18 (6%) GI symptoms: ASA 40 (13%), placebo 58 (18%) Arrhythmia: ASA 27 (9%), placebo 25 (8%) Rash: ASA 38 (12%), placebo 30 (9%)
Fowkes et al5 Patients with asymptomatic PAD and no previous CVD	RCT Total N: 3350 ASA vs placebo Good	Major hemorrhage (hemorrhagic stroke, subarachnoid/subdural hemorrhage, GI bleeding), GI ulcer, retinal hemorrhage, severe anemia (10 y)	Major hemorrhage: ASA 2.0%, placebo 1.2% GI ulcer: ASA 0.8%, placebo 0.5% Retinal hemorrhage: ASA 0.1%, placebo 0.2% Severe anemia: ASA 25, placebo 16
Catalano et al6 CLIPS study Patients with IC	RCT Total N: 181 ASA vs placebo Fair	Bleeding (2 y)	ASA 3% (1 melena, 2 retinal hemorrhage, 1 epistaxis), placebo 0%
Cacoub et al11 CHARISMA study PAD subgroup (92% CI, 8% asymptomatic)	RCT Total N: 3096 Clopidogrel/ASA vs ASA Good	Bleeding (based on GUSTO criteria) (28 m)	Severe bleeding Clopidogrel/ASA 1.7%, ASA 1.7%, P=0.90 Moderate bleeding: Clopidogrel/ASA 2.5%, ASA 1.9%, P=0.26 Minor bleeding: Clopidogrel/ASA 34.4%, ASA 20.8%, P<0.001
Cassar et al14 Patients with IC status post‐PTA	RCT Total N: 132 Clopidogrel/ASA vs. ASA Good	GI bleeding, rash, hematoma, bruising (30 days)	GI bleeding: Clopidogrel/ASA 1, ASA 0 Rash: Clopidogrel/ASA 2, ASA 2 Hematoma: Clopidogrel/ASA 2 peripheral and 1 retroperitoneal ASA 2 Bruising: Clopidogrel/ASA 25, ASA 16
Belch et al15 CASPAR study Patients with IC or CLI status postunilateral bypass graft	RCT Total N: 851 Clopidogrel/ASA vs ASA Good	Bleeding (based on GUSTO criteria) (2 y)	All Bleeding: Clopidogrel 71 (16.7%), placebo 30 (7.1%), P=0.001 Severe bleeding: Clopidogrel 9 (2.1%); placebo 5 (1.2%), P=NS Moderate bleeding: clopidogrel 16 (3.8%); placebo 4 (0.9%), P=0.007 Mild bleeding: Clopidogrel 46 (10.8%); placebo 21 (5%), P=0.002
Tepe et al16 MIRROR study Patients with IC or CLI status post‐PTA	RCT Total N: 80 Clopidogrel/ASA vs ASA Good	Bleeding (6 m)	Bleeding: Clopidogrel 1 GI ulcer bleed (2.5%), placebo 2 minor access site bleeding (5%), P=0.559

ASA indicates acetylsalicylic acid; CI, confidence interval; CLI, critical limb ischemia; CVD, cardiovascular disease; GI, gastrointestinal; HR, hazard ratio; IC, intermittent claudication; m, month/months; N, number of patients; NS, not significant; PTA, percutaneous transluminal angioplasty; RCT, randomized, controlled trial; y, year/year.

Adapted from Jones et al.²