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Table 1. Comparison of Primary Prevention Trials of Aspirin That Enrolled Patients With Diabetes (N=11 787)

Study/Year (Ref.)	Aspirin Dose (Study Design)	Follow-Up (Years)	Number Enrolled With Diabetes	% Female	Age (Years) (Minimum/Mean)	CHD Endpoint	CHD Endpoint Event Rate (Control vs. Aspirin)	10-Year Extrapolated CHD Event Ratesi	RR (95% CI)ii	Stroke Events for Aspirin vs. Control: RR (95% CI)
PHS DM/1989 (12)	325 mg every other day (2 × 2 factorial design with 50 mg beta carotene)	5.0	533	70	>40/NA	Fatal + nonfatal MI	10.5% vs. 6.2%iii (27/258 vs. 17/275)	21% vs. 12.4%	0.59 (0.33–1.06)	16 vs. 10: 1.50 (0.69–3.25)
ETDRS/1992 (18)	650 mg daily	5.0	3711	44	>18/NA	Fatal + nonfatal MI	15.3% vs. 13.0% (283/1855 vs. 241/1856)	30.6% vs. 26.0%	0.85 (0.73–1.00)	92 vs. 78: 1.18 (0.88–1.58)
PPP DM/2003iv (16)	100 mg daily (2 × 2 design with 30 mg vitamin E)	3.7	1031	52	>50/64	Fatal + nonfatal MI	2.0% vs. 1.0% (10/512 vs. 5/519)	5.4% vs. 2.7%	0.49 (0.17–1.43)	10 vs. 11: 0.90 (0.38–2.09)
WHS DM/2005 (17)	100 mg every other day (2 × 2 factorial design with 600 IU vitamin E every other day)	10.1	1027	100	>45/55	Fatal + nonfatal MIv	5.9% vs. 7.9% (29/494 vs. 42/533)	5.9% vs. 7.9%	1.34 (0.85–2.12)	15 vs. 31: 0.45 (0.25–0.82)
JPAD/2008 (10)	81–100 mg daily (open label treatment assignment, blinded endpoint assessment)	4.4	2539	46	>30/65	Fatal + nonfatal MI	1.1% vs. 1.0% (14/1277 vs. 12/1262)	2.5% vs. 2.3%	0.87 (0.40–1.87)	22 vs. 34: 0.65 (0.39–1.11)
POPADAD/2008 (9)	100 mg daily (2 × 2 factorial design including anti-oxidants)	6.7	1276	56	>40/60	CHD death + nonfatal MI	12.9% vs. 13.9% (82/638 vs. 89/638)	19.3% vs. 20.7%	1.09 (0.82–1.44)	37 vs. 50: 0.74 (0.49–1.12)
TPT DM/1998 (data from ATT) (5)	75 mg daily	6.7	68	0	>45/58	MCE	15.4% vs. 13.8% (6/39 vs. 4/29)	23.0% vs. 20.6%	0.90 (0.28–2.89)	1 vs. 2: 0.67 (0.06–7.06)
BMD/1988 (data from ATT) (5)	500 mg daily	5.6	101	0	>50/NA	MCE	18.8% vs. 18.8% (6/32 vs. 13/69)	33.48% vs. 33.6%	1.00 (0.42–2.40)	3 vs. 1: 1.39 (0.15–12.86)
HOT DM/1998 (data from ATT) (5)	75 mg daily (co-randomized to one of three diastolic BP goals)	3.8	1501	47	>50/62	MCE	3.6% vs. 2.8% (27/749 vs. 21/752)	9.5% vs. 7.3%	0.77 (0.44–1.36)	22 vs. 24: 0.91 (0.52–1.61)

ⁱ 10-year extrapolated CHD event rate calculated by (10 ÷ study duration) × event rate. ⁱⁱ Calculated based on event counts. ⁱⁱⁱ Values slightly different from original PHS report based on updated ICD-9 coding information obtained by the ATT trialists. ^iv Data used from 2003 PPP diabetic substudy (16); number with diabetes is discrepant from original PPP publication (15) due to continued enrollment and follow-up of diabetic patients beyond the original study period. ^v Event rates slightly different than original 2005 report due to 11 extra MI/CHD deaths (6 in aspirin group and 5 in placebo) reported to the ATT study group vs. original publication.
ATT indicates Antithrombotic Trialists' Collaboration; CHD, coronary heart disease; DM, diabetes mellitus; IU, international unit; MCE, major coronary event (CHD death + nonfatal MI + sudden death); MI, myocardial infarction; NA, not available; and RR, relative risk.

The effect of aspirin for primary prevention of CVD events in adults with diabetes is currently unclear. Trials to date have reached mixed results, but overall suggest that aspirin modestly reduces risk of cardiovascular events. More research is needed to better define the specific effects of aspirin in diabetes, including any sex-specific differences. For now, we recommend the following:

Low-dose (75 to 162 mg/day) aspirin use for prevention is reasonable for adults with diabetes and no previous history of vascular disease who are at increased CVD risk (10 year risk of CVD events over 10%) and who are not at increased risk for bleeding (based on a history of previous gastrointestinal bleeding or peptic ulcer disease or concurrent use of other medications that increase bleeding risk, such as NSAIDS or warfarin). Those adults with diabetes at increased CVD risk include most men over age 50 years and women over age 60 years who have one or more of the following additional major risk factors: smoking, hypertension, dyslipidemia, family history of premature CVD, and albuminuria. (ACCF/AHA Class IIa, Level of Evidence: B) (ADA Level of Evidence: C)
Aspirin should not be recommended for CVD prevention for adults with diabetes at low CVD risk (men under age 50 years and women under 60 years with no major additional CVD risk factors; 10-year CVD risk under 5%) as the potential adverse effects from bleeding offset the potential benefits. (ACCF/AHA Class III, Level of Evidence: C) (ADA Level of Evidence: C)
Low-dose (75 to 162 mg/day) aspirin use for prevention might be considered for those with diabetes at intermediate CVD risk (younger patients with one or more risk factors, or older patients with no risk factors, or patients with 10-year CVD risk of 5% to 10%) until further research is available. (ACCF/AHA Class IIb, Level of Evidence: C) (ADA Level of Evidence: E)