Table ASummary SOE for KQ 1: Comparative effectiveness and safety of antiplatelet therapy for adults with PADa

ComparisonPopulationOutcome
SOE
Results or Effect Estimate (95% Confidence Interval)
Aspirin vs. placebo in adults with asymptomatic or symptomatic PAD at 2+ yearsAsymptomatic populationAll-cause mortality

SOE=High
2 RCTs, 3,986 patients
HR 0.93 (0.71 to 1.24)
HR 0.95 (0.77 to 1.16)
No difference
Nonfatal MI

SOE=High
2 RCTs, 3,986 patients
HR 0.98 (0.68 to 1.42)
HR 0.91 (0.65 to 1.29)
No difference
Nonfatal stroke

SOE=High
2 RCTs, 3,986 patients
HR 0.71 (0.44 to 1.14)
HR 0.97 (0.62 to 1.53)
No difference
Cardiovascular mortality

SOE=Moderate
2 RCTs, 3,986 patients
HR 1.23 (0.79 to 1.92)
HR 0.95 (0.77 to 1.17)
No difference
Composite vascular events

SOE=High
2 RCTs, 3,986 patients
HR 0.98 (0.76 to 1.26)
HR 1.00 (0.85 to 1.17)
No difference
Functional outcomes
Quality of life
Safety concerns (subgroups)

SOE=Insufficient
0 studies
Modifiers of effectiveness (subgroups)

SOE=Insufficient
2 RCTs, 3,986 patients
Inconclusive evidence due to imprecision, with 1 study reporting similar rates of cardiovascular outcomes by age, sex, or baseline ABI and 1 study reporting similar rates of cardiovascular mortality and stroke by diabetic status.
Safety concerns

SOE=Insufficient
2 RCTs, 3,986 patients
Inconclusive evidence due to heterogeneous results between aspirin and placebo in regard to major hemorrhage and GI bleeding rates.
IC populationNonfatal MI

SOE=Low
1 RCT, 181 patients
HR 0.18 (0.04 to 0.82)
Favors aspirin.
Nonfatal stroke

SOE=Insufficient
1 RCT, 181 patients
HR 0.54 (0.16 to 1.84)
Inconclusive evidence due to imprecision.
Cardiovascular mortality

SOE=Insufficient
1 RCT, 181 patients
HR 1.21 (0.32 to 4.55)
Inconclusive evidence due to imprecision.
Composite vascular events

SOE=Low
1 RCT, 181 patients
HR 0.35 (0.15 to 0.82)
Favors aspirin.
Functional outcomes
Quality of life
Safety concerns (subgroups

SOE=Insufficient
0 studies
Modifiers of effectiveness (subgroups)

SOE=Insufficient
1 RCT, 216 patients
Inconclusive evidence due to imprecision, with 1 study reporting similar rates in vessel patency by sex.
Safety concerns

SOE=Insufficient
1 RCT, 181 patients
Inconclusive evidence due to imprecision, with 1 study reporting a bleeding rate of 3% in aspirin group and 0% in placebo group.
CLI populationNonfatal MI

SOE=Insufficient
1 observational study, 113 patients
Inconclusive evidence due to imprecision, with 1 study reporting MI rate of 1.2% in aspirin group and 5.9% in no-aspirin group.
Nonfatal stroke

SOE=Insufficient
1 observational study, 113 patients
Inconclusive evidence due to imprecision, with 1 study reporting stroke rate of 2.5% in aspirin group and 8.8% in no-aspirin group.
Cardiovascular mortality

SOE=Insufficient
1 observational study, 113 patients
Inconclusive evidence due to imprecision, with 1 study reporting cardiovascular mortality rate of 33% in aspirin group and 26% in no-aspirin group‥
Functional outcomes
Quality of life
Modifiers of effectiveness (subgroups)
Safety concerns
Safety concerns (subgroups)

SOE=Insufficient
0 studies
Clopidogrel vs. aspirin in adults with IC at 2 years (CAPRIE)Nonfatal MI

SOE=Moderate
1 RCT, 6,452 patients
HR 0.62 (0.43 to 0.88)
Favors clopidogrel.
Nonfatal stroke

SOE=Low
1 RCT, 6,452 patients
HR 0.95 (0.68 to 1.31)
No difference.
Cardiovascular mortality

SOE=Moderate
1 RCT, 6,452 patients
HR 0.76 (0.64 to 0.91)
Favors clopidogrel.
Composite cardiovascular events

SOE=Moderate
1 RCT, 6,452 patients
HR 0.78 (0.65 to 0.93)
Favors clopidogrel.
All-cause mortality
Functional outcomes
Quality of life
Modifiers of effectiveness (subgroups)
Safety concerns
Safety concerns (subgroups)

SOE=Insufficient
0 studies
Symptomatic–asymptomatic population (CHARISMA)All-cause mortality

SOE=Moderate
1 RCT, 3,096 patients
HR 0.89 (0.68 to 1.16)
No difference.
Nonfatal MI

SOE=Low
1 RCT, 3,096 patients
HR 0.63 (0.42 to 0.95)
Favors dual antiplatelet.
Nonfatal stroke

SOE=Low
1 RCT, 3,096 patients
HR 0.79 (0.51 to 1.22)
No difference.
Cardiovascular mortality

SOE=Low
1 RCT, 3,096 patients
HR 0.92 (0.66 to 1.29)
No difference.
Composite cardiovascular events

SOE=Moderate
1 RCT, 3,096 patients
HR 0.85 (0.66 to 1.09)
No difference.
Functional outcomes
Quality of life
Safety concerns (subgroups) Modifiers of effectiveness (subgroups)

SOE=Insufficient
0 studies
Safety concerns

SOE=Insufficient
1 RCT, 3,096 patients
Inconclusive evidence due to low rates of severe and moderate bleeding, although minor bleeding was significantly higher with DAPT (34.4%) vs. ASA (20.8%).
IC–CLI population (CASPAR, MIRROR, Cassar)All-cause mortality

SOE=Insufficient
2 RCTs, 931 patients
CASPAR, HR 1.44 (0.77 to 2.69)
MIRROR, OR 0.33 (0.01 to 8.22)
Inconclusive evidence due to imprecision.
Nonfatal MI

SOE=Insufficient
1 RCT, 851 patients
CASPAR, HR 0.81 (0.32 to 2.06)
Inconclusive evidence due to imprecision.
Nonfatal stroke

SOE=Low
1 RCT, 851 patients
CASPAR, HR 1.02 (0.41 to 2.55)
No difference.
Cardiovascular mortality

SOE=Insufficient
1 RCT, 851 patients
CASPAR, HR 1.44 (0.77 to 2.69)
Inconclusive evidence due to imprecision.
Composite cardiovascular events2 RCTs, 931 patients
CASPAR, HR 1.09 (0.65 to 1.82), No difference
SOE=Low (CASPAR) SOE=Insufficient (MIRROR)MIRROR, OR 0.71 (0.28 to 1.81),
Inconclusive evidence due to imprecision.
Functional outcomes
Quality of life
Safety concerns (subgroups)

SOE=Insufficient
0 studies
Modifiers of effectiveness (subgroups)

SOE=Insufficient
1 RCT, 851 patients
Inconclusive evidence due to imprecision, with 1 study reporting that patients with prosthetic graft had lower cardiovascular events on DAPT.
Safety concerns

SOE=Insufficient
3 RCTs, 1,034 patients
Inconclusive evidence due to inconsistent results from individual studies: CASPAR study showed statistically significant higher rates of moderate and minor bleeding with DAPT; Cassar study showed more bruising with DAPT but no significant difference in gastrointestinal bleeding or hematoma; MIRROR study showed no significant difference in bleeding.
a

Grey background indicates insufficient SOE.

Abbreviations: ABI=ankle-brachial index; CLI=critical limb ischemia; DAPT=dual antiplatelet therapy; HR=hazard ratio; IC=intermittent claudication; OR=odds ratio; RCT=randomized controlled trial; SOE=strength of evidence.

Grey background indicates insufficient SOE.

From: Executive Summary

Cover of Treatment Strategies for Patients With Peripheral Artery Disease
Treatment Strategies for Patients With Peripheral Artery Disease [Internet].
Comparative Effectiveness Reviews, No. 118.
Jones WS, Schmit KM, Vemulapalli S, et al.

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