Table 2.
Summary SOE for Comparative Effectiveness and Safety of Antiplatelet Therapy for Adults With PAD
| Outcome SOE | Results or Effect Estimate (95% CI) |
|---|---|
| Aspirin vs placebo in adults with asymptomatic or symptomatic PAD at 2+ years | |
| Asymptomatic population | |
| All‐cause mortality SOE=high |
2 RCTs, 3986 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, 3986 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, 3986 patients HR 0.71 (0.44 to 1.14) HR 0.97 (0.62 to 1.53) No difference |
| CV mortality SOE=moderate |
2 RCTs, 3986 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, 3986 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, 3986 patients Inconclusive evidence owing to imprecision, with 1 study reporting similar rates of CV outcomes by age, sex, or baseline ABI and 1 study reporting similar rates of CV mortality and stroke by diabetic status |
| Safety concerns SOE=insufficient |
2 RCTs, 3986 patients Inconclusive evidence due to heterogeneous results between aspirin and placebo in regard to major hemorrhage and GI bleeding rates |
| IC population | |
| Nonfatal 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 owing to imprecision |
| CV mortality SOE=insufficient |
1 RCT, 181 patients HR 1.21 (0.32 to 4.55) Inconclusive evidence owing 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 owing to imprecision, with 1 study reporting similar rates in vessel patency by sex |
| Safety concerns SOE=insufficient |
1 RCT, 181 patients Inconclusive evidence owing to imprecision, with 1 study reporting a bleeding rate of 3% in aspirin group and 0% in placebo group |
| CLI population | |
| Nonfatal MI SOE=insufficient |
1 observational study, 113 patients Inconclusive evidence owing 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 owing to imprecision, with 1 study reporting stroke rate of 2.5% in aspirin group and 8.8% in no‐aspirin group |
| CV mortality SOE=insufficient |
1 observational study, 113 patients Inconclusive evidence owing to imprecision, with 1 study reporting CV 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, 6452 patients HR 0.62 (0.43 to 0.88) Favors clopidogrel |
| Nonfatal stroke SOE=low |
1 RCT, 6452 patients HR 0.95 (0.68 to 1.31) No difference |
| CV mortality SOE=moderate |
1 RCT, 6452 patients HR 0.76 (0.64 to 0.91) Favors clopidogrel |
| Composite CVEs SOE=moderate |
1 RCT, 6452 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 |
| Clopidogrel/aspirin vs aspirin in adults with PAD at 2 years | |
| Symptomatic‐asymptomatic population (CHARISMA) | |
| All‐cause mortality SOE=moderate |
1 RCT, 3096 patients HR 0.89 (0.68 to 1.16) No difference |
| Nonfatal MI SOE=low |
1 RCT, 3096 patients HR 0.63 (0.42 to 0.95) Favors dual antiplatelet |
| Nonfatal stroke SOE=low |
1 RCT, 3096 patients HR 0.79 (0.51 to 1.22) No difference |
| CV mortality SOE=low |
1 RCT, 3096 patients HR 0.92 (0.66 to 1.29) No difference |
| Composite CVEs SOE=moderate |
1 RCT, 3096 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, 3096 patients Inconclusive evidence owing 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 owing to imprecision |
| Nonfatal stroke SOE=low |
1 RCT, 851 patients CASPAR, HR 1.02 (0.41 to 2.55) No difference |
| CV mortality SOE=insufficient |
1 RCT, 851 patients CASPAR, HR 1.44 (0.77 to 2.69) Inconclusive evidence owing to imprecision |
| Composite CVEs SOE=low (CASPAR) SOE=insufficient (MIRROR) |
2 RCTs, 931 patients CASPAR, HR 1.09 (0.65 to 1.82), no difference MIRROR, OR 0.71 (0.28 to 1.81), inconclusive evidence owing to imprecision |
| Revacularization SOE=insufficient |
2 RCTs, 931 patients CASPAR, HR 0.89 (0.65 to 1.23) MIRROR, 5% dual therapy vs 20% aspirin, P=0.04 Inconclusive evidence owing to imprecision and study heterogeneity |
| Functional outcomes Quality of life Safety concerns (subgroups) SOE=insufficient |
0 studies |
| Modifiers of effectiveness (subgroups) SOE=insufficient |
1 RCT, 851 patients Inconclusive evidence owing to imprecision, with 1 study reporting that patients with prosthetic graft had lower CV events on DAPT |
| Safety concerns SOE=insufficient |
3 RCTs, 1034 patients Inconclusive evidence owing 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 GI bleeding or hematoma; MIRROR study showed no significant difference in bleeding |
ABI indicates ankle‐brachial index; ASA, acetylsalicylic acid; CI, confidence interval; CLI, critical limb ischemia; CV, cardiovascular; CVEs, cardiovascular events; DAPT, dual antiplatelet therapy; GI, gastrointestinal; HR, hazard ratio; IC, intermittent claudication; OR, odds ratio; RCT, randomized, controlled trial; SOE, strength of evidence.
Adapted from Jones et al.2