Table 3.
Cardiovascular Outcomes from Clinical Studies of Polyvascular Disease
| Data Source | Study Type | Qualifying Vascular Territories | Patients with PAD/Total Sample (%) | Definition of MACEs | Impact on MACEs | Definition of MALEs | Impact on MALEs |
|---|---|---|---|---|---|---|---|
| CRUSADE131 | Observational Registry | CAD – A or S PAD – S CVD – S |
11,345/111,972 (10.1) | In-hospital mortality, MI, stroke, and HF | 1 bed: OR 1.07 (95% CI, 1.02–1.12) 2 beds: OR 1.25 (95% CI, 1.18–1.33) 3 beds: OR 1.31 (95% CI, 1.15–1.46) |
-- | -- |
| REACH120 | Observational Registry | CAD – S PAD – S CVD – S |
5,872/68,236 (8.6) | MI, stroke, or cardiovascular mortality | Polyvascular disease vs. atherosclerotic risk factors: HR 1.99 (95% CI, 1.78–2.24) | -- | -- |
| MarketScan + Medicare126 | Observational Claims Data | CAD – A-S PAD – A-S CVD – A-S |
156,129/943,232 (16.6) | MI, coronary revascularization, stroke, carotid revascularization, ALI, lower extremity revascularization, or amputation | 2 vs. 1 bed: HR 1.45 (95% CI, 1.42–1.48) 3 vs. 1 bed: HR 2.08 (95% CI, 2.03–2.14) |
ALI, lower extremity revascularization, or amputation | 2 vs. 1 bed: HR 2.18 (95% CI, 2.02–2.36) 3 vs. 1 bed: HR 3.91 (95% CI, 3.58–4.28) |
| CAPRIE132 | Randomized Controlled Trial | CAD – S PAD – S CVD – S |
6,452/19,185 (33.6) | MI, stroke, or cardiovascular mortality | Polyvascular vs. single bed: RRR 12.4%; ARR 2.45%; NNT 41 | -- | -- |
| TRA 2°P-TIMI 50133 | Randomized Controlled Trial | CAD – S PAD – S CVD – S |
3,787/26,449 (14.3) | MI, stroke, or cardiovascular mortality at 3 years | 1 bed: 7.8% 2 beds: 14.7% 3 beds: 21.7% |
Lower extremity revascularization | 1 bed: 7.8% 2 beds: 14.7% 3 beds: 21.7% |
| FOURIER104 | Randomized Controlled Trial | CAD – S PAD – S CVD – S |
3,642/27,564 (13.2) | MI, stroke, or cardiovascular mortality | Kaplan-Meier incidence rate at 30 months PAD + MI or stroke: 14.9% PAD only: 10.3% MI or stroke only: 7.6% |
-- | -- |
| PEGASUS-TIMI 54134 | Randomized Controlled Trial | CAD – S PAD – A or S |
1,143/21,162 (5.4) | MI, stroke, or cardiovascular mortality | PAD + CAD vs. PAD: HR 1.60 (95% CI, 1.20–2.13) | -- | -- |
| EUCLID135 | Randomized Controlled Trial | CAD – S PAD – A or S CVD – S |
13,885/13,885 (100.0) | MI, stroke, or cardiovascular mortality | PAD + cerebrovascular disease: HR 1.34 (95% CI, 1.15–1.57) PAD + CAD: HR 1.65 (95% CI, 1.43–1.91) PAD + CAD + cerebrovascular disease: HR 1.99 (95% CI, 1.69–2.34) |
Lower extremity revascularization | PAD + CVD: HR 1.17 (95% CI, 1.02–1.35) PAD + CAD: HR 1.17 (95% CI, 1.03–1.34) PAD + CAD + CVD: HR 1.34 (95% CI, 1.15–1.57) |
| SAVOR-TIMI 53123 | Randomized Controlled Trial | CAD – S PAD – S CVD – S |
1,959/16,492 (11.9) | MI, stroke, or cardiovascular mortality | 1 bed: HR 1.95 (95% CI, 1.63–2.35) 2 beds: HR 3.54 (95% CI, 2.84–4.43) 3 beds: HR 4.64 (95% CI, 2.87–7.15) |
-- | -- |
| LEADER124 | Randomized Controlled Trial | CAD – A,S PAD – S CVD – A or S |
1,184/9,340 (12.7) | MI, stroke, or cardiovascular mortality | Polyvascular vs. single bed: HR 1.52 (95% CI, 1.33–1.73) | -- | -- |
| IMPROVE-IT125 | Randomized Controlled Trial | CAD – S PAD – A or S CVD – S |
1,005/18,144 (5.5) | MI, stroke, or cardiovascular mortality | Polyvascular vs. single bed: HR 1.55 (95% CI, 1.41–1.70) | Lower extremity revascularization | Polyvascular vs. single bed: HR 4.77 (95% CI, 3.75–6.06) |
| Amputation | Polyvascular vs. single bed: HR 5.96 (95% CI, 2.74–12.94) |
A refers to asymptomatic; A-S, symptoms not assessed in qualifying events; ALI, acute limb ischemia; ARR, absolute risk reduction; CAD, coronary artery disease; CAPRIE, Clopidogrel vs. Aspirin in Patients at Risk of Ischemic Events; CI, confidence interval; COMPASS, Cardiovascular Outcomes for People Using Anticoagulation Strategies; CRUSADE, Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines; CVD, cerebrovascular disease; EUCLID, Effects of Ticagrelor and Clopidogrel in Patients with Peripheral Artery Disease; FOURIER, Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk; HF, heart failure; HR, hazard ratio; IMPROVE-IT, Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LEADER, Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Results; MACE, major adverse cardiovascular events; MALE, major adverse limb events; MI, myocardial infarction; OR, odds ratio; PAD refers to peripheral artery disease; PEGASUS-TIMI 54, Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin; REACH, Reduction of Atherothrombosis for Continued Health; RRR, relative risk reduction; S, symptomatic; SAVOR-TIMI 53, Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-TIMI 53; TRA2°P-TIMI 50=Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients With Atherosclerosis-TIMI 50