PLATELET ACTIVITY IS ASSOCIATED WITH INCIDENCE OF MAJOR BLEEDING IN PERIPHERAL ARTERY DISEASE PATIENTS UNDERGOING LOWER EXTREMITY REVASCULARIZATION

Intensive antithrombotic therapy reduces major adverse cardiovascular events (MACE) and major adverse limb events (MALE) in patients with peripheral artery disease (PAD). Recent studies have suggested heterogeneity in risk and benefit in those with and without concomitant coronary artery disease (CAD) and peripheral revascularization. We evaluated the risk of MACE and MALE in patients with PAD stratified by history of concomitant CAD and prior peripheral revascularization and whether the efficacy and safety of vorapaxar were similar in these subgroups. The TRA 2°P-TIMI 50 trial randomized 26,449 patients with prior MI, ischemic stroke, or PAD to vorapaxar or placebo. This analysis examined the effect of vorapaxar in a broad population of 6136 patients with PAD. Overall, vorapaxar significantly reduced MACE (HR 0.85, 95% CI 0.73, 0.99; p = 0.034) and MALE (HR 0.70, 95% CI 0.53, 0.92; p = 0.011) in patients with PAD. The absolute risk reduction (ARR) for MACE was greater in patients with PAD and CAD versus those with PAD alone (–2.2% vs 0.1%: number needed to treat (NNT) 45 vs 1000). Conversely, the ARR for MALE was higher in those with prior lower extremity revascularization (2.5% vs 0.2%: NNT 40 vs 500). Vorapaxar increased major bleeding (HR 1.39, 95% CI 1.12, 1.71; p = 0.003). The net clinical outcome in all patients with PAD was reduced with vorapaxar (HR 0.82, 95% CI 0.72, 0.94; p = 0.004), with benefits driven by reductions in MACE for those with CAD and by reductions in MALE for those with prior peripheral revascularization. Among patients with PAD, vorapaxar resulted in a net clinical benefit; however, the drivers of benefit were heterogeneous, with greater reductions in MACE in those with concomitant CAD and greater reductions in MALE in those with prior lower extremity revascularization, and unclear benefit in patients with neither. These clinical characteristics may be useful in identifying the subgroups of patients with PAD most likely to benefit from potent antithrombotic therapies. ClinicalTrials.gov Identifier: NCT00526474

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Letter by Moris et al Regarding Article, “Ticagrelor Compared With Clopidogrel in Patients With Prior Lower Extremity Revascularization for Peripheral Artery Disease”

Circulation ◽

10.1161/circulationaha.116.026865 ◽

2017 ◽

Vol 135 (23) ◽

Author(s):

Demetrios Moris ◽

Nikolaos Patelis ◽

Stavros Kakkos

Keyword(s):

Lower Extremity ◽

Peripheral Artery Disease ◽

Peripheral Artery ◽

Artery Disease ◽

Lower Extremity Revascularization

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Comparative effectiveness study of self-directed walking exercise, lower extremity revascularization, and functional decline in peripheral artery disease

Journal of Vascular Surgery ◽

10.1016/j.jvs.2012.09.068 ◽

2013 ◽

Vol 57 (4) ◽

pp. 990-996.e1 ◽

Cited By ~ 14

Author(s):

Mary M. McDermott ◽

Melina Kibbe ◽

Jack M. Guralnik ◽

William H. Pearce ◽

Lu Tian ◽

...

Keyword(s):

Lower Extremity ◽

Peripheral Artery Disease ◽

Comparative Effectiveness ◽

Functional Decline ◽

Effectiveness Study ◽

Peripheral Artery ◽

Comparative Effectiveness Study ◽

Walking Exercise ◽

Artery Disease ◽

Lower Extremity Revascularization

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Ankle-Brachial Index for Risk Stratification in Patients With Symptomatic Peripheral Artery Disease With and Without Prior Lower Extremity Revascularization: Observations From the EUCLID Trial

Circulation Cardiovascular Interventions ◽

10.1161/circinterventions.120.009871 ◽

2021 ◽

Author(s):

William R. Hiatt ◽

Connie N. Hess ◽

Marc P. Bonaca ◽

Sarah Kavanagh ◽

Manesh R. Patel ◽

...

Keyword(s):

Lower Extremity ◽

Peripheral Artery Disease ◽

Ankle Brachial Index ◽

Cubic Spline ◽

Hazard Ratio ◽

Acute Limb Ischemia ◽

Peripheral Artery ◽

Increased Risk ◽

Artery Disease ◽

Lower Extremity Revascularization

Background: A reduced ankle-brachial index (ABI) is a measure of atherosclerosis and is associated with ischemic risk in the general population. Whether this relationship is maintained in peripheral artery disease after lower extremity revascularization (LER), which can modify ABI, is unknown. Methods: The EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) enrolled 13 885 patients with symptomatic peripheral artery disease; 57% with prior LER, and 43% with ABI ≤0.80. The primary major adverse cardiovascular events (MACE) outcome was a composite of cardiovascular death, myocardial infarction, or ischemic stroke. Major adverse limb events (MALE) included acute limb ischemia and major amputation. An adjusted Cox proportional hazards model demonstrated a nonlinear relationship between ABI and outcomes. A restricted cubic spline model with 4 knots was developed to identify the best fitting model to describe the relationship between ABI and MACE and MALE risk. Results: Baseline ABI (mean±SD) was 0.77±0.21 in participants with prior LER and 0.63±0.14 in those without prior LER ( P <0.0001). There was no statistical interaction between prior LER and ABI, meaning the shapes of the cubic spline models were similar between groups. In those with prior LER, for every 0.10 unit lower ABI below an ABI of 1.00, the hazard ratio for MACE was 1.08 (95% CI, 1.04–1.12; P <0.0001), below an ABI of 0.80 the hazard ratio for MALE was 1.32 (95% CI, 1.21–1.43; P <0.0001). In patients without prior LER, every 0.10 unit lower ABI below an ABI of 0.70 was associated with increased risk for MACE (hazard ratio, 1.14 [95% CI, 1.06–1.23]; P =0.0004) and MALE (hazard ratio, 1.27 [95% CI, 1.08–1.49]; P =0.003). Conclusions: Patients with established peripheral artery disease, particularly those with prior LER, have an increased risk of MACE and MALE. The ABI remains a strong predictor of MACE and MALE ischemic events with an inverse relationship below an ABI threshold for patients with and without prior LER. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01732822.

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Chronic kidney disease and outcomes of lower extremity revascularization for peripheral artery disease

Atherosclerosis ◽

10.1016/j.atherosclerosis.2019.12.016 ◽

2020 ◽

Vol 297 ◽

pp. 149-156 ◽

Cited By ~ 3

Author(s):

Nathaniel R. Smilowitz ◽

Nipun Bhandari ◽

Jeffrey S. Berger

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Lower Extremity ◽

Peripheral Artery Disease ◽

Peripheral Artery ◽

Artery Disease ◽

Lower Extremity Revascularization

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Antiplatelet therapy with or without anticoagulant therapy for lower extremity peripheral artery disease: A systematic review

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxab226 ◽

2021 ◽

Author(s):

Donna Rahmatian ◽

Arden R Barry

Keyword(s):

Lower Extremity ◽

Antiplatelet Therapy ◽

Peripheral Artery Disease ◽

Anticoagulant Therapy ◽

Major Bleeding ◽

Low Dose ◽

Risk Of Bias ◽

Major Adverse Cardiovascular Events ◽

Peripheral Artery ◽

Artery Disease

Abstract Purpose To identify randomized controlled trials that compared antiplatelet monotherapy to combination antiplatelet plus anticoagulant therapy and evaluated major adverse cardiovascular events (MACE) or major adverse limb events (MALE), death, or bleeding in patients with lower extremity peripheral artery disease (PAD). Summary A systematic search of MEDLINE, Embase, and CENTRAL databases revealed 5 trials. Two trials consisted of patients with stable PAD, while 3 trials examined patients with PAD post revascularization. Antiplatelet therapy was mostly aspirin (81-325 mg daily), and anticoagulation included rivaroxaban 2.5 mg twice daily or warfarin. Duration of follow-up ranged from 12 to 38 months. Two trials had low risk of bias, whereas 3 trials had high/unclear risk of bias. For patients with stable PAD, one trial showed that use of warfarin (or acenocoumarol) with antiplatelet therapy did not reduce MACE, MALE, or cardiovascular or all-cause death but increased the risk of life-threatening bleeding. A second trial demonstrated that low-dose rivaroxaban plus antiplatelet therapy lowered the risk of MACE and MALE, with no effect in preventing cardiovascular or all-cause death, but increased the risk of major bleeding. For patients with PAD post revascularization receiving warfarin and antiplatelet therapy, 2 trials showed no benefit in MACE or MALE but increased or similar rates of all-cause death and major bleeding. In a third trial, low-dose rivaroxaban plus aspirin reduced occurrence of the composite of MACE and MALE but increased major bleeding, with no effect on cardiovascular or all-cause death. Conclusion Dual-pathway inhibition with low-dose rivaroxaban and aspirin reduced MACE and MALE in patients with stable or revascularized PAD, but net clinical benefit is questionable.

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