Abstract 14170: Reduction in Venous Thromboembolism With Rivaroxaban versus Placebo in Peripheral Artery Disease After Lower Extremity Revascularization: Insights From VOYAGER PAD

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Connie N Hess ◽  
Sonia Anand ◽  
Rupert Bauersachs ◽  
Manesh R Patel ◽  
E. Sebastian Debus ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Low Dose ◽  
Peripheral Artery ◽  
Atherosclerotic Vascular Disease ◽  
Thrombotic Risk ◽  
Artery Disease ◽  
Lower Extremity Revascularization ◽  
Over Time

Background: Prior studies suggest that atherosclerotic vascular disease may be associated with risk of venous thromboembolism (VTE), though the relationship remains uncertain and has not been well-studied in peripheral artery disease (PAD) after lower extremity revascularization (LER). Hypothesis: We hypothesized that patients with PAD undergoing LER are at risk for VTE and that this risk may be reduced by low-dose rivaroxaban plus aspirin versus aspirin alone. Methods: VOYAGER PAD randomized 6,564 PAD patients undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of aspirin 100 mg daily. Clopidogrel was allowed for up to 6 months. Patients could not be enrolled if they had an indication for therapeutic anticoagulation, including secondary prevention of VTE. Symptomatic VTE was a prespecified secondary endpoint. Results: Over a median of 28 months, there were 66 patients with VTE. In patients randomized to placebo, risk for VTE accrued steadily after randomization at a rate of ~0.5% per year resulting in a 3-year rate of 1.66%. Compared with placebo, rivaroxaban reduced the risk of VTE by 39% (HR 0.61, 95% CI 0.37-1.00, p=0.047), with benefit apparent early and sustained over time (Figure). The efficacy of rivaroxaban was not modified by use of clopidogrel at randomization (without clopidogrel HR 0.55, 95% CI 0.29, 1.07; with clopidogrel HR 0.69, 95% CI 0.32, 1.48; p-interaction = 0.67). Conclusions: PAD is associated with continuous and linearly increasing risk for VTE after LER. A strategy of low-dose rivaroxaban plus aspirin versus aspirin alone reduced this risk by 39% with benefits apparent early and continued over time. The addition of clopidogrel does not modify this benefit. VTE, along with arterial thrombotic events, is part of the adverse thrombotic risk profile in PAD patients, and low-dose rivaroxaban plus aspirin provides protection against venous and arterial thrombosis.

scholarly journals Reduction in Acute Limb Ischemia with Rivaroxaban versus Placebo in Peripheral Artery Disease after Lower Extremity Revascularization: Insights from VOYAGER PAD

Circulation ◽  
2021 ◽  
Author(s):  
Connie N. Hess ◽  
E. Sebastian Debus ◽  
Mark R. Nehler ◽  
Sonia S. Anand ◽  
Manesh R. Patel ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Cumulative Incidence ◽  
Low Dose ◽  
Limb Ischemia ◽  
Major Amputation ◽  
Acute Limb Ischemia ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Lower Extremity Revascularization

Background: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability, and mortality. Prior lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking. Methods: VOYAGER PAD (NCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke, or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan Meier estimates, and Cox proportional-hazards models were used to generate hazard ratios and associated confidence intervals. Analyses were performed as intention-to-treat. Results: Among 6,564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, prior LER, baseline ABI <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (HR 2.59, 95% CI 1.98-3.39) and major amputation (HR 24.87, 95% CI 18.68-33.12). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction 2.6% at 3 years, HR 0.67, 95% CI 0.55-0.82, P=0.0001), with benefit starting early (HR 0.45, 95% CI 0.24-0.85, P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and ICU stay, HR 0.58, 95% CI 0.40-0.83, P=0.003) and regardless of LER type (surgical vs endovascular revascularization, p-interaction=0.42) or clopidogrel use (p-interaction=0.59). Conclusions: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.

Effect of vorapaxar on cardiovascular and limb outcomes in patients with peripheral artery disease with and without coronary artery disease: Analysis from the TRA 2°P-TIMI 50 trial

2020 ◽  
Vol 25 (2) ◽  
pp. 124-132 ◽  
Author(s):  
Arman Qamar ◽  
David A Morrow ◽  
Mark A Creager ◽  
Benjamin M Scirica ◽  
Jeffrey W Olin ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Absolute Risk ◽  
Major Adverse Cardiovascular Events ◽  
Number Needed To Treat ◽  
Peripheral Artery ◽  
Artery Disease ◽  
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

scholarly journals 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

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.

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

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.

Time to Traverse Lesion Association with Outcomes in Lower Extremity Revascularization for Peripheral Artery Disease

2020 ◽  
Vol 231 (4) ◽  
pp. S360
Author(s):  
Pavitra Ravishankar ◽  
Alexander Harrison King ◽  
Jones P. Thomas ◽  
Karem Clementina Harth ◽  
Benjamin D. Colvard ◽  
...  
Keyword(s):  
Lower Extremity ◽  
Peripheral Artery Disease ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Lower Extremity Revascularization
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