Effect of Rivaroxaban and Aspirin in Patients with Peripheral Artery Disease Undergoing Surgical Revascularization: Insights from the VOYAGER PAD Trial

Circulation ◽  
2021 ◽  
Author(s):  
E. Sebastian Debus ◽  
Mark R. Nehler ◽  
Nicholas Govsyeyev ◽  
Rupert M. Bauersachs ◽  
Sonia S. Anand ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Placebo Group ◽  
Peripheral Artery Disease ◽  
Major Bleeding ◽  
Cumulative Incidence ◽  
Efficacy And Safety ◽  
Peripheral Artery ◽  
Safety Outcome ◽  
Fatal Bleeding ◽  
Artery Disease

Background: Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. VOYAGER PAD demonstrated that rivaroxaban significantly reduced this risk. The efficacy and safety of rivaroxaban has not been described in patients who underwent surgical LER. Methods: The VOYAGER PAD trial randomized patients with PAD after surgical and endovascular LER to rivaroxaban 2.5mg twice daily plus aspirin or matching placebo plus aspirin and followed for a median of 28 months. The primary endpoint was a composite of acute limb ischemia, major vascular amputation, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. International Society on Thrombosis and Haemostasis (ISTH) bleeding was a secondary safety outcome. All efficacy and safety outcomes were adjudicated by a blinded independent committee. Results: Of the 6564 randomized, 2185 (33%) underwent surgical LER and 4379 (67%) endovascular. Compared to placebo, rivaroxaban reduced the primary endpoint consistently regardless of LER method (p-interaction 0.43). Following surgical LER, the primary efficacy outcome occurred in 199 (18.4%) patients in the rivaroxaban group and 242 (22.0%) patients in the placebo group with a cumulative incidence at 3 years of 19.7% and 23.9%, respectively (HR 0.81, 95% CI 0.67 - 0.98; p=0.026). In the overall trial, TIMI major bleeding and ISTH major bleeding were increased with rivaroxaban. There was no heterogeneity for TIMI major bleeding (p-interaction 0.17) or ISTH major bleeding (p-interaction 0.73) based on LER approach. Following surgical LER, the principal safety outcome occurred in 11 (1.0%) patients in the rivaroxaban group and 13 (1.2%) patients in the placebo group; 3-year cumulative incidence 1.3% and 1.4% respectively (HR 0.88, 95% CI 0.39-1.95; p=0.75) Among surgical patients, the composite of fatal bleeding or intracranial hemorrhage (p=0.95) and postprocedural bleeding requiring intervention (p=0.93) were not significantly increased. Conclusions: The efficacy of rivaroxaban is associated with a benefit in surgical LER patients. While bleeding was increased with rivaroxaban plus aspirin, the incidence was low, with no significant increase in fatal bleeding, intracranial hemorrhage or postprocedural bleeds requiring intervention. Clinical Trial Registration: URL: https://clinicaltrials.gov Unique Identifier: NCT02504216

scholarly journals Incidence of myocardial infarction, heart failure, and cardiovascular mortality in patients with peripheral artery disease: nationwide trends between 1997 and 2016

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
S Kamil ◽  
T S G Sehested ◽  
K Houlind ◽  
J F Lassen ◽  
G Gislason ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Peripheral Artery Disease ◽  
Cumulative Incidence ◽  
Incidence Rates ◽  
Peripheral Artery ◽  
The Past ◽  
Artery Disease ◽  
First Time ◽  
Time Diagnosis

Abstract Background Over the past decades there has been a shift in cardiovascular (CV) risk factors with improved outcomes. Updated trends in incidence of myocardial infarction (MI) and heart failure (HF) in peripheral artery disease (PAD) are warranted. Purpose We aimed to investigate trends in the incidence of MI, HF, and CV mortality in PAD patients during the past two decades. Methods Nationwide registers were used to identify all patients aged ≥18 years, with first-time diagnosis of PAD between 1997 and 2016. Age-standardized incidence rates per 1,000 person-years (IR) were calculated to estimate trends of MI, HF, and CV mortality. Furthermore, risk of MI, HF, and CV mortality was estimated by 1-year cumulative-incidence with death as competing risk. Results A total of 136,746 patients with first-time diagnosis of PAD were included. Mean age was 70.01 [IQR 61–77 years], and 53.05% of the identified patients were male. The 1-year cumulative-incidence of MI in patients with PAD were 1.88% for year 1997–2000, 2.12% for year 2001–2005, 1.59% for year 2006–2010, and 1.32% for year 2011–2016, respectively. The 1-year cumulative-incidence of HF in patients with PAD were 1.71%, 1.48%, 1.25%, and 1.11% for the 1997–2000, 2001–2005, 2006–2010, and 2011–2016 year-groups, respectively. Furthermore the 1-year cumulative-incidence of CV mortality in patients with PAD were 12.0%, 9.41%, 8.75%, and 7.80% for the 1997–2000, 2001–2005, 2006–2010, and 2011–2016 year-groups, respectively. Likewise, the age-standardized incidence rates pr. 1,000 person-years showed increasing trends of MI up until 2002 with an estimated annual percent change (APC) of +0.6 (95% CI 3.3–16.1, p-value 0.2). After year 2002 the IR decreased significantly with an estimated APC of −5.0 (95% CI 3.7–6.3, p<0.0001). The age-standardized IR for HF decreased with an estimated APC of −3.3 (95% CI 2.0–4.6, p<0.0001), and similarly for CV death decreased by −3.5 (95% CI 3.0–4.0, p<0.0001). Conclusion The incidence of MI and HF in patients with PAD has significantly decreased over time together with a subsequent decline in CV mortality. This may suggest that the improvements in preventive strategies aimed at reducing CV risk are effective and contributes to lower incidence of MI and HF and thereby improved mortality rates in the past two decades. FUNDunding Acknowledgement Type of funding sources: None.

scholarly journals Influence of Peripheral Artery Disease and Statin Therapy on Apolipoprotein Profiles

2013 ◽  
Vol 2013 ◽  
pp. 1-7
Author(s):  
Andrew W. Gardner ◽  
Petar Alaupovic ◽  
Donald E. Parker ◽  
Polly S. Montgomery ◽  
Omar L. Esponda ◽  
...  
Keyword(s):  
Physical Activity ◽  
Myocardial Infarction ◽  
Statin Therapy ◽  
Peripheral Artery Disease ◽  
Apolipoprotein B ◽  
Ldl Cholesterol ◽  
Risk Profile ◽  
Peripheral Artery ◽  
Artery Disease ◽  
Plasma Apolipoprotein

Apolipoprotein B is a stronger predictor of myocardial infarction than LDL cholesterol, and it is inversely related to physical activity and modifiable with exercise training. As such, apolipoprotein measures may be of particular relevance for subjects with PAD and claudication. We compared plasma apolipoprotein profiles in 29 subjects with peripheral artery disease (PAD) and intermittent claudication and in 39 control subjects. Furthermore, we compared the plasma apolipoprotein profiles of subjects with PAD either treated (n=17) or untreated (n=12) with statin medications. For the apolipoprotein subparticle analyses, subjects with PAD had higher age-adjusted Lp-B:C (P<0.05) and lower values of Lp-A-I:A-II (P<0.05) than controls. The PAD group taking statins had lower age-adjusted values for apoB (P<0.05), Lp-A-II:B:C:D:E (P<0.05), Lp-B:E + Lp-B:C:E (P<0.05), Lp-B:C (P<0.05), and Lp-A-I (P<0.05) than the untreated PAD group. Subjects with PAD have impaired apolipoprotein profiles than controls, characterized by Lp-B:C and Lp-A-I:A-II. Furthermore, subjects with PAD on statin medications have a more favorable risk profile, particularly noted in multiple apolipoprotein subparticles. The efficacy of statin therapy to improve cardiovascular risk appears more evident in the apolipoprotein sub-particle profile than in the more traditional lipid profile of subjects with PAD and claudication. This trial is registered with ClinicalTrials.govNCT00618670.

461Modulation of ischemic and bleeding risk by peripheral artery disease after an acute coronary syndrome

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Cespon Fernandez ◽  
S Raposeiras Roubin ◽  
E Abu-Assi ◽  
S Manzano-Fernandez ◽  
F Dascenzo ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Peripheral Artery Disease ◽  
Cumulative Incidence ◽  
Bleeding Risk ◽  
Peripheral Artery ◽  
Data Set ◽  
Coronary Syndrome ◽  
Artery Disease ◽  
The Impact

Abstract Introduction Peripheral artery disease (PAD) is associated with heightened ischemic and bleeding risk in patients with acute coronary syndrome (ACS). With this study from real-life patients, we try to analyze the balance between ischemic and bleeding risk during treatment with dual antiplatelet therapy (DAPT) after an ACS according to the presence or not of PAD. Methods The data analyzed in this study were obtained from the fusion of 3 clinical registries of ACS patients: BleeMACS (2004–2013), CardioCHUVI/ARRITXACA (2010–2016) and RENAMI (2013–2016). All 3 registries include consecutive patients discharged after an ACS with DAPT and undergoing PCI. The merged data set contain 26,076 patients. A propensity-matched analysis was performed to match the baseline characteristics of patients with and without PAD. The impact of prior PAD in the ischemic and bleeding risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For ischemic risk we have considered a new acute myocardial infarction (AMI), whereas for bleeding risk we have considered major bleeding (MB) defined as bleeding requiring hospital admission. Follow-up time was censored by DAPT suspension/withdrawal. Results From the 26,076 ACS patients, 1,600 have PAD (6.1%). Patients with PAD were older, and with more cardiovascular risk factors. DAPT with prasugrel/ticagrelor was less frequently prescribed in patients with PAD in comparison with the rest of the population (8.2% vs 22.8%, p<0.001). During a mean follow-up of 12.2±4.8 months, 964 patients died (3.7%), and 640 AMI (2.5%) and 685 MB (2.6%) were reported. After propensity-score matching, we obtained two matched groups of 1,591 patients. Patients with PAD showed a significant higher risk of both AMI (sHR 2.17, 95% CI 1.51–3.10, p<0.001) and MB (sHR 1.51, 95% CI 1.07–2.12, p=0.018), in comparison with those without PAD. The cumulative incidence of AMI was 63.9 and 29.8 per 1,000 patients/year in patients with and without PAD, respectively. The cumulative incidence of MB was 55.9 and 37.6 per 1,000 patients/year in patients with and without PAD, respectively. The rate difference per 1,000 patient-years for AMI between patients with and without PAD was +34.1 (95% CI 30.1–38.1), and for MB +18.3 (16.1–20.4). The net balance between ischemic and bleeding events comparing patients with and without PAD was positive (+15.8 per 1,000 patients/year, 95% CI 9.7–22.0). Conclusions PAD was associated with higher ischemic and bleeding risk after hospital discharge for ACS treated with DAPT. However, the balance between ischemic and bleeding risk was positive for patients with PAD in comparison with patients without PAD. As summary, ACS patients with PAD had an ischemic risk greater than the bleeding risk.

scholarly journals Comparison of the Efficacy and Safety Outcomes of Edoxaban in 8040 Women Versus 13 065 Men With Atrial Fibrillation in the ENGAGE AF-TIMI 48 Trial

Circulation ◽  
2021 ◽  
Vol 143 (7) ◽  
pp. 673-684
Author(s):  
Thomas A. Zelniker ◽  
Maddalena Ardissino ◽  
Felicita Andreotti ◽  
Michelle L. O’Donoghue ◽  
Ophelia Yin ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Major Bleeding ◽  
Hemorrhagic Stroke ◽  
Factor Xa ◽  
Efficacy And Safety ◽  
Similar Reduction ◽  
Similar Treatment ◽  
Endogenous Factor ◽  
Fatal Bleeding ◽  
Artery Disease

Background: Female sex is an independent risk factor for stroke and systemic embolic events in patients with atrial fibrillation. This study aimed to examine the efficacy and safety profile of edoxaban in women versus men. Methods: The ENGAGE AF-TIMI 48 trial (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) randomly assigned 21 105 patients (8040 women) with atrial fibrillation and CHADS 2 score ≥2 either to a higher-dose edoxaban regimen, a lower-dose edoxaban regimen, or warfarin. The primary end points of the trial were the composite of stroke or systemic embolic events (efficacy), and International Society on Thrombosis and Haemostasis–defined major bleeding (safety). Results: In comparison with men, women were older, had lower body weight, were more likely to have hypertension and renal dysfunction, but less likely to smoke, drink alcohol, or have diabetes or coronary artery disease. Pretreatment endogenous factor Xa activity was significantly higher in women than in men (92.5% versus 86.1%, P <0.001). Treatment with edoxaban in women resulted in greater peak edoxaban concentration and inhibition of endogenous factor Xa in comparison with men, resulting in similar endogenous factor Xa activity between the sexes 2 to 4 hours after dose. Treatment with higher-dose edoxaban regimen (versus warfarin) resulted in similar reduction in the risk of stroke/systemic embolic events (women: hazard ratio [HR], 0.87 [0.69–1.11], men: HR, 0.87 [0.71–1.06]; P -interaction=0.97) and major bleeding (women: HR, 0.74 [0.59–0.92], men: HR, 0.84 [0.72–0.99]; P -interaction=0.34) in women and men. However, women assigned to higher-dose edoxaban regimen experienced greater reductions in hemorrhagic stroke (HR, 0.30 [95% CI, 0.15–0.59] versus HR, 0.70 [95% CI, 0.46–1.06]), intracranial bleeding (HR, 0.20 [95% CI, 0.10–0.39] versus HR, 0.63 [95% CI, 0.44–0.89]), and life-threatening or fatal bleeding (HR, 0.25 [95% CI, 0.15–0.42] versus HR, 0.72 [95% CI, 0.54–0.96]) than men (each P -interaction<0.05). Conclusions: Despite many differences in baseline characteristics between women and men and higher baseline endogenous factor Xa levels in women, the intensity of anticoagulation achieved with edoxaban between the sexes was similar. Treatment with higher-dose edoxaban regimen resulted in an even greater reduction in hemorrhagic stroke and several serious bleeding outcomes in women than in men, whereas the efficacy profile was similar between sexes.

scholarly journals Aspirin Resistance Predicts Adverse Cardiovascular Events in Patients with Symptomatic Peripheral Artery Disease

2016 ◽  
Vol 43 (6) ◽  
pp. 482-487 ◽  
Author(s):  
Tilak Pasala ◽  
Jennifer Soo Hoo ◽  
Mary Kate Lockhart ◽  
Rehan Waheed ◽  
Prasanna Sengodan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Peripheral Artery Disease ◽  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Aspirin Resistance ◽  
Secondary Outcome ◽  
Peripheral Artery ◽  
Significant Difference ◽  
Artery Disease

Antiplatelet therapy reduces the risk of myocardial infarction, stroke, and vascular death in patients who have symptomatic peripheral artery disease. However, a subset of patients who take aspirin continues to have recurrent cardiovascular events. There are few data on cardiovascular outcomes in patients with peripheral artery disease who manifest aspirin resistance. Patients with peripheral artery disease on long-term aspirin therapy (≥4 wk) were tested for aspirin responsiveness by means of the VerifyNow Aspirin Assay. The mean follow-up duration was 22.6 ± 8.3 months. The primary endpoint was a composite of death, myocardial infarction, or ischemic stroke. Secondary endpoints were the incidence of vascular interventions (surgical or percutaneous), or of amputation or gangrene caused by vascular disease. Of the 120 patients enrolled in the study, 31 (25.8%) were aspirin-resistant and 89 (74.2%) were aspirin-responsive. The primary endpoint occurred in 10 (32.3%) patients in the aspirin-resistant group and in 13 (14.6%) patients in the aspirin-responsive group (hazard ratio=2.48; 95% confidence interval, 1.08–5.66; P=0.03). There was no significant difference in the secondary outcome of revascularization or tissue loss. By multivariate analysis, aspirin resistance and history of chronic kidney disease were the only independent predictors of long-term adverse cardiovascular events. Aspirin resistance is highly prevalent in patients with symptomatic peripheral artery disease and is an independent predictor of adverse cardiovascular risk. Whether intervening in these patients with additional antiplatelet therapies would improve outcomes needs to be explored.

scholarly journals Peripheral artery disease and outcomes in patients with acute myocardial infarction

Open Heart ◽  
2019 ◽  
Vol 6 (1) ◽  
pp. e001004 ◽  
Author(s):  
Rubina Attar ◽  
Axel Wester ◽  
Sasha Koul ◽  
Svend Eggert ◽  
Pontus Andell
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Peripheral Artery Disease ◽  
Ankle Brachial Index ◽  
Real Life ◽  
Clinical Event ◽  
High Risk Population ◽  
Peripheral Artery ◽  
St Elevation ◽  
Artery Disease

AimTo describe the population of patients with previously diagnosed peripheral artery disease (PAD) experiencing a myocardial infarction (MI) and to investigate 1-year major adverse cardiac events (MACE: all-cause mortality, reinfarction, stroke and heart failure hospitalisation) following MI.BackgroundMI patients with PAD constitute a high-risk population with adverse cardiac outcomes. Contemporary real-life data regarding the clinical characteristics of this patient population and clinical event rates following MI remain scarce.MethodsThis observational study included all MI patients presenting with ST-elevation MI or non-ST-elevation MI between 01 January 2005 and 31 December 2014 with (n=4213) and without (n=106 763) a concurrent PAD diagnosis, identified in the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies registry and the National Patient Registry (PAD prevalence: 3.8%). Cox proportional hazard models were applied to compare the outcome between the two populations.ResultsMI patients with PAD were older and more often burdened with comorbidities, such as diabetes, hypertension and previous MI. After adjustments, PAD was significantly associated with higher rates of MACE (HR 1.35, 95% CI 1.27 to 1.44), mortality (HR 1.59, 95% CI 1.43 to 1.76), reinfarction (HR 1.48, 95% CI 1.32 to 1.66), stroke (HR 1.27, 95% CI 1.05 to 1.53), heart failure (HR 1.29, 95% CI 1.20 to 1.40) and bleeding (HR 1.26, 95% CI 1.09 to 1.47) at 1 year.ConclusionA concurrent PAD diagnosis was independently significantly associated with higher rates of adverse outcomes following MI in a nationwide real-life MI population. The low prevalence of PAD compared with previous studies suggests significant underdiagnosing. Future studies should investigate if PAD screening with ankle–brachial index may increase diagnosing and subsequently lead to improved treatment of polyvascular disease

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.

Sign in / Sign up

Export Citation Format

Share Document