scholarly journals Vorapaxar in the treatment of cardiovascular diseases

2020 ◽  
Vol 16 (5) ◽  
pp. 373-384
Author(s):  
Udaya S Tantry ◽  
Kevin P Bliden ◽  
Rahul Chaudhary ◽  
Marko Novakovic ◽  
Amit Rout ◽  
...  

Vorapaxar specifically and effectively inhibits protease activated receptor-1 and may reduce thrombin-mediated ischemic events without interfering primary hemostasis. In the TRA-2P-TIMI 50 trial, vorapaxar reduced the risk of primary ischemic outcome but with increased bleeding risk. In the post hoc analysis, in patients with a history of myocardial infarction, peripheral artery disease, the net clinical outcome favored vorapaxar therapy with 10% reduction in cardiovascular death, myocardial infarction, stroke, urgent coronary revascularization and moderate or severe bleeding. Based on these favorable results, vorapaxar was approved for the reduction of thrombotic cardiovascular events in patients with prior myocardial infarction or with peripheral artery disease on top of standard antiplatelet therapy. A careful patient selection is needed to balance efficacy versus safety.

2019 ◽  
Vol 24 (38) ◽  
pp. 4516-4517 ◽  
Author(s):  
Diamantis I. Tsilimigras ◽  
Demetrios Moris ◽  
Georgios Karaolanis ◽  
Stavros K. Kakkos ◽  
Konstantinos Filis ◽  
...  

Peripheral artery disease (PAD) is the third most common manifestation of atherosclerosis after coronary artery (CAD) and cerebrovascular disease (CVD). People with PAD have plaque findings in other vascular territories as well and, thus, are at increased risk of major adverse cardiovascular or cerebrovascular events (MACCE), including myocardial infarction, and stroke. In that context, the COMPASS multicenter, randomized controlled trial showed that the risk of MACCE was significantly reduced by 24% in the rivaroxaban plus aspirin arm compared with aspirin alone (4.1% vs 5.4% respectively; HR: 0.76, 95% CI: 0.66 to 0.86). Interestingly, the rivaroxaban/aspirin arm also showed a reduction in cardiovascular death (HR: 0.78; 95% CI: 0.64-0.96]) and allcause mortality (HR: 0.82; 95% CI: 0.71-0.96) by 22% and 18%, respectively. Recently, the FDA approved the use of the dual pathway approach, rivaroxaban 2.5 mg twice daily plus aspirin 75-100mg once daily, to reduce the risk of major cardiovascular (CV) events, such as CV death, myocardial infarction and stroke, in people with CAD as well as PAD. In comparing rivaroxaban plus aspirin versus aspirin alone, a preliminary economic analysis showed that saving per patient was USD 462 for events and USD 220 for procedures with a total reduction of USD 682 per participant in the US with the combination group (rivaroxaban plus aspirin). The data from COMPASS trial suggest that low dose rivaroxaban plus aspirin may be a preferred treatment strategy in PAD patients in whom the bleeding risk is deemed to be favourable.


Author(s):  
Jennifer A. Rymer ◽  
Hillary Mulder ◽  
Dennis I. Narcisse ◽  
Frank Rockhold ◽  
William R. Hiatt ◽  
...  

Background: Patients with peripheral artery disease have a high risk of future cardiovascular disease events and mortality. Little is known about the changes in symptom classification over time in patients with peripheral artery disease and the association of changes in symptom classification with subsequent cardiovascular disease events. Methods: In this analysis of the EUCLID trial (Examining Use of Ticagrelor in Peripheral Artery Disease), we examined the changes in Rutherford classification (RC) of patients over 12 months. We examined the baseline characteristics of patients by change in symptom classification at 12 months (improved=decreased RC, no change, or worsened=increased RC), and the association between changes in symptom classification (RC) at 12 months and subsequent cardiovascular disease events. Results: Among 12 759 patients, 3240 (25%) were classified as improved by RC at 12 months, 8132 (64%) as no change, and 1387 (11%) as worsened. At 12 months, many patients who were asymptomatic or had mild/moderate claudication at enrollment had no change in symptom classification over 12 months (73.7% and 70.9%). Patients who worsened over 12 months were more likely to have comorbidities (diabetes mellitus and prior myocardial infarction) and more events (myocardial infarction, amputation, and major bleeding) by 12 months postrandomization, all P <0.001. Worsened symptom classification over 12 months was associated with increased risk of all-cause death (adjusted hazard ratio, 1.29 [95% CI, 1.03–1.62]), major amputation (adjusted hazard ratio, 4.12 [95% CI, 2.46–6.88]), and a composite of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio, 1.30 [95% CI, 1.05–1.62]), all P <0.05 after 12 months postrandomization. Conclusions: Patients with comorbidities and prior history of cardiovascular disease events at baseline and within the first 12 months of the trial were more likely to have worsened symptom classification at 12 months. Worsening symptom classification over 12 months was associated subsequently with an increased risk of all-cause death, amputation, and a composite of cardiovascular death, myocardial infarction, or stroke. Graphic Abstract: A graphic abstract is available for this article.


Heart ◽  
2021 ◽  
pp. heartjnl-2020-318758
Author(s):  
Gilles R Dagenais ◽  
Leanne Dyal ◽  
Jacqueline J Bosch ◽  
Darryl P Leong ◽  
Victor Aboyans ◽  
...  

ObjectiveIn patients with chronic coronary or peripheral artery disease enrolled in the Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, randomised antithrombotic treatments were stopped after a median follow-up of 23 months because of benefits of the combination of rivaroxaban 2.5 mg two times per day and aspirin 100 mg once daily compared with aspirin 100 mg once daily. We assessed the effect of switching to non-study aspirin at the time of early stopping.MethodsIncident composite of myocardial infarction, stroke or cardiovascular death was estimated per 100 person-years (py) during randomised treatment (n=18 278) and after study treatment discontinuation to non-study aspirin (n=14 068).ResultsDuring randomised treatment, the combination compared with aspirin reduced the composite (2.2 vs 2.9/100 py, HR: 0.76, 95% CI 0.66 to 0.86), stroke (0.5 vs 0.8/100 py, HR: 0.58, 95% CI 0.44 to 0.76) and cardiovascular death (0.9 vs 1.2/100 py, HR: 0.78, 95% CI 0.64 to 0.96). During 1.02 years after early stopping, participants originally randomised to the combination compared with those randomised to aspirin had similar rates of the composite (2.1 vs 2.0/100 py, HR: 1.08, 95% CI 0.84 to 1.39) and cardiovascular death (1.0 vs 0.8/100 py, HR: 1.26, 95% CI 0.85 to 1.86) but higher stroke rate (0.7 vs 0.4/100 py, HR: 1.74, 95% CI 1.05 to 2.87) including a significant increase in ischaemic stroke during the first 6 months after switching to non-study aspirin.ConclusionDiscontinuing study rivaroxaban and aspirin to non-study aspirin was associated with the loss of cardiovascular benefits and a stroke excess.Trial registration numberNCT01776424.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Kamil ◽  
T.S.G Sehested ◽  
K Houlind ◽  
J.F Lassen ◽  
G Gislason ◽  
...  

Abstract Background Peripheral artery disease (PAD) is associated with increased cardiovascular (CV) morbidity and mortality. Aggressive management of risk factors and lifestyle modification may improve outcomes for patients with PAD. The present study aims to investigate changes in use of cardioprotective medication after the incident diagnosis of PAD between 1997 and 2016. Methods By using Danish national healthcare registries, we identified all patients with first-time diagnosis of PAD between 1997 and 2016. These patients were classified into 2 main groups: PAD-all (n=167,762) that includes all PAD patients with or without a history of CVD, including myocardial infarction (MI), atrial fibrillation (AF), and stroke (n=167,761) and PAD-only (n=87,935) that comprise patients with PAD without a history of AF, MI, and stroke. We calculated temporal trends and assessed comparative use of cardioprotective medication in the first 12 months after the incident diagnosis of PAD. Results Our results showed an improved use of cardioprotective medication temporally in both groups. However, PAD-all were marginally better treated (Aspirin, 3.5% - 48.4%; Clopidogrel, 0% - 17.6%; VKA 0.9% - 7.8%; NOACs 0.0% - 10.1%; Statins, 1.9%- 58.1%; ACE-inhibitors, 1.2% - 20.6%), compared to PAD-only (Aspirin, 2.9% - 54.4%; Clopidogrel, 0% - 11.9%; VKA 0.9% - 2.4%; NOACs 0.0% - 3.4%; Statins, 1.5%- 56.9%; ACE-inhibitors, 0.9% - 17.2%), respectively. Proportion of PAD patients treated with any cardioprotective medication was greater among those with a history of MI or stroke. Whereas, PAD patients with a history of AF were substantially better treated with VKA and NOACs. Conclusion In this nationwide study, use of cardioprotective medication increased considerably with time, but there remains an underuse of guideline-recommended therapy in patients with PAD. Funding Acknowledgement Type of funding source: None


2013 ◽  
Vol 2013 ◽  
pp. 1-7
Author(s):  
Andrew W. Gardner ◽  
Petar Alaupovic ◽  
Donald E. Parker ◽  
Polly S. Montgomery ◽  
Omar L. Esponda ◽  
...  

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.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Cespon Fernandez ◽  
S Raposeiras Roubin ◽  
E Abu-Assi ◽  
S Manzano-Fernandez ◽  
F Dascenzo ◽  
...  

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.


2019 ◽  
Vol 27 (3) ◽  
pp. 296-307 ◽  
Author(s):  
Thomas Vanassche ◽  
Peter Verhamme ◽  
Sonia S Anand ◽  
Olga Shestakovska ◽  
Keith AA Fox ◽  
...  

Aims Secondary prevention in patients with coronary artery disease and peripheral artery disease involves antithrombotic therapy and optimal control of cardiovascular risk factors. In the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) study, adding low-dose rivaroxaban on top of aspirin lowered cardiovascular events, but there is limited data about risk factor control in secondary prevention. We studied the association between risk factor status and outcomes, and the impact of risk factor status on the treatment effect of rivaroxaban, in a large contemporary population of patients with coronary artery disease or peripheral artery disease. Methods and results We reported ischemic events (cardiovascular death, stroke, or myocardial infarction) in participants from the randomized, double-blind COMPASS study by individual risk factor (blood pressure, smoking status, cholesterol level, presence of diabetes, body mass index, and level of physical activity), and by number of risk factors. We compared rates and hazard ratios of patients treated with rivaroxaban plus aspirin vs aspirin alone within each risk factor category and tested for interaction between risk factor status and antithrombotic regimen. Complete baseline risk factor status was available in 27,117 (99%) patients. Status and number of risk factors were both associated with increased risk of ischemic events. Rates of ischemic events (hazard ratio 2.2; 95% confidence interval 1.8–2.6) and cardiovascular death (hazard ratio 2.0; 1.5–2.7) were more than twofold higher in patients with 4–6 compared with 0–1 risk factors ( p < 0.0001 for both). Rivaroxaban reduced event rates independently of the number of risk factors ( p interaction 0.93), with the largest absolute benefit in patients with the highest number of risk factors. Conclusion More favorable risk factor status and low-dose rivaroxaban were independently associated with lower risk of cardiovascular events.


2011 ◽  
Vol 58 (13) ◽  
pp. 1386-1392 ◽  
Author(s):  
Christina L. Wassel ◽  
Rohit Loomba ◽  
Joachim H. Ix ◽  
Matthew A. Allison ◽  
Julie O. Denenberg ◽  
...  

Vascular ◽  
2020 ◽  
pp. 170853812093892 ◽  
Author(s):  
Carlos Cantú-Brito ◽  
Erwin Chiquete ◽  
Javier F Antezana-Castro ◽  
Liz Toapanta-Yanchapaxi ◽  
Ana Ochoa-Guzmán ◽  
...  

Objectives The frequency and implications of peripheral artery disease (PAD) in some risk groups are not entirely characterized in Latin America. We studied PAD prevalence, risk factors, and six-month outcomes in stable outpatients with a history of a recent acute coronary syndrome (ACS), or at high coronary risk. Methods We recruited 830 outpatients in 43 Mexican sites (median age: 64.8 years; 57.8% men). Inclusion criteria were age >18 years, and ACS within 30 days, or age <55 years plus ≥2 major vascular risk factors, or age ≥55 years plus ≥1 vascular risk factors. Patients received standardized assessments at baseline and six-month follow-up for medical history, ankle-brachial index (ABI), and the Edinburgh Claudication Questionnaire (ECQ). Results ABI <0.8 was found in 10.5%, <0.9 in 22.5%, >1.3 in 4.8%, and >1.4 in 3.6%, without differences according to sex or selection criteria. Positive ECQ was found in 7.6%. ABI <0.9 was directly associated with age, diabetes, ACS, and chronic kidney disease, but inversely associated with BMI >27. The six-month case-fatality and atherothrombotic events rates were 1.6% and 3.6%, respectively. In patients with ABI <0.9 and ABI <0.8, the six-month case-fatality rates were 2.5% ( p =  0.27) and 5.4% ( p =  0.03), respectively. In a Cox proportional-hazards model, baseline factors associated with death were age ≥65, ABI <0.8, and ACS. Conclusions Subclinical PAD is more common than symptomatic claudication in high-risk coronary outpatients. Low ABI is associated with reduced short-term survival in patients with recent ACS or at high coronary risk.


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