Antithrombotic treatment in peripheral artery disease

VASA ◽  
2018 ◽  
Vol 47 (2) ◽  
pp. 99-108 ◽  
Author(s):  
Dan-Mircea Olinic ◽  
Dan Alexandru Tataru ◽  
Calin Homorodean ◽  
Mihail Spinu ◽  
Maria Olinic
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Total Mortality ◽  
Scientific Data ◽  
Major Adverse Cardiovascular Events ◽  
Limb Ischaemia ◽  
Peripheral Artery ◽  
Autologous Vein ◽  
Acute Limb Ischaemia ◽  
Increased Risk

Abstract. This review treats antithrombotic use for peripheral arterial disease (PAD). In asymptomatic patients, there are no scientific data to support single antiplatelet therapy (SAPT) for primary prophylaxis. In symptomatic PAD, SAPT with aspirin or clopidogrel is indicated. The efficacy of aspirin is controversial. Clopidogrel may be preferred over aspirin. Ticagrelor is not superior to clopidogrel in reducing major adverse cardiovascular events and major adverse limb events, but lowers the risk of ischaemic stroke. In symptomatic PAD, dual antiplatelet therapy (DAPT) with clopidogrel and aspirin does not provide benefit over SAPT with aspirin alone and is associated with increased risk of major bleeding. DAPT with ticagrelor 60 mg b. i. d. and aspirin provides a significant major adverse cardiovascular events reduction in symptomatic PAD patients and may be considered in PAD patients with prior myocardial infarction. The use of a new thrombin receptor antagonist, vorapaxar, on top of SAPT or DAPT with aspirin and/or clopidogrel, reduces the risk of acute limb ischaemia and peripheral artery revascularization in patients with symptomatic PAD, at the cost of an increased risk for bleeding. Rivaroxaban (2.5 mg b. i. d.) plus aspirin (100 mg daily) is the first antithrombotic association that proved significant benefit for PAD patients, in terms of strong endpoints – total mortality and cardiovascular mortality. Therefore, this association shows the strongest evidence for secondary prevention of symptomatic PAD patients. In PAD patients undergoing percutaneous peripheral interventions, at least four weeks of DAPT with aspirin and clopidogrel is recommended after infrainguinal stent implantation. Stenting below-the-knee arteries is often followed by a longer period of DAPT, but no specific evidence is available. Anticoagulation is mandatory to prevent arterial occlusion during radial or brachial invasive procedures. The strategy includes use of unfractioned heparin, bivalirudin or enoxaparin. Vitamin K antagonists may be considered after autologous vein infrainguinal bypass.

scholarly journals Efficacy and Safety of Antiplatelet Therapies in Symptomatic Peripheral Artery Disease: A Systematic Review and Network Meta-Analysis

2020 ◽  
Vol 18 ◽  
Author(s):  
Marco De Carlo ◽  
Giovanni Di Minno ◽  
Tobias Sayre ◽  
Mir Sohail Fazeli ◽  
Gaye Siliman ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Meta Analysis ◽  
Bleeding Risk ◽  
Major Adverse Cardiovascular Events ◽  
Limb Ischaemia ◽  
All Cause Mortality ◽  
Artery Disease ◽  
Randomised Controlled

Background: Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on antiplatelet therapy for PAD. Methods: We searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses. Results: We analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval [CrI] 0.65- 0.93) and ticagrelor (HR 0.80; 95%CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95%CrI 0.43- 1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk. Conclusion: This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.

scholarly journals Artificial-Intelligence-Assisted Discovery of Genetic Factors for Precision Medicine of Antiplatelet Therapy in Diabetic Peripheral Artery Disease

Biomedicines ◽  
2022 ◽  
Vol 10 (1) ◽  
pp. 116
Author(s):  
Chi-Hsiao Yeh ◽  
Yi-Ju Chou ◽  
Tsung-Hsien Tsai ◽  
Paul Wei-Che Hsu ◽  
Chun-Hsien Li ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Precision Medicine ◽  
Antiplatelet Therapy ◽  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Genetic Factors ◽  
Genome Wide Association Study ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

An increased risk of cardiovascular events was identified in patients with peripheral artery disease (PAD). Clopidogrel is one of the most widely used antiplatelet medications. However, there are heterogeneous outcomes when clopidogrel is used to prevent cardiovascular events in PAD patients. Here, we use an artificial intelligence (AI)-assisted methodology to identify genetic factors potentially involved in the clopidogrel-resistant mechanism, which is currently unclear. Several discoveries can be pinpointed. Firstly, a high proportion (>50%) of clopidogrel resistance was found among diabetic PAD patients in Taiwan. Interestingly, our result suggests that platelet function test-guided antiplatelet therapy appears to reduce the post-interventional occurrence of major adverse cerebrovascular and cardiac events in diabetic PAD patients. Secondly, AI-assisted genome-wide association study of a single-nucleotide polymorphism (SNP) database identified a SNP signature composed of 20 SNPs, which are mapped into 9 protein-coding genes (SLC37A2, IQSEC1, WASHC3, PSD3, BTBD7, GLIS3, PRDM11, LRBA1, and CNR1). Finally, analysis of the protein connectivity map revealed that LRBA, GLIS3, BTBD7, IQSEC1, and PSD3 appear to form a protein interaction network. Intriguingly, the genetic factors seem to pinpoint a pathway related to endocytosis and recycling of P2Y12 receptor, which is the drug target of clopidogrel. Our findings reveal that a combination of AI-assisted discovery of SNP signatures and clinical parameters has the potential to develop an ethnic-specific precision medicine for antiplatelet therapy in diabetic PAD patients.

scholarly journals Sortilin levels correlate with major cardiovascular events of diabetic patients with peripheral artery disease following revascularization: a prospective study

2020 ◽  
Author(s):  
Federico Biscetti ◽  
Elisabetta Nardella ◽  
Maria Margherita Rando ◽  
Andrea Leonardo Cecchini ◽  
Nicola Bonadia ◽  
...  
Keyword(s):  
Peripheral Artery Disease ◽  
Cardiovascular Events ◽  
Vascular Complications ◽  
Major Adverse Cardiovascular Events ◽  
Diabetic Patients ◽  
Operating Characteristics ◽  
Peripheral Artery ◽  
Increased Risk ◽  
Artery Disease

Abstract Background: Peripheral artery disease (PAD) represents one of the most relevant vascular complications of type 2 diabetes mellitus (T2DM). Moreover, T2DM patients suffering from PAD have an increased risk of major adverse cardiovascular events (MACE) and major adverse limb events (MALE). Sortilin, a protein involved in apolipoproteins trafficking, is associated with lower limb PAD in T2DM patients.Objective: To evaluate the relationship between baseline level of Sortilin levels, MACE and MALE occurrence after revascularization of T2DM patients with PAD and chronic limb-threatening ischemia (CLTI).Research Design and Methods: We performed a prospective non-randomized study including 230 statin-free T2DM patients with PAD and CLTI. Sortilin serum levels were measured before the endovascular intervention and incident outcomes were assessed during a 12-month follow-up.Results: Sortilin levels were significantly increased in individuals with more aggressive PAD (2.25 ± 0.51 ng/mL vs 1.44 ± 0.47 ng/mL, p < 0.001). During follow-up, 83 MACE and 116 MALE occurred. In patients, who then developed MACE and MALE, Sortilin was higher. In particular, 2.46 ± 0.53 ng/mL vs 1.55 ± 0.42 ng/mL, p < 0.001 for MACE and 2.10 ± 0.54 ng/mL vs 1.65 ± 0.65 ng/mL, p < 0.001 for MALE. After adjusting for traditional atherosclerosis risk factors, the association between Sortilin and vascular outcomes remained significant in a multivariate analysis. In our receiver operating characteristics (ROC) curve analysis using Sortilin levels the prediction of MACE incidence improved [area under the curve (AUC) = 0.94] and MALE (AUC = 0.72).Conclusions: This study demonstrates that Sortilin correlates with incidence of MACE and MALE after endovascular revascularization in a diabetic population with PAD and CLTI.

Abstract 14325: Pooled Analysis of Bleeding, Major Adverse Cardiovascular Events and Mortality in Clinical Trials of Time-constrained Dual-antiplatelet Therapy After Percutaneous Coronary Intervention

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jennifer Ramsay ◽  
John McClure ◽  
Colin Berry
Keyword(s):  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Dual Antiplatelet Therapy ◽  
Pooled Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Bleeding Events ◽  
P2y12 Inhibitor ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Reduced Risk

Introduction: The net clinical benefit of dual antiplatelet therapy (DAPT) reflects the paradoxical effects of an increased risk of bleeding and a reduced risk of major adverse cardiovascular events (MACE). A time-constrained approach to DAPT has been recently investigated in five multicenter trials including GLOBAL LEADERS, STOP-DAPT2, SMART-CHOICE, TWIGHLIGHT and TICO. Methods: We undertook a pooled analysis of these trials to assess the overall associations between time-constrained P2Y12 inhibitor monotherapy (“aspirin free regimen”) for bleeding events, MACE and all-cause mortality as compared to standard care with DAPT for at least 12 months post-PCI. We implemented a DerSimonian and Laird random effects meta-analysis using the metafor package in R. Results: 32,361 randomized trial participants, including 16,898 (52.2%) with a history of ACS, underwent PCI and had outcome data available. P2Y12 inhibitor monotherapy from 1 - 3 months was associated with a reduced risk for bleeding (hazard ratio (HR) (95% confidence interval (CI)) 0.60 (0.45, 0.81); p=0.024), including in the ACS group in which the magnitude of risk reduction was greatest (HR (95% CI) 0.50 (0.41, 0.61). The estimates of the effect of P2Y12 inhibitor monotherapy on the hazard were also favorable for MACE (0.88 (0.77, 1.02)) and all-cause mortality (95% CI 0.85 (0.71, 1.03)). Conclusions: Compared with DAPT for 12 months post-PCI, P2Y12 inhibitor monotherapy from 1-3 months substantially reduces the risk of major and fatal bleeding and, in addition, potentially protective effects, for MACE and all-cause mortality. Considering patient safety, the results support a strategy of DAPT for 1-3 months followed by ‘aspirin free’ P2Y12 inhibitor monotherapy.

Perioperative implications of newer generation drug-eluting coronary stents: A narrative review

2021 ◽  
pp. 0310057X2098479
Author(s):  
David A Milder ◽  
Peter CA Kam
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Cardiac Surgery ◽  
Antiplatelet Therapy ◽  
Cardiovascular Events ◽  
Coronary Intervention ◽  
Drug Eluting Stents ◽  
Major Adverse Cardiovascular Events ◽  
Increased Risk ◽  
Percutaneous Coronary ◽  
Drug Eluting

Newer generation drug-eluting stents are the most commonly inserted stent in the setting of percutaneous coronary intervention. This narrative review focuses on the evidence underpinning the perioperative management of patients with newer generation drug-eluting stents undergoing non-cardiac surgery. Six studies reported the incidence of major adverse cardiovascular events according to the time interval from percutaneous coronary intervention to non-cardiac surgery, and the comparative risks of newer and first generation drug-eluting stents. No study demonstrated an increased risk of major adverse cardiovascular events once three months had elapsed between stent implantation and non-cardiac surgery. Only one study included patients with third and fourth generation drug-eluting stents. Seven studies analysed the relationship between antiplatelet therapy, major adverse cardiovascular events and perioperative bleeding. The risks of major adverse cardiovascular events do not appear to be increased if antiplatelet therapy is ceased for less than seven days but are increased if it is discontinued for more than seven days. Most studies reported no differences in the incidence of major bleeding associated with antiplatelet therapy. The risk of perioperative major adverse cardiovascular events in non-cardiac surgery does not appear to be increased after three months following implantation with newer generation drug-eluting stents. However, the possibility of increased risk cannot be excluded as most studies were inadequately powered. The thrombotic risk is substantially reduced in patients with fourth (polymer free) generation drug-eluting stents, and urgent non-cardiac surgery can be considered one month after percutaneous coronary intervention. Larger multicentre studies are needed to define the optimal window for non-cardiac surgery after percutaneous coronary intervention and provide definitive perioperative strategies for patients presenting for non-cardiac surgery after the implantation of newer generation drug-eluting stents.

Antithrombotic Therapy in Lower Extremity Artery Disease

2020 ◽  
Vol 18 (3) ◽  
pp. 215-222 ◽  
Author(s):  
Mislav Vrsalovic ◽  
Victor Aboyans
Keyword(s):  
Lower Extremity ◽  
Antiplatelet Therapy ◽  
Antithrombotic Therapy ◽  
Cardiovascular Events ◽  
Cardiovascular Outcomes ◽  
Lower Limbs ◽  
Stent Type ◽  
Increased Risk ◽  
Artery Disease ◽  
Lower Extremity Artery Disease

Lower extremity artery disease (LEAD) is a marker of a more advanced atherosclerotic process often affecting multiple vascular beds beyond the lower limbs, with a consequent increased risk for all-cause and cardiovascular mortality. Antithrombotic therapy is the cornerstone of management of these patients to prevent ischaemic cardiovascular and limb events and death. In patients with symptomatic LEAD, the efficacy of aspirin has been established long ago for the prevention of cardiovascular events. In the current guidelines, clopidogrel may be preferred over aspirin following its incremental ability to prevent cardiovascular events, while ticagrelor is not superior to clopidogrel in reducing cardiovascular outcomes. Dual antiplatelet therapy (DAPT, aspirin with clopidogrel) is currently recommended for at least 1 month after endovascular interventions irrespective of the stent type. Antiplatelet monotherapy is recommended after infra-inguinal bypass surgery, and DAPT may be considered in below-the-knee bypass with a prosthetic graft. In symptomatic LEAD, the addition of anticoagulant (vitamin K antagonists) to antiplatelet therapy increased the risk of major and life-threatening bleeding without benefit regarding cardiovascular outcomes. In a recent trial, low dose of direct oral anticoagulant rivaroxaban plus aspirin showed promising results, not only to reduce death and major cardiovascular events, but also major limb events including amputation. Yet, this option should be considered especially in very high risk patients, after considering also the bleeding risk. Despite all the evidence accumulated since >40 years, many patients with LEAD remain undertreated and deserve close attention and implementation of guidelines advocating the use of antithrombotic therapies, tailored according to their level of risk.

scholarly journals Risk of colonoscopic post-polypectomy bleeding in patients on single antiplatelet therapy: systematic review with meta-analysis

2022 ◽  
Author(s):  
Marco Valvano ◽  
Stefano Fabiani ◽  
Marco Magistroni ◽  
Antonio Mancusi ◽  
Salvatore Longo ◽  
...  
Keyword(s):  
Antiplatelet Therapy ◽  
Meta Analysis ◽  
Antiplatelet Agents ◽  
Disease Recurrence ◽  
Major Adverse Cardiovascular Events ◽  
Control Group ◽  
P2y12 Inhibitors ◽  
Randomized Controlled ◽  
Electronic Search ◽  
Increased Risk

Abstract Background It was not yet fully established whether the use of antiplatelet agents (APAs) is associated with an increased risk of colorectal post-polypectomy bleeding (PPB). Temporarily, discontinuation of APAs could reduce the risk of PPB, but at the same time, it could increase the risk of cardiovascular disease recurrence. This study aimed to assess the PPB risk in patients using APAs compared to patients without APAs or anticoagulant therapy who had undergone colonoscopy with polypectomy. Methods A systematic electronic search of the literature was performed using PubMed/MEDLINE, Scopus, and CENTRAL, to assess the risk of bleeding in patients who do not interrupt single antiplatelet therapy (P2Y12 inhibitors or aspirin) and undergone colonoscopy with polypectomy. Results Of 2417 identified articles, 8 articles (all of them were non-randomized studies of interventions (NRSI); no randomized controlled trials (RCT) were available on this topic) were selected for the meta-analysis, including 1620 patients on antiplatelet therapy and 13,321 controls. Uninterrupted APAs single therapy was associated with an increased risk of PPB compared to the control group (OR 2.31; CI 1.37–3.91). Patients on P2Y12i single therapy had a higher risk of both immediate (OR 4.43; CI 1.40–14.00) and delayed PPB (OR 10.80; CI 4.63–25.16) compared to the control group, while patients on aspirin single therapy may have a little to no difference increase in the number of both immediate and delayed PPB events. Conclusions Uninterrupted single antiplatelet therapy may increase the risk of PPB, but the evidence is very uncertain. The risk may be higher in delayed PPB. However, in deciding to discontinue APAs before colonoscopy with polypectomy, the potential higher risk of major adverse cardiovascular events should always be assessed.

scholarly journals Comparison of In-hospital Major Adverse Cardiovascular Events in Patients of Acute Inferior Myocardial Infarction With or Without Precordial ST Segment Depression

2017 ◽  
pp. 180-9
Author(s):  
Jaya Suganti ◽  
Abdullah Afif Siregar ◽  
Harris Hasan
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Events ◽  
Multiple Logistic Regression Analysis ◽  
Major Adverse Cardiovascular Events ◽  
Bivariate Analysis ◽  
P Value ◽  
Inferior Myocardial Infarction ◽  
St Segment ◽  
Increased Risk ◽  
Acute Inferior Myocardial Infarction

Background: The clinical implications of precordial ST segment depression (PSTD) during acute inferior myocardial infarction has been an area of debate, and still under investigation with conflicting results. Based on previous studies, the presence of PSTD defines a high risk subset of patients with acute inferior myocardial infarction due to a more extensive myocardial ischemia that lead to a higher incidence of major adverse cardiovascular events (MACE). Despite of these results, others still considered this ECG finding as a benign electrical phenomenon. The aim of this study is to compare the incidence of in-hospital MACE in patients of acute inferior myocardial infarction with or without PSTD and to know whether PSTD can be used as a predictor of in-hospital MACE in acute inferior myocardial infarction.Methods: A total of 96 acute inferior myocardial infarction patients admitted from December 2013-2015 at Cardiology Department of Haji Adam Malik General Hospital were retrospectively analyzed. Patients were divided into two groups based on the presence of PSTD on admission ECG. Bivariate and multivariate analyses were performed to study the association between PSTD and in-hospital MACE, p value<0.05 was considered statistically significant.Results: The bivariate analysis showed that in-hospital MACE was significantly higher in patients of acute inferior myocardial infarction with PSTD than without PSTD (92% vs 8%, p<0.001). On multiple logistic regression analysis, patients of acute inferior myocardial infarction with PSTD have a 5.4 fold increased risk of in-hospital MACE than patients without PSTD (OR 5.480; 95% CI 1.759-17.067, p=0.003).Conclusion: The presence of precordial ST segment depression on admission ECG in acute inferior myocardial infarction patients was associated with a higher in-hospital MACE and was an independent predictor of in-hospital MACE.

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