Effect of antiplatelet agents clopidogrel, aspirin, and cilostazol on circulating tissue factor procoagulant activity in patients with peripheral arterial disease

2006 ◽  
Vol 96 (12) ◽  
pp. 738-743 ◽  
Author(s):  
Vijender Vaidyula ◽  
Shagun Bagga ◽  
Gauthami Jalagadugula ◽  
John Gaughan ◽  
Douglas Wilhite ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Tissue Factor ◽  
Factor Viia ◽  
Phosphodiesterase Inhibitor ◽  
Antiplatelet Agents ◽  
Arterial Disease ◽  
Procoagulant Activity ◽  
Treatment Regimens ◽  
Plasma Factor ◽  
Peripheral Arterial

SummaryTissue factor (TF) is the physiological initiating mechanism for blood coagulation. Platelets play an important role in monocyte TF expression, thrombosis and inflammation. Aspirin, clopidogrel and cilostazol, which inhibit platelet responses by different mechanisms, are widely used in patients with arterial diseases. We tested the hypothesis that platelet-inhibiting agents inhibit the levels of circulatingTF procoagulant activity (TF-PCA) in patients with peripheral arterial disease (PAD).Twenty-six patients with lower extremity PAD, average age 65.9 ± 8.4 years (mean± SEM), were studied at baseline and following sequential twoweek treatment regimens with aspirin (325 mg daily), clopidogrel (75 mg daily) or a phosphodiesterase inhibitor cilostazol (100 mg twice daily) singly, and with each possible combination of these agents. Circulating TF-PCA in whole blood, and plasma factor VIIa, prothrombin fragment F1.2, thrombin-antithrombin complexes (TAT), and P-selectin were measured. Baseline TFPCA levels in the patients were elevated (131 ± 19 U/ml) compared to control subjects (23 ± 2, p<0.0001).TF-PCA levels declined following treatment with clopidogrel alone, and with combinations of clopidogrel with aspirin or cilostazol, with the lowest levels being with the triple-drug combination. Plasma P-selectin declined in all treatment groups. No changes were noted in plasma factorVIIa, F1.2 or TAT.In conclusion, treatment of PAD patients with antiplatelet agents decreases circulatingTF, a molecule with prothrombotic and proinflammatory effects. These findings suggest an unrecognized mechanism, beyond inhibiting aggregation responses, for the efficacy of antiplatelet drugs in patients with arterial diseases.

scholarly journals Role and Management of Coagulation Disorders in Peripheral Arterial Disease

2012 ◽  
Vol 101 (2) ◽  
pp. 94-99 ◽  
Author(s):  
R. Lassila
Keyword(s):  
Risk Factors ◽  
Peripheral Arterial Disease ◽  
Management Strategies ◽  
Antiplatelet Agents ◽  
Arterial Disease ◽  
Medical Attention ◽  
Stable Form ◽  
Vascular Surgeon ◽  
Atherothrombotic Disease ◽  
Peripheral Arterial

Peripheral arterial disease (PAD) has often underlying risk factors, of which diabetes and cigarette smoking are the most common. Enhanced platelet activation and interaction with vessel wall associate with atherothrombotic disease, but also increased fibrinogen levels, thrombin generation and fibrin turnover are typical for PAD. The pathogenic role of fibrinogen, thrombin formation and fibrin degradation is suggested not only in acute thrombotic complications, but also in the stable form of PAD, where these markers associate with the functional severity (ankle-brachial blood pressure index). The coagulation-specific etiologies of PAD should be suspected if the atherothrombotic disease has severe manifestations, especially while the traditional risk factors are absent, or if the patient has also a history of venous thromboembolism. Malignant disease may be present in form of peripheral arterial thrombosis as well. Thrombophilia may expose patients to idiopathic thrombosis – both spontaneously and after vascular interventions. The management of these patients includes often combination therapies with antiplatelet agents and anticoagulants. Obviously, the strict policy to avoid risk factors and to treat them well in avoidance of progression of arterial disease is highly important. In the absence of published follow-up data the evidence to support the management strategies is weak and individual tailoring of efficacious and safe antithrombotic drug therapy remains our challenge. These patients benefit from continuous medical attention by the experts in the field of angiology. Management of PAD is an excellent example of the multidisciplinary approach where the hematologist meets the vascular surgeon or interventional radiologist to secure the best available patient care.

scholarly journals Reinitiation and Subsequent Discontinuation of Antiplatelet Treatment in Nonpersistent Older Patients with Peripheral Arterial Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1280
Author(s):  
Martin Wawruch ◽  
Jan Murin ◽  
Tomas Tesar ◽  
Martina Paduchova ◽  
Miriam Petrova ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Antiplatelet Therapy ◽  
Cox Regression ◽  
Antiplatelet Agents ◽  
Arterial Disease ◽  
University Education ◽  
Chronic Obstructive ◽  
Factors Associated ◽  
Antiplatelet Medication ◽  
Peripheral Arterial

The successful treatment of peripheral arterial disease (PAD) depends on adequate adherence to medications including antiplatelet agents. The aims of this study were (a) to identify the proportion of nonpersistent patients who reinitiated antiplatelet therapy and how many of them discontinued therapy after reinitiation, and (b) to identify patient- and medication-related characteristics associated with the likelihood of reinitiation and discontinuation among reinitiators. The analysis of reinitiation was conducted on 3032 nonpersistent users of antiplatelet agents aged ≥65 years, with PAD newly diagnosed in 2012. Discontinuation (i.e., a treatment gap of ≥6 months without antiplatelet medication prescription) was analysed in 2006 reinitiating patients. To identify factors associated with the likelihood of reinitiation and discontinuation, Cox regression with time-dependent covariates was used. Reinitiation was recorded in 2006 (66.2%) of 3032 patients who had discontinued antiplatelet medication. Among these 2006 reinitiators, 1078 (53.7%) patients discontinued antiplatelet therapy again. Ischemic stroke and myocardial infarction during nonpersistence and bronchial asthma/chronic obstructive pulmonary disease were associated with an increased likelihood of reinitiation. University education was associated with discontinuation among reinitiators. Factors associated with the probability of reinitiation and discontinuation in reinitiators make it possible to identify older PAD patients in whom “stop-starting” behaviour may be expected.

Antiplatelet Treatment in Peripheral Arterial Disease: The Role of Novel Antiplatelet Agents

2016 ◽  
Vol 22 (29) ◽  
pp. 4610-4616 ◽  
Author(s):  
Chris Klonaris ◽  
Nikolaos Patelis ◽  
Anja Drebes ◽  
Sean Matheiken ◽  
Theodoros Liakakos
Keyword(s):  
Peripheral Arterial Disease ◽  
Antiplatelet Agents ◽  
Arterial Disease ◽  
Antiplatelet Treatment ◽  
Peripheral Arterial

Factor VIIa and tissue factor procoagulant activity in diabetes mellitus after acute ischemic stroke: Impact of hyperglycemia

2007 ◽  
Vol 98 (11) ◽  
pp. 1007-1013 ◽  
Author(s):  
Vijender Vaidyula ◽  
Uday Kanamalla ◽  
Michael De Angelis ◽  
John Gaughan ◽  
Nina Gentile ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Ischemic Stroke ◽  
Acute Stroke ◽  
Acute Ischemic Stroke ◽  
Tissue Factor ◽  
Factor Viia ◽  
Procoagulant Activity ◽  
Diabetic Patients ◽  
Stroke Severity ◽  
Plasma Factor

SummaryAlterations in blood coagulation may explain the poorer neurological outcome with diabetes mellitus and hyperglycemia after acute ischemic stroke. We studied the relationships between diabetes mellitus, hyperglycemia, whole blood tissue factor procoagulant activity (TF-PCA) and plasma Factor VIIa (FVIIa) in ten patients with type 2 diabetes mellitus and 11 non-diabetic patients at baseline and 6, 12, 24, and 48 hours (h) after presentation for acute stroke. In addition, we examined plasma prothrombin fragment 1+2 (F1.2) and thrombin-antithrombin complexes (TAT) as markers of thrombin generation. Stroke severity, assessed by National Institute of Health Stroke Scale (NIHSS), was similar at baseline (p=0.26) but worse in diabetic (8.20 ± 4.3) than nondiabetic patients (2.67 ± 2.1,p=0.023) at 48 h. At presentation, diabetic patients had higher FVIIa (p=0.004) and lower TF-PCA (p=0.027) than non-diabetic patients but both were higher than in normal control subjects. FVIIa levels remained higher in diabetic patients at 6, 12 and 24 h after stroke. In diabetic patients, FVIIa (r=0.40, p=0.02) and TF-PCA (r=0.50, p=0.02) correlated with blood glucose; and, FVIIa correlated with plasma F1.2 (r=0.34, p=0.002) and TAT levels (r=0.62, p<0.0001). In non-diabetic patients, TF-PCA, but not FVIIa, correlated with F1.2 (r=0.402, p=0.010) andTAT (r=0.39, p=0.011). Combining both groups, NIHSS scores were positively related to FVIIa levels (r=0.50,p=0.021) and inversely related toTF-PCA levels (r=-0.498, p=0.02). Acute ischemic stroke patients with diabetes and hyperglycemia have a more intense procoagulant state compared with nondiabetic patients. This is related to glucose levels and provides a potential mechanism for the observed worse prognosis in such patients after acute stroke.

scholarly journals Antiplatelet Therapy in Secondary Prevention in Patients with Ischaemic Peripheral Arterial Disease

2020 ◽  
pp. 1-5
Author(s):  
Pavel Chrbolka ◽  
Zoltán Paluch ◽  
Pavel Chrbolka ◽  
Gergely Pallag
Keyword(s):  
Clinical Trials ◽  
Peripheral Arterial Disease ◽  
Antiplatelet Therapy ◽  
Antiplatelet Agents ◽  
Arterial Disease ◽  
Effective Therapy ◽  
Antiplatelet Drugs ◽  
Limb Ischaemia ◽  
Acute Limb Ischaemia ◽  
Peripheral Arterial

Introduction: Globally, peripheral arterial disease affects almost 200 million individuals at high risk of developing another type of cardiovascular disease with an annual incidence of cardiovascular events and cardiovascular mortality of 4-5% and a risk of acute limb ischaemia and amputation of 5%. All patients with clinical symptomatology of peripheral arterial disease should be treated with statins and antiplatelet drugs. Evidence Acquisition: The authors provide an overview, from the perspective of a clinical pharmacologist, of the pharmacokinetic properties of the antiplatelet agents available, mechanisms of their action, and differences among individual agents in side effects, efficacy and safety as well as a comparison of clinical trials. Evidence Synthesis: In a significant proportion of patients, therapy with clopidogrel is modified, with genetic polymorphism demonstrably preventing effective therapy in a proportion of patients. In cases where an antiplatelet agent other than aspirin is chosen, clopidogrel therapy is rational only if a genetic mutation resulting in ineffective therapy has been ruled out. Effective therapy can be accomplished using the more modern antiplatelet agents with balanced pharmacokinetic and pharmacodynamic properties. Conclusions: Several questions related to treatment of patients with peripheral arterial disease remain to be answered. Expert views on recommended antiplatelet therapy diverge. It would be unethical to ignore the fact that therapy may be ineffective in a proportion of clopidogrel-treated patients. Guidelines for the treatment and prevention of peripheral arterial disease should offer alternative antiplatelet drugs or recommendations to verify a patient´s genetic predisposition. Further clinical trials are warranted to assess the efficacy of individual antiplatelet agents and doses thereof in patients with peripheral arterial disease.

scholarly journals Adherence to Antiplatelet Medications among Persistent and Non-Persistent Older Patients with Peripheral Arterial Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1800
Author(s):  
Martin Wawruch ◽  
Jan Murin ◽  
Tomas Tesar ◽  
Martina Paduchova ◽  
Miriam Petrova ◽  
...  
Keyword(s):  
Peripheral Arterial Disease ◽  
Antiplatelet Agents ◽  
Arterial Disease ◽  
Medication Administration ◽  
Study Cohort ◽  
Binary Logistic Regression Model ◽  
Adherence To Medication ◽  
Antiplatelet Medication ◽  
Patient Groups ◽  
Peripheral Arterial

Secondary prevention of peripheral arterial disease (PAD) includes administration of antiplatelet agents, and adherence to medication is a requirement for an effective treatment. The aim of this study was to analyse adherence measured using the proportion of days covered (PDC) index separately in persistent and non-persistent patients, and to identify patient- and medication-related characteristics associated with non-adherence in these patient groups. The study cohort of 9178 patients aged ≥ 65 years in whom PAD was diagnosed in 1/–12/2012 included 6146 persistent and 3032 non-persistent patients. Non-adherence was identified as PDC < 80%. Characteristics associated with non-adherence were determined using the binary logistic regression model. In the group of persistent patients, 15.3% of subjects were identified as non-adherent, while among non-persistent patients, 26.9% of subjects were non-adherent to antiplatelet medication. Administration of dual antiplatelet therapy (aspirin and clopidogrel) and a general practitioner as index prescriber were associated with adherence in both patient groups. Our study revealed a relatively high proportion of adherent patients not only in the group of persistent patients but also in the group of non-persistent patients before discontinuation. These results indicate that most non-persistent PAD patients discontinue antiplatelet treatment rapidly after a certain period of adherence.

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