phenprocoumon and Coronary-Artery-Disease

The optimal long-term antithrombotic treatment of patients with coexisting atrial fibrillation and stable coronary artery disease is unresolved, and commonly, a single antiplatelet agent is added to oral anticoagulation. We investigated the effectiveness and safety of adding antiplatelet therapy to vitamin K antagonist (VKA) in atrial fibrillation patents with stable coronary artery disease.. Atrial fibrillation patients with stable coronary artery disease (defined as 12 months from an acute coronary event) between 2002 and 2011 were identified. The subsequent risk of cardiovascular events and serious bleeding events (those that required hospitalization) was examined with adjusted Cox regression models according to ongoing antithrombotic therapy. A total of 8700 patients were included (mean age, 74.2 years; 38% women). During a mean follow-up of 3.3 years, crude incidence rates were 7.2, 3.8, and 4.0 events per 100 person-years for myocardial infarction/coronary death, thromboembolism, and serious bleeding, respectively. Relative to VKA monotherapy, the risk of myocardial infarction/coronary death was similar for VKA plus aspirin (hazard ratio, 1.12 [95% confidence interval, 0.94-1.34]) and VKA plus clopidogrel (hazard ratio, 1.53 [95% confidence interval, 0.93-2.52]). The risk of thromboembolism was comparable in all regimens that included VKA, whereas the risk of bleeding increased when aspirin (hazard ratio, 1.50 [95% confidence interval, 1.23-1.82]) or clopidogrel (hazard ratio, 1.84 [95% confidence interval, 1.11-3.06]) was added to VKA.. In atrial fibrillation patients with stable coronary artery disease, the addition of antiplatelet therapy to VKA therapy is not associated with a reduction in risk of recurrent coronary events or thromboembolism, whereas risk of bleeding is increased significantly. The common practice of adding antiplatelet therapy to oral VKA anticoagulation in patients with atrial fibrillation and stable coronary artery disease warrants reassessment.

Topics: Aged; Aged, 80 and over; Anticoagulants; Aspirin; Atrial Fibrillation; Clopidogrel; Cohort Studies; Comorbidity; Coronary Artery Disease; Drug Therapy, Combination; Female; Hemorrhage; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Phenprocoumon; Platelet Aggregation Inhibitors; Risk Factors; Stroke; Ticlopidine; Vitamin K; Warfarin

Vitamin K antagonists not only influence the synthesis of coagulation factors but also the activation of other vitamin K dependent proteins. Among other possible side effects, arterial calcification has been focused on in recent years.. Four patients under long-term anticoagulation for more than 10 years developed medial calcific sclerosis. In case 1 we identified an unexplained medial calcific sclerosis on x-ray after a trauma by chance. After that we examined the ankle-brachial index of blood pressure in all patients who had received long-term anticoagulation for more than 10 years. Where the index exceeded 1,3 we performed a x-ray-examination of the forefoot. Of the four described patients no one suffered from diabetes mellitus, renal failure or hyperparathyreoidism. Serum calcium was normal in all patients. The severity of the medial calcific sclerosis could not be explained by the initial vascular risk factors.. In certain patients, even at low vascular risk, a medial calcific sclerosis can appear under long-term anticoagulation with vitamin K antagonists. We conclude that vitamin K antagonists inhibit several proteins which protect the vessels from calcification leading to medial calcific sclerosis.

Topics: Aged; Aged, 80 and over; Ankle Brachial Index; Anticoagulants; Atrial Fibrillation; Coronary Artery Disease; Forefoot, Human; Heart Valve Prosthesis Implantation; Humans; Incidental Findings; Long-Term Care; Male; Middle Aged; Monckeberg Medial Calcific Sclerosis; Phenprocoumon; Postoperative Complications; Vitamin K

A relevant proportion of patients receiving aspirin and clopidogrel after percutaneous coronary intervention (PCI) also require oral anticoagulation with a coumarin derivative such as phenprocoumon. Both clopidogrel and phenprocoumon are metabolized by the hepatic cytochrome P450 system and a drug-drug interaction may exist at this level. The aim of this study was to investigate the impact of phenprocoumon on the antiplatelet effects of clopidogrel in patients with coronary artery disease.. Patients (n = 1223) eligible for this study were under dual maintenance antiplatelet treatment with aspirin and clopidogrel. Adenosine diphosphate-induced platelet aggregation (in AU*min) was measured with multiple electrode platelet aggregometry on a Multiplate analyzer (Dynabyte, Munich, Germany). From the entire study population, 124 (10.1%) patients were under concomitant phenprocoumon treatment at the time point of platelet function testing. Platelet aggregation (median [interquartile range]) was significantly higher in patients with (n = 124) concomitant phenprocoumon treatment compared with patients without (n = 1099) phenprocoumon treatment (308 [190-493] AU*min vs. 224 [145-390] AU*min; P = 0.0001, adjusted P = 0.002).. Phenprocoumon significantly attenuates the antiplatelet effects of clopidogrel. The impact of this interaction on the risk of thrombotic and bleeding events after PCI requires further investigations.

Topics: Adenosine Diphosphate; Administration, Oral; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Clopidogrel; Coronary Artery Disease; Cross-Sectional Studies; Drug Interactions; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Multivariate Analysis; Phenprocoumon; Platelet Aggregation; Platelet Aggregation Inhibitors; Ticlopidine