phenprocoumon and Coronary-Disease

Combined antiplatelet therapy after coronary stent placement is superior to anticoagulation with respect to early outcome. It is unclear if this benefit is maintained during long-term follow-up. This study reports on the 4-year clinical outcome of patients randomized in the Intracoronary Stenting and Antithrombotic Regimen trial. In the Intracoronary Stenting and Antithrombotic Regimen trial, 517 patients were randomized after successful placement of Palmaz-Schatz stents: 257 to aspirin and ticlopidine, and 260 to aspirin and phenprocoumon. Ticlopidine and phenprocoumon were given for 4 weeks. At 30 days, patients with ticlopidine had significantly fewer adverse cardiac events (1.6% vs 6.2%; p = 0.007), nonfatal myocardial infarction (0.8% vs 3.5%; p = 0.034), and target vessel revascularization procedures (1.2% vs 5.4%; p = 0.007). At 4 years, rates for any adverse cardiac events were 22.6% versus 28.5% (p = 0.078), for nonfatal myocardial infarction 0.9% versus 5.8% (p = 0.003), and for target vessel revascularization 18.3% versus 22.7% (p = 0.21). The absolute difference in event rates (4.6% after 30 days) was maintained after 4 years (5.9%). Event rates beyond day 30 were not significantly different (21.1% vs 22.5%; p = 0.78), nor were the rates beyond the first year, which were very low (5.2% vs 3.6%; p = 0.50). This study shows that the benefit of combined antiplatelet therapy evident after 30 days is maintained after 4 years. Independent of the initial regimen, rates of adverse cardiac events are low beyond the first year.

Topics: Angioplasty, Balloon; Anticoagulants; Aspirin; Coronary Angiography; Coronary Disease; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Recurrence; Statistics, Nonparametric; Stents; Survival Analysis; Ticlopidine; Treatment Outcome

This study was designed to investigate the role of inflammation on the occurrence of angiographic restenosis 6 months after coronary stent implantation and the influence of different kinds of antithrombotic and antiplatelet strategies on inflammation.. In an open randomized trial, 40 consecutive patients were treated with aspirin (100 mg. day(-1)) and either ticlopidine (2x250 mg. day(-1)) (n=17), or phenprocoumon (INR 2.0-3.0) and dipyridamole (3x160 mg. day(-1)) (n=23) after successful elective coronary stent implantation. Plasma levels of C-reactive protein were determined one day before stent implantation and serially thereafter twice daily up to 120 h. C-reactive protein plasma levels increased significantly (P<0.0001) after stent implantation. Phenprocoumon and dipyridamole or ticlopidine had no effect on C-reactive protein plasma levels (P=0.51) or the occurrence of angiographic restenosis (P=0.48). C-reactive protein plasma levels were significantly higher in patients with lesion type C compared to types A or B (P=0.035), respectively. C-reactive protein plasma levels were significantly higher and mean shoulder levels occurred 48 h later in patients with restenosis compared to patients without restenosis after 6 months (P=0.038).. Elevated C-reactive protein plasma levels still persisting 96 h after stent implantation might reflect a prolonged inflammatory reaction to coronary stent implantation which might causally be involved in pathophysiological mechanisms leading to restenosis.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Biomarkers; C-Reactive Protein; Coronary Angiography; Coronary Disease; Dipyridamole; Drug Therapy, Combination; Female; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Prognosis; Stents; Ticlopidine

In a prospective randomized trial in 42 patients undergoing coronary artery bypass surgery, we analyzed the long term platelet inhibiting effects of 50 mg acetylsalicylic acid (ASA) by itself and in combination with dipyridamole (2 x 200 mg), in comparison with phenprocoumon. Three and six months therapy led to significant inhibition of maximum aggregation induced by collagen 1 microgram/ml in platelet rich plasma (PRP) by more than 50% (p < or = 0.05). In PRP stimulated with 5 micrograms/ml collagen maximum inhibition amounted to nearly 20% (n.s.). The groups treated with ASA/ASA + dipyridamole showed an ADP threshold concentration 2.5 times higher than the group treated with phenprocoumon (p < or = 0.05). After stimulation with collagen 1 microgram/ml and 5 micrograms/ml thromboxane B2 synthesis in vitro in both groups treated with ASA was reduced to 1% of the base line values (p < or = 0.01). Inhibition of aggregation in whole blood appeared evident, but was not statistically significant due to considerable fluctuation of measurement. An additional effect of dipyridamole was not detectable. In conclusion, treatment with 50 mg ADA/d results in a lasting, effective inhibition of aggregation of platelets in patients with coronary artery bypass surgery. There is no synergistic effect of additional dose of 400 mg dipyridamole/d.

Topics: Anticoagulants; Aspirin; Blood Platelets; Coronary Artery Bypass; Coronary Disease; Dipyridamole; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Prospective Studies; Thromboxane B2; Time Factors

The Intracoronary Stenting and Antithrombotic Regimen (ISAR) trial is a randomized comparison of combined antiplatelet with anticoagulant therapy after coronary Palmaz-Schatz stent placement. The objective of this study was to compare early and late clinical and angiographic outcome in a subgroup of patients with stent placement for acute myocardial infarction.. Stenting has become a treatment option for acute myocardial infarction, but it is not known which antithrombotic regimen is more adequate after stent implantation.. One hundred twenty-three patients with successful stenting after acute myocardial infarction were randomized to receive aspirin plus ticlopidine (n = 61) or intense anticoagulant therapy (n = 62). Six-month repeat angiography was performed in 101 (86.3%) eligible patients.. During the first 30 days after stenting, patients with antiplatelet therapy had a significantly lower clinical event rate (3.3% vs. 21.0%, p = 0.005) and stent vessel occlusion rate (0% vs. 9.7%, p = 0.03) and a trend to fewer cardiac events (1.6% vs. 9.7%, p = 0.12). After 6 months, the survival rate free of recurrent myocardial infarction was higher in patients with antiplatelet therapy (100% vs. 90.3%, p = 0.03), and the rate of stent vessel occlusion was lower (1.6% vs. 14.5%, p = 0.02). Both groups had comparable restenosis rates (26.5% vs. 26.9%, p = 0.87).. This study demonstrates that combined antiplatelet therapy after stent placement in patients with acute myocardial infarction is associated with an overall better clinical and angiographic outcome than anticoagulant therapy.

Topics: Anticoagulants; Aspirin; Coronary Angiography; Coronary Disease; Female; Follow-Up Studies; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Phenprocoumon; Platelet Aggregation Inhibitors; Recurrence; Stents; Survival Rate; Ticlopidine; Time Factors; Treatment Outcome

The Intracoronary Stenting and Antithrombotic Regimen (ISAR) Trial is a randomized study in which antiplatelet therapy is compared with anticoagulant therapy after coronary stent placement, showing a significantly lower rate of noncardiac and cardiac events with antiplatelet therapy. The present study is a report of the analysis of a prospective risk stratification protocol in the ISAR Trial and the association with the incidence of adverse cardiac events and stent vessel occlusion.. In all 517 patients randomized in the ISAR Trial, risk stratification was done with a list of 18 clinical, procedural, and angiographic variables: 165 patients with two or fewer criteria were classified as low risk, 148 patients with three criteria were classified as intermediate risk, and 204 patients with four or more criteria were classified as high risk. Within a 30-day follow-up, cardiac event rate (death, myocardial infarction, repeat intervention) was 6.4% for high-risk, 3.4% for intermediate-risk, and 0% for low-risk patients (P<.01). Stent vessel occlusion occurred in 5.9%, 2.7%, and 0%, respectively (P<.01). There was no significant difference between anticoagulant and antiplatelet therapy in the low- and intermediate-risk groups. In high-risk patients, however, the cardiac event rate was 12.6% with anticoagulant therapy and 2.0% with antiplatelet therapy (P=.007), and the rate of stent vessel occlusion was 11.5% and 0%, respectively (P<.001).. This risk stratification protocol can help to identify patients at risk for adverse cardiac events and stent vessel occlusion. Patients in the high-risk group had the most benefit from antiplatelet therapy. These data suggest that antiplatelet therapy is the therapy of choice after coronary stenting specifically for patients with acute ischemic syndromes, difficult procedures, or suboptimal final results.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Cardiovascular Diseases; Combined Modality Therapy; Coronary Disease; Death, Sudden, Cardiac; Fibrinolytic Agents; Heparin; Humans; Incidence; Myocardial Infarction; Phenprocoumon; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Recurrence; Reoperation; Risk Factors; Stents; Ticlopidine

Platelets and mural thrombus at the lesion site may play a key role in initiating the restenosis process after coronary interventions. The ISAR Trial provides a comparison of the outcomes of patients randomized to two different antithrombotic regimens administered for 4 weeks after successful coronary stent placement: combined antiplatelet therapy (aspirin plus ticlopidine) or a conventional anticoagulant regimen (phenprocoumon with initial overlapping heparin plus aspirin). Within the first 4 weeks after stent placement, combined antiplatelet therapy has been associated with a significant reduction of ischemic complications. In the present study, we examined whether combined antiplatelet therapy administered for 4 weeks after stent placement is able to reduce the process of restenosis at 6 months.. Of 517 patients initially randomized, 496 were eligible for 6-month angiographic follow-up. Scheduled angiography was performed in 432 of the eligible patients (87.1%), 216 in each group. In a comparison of the two groups, there were no significant differences in clinical and procedural variables or in qualitative and quantitative lesion characteristics before and after stenting. At 6 months, minimal luminal diameter was 1.95+/-0.86 mm in the group with initial combined antiplatelet therapy and 1.90+/-0.87 mm in the group with initial anticoagulant therapy (P=.55). Late lumen loss was 1.10+/-0.81 and 1.15+/-0.75 mm (P=.54), and the restenosis rate was 26.8% and 28.9%, respectively (P=.70). Target lesion revascularization rate was 14.6% in the antiplatelet therapy group and 15.6% in the anticoagulant therapy group (P=.85).. This study shows that combined antiplatelet therapy (aspirin plus ticlopidine) administered for 4 weeks after coronary Palmaz-Schatz stent placement does not result in a detectable benefit for the prevention of restenosis compared with conventional anticoagulant therapy (phenprocoumon with initial overlapping heparin plus aspirin).

Topics: Administration, Oral; Aged; Angioplasty, Balloon; Anticoagulants; Coronary Angiography; Coronary Disease; Drug Therapy, Combination; Female; Follow-Up Studies; Heparin; Humans; Infusions, Intravenous; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Recurrence; Stents; Ticlopidine

The clinical benefit of coronary-artery stenting performed in conjunction with coronary angioplasty is limited by the risk of thrombotic occlusion of the stent as well as hemorrhagic and vascular complications of intensive anticoagulation. We compared antiplatelet therapy with conventional anticoagulant therapy with respect to clinical outcomes 30 days after coronary-artery stenting.. After successful placement of Palmaz-Schatz coronary-artery stents, 257 patients were randomly assigned to receive antiplatelet therapy (ticlopidine plus aspirin) and 260 to receive anticoagulant therapy (intravenous heparin, phenprocoumon, and aspirin). The primary cardiac end point was a composite measure reflecting death from cardiac causes or the occurrence of myocardial infarction, aortocoronary bypass surgery, or repeat angioplasty. The primary noncardiac end point comprised death from noncardiac causes, cerebrovascular accident, severe hemorrhage, and peripheral vascular events.. Of the patients assigned to antiplatelet therapy, 1.6 percent reached a primary cardiac end point, as did 6.2 percent of those assigned to anticoagulant therapy (relative risk, 0.25; 95 percent confidence interval, 0.06 to 0.77). With antiplatelet therapy, there was an 82 percent lower risk of myocardial infarction than in the anticoagulant-therapy group, and a 78 percent lower need for repeat interventions. Occlusion of the stented vessel occurred in 0.8 percent of the antiplatelet-therapy group and in 5.4 percent of the anticoagulant-therapy group (relative risk, 0.14; 95 percent confidence interval, 0.02 to 0.62). A primary noncardiac end point was reached by 1.2 percent of the antiplatelet-therapy group and 12.3 percent of the anticoagulant-therapy group (relative risk, 0.09; 95 percent confidence interval, 0.02 to 0.31). Hemorrhagic complications occurred only in the anticoagulant-therapy group (in 6.5 percent). An 87 percent reduction in the risk of peripheral vascular events was observed with antiplatelet therapy.. As compared with conventional anticoagulant therapy, combined antiplatelet therapy after the placement of coronary-artery stents reduces the incidence of both cardiac events and hemorrhagic and vascular complications.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Aspirin; Coronary Disease; Drug Therapy, Combination; Female; Heparin; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation Inhibitors; Postoperative Complications; Prospective Studies; Stents; Ticlopidine

From 1987 until 1991 a large prospective randomized multicentre study was performed in The Netherlands, Germany and Switzerland entitled CABADAS (Prevention of Coronary Artery Bypass graft occlusion by Aspirin, Dipyridamole, and Acenocoumarol/Phenprocoumon Study). The aim of CABADAS was to evaluate the relative efficacy of (1) aspirin, (2) aspirin plus dipyridamole, and (3) oral anticoagulants in the prevention of vein graft occlusion during the first year after aortocoronary bypass surgery. No significant difference was observed in the incidence of graft occlusion among the three treatment groups. In a subgroup of 127 CABADAS patients, studied in the Academic Medical Centre in Amsterdam, the relationship between treatment and clinical status (i.e. symptoms of angina pectoris and exercise capacity) was assessed, and the relationship between treatment and functional status of the vein grafts was determined by means of thallium-201 exercise scintigraphy. There were no differences in symptoms among the three treatment groups in the 127 patients studied. There were no significant differences either among the treatment groups, as regards exercise capacity and the number or intensity of perfusion defects, in the 81 patients who underwent thallium-201 exercise scintigraphy. The three antithrombotic treatment regimens had a similar effect on the clinical status of patients and on the functional status of venous bypass grafts one year after coronary bypass surgery. This finding underscores the CABADAS results in that aspirin may be the preferred treatment option in patients following venous bypass surgery.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Aspirin; Coronary Artery Bypass; Coronary Circulation; Coronary Disease; Dipyridamole; Drug Therapy, Combination; Exercise Test; Female; Fibrinolytic Agents; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Image Processing, Computer-Assisted; Male; Middle Aged; Phenprocoumon; Postoperative Complications; Prospective Studies; Radionuclide Imaging; Saphenous Vein; Thallium Radioisotopes; Treatment Outcome

In a prospective randomised trial, 249 patients who had aortocoronary vein bypass surgery were assigned either to a platelet inhibitory drug regimen or to standard anticoagulant therapy. Treatment was replaced by placebo in half of the patients in each group after 3 months. The platelet inhibitory drug regimen--very low-dose aspirin combined with dipyridamole--was as effective as standard anticoagulant therapy to prevent early and late graft occlusion. Death, myocardial infarction, and severe bleeding occurred significantly more often in patients receiving anticoagulants, whereas mild drug-related gastrointestinal and cerebral side-effects were more common in patients taking platelet inhibitory drugs. Antithrombotic treatment should be continued for at least 1 year after coronary artery bypass graft surgery.

Topics: 4-Hydroxycoumarins; Adult; Aged; Aspirin; Clinical Trials as Topic; Coronary Artery Bypass; Coronary Disease; Coronary Thrombosis; Dipyridamole; Double-Blind Method; Drug Administration Schedule; Drug Evaluation; Drug Therapy, Combination; Female; Follow-Up Studies; Graft Occlusion, Vascular; Humans; Male; Middle Aged; Phenprocoumon; Platelet Aggregation; Platelet Aggregation Inhibitors; Postoperative Complications; Premedication; Prospective Studies; Random Allocation; Saphenous Vein

To evaluate the effect of oral anticoagulant therapy on graft patency rate during the first 2 months after bypass surgery 174 patients were randomly assigned to treatment with phenprocoumon (89) or to a control group (85) starting on day 7 after bypass surgery. Until day 7 all patients received low dose heparin. There was no significant difference between the two groups with respect to age, sex distribution, number of vessels diseased, left ventricular enddiastolic pressure, preoperative exercise tolerance or number of grafts constructed per patient. All patients underwent angiographic evaluation 8 weeks after bypass surgery. Graft patency rate was 90.4% in the treatment group versus 83.6% in the control group (p less than 0.015). None of the grafts with a flow rate of greater than 90 ml/min was occluded 8 weeks after surgery. Oral anticoagulation improved the patency rate of grafts with a flow of less then 90 ml/min.

Topics: 4-Hydroxycoumarins; Adult; Aged; Coronary Artery Bypass; Coronary Circulation; Coronary Disease; Female; Humans; Male; Middle Aged; Phenprocoumon; Prospective Studies; Random Allocation

Topics: Angioplasty, Balloon, Coronary; Aspirin; Atrial Fibrillation; Clopidogrel; Coronary Disease; Coronary Restenosis; Drug Interactions; Drug Therapy, Combination; Fibrinolytic Agents; Hemorrhage; Humans; Phenprocoumon; Proton Pump Inhibitors; Stents; Thromboembolism; Ticlopidine

After stent implantation there is a high risk of acute stent thrombosis. Therefore, a very aggressive anticoagulation drug regimen is necessary. Two patients developed large hematomas of the upperarm that where presumably caused by automatic blood pressure measuring equipment or by a tourniquet used during blood collection. In one patient a complete paralysis of the ulnar and radial nerves resulted.

Topics: Angioplasty, Balloon, Coronary; Anticoagulants; Arm Injuries; Aspirin; Blood Pressure Monitors; Coronary Disease; Drug Therapy, Combination; Hematoma; Heparin; Humans; Male; Middle Aged; Phenprocoumon; Prothrombin Time; Stents

Topics: 4-Hydroxycoumarins; Abdomen, Acute; Coronary Disease; Gastrointestinal Hemorrhage; Hematoma; Humans; Intestine, Small; Laparotomy; Male; Middle Aged; Phenprocoumon