phenprocoumon and Cardiovascular-Diseases

The purpose of this review article is to summarize the literature on diseases that are documented to have an effect on response to warfarin and other VKAs.. We searched the English literature from 1946 to September 2015 via PubMed, EMBASE, and Scopus for the effect of diseases on response vitamin K antagonists including warfarin, acenocoumarol, phenprocoumon, and fluindione.. Among many factors modifying response to VKAs, several disease states are clinically relevant. Liver disease, hyperthyroidism, and CKD are well documented to increase response to VKAs. Decompensated heart failure, fever, and diarrhea may also elevate response to VKAs, but more study is needed. Hypothyroidism is associated with decreased effect of VKAs, and obese patients will likely require higher initial doses of VKAs.. In order to minimize risks with VKAs while ensuring efficacy, clinicians must be aware of the effect of disease states when prescribing these oral anticoagulants.

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Cardiovascular Diseases; Diarrhea; Fibrinolytic Agents; Heart Failure; Humans; Hyperthyroidism; Kidney Failure, Chronic; Liver Diseases; Obesity; Phenindione; Phenprocoumon; Vitamin K; Warfarin

Anticoagulation in cardioversion of atrial fibrillation is currently performed with unfractionated heparin (UFH) and oral anticoagulants, with or without guidance by transesophageal echocardiography (TEE). Low-molecular-weight heparins may reduce the risk of bleeding, may obviate the need for intravenous access, and do not require frequent anticoagulation monitoring.. In a randomized, prospective multicenter trial, we compared the safety and efficacy of enoxaparin administered subcutaneously with intravenous UFH followed by the oral anticoagulant phenprocoumon in 496 patients scheduled for cardioversion of atrial fibrillation of >48 hours' and < or =1 year's duration. Patients were stratified to cardioversion with (n=431) and without (n=65) guidance by TEE. The study aimed to demonstrate noninferiority of enoxaparin compared with UFH+phenprocoumon with regard to the incidence of embolic events, all-cause death, and major bleeding complications. Secondary end points included successful cardioversion, maintenance of sinus rhythm until study end, and minor bleeding complications. Of 496 randomized patients, 428 were analyzed per protocol. Enoxaparin was noninferior to UFH+phenprocoumon with regard to the incidence of the composite primary end point in a per-protocol analysis (7 of 216 patients versus 12 of 212 patients, respectively; P=0.016) and in an intention-to-treat analysis (7 of 248 patients versus 12 of 248 patients, respectively; P=0.013). There was no significant difference between the 2 groups in the number of patients reverted to sinus rhythm.. Enoxaparin is noninferior to UFH+phenprocoumon for prevention of ischemic and embolic events, bleeding complications, and death in TEE-guided cardioversion of atrial fibrillation. Its easier application and more stable anticoagulation may make it the preferred drug for initiation of anticoagulation in this setting.

Topics: Administration, Oral; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Drug Therapy, Combination; Electric Countershock; Enoxaparin; Female; Hemorrhage; Heparin; Humans; Incidence; Infusions, Intravenous; Injections, Subcutaneous; Male; Middle Aged; Phenprocoumon; Safety; Thromboembolism; Treatment Outcome

This study investigated the usefulness and practicability of a platelet function analyzer (PFA-100(TM), DADE-Behring, Germany) to determine individual platelet inhibition in patients treated with acetylsalicylic acid (ASA).. Patients with coronary artery disease (CAD) routinely and during angioplasty (PTCA) receive standard doses of ASA to avoid acute coronary syndromes and abrupt vessel closures without information of the individual efficacy of platelet inhibition.. With the PFA-100(TM) a standardized bleeding time is measured. Whole-blood anticoagulated with 3.2% sodium citrate is aspirated through a capillary ( solidus in circle 200 microm) and through an aperture ( solidus in circle 147 microm). The time until occlusion of the aperture (closure time, CT) by a stable platelet plug induced by shear stress, collagen and epinephrine (COLL/EPI-CT) or shear stress, collagen and adenosine 5'-diphosphate (COLL/ADP-CT) is determined. To examine the usefulness of the PFA-100(TM) as a rapid bedside test and the individual effect of ASA, closure time was measured in healthy individuals (n=17), in patients with stable CAD (n=19) and in patients undergoing PTCA (n=8).. Patients with stable CAD and regular medication with 100 mg ASA per day for at least 3 month showed shorter COLL/ADP-CT in comparison to healthy individuals who took only one single dose of 100 mg ASA. Of the patients with CAD 63% had a COLL/EPI-CT within normal range suggesting a low or no response to ASA. Also only 50% of the patients undergoing PTCA reached the expected COLL/EPI-CT>300 s after an additive single dose of 500 mg ASA intravenously. Neither heparin, phenprocoumon, sex nor different blood sampling methods seem to influence the measurements relevantly.. This pilot study indicates that with the PFA-100(TM) test device a simple and quick measurement of an in vitro bleeding time is possible. It is able to detect an increase in the bleeding time after a single dose of ASA 100 mg in healthy subjects, reflecting a sensitive detection of ASA induced changes in platelet inhibition respective activation. Differences in the individual response to ASA could be observed in healthy subjects, patients with stable CAD and patients undergoing PTCA. Further studies should validate the PFA-100(TM) with standard methods to determine ASA response in patients with cardiovascular disease and investigate implications for treatment and outcome in this patient group.

Topics: Adult; Aged; Anticoagulants; Aspirin; Blood Coagulation Tests; Cardiovascular Diseases; Case-Control Studies; Female; Heparin; Humans; Male; Middle Aged; Phenprocoumon; Pilot Projects; Platelet Aggregation; Platelet Aggregation Inhibitors; Point-of-Care Systems; Sensitivity and Specificity

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

Various methods have been described to evaluate efficacy of anticoagulant therapy using the international normalized ratio (INR). We compared the following approaches: (1) total INR's or the most recent measurement; (2) percent time within therapeutic range, with INR changing directly or halfway between visits; and (3) total observation time assuming INR changing linearly. The study population comprised 1700 post myocardial infarction patients. Treatment comprised 3725 patient-years. There were 61,471 INR assessments with target therapeutic level of 2.8-4.8. Acenocoumarol as well as phenprocoumon were employed. Therapeutic achievement in the first months of treatment was low: less than 60% of INR's were in range. Treatment stabilized after 6 months. Patients on acenocoumarol were within range 70% of the time compared to 80% for phenprocoumon. Method 3 is preferred because it incorporates time and is capable of calculating incidence rates at different INR levels. Our findings call for an urgent improvement of standard of anticoagulant control in the first months following commencement of treatment.

Topics: Acenocoumarol; Aged; Anticoagulants; Cardiovascular Diseases; Convalescence; Double-Blind Method; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Phenprocoumon; Prothrombin Time; Quality Control; Reference Standards; Thromboplastin; Treatment Outcome

The use of long-term oral anticoagulant treatment after myocardial infarction remains controversial because of conflicting findings on mortality in previous trials and the increased risk of bleeding associated with anticoagulants. We have carried out a randomised, placebo-controlled, double-blind, multicentre trial in 3404 hospital survivors of myocardial infarction. Eligible patients were randomly assigned to anticoagulant (nicoumalone or phenprocoumon) or placebo treatment within 6 weeks of discharge. The target prothrombin time was 2.8-4.8 international normalised ratio. During mean follow-up of 37 (range 6-76) months there were 170 deaths among 1700 anticoagulant-treated patients and 189 in 1704 placebo-treated patients (hazard ratio 0.90 [95% CI 0.73-1.11]). Anticoagulant treatment led to significant reductions by comparison with placebo treatment in recurrent myocardial infarction (114 vs 242 patients; hazard ratio 0.47 [0.38-0.59]) and cerebrovascular events (37 vs 62; 0.60 [0.40-0.90]). Major bleeding complications were seen in 73 patients who received anticoagulants and 19 who received placebo. We conclude that long-term oral anticoagulant treatment after myocardial infarction in low-risk patients has a limited effect on mortality but achieves substantial benefit by reducing the risk of cerebrovascular events and recurrent myocardial infarction.

Topics: Acenocoumarol; Administration, Oral; Aged; Cardiovascular Diseases; Cause of Death; Double-Blind Method; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Middle Aged; Myocardial Infarction; Phenprocoumon; Proportional Hazards Models; Recurrence; Risk Factors; Survival Rate

Topics: Adrenomedullin; Adult; Aged; Ankle Brachial Index; Anticoagulants; Asymptomatic Diseases; Atrial Fibrillation; Atrial Natriuretic Factor; C-Reactive Protein; Cardiovascular Diseases; Carotid Intima-Media Thickness; Female; Fibrinogen; Germany; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Phenprocoumon; Protein Precursors; Pulmonary Embolism; Risk Factors; Stroke; Stroke Volume; Vascular Stiffness; Venous Thrombosis; Warfarin

Adherence to the generally complex regimen of coumarin derivatives is vital in order to keep patients in the adequate International Normalized Ratio range. Patients' beliefs about medicines are associated with the level of therapy adherence. Our first aim was to assess beliefs about coumarins. Secondly, we compared the beliefs about coumarins with the beliefs about other cardiovascular drugs.. The Beliefs about Medicines Questionnaire was used to assess medication beliefs. The questionnaire was completed by new users of coumarins indicated for venous thromboembolism or atrial fibrillation. A necessity score and a concerns score were calculated for all patients. The analyses were repeated for users of antihypertensive drugs or statins (not using coumarins).. Three hundred and twenty patients were included in the analysis of the beliefs about coumarins. The mean necessity score was 15.3, the concerns score 12.3 and the necessity-concerns differential 3.0. Patients with venous thromboembolism (n = 71) had higher necessity scores than patients with atrial fibrillation (n = 249; 16.8 vs. 14.9, P < 0.001). The mean necessity score in 493 users of other cardiovascular drugs was 16.1, the concerns score 13.5 and the necessity-concerns differential 2.6. The necessity score was higher in chronic cardiovascular drug users (n = 192) than in new users (n = 301; 17.9 vs. 14.9, P < 0.001).. Coumarin users score higher on the necessity scale than on the concerns scale, which is also the case in users of other cardiovascular drugs. Patients with atrial fibrillation have a less positive attitude towards these drugs than patients with venous thromboembolism, and could therefore benefit more from specific attention.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Data Interpretation, Statistical; Female; Humans; International Normalized Ratio; Male; Middle Aged; Netherlands; Patient Compliance; Patient Medication Knowledge; Phenprocoumon; Surveys and Questionnaires

We present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug-drug interactions with vitamin K antagonists (VKAs). We use the putative interaction between VKAs and tramadol as a case study.. We used a self-controlled case series to estimate the incidence rate ratio (IRR) comparing the rate of INR measurements of ≥4.0 in concomitant tramadol and VKA-exposed periods to VKA-only-exposed periods. Secondary analyses considered specific subgroups, alternative exposure criteria, alternative outcome definitions, and other drugs.. We identified 513 VKA users with at least 1 INR measurement ≥4.0 and concomitant tramadol and VKA exposure during the observation period. The overall IRR was 1.80 (95% confidence interval [CI], 1.53-2.10), with a stronger association among users of phenprocoumon compared to warfarin (IRR, 3.37; 95%CI, 2.50-4.53 and IRR, 1.46; 95%CI, 1.20-1.76, respectively). We observed larger IRRs with stricter outcome definitions. Concomitant tramadol and VKA exposure was also associated with an increased rate of low INR measurements (i.e., <1.5; IRR, 1.70; 95%CI, 1.37-2.13). Morphine and, to some extent, oxycodone, penicillin, beta-blockers, and inhaled beta-agonists were associated with high INR.. The approach successfully identified an interaction between tramadol and VKA. However, associations observed for other drugs with no known VKA interaction suggest that the current approach may have too low specificity to be useful as a screening tool, at least for drugs for which time-varying confounding may be present.

Topics: Age Factors; Aged; Aged, 80 and over; Analgesics, Opioid; Anticoagulants; Cardiovascular Diseases; Codeine; Denmark; Drug Interactions; Female; Humans; Insurance Claim Review; International Normalized Ratio; Male; Pharmacoepidemiology; Phenprocoumon; Prescription Drugs; Sex Factors; Tramadol; Vitamin K; Warfarin

Topics: Administration, Oral; Anticoagulants; Cardiovascular Diseases; Elective Surgical Procedures; Hemorrhage; Heparin; Heparin, Low-Molecular-Weight; Humans; International Normalized Ratio; Perioperative Period; Phenprocoumon; Risk Factors; Thromboembolism; Vitamin K

To determine the frequency of essential cardiovascular risk factors in different vascular ocular diseases. -. We compiled cardiovascular risk factor findings (RFs) from 416 patients with non-inflammatory ocular vascular occlusions in a retrospective study: 134 patients with BRAO, 253 patients with CRAO, and 29 patients with hemi-CRAO. 274 (65.9 %) male and 142 (34.1 %) female patients were examined. Mean age of all patients was 66 years (range: 18-90). The right eye was involved in 221 (53.1 %), left eye in 193 (46.4 %), and both eyes in 2 patients (0.5 %). -. Cardiovascular risk factors (RFs) were found in 243 patients. Three hundred and eight (308) out of 406 patients (75.9 %) presented with arterial hypertension. Hypertension was present in 96 patients with BRAO (73.8 %), in 197 patients with CRAO (79.8 %), and in 15 patients with hemi-CRAO (78.9 %). - RFs such as arterial hypertension, carotid artery diseases, diabetes mellitus, hyperlipidemia, hyperuricemia, and chronic smoking did not differ statistically between patients with BRAO, CRAO or hemi--CRAO. But visible emboli in retinal arteries were observed in patients with BRAO (47 %,), or hemi-CRAO (41.4 %), much more often than in patients with CRAO (11.1 %). -. No statistical differences between the RFs of patients with BRAO, CRAO, or hemi-CRAO were noted. We maintain that every patient with retinal arterial obstruction should undergo extensive examination of essential RFs.

Topics: Adult; Aged; Aged, 80 and over; Amaurosis Fugax; Anticoagulants; Cardiovascular Diseases; Cerebrovascular Disorders; Female; Humans; Hypertension; Male; Middle Aged; Phenprocoumon; Retinal Artery Occlusion; Risk Factors

Physicians face a therapeutic dilemma in patients with acute hemorrhagic stroke requiring long-term, high-intensity anticoagulants because this treatment increases the risk of intracranial hemorrhage (ICH) 8- to 11-fold. We retrospectively studied 15 patients with ICH which occurred under anticoagulation with phenprocoumon, with an international norrmalized ratio (INR) of 2.5-6.5 on admission. Hemispheric, thalamic, cerebellar, intraventricular, or subarachnoid hemorrhage without aneurysm occurred. Absolute indications for anticoagulation were double, mitral, or aortic valve replacement, combined mitral valve failure with atrial fibrillation and atrial enlargement, internal carotid artery-jugular vein graft, frequently recurring deep vein thrombosis with risk of pulmonary embolism, and severe nontreatable ischemic heart disease. As soon as the diagnosis of ICH was established, INR normalization was attempted in all patients by administration of prothrombin complex, fresh frozen plasma, or vitamin K. After giving phenprocoumon antagonists (and neurosurgical therapy in four patients) heparin administration was started. Nine patients received full-dose intravenous and six low-dose subcutaneous heparin. The following observations were made: (a) All patients with effective, full-dose heparin treatment with a 1.5- to 2-fold elevation in partial thromboplastin time after normalization of the INR were discharged without complication. (b) Three of four of the patients with only incomplete correction of the INR (> 1.35) experienced relevant rebleeding within 3 days (all patients with an INR higher than 1.5), two of whom were on full-dose heparin. (c) Three of seven of the patients with normalized INR and without significant PTT elevation developed severe cerebral embolism. Although our data are based on a retrospective analysis, they support treatment with intravenous heparin (partial thromboplastin time 1.5-2 times baseline value) after normalization of the INR in patients with an ICH and an urgent need for anticoagulation.

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Cerebral Hemorrhage; Female; Heparin; Humans; Male; Middle Aged; Partial Thromboplastin Time; Phenprocoumon; Retrospective Studies; Stroke; Venous Thrombosis

In a 5-year retrospective study (1982-1978) in a well defined population of 332 patients (representing greater than or equal to 2140 anticoagulation years) from a heart specialist's practice, the question was studied whether optimum anticoagulation (Quick test between 18-29%, INR 4.0-2.75, Geigy thromboplastin, capillary blood method) with minimum complications could be achieved. In the qualitative study it was found that 75% of Quick determinations were in the optimum range for phenprocoumon, 71.6% for clorindion, 62% for acenocoumarol and 72% for all anticoagulants. 77% of phenprocoumon patients were optimally anticoagulated for more than 3 years. With phenprocoumon there was no difference in intensity of anticoagulation between the oldest and youngest patient groups, as all mean Quick values ranged over 20% (means Q% 1982-1978 = 25, INR = 3.0). It was also shown that after 6 months' anticoagulant therapy it is clearly recognizable whether optimum anticoagulation is feasible or not: at that moment the criteria for halting or continuing anticoagulant therapy can and should be reviewed.

Topics: Aged; Ambulatory Care; Anticoagulants; Blood Coagulation Tests; Cardiovascular Diseases; Female; Hemorrhage; Humans; Longitudinal Studies; Male; Middle Aged; Phenprocoumon; Retrospective Studies; Switzerland

Topics: Aged; Anticoagulants; Cardiovascular Diseases; Coumarins; Geriatrics; Heparin; Humans; Middle Aged; Myocardial Infarction; Phenprocoumon; Prognosis

Topics: Cardiovascular Diseases; Coumarins; Heparin; Humans; Long-Term Care; Myocardial Infarction; Phenprocoumon