acenocoumarol and Cardiovascular-Diseases

There is a special interest in the implementation of pharmacogenetics in clinical practice, although there are some barriers that are preventing this integration. A large part of these pharmacogenetic tests are focused on drugs used in oncology and psychiatry fields and for antiviral drugs. However, the scientific evidence is also high for other drugs used in other medical areas, for example, in cardiology. In this article, we discuss the evidence and guidelines currently available on pharmacogenetics for clopidogrel, warfarin, acenocoumarol, and simvastatin and its implementation in daily clinical practice.

Topics: Acenocoumarol; Anticoagulants; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Clopidogrel; Cytochrome P-450 CYP2C9; Guidelines as Topic; Humans; Pharmacogenetics; Precision Medicine; Simvastatin; Warfarin

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

Atherosclerotic peripheral arterial disease is associated with an increased risk of myocardial infarction, stroke, and death from cardiovascular causes. Antiplatelet drugs reduce this risk, but the role of oral anticoagulant agents in the prevention of cardiovascular complications in patients with peripheral arterial disease is unclear.. We assigned patients with peripheral arterial disease to combination therapy with an antiplatelet agent and an oral anticoagulant agent (target international normalized ratio [INR], 2.0 to 3.0) or to antiplatelet therapy alone. The first coprimary outcome was myocardial infarction, stroke, or death from cardiovascular causes; the second coprimary outcome was myocardial infarction, stroke, severe ischemia of the peripheral or coronary arteries leading to urgent intervention, or death from cardiovascular causes.. A total of 2161 patients were randomly assigned to therapy. The mean follow-up time was 35 months. Myocardial infarction, stroke, or death from cardiovascular causes occurred in 132 of 1080 patients receiving combination therapy (12.2%) and in 144 of 1081 patients receiving antiplatelet therapy alone (13.3%) (relative risk, 0.92; 95% confidence interval [CI], 0.73 to 1.16; P=0.48). Myocardial infarction, stroke, severe ischemia, or death from cardiovascular causes occurred in 172 patients receiving combination therapy (15.9%) as compared with 188 patients receiving antiplatelet therapy alone (17.4%) (relative risk, 0.91; 95% CI, 0.74 to 1.12; P=0.37). Life-threatening bleeding occurred in 43 patients receiving combination therapy (4.0%) as compared with 13 patients receiving antiplatelet therapy alone (1.2%) (relative risk, 3.41; 95% CI, 1.84 to 6.35; P<0.001).. In patients with peripheral arterial disease, the combination of an oral anticoagulant and antiplatelet therapy was not more effective than antiplatelet therapy alone in preventing major cardiovascular complications and was associated with an increase in life-threatening bleeding. (ClinicalTrials.gov number, NCT00125671 [ClinicalTrials.gov].).

Topics: Acenocoumarol; Administration, Oral; Anticoagulants; Aspirin; Atherosclerosis; Cardiovascular Diseases; Clopidogrel; Drug Therapy, Combination; Female; Follow-Up Studies; Hemorrhage; Humans; Incidence; Male; Middle Aged; Peripheral Vascular Diseases; Platelet Aggregation Inhibitors; Ticlopidine; Warfarin

We present a prospective clinical study on use of tranexamic acid mouthwashes in patients taking oral anticoagulants and who have to undergo minor ambulatory oral surgery, without modifying their anticoagulant therapy.. Forty patients (18 men and 22 females) aged from 42 to 81 were studied from April 2000 to December 2002. All patients were under the same anticoagulant, vitamin K antagonist, (Sintrom) for different pathologies. The anticoagulant therapy was not modified neither before nor after surgery. More than 70 oral procedures were carried out under local anesthesia. The International Normalized Ratio of prothrombin time (INR) was<=4. Tranexamic acid 5% (Exacyl) mouthwashes were prescribed during and after surgery.. All the patients were followed up during 2 weeks after surgery. There were no postoperative bleedings.. Use of tranexamic acid mouthwashes under a specific protocol is an efficient, reliable and economic method in preventing postoperative bleeding in patients under oral anticoagulant therapy.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Antifibrinolytic Agents; Cardiovascular Diseases; Dental Care for Chronically Ill; Female; Humans; International Normalized Ratio; Male; Middle Aged; Mouthwashes; Oral Hemorrhage; Oral Surgical Procedures; Postoperative Hemorrhage; Prospective Studies; Tranexamic Acid

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

A double blind study was carried out comparing 10-methoxy-1,6-dimethyl-ergoline-8 beta-methanol-(5-bromonicotinate) (nicergoline, Sermion) and placebo in 60 thromboembolic patients on long-term controlled acenocoumarol treatment. Aim of the trial was to assess the hypothesis of an interaction on both the coagulatory parameters and the clinical findings. No significant variations of the acenocoumarol daily dose were required in nicergoline treated group and no interaction was demonstrated in coagulatory parameters. Prothrombin activity and thrombo-test evaluated fortnightly were not statistically different in nicergoline and placebo groups while the platelet antiaggregating activity of nicergoline was confirmed after a three months' treatment. Bleeding time was unaffected. Minor differences in clinical findings were observed in the two groups.

Topics: Acenocoumarol; Adult; Aged; Cardiovascular Diseases; Clinical Trials as Topic; Double-Blind Method; Drug Interactions; Ergolines; Humans; Middle Aged; Nicergoline; Platelet Aggregation

Time in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients.. We calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8 months (1755 patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death.. Mean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13-58%, 59-74%, and 75-100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p<0.001). On Cox proportion hazard analysis, the 2nd vs. 1st tertile of TTR (p=0.002, hazard ratio [HR] 0.347, confidence interval [CI] 95% 0.177-0.680), 3rd vs. 1st tertile of TTR (p<0.001, HR 0.164, CI 95% 0.067-0.402), age (p<0.001, HR 1.094, CI 95% 1.042-1.148), history of stroke/TIA (p=0.015, HR 2.294, CI 95% 1.172-4.490) and smoking (p=0.003, HR 3.450, CI 95% 1.532-7.769) predicted MACE.. TTR was an independent predictor of MACE in our cohort of AF patients. Our findings suggest that a good anticoagulation control is necessary to reduce not only the risk of stroke but also that of MACE.

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Follow-Up Studies; Hemorrhage; Humans; Male; Myocardial Infarction; Patient Outcome Assessment; Proportional Hazards Models; Prospective Studies; Regression Analysis; Stroke; Vitamin K; 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

Oral anticoagulants of the coumarin type have an inconveniently narrow therapeutic window, making their use difficult. In Mexico, genetic variables that participate in the heterogeneity of the therapeutic response remain poorly investigated. With the focus on warfarin, extensive pharmacogenomic studies have been performed, including those on the CYP450 family and APOE. The objective of this study was to determine the contribution of CYP2C9, CYP2C19, and APOE polymorphisms to the variations in response to the doses of acenocoumarol, which is the main anticoagulant prescribed to the Mexican population. The polymerase chain reaction-restriction fragment length polymorphism method was applied to identify 2 and 3 of CYP2C9, 2 of CYP2C19, and APOE variants. The genetic distribution of every polymorphism tested showed high variability when compared with other populations worldwide. Our results showed statistical differences only in the CYP2C19 gene between the 1 1 and 1 2 groups, with effective acenocoumarol doses of 2.56 ± 1.34 mg/day vs 1.35 ± 0.84 mg/day (P = 0.005), respectively. Multiple regression analysis, including patient age and both the CYP2C9 and CYP2C19 genes, showed that these variables explained more than 20% of the dose variations. This is the first report in Mexico searching for the relationship between CYP450 and APOE polymorphisms and the dose requirements of acenocoumarol. Our results suggest that, in the Mexican population, CYP2C19 is more involved in acenocoumarol metabolism than CYP2C9 and APOE. Besides considering the age factor, pharmacogenetic testing for CYP2C19 2 before initiating acenocoumarol treatment could lead to a safer anticoagulation therapy in Mexican patients.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Apolipoproteins E; Aryl Hydrocarbon Hydroxylases; Cardiovascular Diseases; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C9; Female; Gene Frequency; Genetic Association Studies; Humans; Inactivation, Metabolic; Male; Middle Aged; Polymorphism, Single Nucleotide

Topics: Acenocoumarol; Adult; Antiphospholipid Syndrome; Calcium; Cardiovascular Diseases; Female; Growth Hormone; Humans; Hyperhomocysteinemia; Hyperparathyroidism; Ischemia; Magnetic Resonance Imaging

Recently there are several evidence based facts about the beneficial effect of oral anticoagulant therapy in patients with cardiovascular diseases. In the other hand the often serious bleeding complications as well as the ineffective antithrombotic therapy should be avoided.. Authors had examined with a questionnaire some characteristic parameters of oral anticoagulant therapy in Hungarian hospitals. Based on the results they carried out a retrospective survey (488 consecutive patients) on the accuracy and other peculiarity of long-term acenocoumarol therapy in the district of County Hospital Gyula.. Mean value of all coagulation test's results (INR: 2.72 +/- 1.07, prothrombin %: 36.11 +/- 10.52) suggest a relatively favourable therapeutic activity in the patients required acenocoumarol therapy. According to their data the proportion of newly introduced anticoagulant therapy secondary to atrial fibrillation was highly increased (42%). They stated that the accuracy of documentation in conducting of oral anticoagulant therapy should be improved and it would be the time to use obligatory the INR value in the clinical practice. They found the best therapeutic punctuality among the patients controlled in the Special Cardiological Outpatient Department. There were relatively few event of serious bleedings. The authors called attention to the patients (about 5%) who were treated without any special cause for a longer period of time than it was necessary. They emphasize the pivotal role of permanent education of patients and the importance of their therapeutic compliance in the appropriate oral anticoagulant control.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Anticoagulants; Atrial Fibrillation; Cardiovascular Diseases; Female; Heart Valve Prosthesis; Hemorrhage; Humans; Hungary; International Normalized Ratio; Male; Middle Aged; Outpatients; Patient Compliance; Patient Education as Topic; Prothrombin; Quality of Health Care; Retrospective Studies; Surveys and Questionnaires; Thromboembolism; Venous Thrombosis

Wheezing is a little known but possible presentation feature of acute pulmonary embolism.. A retrospective review of the records of 154 consecutive patients with acute pulmonary embolism, who survived long enough for diagnostic evaluation.. Fourteen patients with acute pulmonary embolism (9.1%) had wheezing at presentation. Wheezing was more frequent in patients with previous cardiopulmonary disease than in those without previous cardiopulmonary disease, although this did not reach statistical significance (13.5 versus 6.9%; P=0.17). Dyspnoea, cough and respiratory failure were more frequent with statistical significance in our patients with wheezing than in those without wheezing. The hospital mortality rate was similar in both groups.. Wheezing in acute pulmonary embolism may be more frequent in patients with previous cardiopulmonary disease. However, wheezing also occurs in patients with acute pulmonary embolism without previous cardiopulmonary disease. Wheezing may be a sign of severity in acute pulmonary embolism.

Topics: Acenocoumarol; Acute Disease; Aged; Anticoagulants; Cardiovascular Diseases; Female; Heparin; Humans; Male; Middle Aged; Pulmonary Embolism; Respiratory Sounds; Retrospective Studies; Spain; Thrombolytic Therapy

Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications. We studied the frequency of bleeding complications in outpatients treated routinely in anticoagulation clinics.. In a prospective cohort from thirty-four Italian anticoagulation clinics, 2745 consecutive patients were studied from the start of their oral anticoagulation (warfarin in 64%, acenocourmarol in the rest). The target anticoagulation-intensity was low (international normalised ratio [INR] < or = 2.8) in 71% of the patients and high (> 2.8) in the remainder. We recorded demographic details and the main indication for treatment and, every 3-4 months, INR and outcome events. Such events included all complications (bleeding, thrombosis, other), although only bleeding events are reported here, and deaths. We divided bleeding into major and minor categories.. 43% of the patients were women. Nearly three-fifths of the patients were aged 60-79; 8% were over 80. The main indication for treatment was venous thrombolism (33%), followed by non-ischaemic heart disease (17%). Mean follow-up was 267 days. Over 2011 patient-years of follow-up, 153 bleeding complications occurred (7.6 per 100 patient-years). 5 were fatal (all cerebral haemorrhages, 0.25 per 100 patient-years), 23 were major (1.1), and 125 were minor (6.2). The rate of events was similar between sexes, coumarin type, size of enrolling centre, and target INR. The rate was higher in older patients: 10.5 per 100 patient-years in those aged 70 or over, 6.0 in those aged under 70 (relative risk 1.75, 95% Cl 1.29-2.39, p < 0.001). The rate was also higher when the indication was peripheral and/or cerebrovascular disease than venous thromboembolism plus other indications (12.5 vs 6.0 per 100 patient-years) (1.80, 1.2-2.7, p < 0.01), and during the first 90 days of treatment compared with later (11.0 vs 6.3, 1.75, 1.27-2.44, p < 0.001). A fifth of the bleeding events occurred at low anticoagulation intensity (INR < 2, rate 7.7 per 100 patient-years of follow-up). The rates were 4.8, 9.5, 40.5, and 200 at INRs 2.0-2.9, 3-4.4, 4.5-6.9, and over 7, respectively (relative risks for INR > 4.5, 7.91, 5.44-11.5, p < 0.0001).. We saw fewer bleeding events than those recorded in other observational and experimental studies. Oral anticoagulation has become safer in recent years, especially if monitored in anticoagulation clinics. Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing.

Topics: Acenocoumarol; Administration, Oral; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Cohort Studies; Female; Hemorrhage; Humans; Italy; Male; Middle Aged; Prospective Studies; Risk Factors; Warfarin

The authors describe the possibilities of tooth extraction in patients who receive anticoagulant therapy. They propose the hospitalization of these patients. The authors also account of good results wits utilizing Lyostipt and Dicynone.

Topics: Acenocoumarol; Adult; Aged; Aged, 80 and over; Anticoagulants; Cardiovascular Diseases; Ethamsylate; Female; Hemorrhage; Hemostatics; Humans; Male; Middle Aged; Thrombolytic Therapy; Tooth Extraction

The Omniscience prosthetic heart valve has been clinically evaluated in 44 patients operated on between January and July, 1981. There were 23 aortic valve replacements (AVR), 18 mitral valve replacements (MVR) and 3 double valve replacements (DVR). Mean age was 48 +/- 11 years. Preoperatively, 61% patients were in New York Heart Association (NYHA) functional class IV, 36% in class III and 2% in class II. The hospital mortality rate was 4.5%. Actuarial freedom from thromboembolic events was 97.4 +/- 2.6% (3 1/2 years of follow-up). Postoperatively, 93% of the patients were in NYHA class I and 7% in class II. There were 7 cases of periprosthetic leak requiring reoperation (6 AVR, 1 MVR) for an overall incidence of 6.3% per patient year. In all these cases the causative factor was considered to be the Dacron sewing ring. All patients survived the reoperation. The actuarial survival rate was 93.9 +/- 5.9% for AVR and 93.7 +/- 6.1% for MVR. These data would suggest that the Omniscience prosthesis represents an acceptable device for heart valve replacement, except for the high incidence of periprosthetic leakage, related to the Dacron sewing ring. Recent modification of the valve-construction including a Teflon sewing ring may avoid the relatively high rates of periprosthetic leakage following implantation of this mechanical valve.

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Cardiovascular Diseases; Equipment Design; Equipment Failure; Evaluation Studies as Topic; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Reoperation; Thromboembolism

Topics: Acenocoumarol; Adult; Aged; Cardiovascular Diseases; Female; Heart Valve Prosthesis; Humans; Male; Middle Aged; Postoperative Complications; Prothrombin

Topics: Acenocoumarol; Cardiovascular Diseases; Humans; Prothrombin Time

Topics: Acenocoumarol; Adult; Cardiovascular Diseases; Female; Humans; Male; Middle Aged

Topics: Acenocoumarol; Adult; Cardiovascular Diseases; Female; Humans; Male; Middle Aged

Topics: Acenocoumarol; Adult; Cardiovascular Diseases; Female; Humans; Male; Middle Aged

Topics: Acenocoumarol; Adult; Cardiovascular Diseases; Embolism; Female; Humans; Male; Middle Aged; Thrombosis

Topics: Acenocoumarol; Antifibrinolytic Agents; Cardiovascular Diseases; Fibrinolysis; Humans

Topics: Acenocoumarol; Aged; Cardiovascular Diseases; Female; Humans; Male; Middle Aged; Thrombosis

Topics: Acenocoumarol; Adult; Aged; Anticoagulants; Blood Coagulation Tests; Cardiovascular Diseases; Dicumarol; Female; Hemorrhage; Heparin; Humans; Hypertension; Male; Middle Aged; Phenindione

Topics: Acenocoumarol; Anticoagulants; Cardiovascular Diseases; Humans; Leg; Long-Term Care; Lower Extremity; Vascular Diseases

Topics: Acenocoumarol; Cardiovascular Diseases; Coumarins

Topics: Acenocoumarol; Cardiovascular Diseases; Cerebellum; Coumarins; Myocardial Infarction