[Anticoagulation and thrombophilia in pregnancy]. / Antikoagulation und Gerinnungsstörungen in der Schwangerschaft.

A review of coagulation disturbances during pregnancy and the current management of the anticoagulated patient with heart valve prostheses, atrial fibrillation, and thromboembolic events is presented. All patients with mechanical heart valve prostheses require life-long oral anticoagulation with coumarin or one of its derivatives. Recommendations for the treatment and prevention of thromboembolic events are discussed. The advantages and disadvantages of three different treatment approaches to anticoagulation during pregnancy are discussed and recommendations for the management in different situations are outlined with delineation of specific risks for the mother and the fetus.

[Role of hormone-replacement therapy for prevention of coronary artery disease in women]. / Stellenwert der Hormonersatztherapie zur Prävention der koronaren Herzerkrankung bei Frauen.

The postmenopausal increase in the incidence of coronary artery disease implied a protective effect of estrogens. Nonrandomized, clinical and experimental studies have supported this notion. In the first randomized study (HERS 1998) no protective effect on prognosis of postmenopausal women with coronary artery disease was demonstrated. Also, in healthy postmenopausal women no beneficial effect of a hormone-replacement therapy on coronary events was shown (WHI-Study 2002, 2004). Therefore, hormone-replacement therapy is not recommended for prophylaxis of cardiovascular disease in healthy women or in women with documented coronary artery disease (Recommendation class I, evidence-level A). The continuation or the start of a hormone- replacement therapy is only justified for therapy of severe menopausal symptoms. Women should be informed that changes in lifestyle including not smoking, a heart healthy diet, and regular exercise are the most important measures to prevent cardiovascular diseases.

[Anticoagulation in pregnancy and post partum in heat valve diseases, thrombosis or atrial fibrillation: fetal risk versus maternal thromboembolism]. / Antikoagulation in graviditate und post partum bei Vitien, Thrombosen oder Vorhofflimmern: fötale Bedrohung versus maternelle Thromboembolie.

Patients with mechanical valve prostheses are at high risk for thromboembolic events, valve thrombosis and mortality during pregnancy. The most effective anticoagulation for the mother is achieved with oral anticoagulants which may be associated with embryopathy in the baby. The risk of embryopathy and the risk of hemorrhage during the remainder of the pregnancy depend on the intensity of anticoagulation induced in the fetus and the dose of the oral anticoagulant used. Recent studies suggest that a warfarin dose of less than 5 mg and an INR of less than 3 does not induce embryopathy and is associated with a low rate of fetal complications (15%). Heparin has been recommended as the anticoagulant of choice during pregnancy, because it does not cross the placental barrier and does not cause embryopathy. Yet all forms of unfractionated heparin application (low dose, aPTT-ratio-adjusted, during the entire pregnancy or during the first trimester) are associated with a higher rate of maternal complications and death than oral anticoagulants given throughout pregnancy until the 36th week of pregnancy. Also the total fetal outcome (abortion and stillbirth) is not improved by heparin. To avoid fetal and maternal complications, particularly hemorrhage during premature labor, mothers should be admitted to the hospital in the 36th week for conversion from oral anticoagulants to heparin, preferentially given i.v. prior to delivery. Vaginal delivery should be avoided under therapeutic oral anticoagulation and cesarean section preferred after neutralization of anticoagulation. The optimal INR-monitored intensity of anticoagulation by the patient is one promising way to reduce complications and increase efficacy and safety. Randomized studies including low molecular weight heparin and oral anticoagulants in patients with mechanical valve prostheses are needed, with careful monitoring of laboratory parameters and cardiac follow-up. This requires close cooperation between cardiologists, gynecologists and hemostaseologists.

[Current recommendations for prevention of thromboembolism in patients with heart valve prostheses]. / Aktuelle Empfehlungen zur Thrombembolieprophylaxe bei Herzklappenprothesen.

Within the last few years, marked progress has been made in the prevention of thromboembolic events in patients with mechanical heart valves. Thus, therapy has become more effective and is associated with less risk. This includes a number of developments like the introduction of the internationalized, normalized ratio (INR) for determination of the intensity of anticoagulation, the concept of a risk factor-adjusted, prosthesis specific, individualized indication for and intensity of anticoagulation and the possibility for self-determination of anticoagulation intensity by the patient. Prospective, randomized studies on the effect of different intensities of anticoagulation allowed definitions of individualized anticoagulation target levels and were the basis for guidelines on clinical management of anticoagulation. In spite of this progress, thromboembolic complications and anticoagulation associated bleedings are still the most frequent complications after valve replacement. The guidelines published by the professional societies on anticoagulation should be followed more closely in daily clinical practice. The management of oral anticoagulant treatment can be improved by following the concept of a risk factor-adjusted indication for and intensity of oral anticoagulant treatment as well as the use of the INR for monitoring the intensity of anticoagulation. Intensive education of the patient, implementation of self-testing by suitable patients and increasing the frequency of testing can further contribute to improvement.

[Current recommendations for prevention of thromboembolic events in patients with heart valve prostheses]. / Aktuelle Empfehlungen zur Thrombembolieprophylaxe bei Herzklappenprothesen.

Within the last few years, marked progress has been made in the prevention of thromboembolic events in patients with mechanical heart valves. Thus, therapy has become more effective and is associated with less risk. This includes a number of developments like the introduction of the internationalized, normalized ratio (INR) for determination of the intensity of anticoagulation, the concept of a risk factor-adjusted, prosthesis specific, individualized indication for and intensity of anticoagulation and the possibility for self-determination of anticoagulation intensity by the patient. Prospective, randomized studies on the effect of different intensities of anticoagulation allowed definitions of individualized anticoagulation target levels and were the basis for guidelines on clinical management of anticoagulation. In spite of this progress, thromboembolic complications and anticoagulation associated bleedings are still the most frequent complications after valve replacement. The guidelines published by the professional societies on anticoagulation should be followed more closely in daily clinical practice. The management of oral anticoagulant treatment can be improved by following the concept of a risk factor-adjusted indication for and intensity of oral anticoagulant treatment as well as the use of the INR for monitoring the intensity of anticoagulation. Intensive education of the patient, implementation of self-testing by suitable patients and increasing the frequency of testing can further contribute to improvement.

Coronary artery disease--is menopause a risk factor?

UNLABELLED: Cardiovascular disease, especially coronary artery disease (CAD), are leading causes of morbidity and mortality in women over the age of 50, whereas this is rarely the case in younger women. This fact, the overall lower incidence of and the 10-15 year retarded occurrence of CAD in women, has led to the controversially discussed question whether menopause is a risk factor for CAD. There has been universal agreement that surgically induced early menopause with bilateral oophorectomy is a risk factor for CAD, associated with a relative risk of 2, unless estrogen is replaced. Yet pertinent naturally occurring menopause studies showed variable results. This review focuses on the criteria required for an association to be accepted as a risk factor. The occurrence of natural menopause is influenced by preexisting risk factors in different, partly opposing ways. Smoking leads to an earlier occurrence of menopause, obesity, hypertension and diabetes to a later occurrence. These complex interactions complicate statistical analysis. Natural menopause is associated with profound biochemical and metabolic changes, which are established risk factors, e.g., increase in LDL and decrease in HDL cholesterol. These biochemical and metabolic changes are the mechanisms by which menopause can act as a risk factor. CONCLUSIONS: Menopause can be accepted as a risk factor, even if not all requirements, particularly that of reversibility, are fulfilled. The occurrence of menopause indicates the transition from a low to a higher risk for CAD in women.

[Anticoagulation in surgery, after hemorrhagic complications and in pregnancy]. / Antikoagulation bei Operationen, nach Blutungskomplikationen und bei Schwangerschaft.

A review of the current management of the anticoagulated patient with heart valve prosthesis is presented. All patients with mechanical heart valve prostheses require life-long oral anticoagulation with coumarin or one of its derivatives. Recommendations for the prevention of thromboembolic events and bleeding complications in patients undergoing noncardiac operations are given. Furthermore, risk factors for hemorrhagic complications during long-term oral anticoagulation are discussed as well as management in case of acute bleeding. The advantages and disadvantages of three different treatment approaches to anticoagulation during pregnancy are discussed with delineation of specific risks for the mother and the fetus.

Cardiac rehabilitation: where are we going?

Several components of cardiac rehabilitation can be considered to be of proven value: smoking cessation reduces cardiac events by 50% in observational studies, dietary modification such as the so-called Mediterranean diet--if rigorously applied--reduces cardiac events, decreases progression and has favourable effects on hypertension, osteoporosis and the risk of cancer. Cholesterol lowering by HMG-CoA reductase inhibitors is cost effective but not practiced widely enough. Exercise training programmes improve functional capacity and symptoms particularly in patients with compensated heart failure. The prognostic implications are unclear at present. Stress modification is useful and return to work may be enhanced by cardiac rehabilitation. Cardiac rehabilitation, as a multifactorial intervention prevents progression, improves well being and prognosis, and should be an integral part of the cardiological management after a cardiac event.

Cardiac rehabilitation.

Cardiac rehabilitation as a multifactorial intervention has been shown to improve functional capacity, emotional well-being, return to work rate and longevity. Cardiac rehabilitation is cost effective, and in many aspects represents causal therapy. The meta-analyses do not include studies where pharmacological lipid lowering was used. The use of generally accepted and recommended medical treatment strategies in the EuroAspire study has been below the expected rate, Therefore, cardiac rehabilitation programmes should educate the patient and emphasize the need to apply the appropriate medical regimen in addition to the non-pharmacological treatment modalities of cardiac rehabilitation to achieve maximal benefit. Cardiac rehabilitation has an important role in assuring the application of the available knowledge, to avoid cardiac complications and progression of disease, and improve cardiorespiratory fitness and survival. Cardiac rehabilitation should therefore be an integral part of cardiological management after a cardiac event.

Age-dependent differences in the anticoagulant effect of phenprocoumon in patients after heart valve surgery.

OBJECTIVE: An enhanced response to warfarin and an increased risk of major bleeding has been observed in older patients. The reason for this increase in sensitivity remains unknown. It could be due to pharmacodynamic reasons, pharmacokinetic reasons, or both. METHODS: We therefore followed an anticoagulant regimen with phenprocoumon in 19 older (76 years) and 19 younger patients (50 years) following heart valve replacement. INR values were determined frequently. At the 4th and around the 24th day after starting treatment with phenprocoumon, we also measured the total and unbound plasma concentration of phenprocoumon. RESULTS: The dose requirement to obtain the desired anticoagulant effect was significantly lower in the older patients than in the younger patients (26.3 vs. 37.3 micrograms.kg-1.day-1). The total plasma concentration (2.19 vs. 2.43 micrograms.ml-1), the percentage unbound drug in the plasma (0.61 vs. 0.64%) and the unbound plasma concentration (13.8 vs. 15.1 ng.ml-1) did not differ significantly between older and younger patients. The dose-adjusted INR (INR/dose) was higher in the older patients (110 vs. 67) but the INR adjusted for the unbound plasma concentration (INR/Cuss) which reflects the intrinsic sensitivity to the drug, was not significantly different (192 vs. 173). However, the older patients had an about 30% significantly lower metabolic clearance based on unbound drug (84 vs. 115 ml.kg-1.h-1). CONCLUSIONS: Older patients (> 70 years) require a dose approximately 30% lower than younger patients (< 160 years). Pharmacokinetic reasons (reduced metabolic clearance) are mainly responsible for the lower dose requirement of the older patients after heart valve surgery.

Prevention of thromboembolic events in valvular heart disease.

Thromboembolic events are major causes of morbidity and mortality in patients with native heart valve disease and artificial heart valves. Oral anticoagulation can reduce these complications. The indication for and intensity of oral anticoagulation depends on both, the risk for thromboembolic events and the risk of hemorrhage. The indications for oral anticoagulation in the various pathological conditions are defined. Risk factor adjusted intensity of oral anticoagulation and risk factor modification are new and very important aspects in the management of these patients which may lead to a reduction in anticoagulation associated complications and an improvement in antithrombotic effectivity. Further studies to identify the optimal therapeutic ranges of anticoagulation for the individual patient are needed. Multi-centre prospective randomized studies in this field should help us to answer the still open questions including new hemostatic molecular markers to further identify patients with different risk profiles.