Orale Thrombozytenhemmung in der primären und sekundären Prävention

Cardiovascular disease is the leading cause of death in western societies, with further increasing incidence. Therefore both, primary and secondary prevention play a pivotal role. Medicamentous prevention schemes include the antithrombotic drugs acetylsalicylic acid (ASS) and clopidogrel. A number of studies tested the efficacy and safety of ASS for primary prevention. A meta-analysis of these primary prevention trials could demonstrate a decrease of cardiovascular events only for patients being at high cardiovascular risk. However, since ASS does not influence the mortality but is significantly increasing the risk for bleeding, careful risk stratification is indispensable prior to preventive chronic administration of the drug. Therapy with ASS in the secondary prevention is commonly accepted and clearly evidence-based given that a meta-analysis of 145 trials could demonstrate a significant decrease in mortality. A daily dose of 100 mg has been shown to achieve sufficient antithrombotic effects with an acceptable rate of side effects. Clopidogrel is currently not used for primary prevention, since evidence is lacking and the costs are high. For secondary prevention after acute coronary syndromes, a decrease of cardiovascular events could be demonstrated for clopidogrel. This benefit was especially pronounced after percutaneous coronary interventions. However, clopidogrel could not decrease the mortality. Therefore, long-term treatment with clopidogrel in the secondary prevention should be based on a critical appraisal of risk and benefit on the one hand and socioeconomic aspects on the other hand.     

Cardiac failure in coronary heart disease

Cardiac failure, which used to be rare in coronary heart disease, is now its most common complication. Coronary heart disease can cause or appear as cardiac failure through one or more of 12 mechanisms: acute myocardial infarction, acute reversible ischemia, right ventricular dysfunction, cardiogenic shock, acute mitral regurgitation, ventricular septal perforation, cardiac free wall rupture, ischemic cardiomyopathy, ventricular aneurysm, coexisting diseases, iatrogenesis, and pseudoheart failure. An understanding of the responsible mechanism or mechanisms is essential not only for appropriate treatment but also for prognostication. Various therapeutic modalities, both medical and surgical, should be able to improve not only symptoms but also survival. Current efforts in the management of patients with cardiac failure as a result of coronary heart disease should be aimed at prevention, both primary and secondary.     

Prim?r- und Sekund?rpr?vention des Schlaganfalls

Despite considerable advances in acute stroke therapy, stroke prevention remains the most promising approach for reducing the burden of stroke. A healthy lifestyle and the treatment of cardiometabolic risk factors are the cornerstones of both primary and secondary stroke prevention. Due to a proportionately higher risk of bleeding complications, platelet inhibitors are not recommended for primary stroke prevention. Platelet inhibitors are effective in the secondary prevention of stroke with acetyl salicylic acid (ASS) and clopidogrel showing the most consistent data. New oral anticoagulants are slightly more effective than coumarin and significantly reduce the risk of intracranial hemorrhage. They offer the opportunity to bring more patients with atrial fibrillation at risk for stroke into anticoagulation particularly those on ASS therapy. Surgery for patients with asymptomatic carotid artery stenosis should be viewed critically with respect to an only marginal benefit and improvement in medical therapies. Carotid endarterectomy remains the gold standard for patients with symptomatic carotid stenosis because of an increased procedural stroke risk with carotid stenting. Patients with symptomatic intracranial stenosis or cryptogenic stroke and a patent foramen ovale should receive only medical treatment.     

Statins for primary and secondary prevention of coronary heart disease. A scientific review.

Cardiovascular disease has an elevated prevalence in the general population, with increasing incidence with advancing age. Epidemiological studies clearly show that higher concentrations of serum lipids (especially cholesterol) constitute a major individual risk factor, and that their treatment reduces the incidence of cardiovascular disease, especially coronary heart disease (CHD). The best evidence supporting the importance of hypercholesterolemia as a major risk factor for CHD arises from large randomized controlled trials (RCTs), which show that by lowering total cholesterol and low-density lipoprotein concentrations, and increasing high-density lipoprotein concentrations, coronary event rates and cardiovascular mortality are diminished. Also, hyperlipidemia is frequently found in patients suffering from premature CHD and, in most cases, has a familial genetic component. The benefit from lowering cholesterol is found in primary prevention (patients with hypercholesterolemia but no known CHD), as well as in secondary prevention (patients with known CHD, in whom the aim is to improve prognosis). The main objective of this paper is to present and discuss the most valid, important and applicable scientific evidence on the primary and secondary prevention of coronary heart disease using statins. We have based our discussion on large RCTs that studied clinically relevant outcomes (mortality, morbidity, event rates, etc.), published over the last 10 years, as well as on systematic reviews and/or meta-analyses of RCTs published over the last 5 years. Both types of evidence were selected from secondary scientific sources. We conclude with practical evidence-based recommendations on the selection of patients for primary and secondary prevention with statins.     

Benefit of combined resynchronization and defibrillator therapy in heart failure patients with and without ventricular arrhythmias.

OBJECTIVES: We attempted to assess the efficacy of combined cardiac resynchronization therapy-implantable cardioverter-defibrillator (CRT-ICD) in heart failure patients with and without ventricular arrhythmias. BACKGROUND: Because CRT and ICDs both lower all-cause mortality in patients with advanced heart failure, combination of both therapies in a single device is challenging. METHODS: A total of 191 consecutive patients with advanced heart failure, left ventricular ejection fraction <35%, and a QRS duration >120 ms received CRT-ICD. Seventy-one patients had a history of ventricular arrhythmias (secondary prevention); 120 patients did not have prior ventricular arrhythmias (primary prevention). During follow-up, ICD therapy rate, clinical improvement after 6 months, and mortality rate were evaluated. RESULTS: During follow-up (18 +/- 4 months), primary prevention patients experienced less appropriate ICD therapies than secondary prevention patients (21% vs. 35%, p < 0.05). Multivariate analysis revealed, however, no predictors of ICD therapy. Furthermore, a similar, significant, improvement in clinical parameters was observed at 6 months in both groups. Also, the mortality rate in the primary prevention group was lower than in the secondary prevention group (3% vs. 18%, p < 0.05). CONCLUSIONS: As 21% of the primary prevention patients and 35% of the secondary prevention patients experienced appropriate ICD therapy within 2 years after implant, and no predictors of ICD therapy could be identified, implantation of a CRT-ICD device should be considered in all patients eligible for CRT.     

Hormone replacement therapy and coronary heart disease: results of randomized trials

A number of lines of evidence have suggested that postmenopausal hormone replacement therapy might be useful in the primary and secondary prevention of coronary heart disease (CHD). Data from recent randomized trials are consistent in showing no overall benefit of hormone replacement therapy as a continuous combined regimen of estrogen and a progestin (PERT) in preventing the development of CHD or preventing recurrent events or progression of atherosclerosis. The randomized trials also raise questions about hormone replacement therapy in the form of estrogen alone (ERT) for prevention of CHD and CHD recurrence. Other interventions to prevent CHD and decrease morbidity and mortality in women with established disease have a strong evidence base. Hormone replacement therapy should not be recommended to prevent CHD or CHD recurrence until and unless data from randomized trials establish this as a benefit.     

Heart failure post-myocardial infarction: a review of the issues

In most patients with heart failure due to left ventricular systolic dysfunction, the underlying cause is coronary heart disease. To reduce progression to heart failure in a patient with acute myocardial infarction, it is important to achieve the earliest possible reperfusion, whether by thrombolysis or primary percutaneous coronary intervention. Every patient with acute myocardial infarction should have an assessment of their left ventricular function, the potential for reversibility should be considered, and reversible ischaemia should be identified. Left ventricular dysfunction does not only occur with ST segment elevation myocardial infarction but is also commonly associated with non-ST segment elevation myocardial infarction. Secondary prevention is crucial and this requires long term commitment by the patient and the health care system. Heart failure and left ventricular dysfunction are treatable but require a multidisciplinary, integrated network approach.     

Increasing evidence-based treatments to reduce coronary heart disease mortality in Sweden: quantifying the potential gains

Abstract. Björck L, Capewell S, Bennett K, Lappas G, Rosengren A (Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden; University of Liverpool, Liverpool, United Kingdom; Trinity College and St. James’s Hospital, Dublin, Ireland). Increasing evidence‐based treatments to reduce coronary heart disease mortality in Sweden: quantifying the potential gains. J Intern Med 2011; 269 : 452–467. Objectives. Between 1986 and 2002, coronary heart disease (CHD) mortality in Sweden fell by more than 50%. Approximately one‐third (4800 fewer deaths) of this decline in age‐adjusted CHD mortality could be attributed to treatments in patients with CHD and primary prevention medications. High treatment levels were achieved in some cases, but in others, only 50–80% of eligible patients received appropriate therapy. We therefore examined to what extent increasing the use of specific treatments in eligible patients might have reduced CHD mortality rates in Sweden. Design and methods. We used the previously validated IMPACT CHD model to combine data on CHD patient numbers, medical and surgical uptake levels and treatment effectiveness. We estimated the number of deaths prevented or postponed for 2002 (baseline scenario) and for an alternative scenario (if at least 60% of eligible patients were treated). Results. If treatments were increased to consistently cover at least 60% of eligible patients, approximately 8900 deaths could have been postponed or prevented, representing a potential gain of approximately 4100 fewer deaths than actually occurred in 2002. Approximately 45% of the 4100 gain would have come from primary prevention with statins, 23% from acute coronary syndrome treatments, 15% from secondary prevention therapies and 15% from treatments for heart failure. Conclusion. Increasing the proportion of eligible patients with CHD who receive evidence‐based treatment could have resulted in approximately 4100 fewer deaths in 2002, almost doubling the actual mortality reduction. These findings further emphasize the importance of aggressively identifying and treating patients with CHD and high‐risk individuals.     

Therapy to reduce risk of coronary heart disease

Recent primary and secondary intervention studies have shown that reduction of low-density lipoprotein cholesterol (LDL-C) with statins significantly reduced coronary heart disease (CHD) morbidity and mortality. However, many patients with dyslipidemia who have or are at risk for CHD do not reach target LDL-C goals. The recently updated National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III guidelines identify a group of patients at very high risk for CHD for more aggressive LDL-C reduction and reaffirm the importance of high-density lipoprotein cholesterol (HDL-C) by raising the categorical threshold to 40 mg/dl. Lipid-lowering therapy needs to be more aggressive in both primary and secondary prevention settings, and therapy should be considered to increase HDL-C as well as lower LDL-C in order to improve patient outcomes. Both combination therapy and the next generation of statins may provide improved efficacy across the dyslipidemia spectrum.     

Primary diastolic heart failure

Diastolic heart failure is defined clinically when signs and symptoms of heart failure are present in the presence of preserved left ventricular systolic function (ejection fraction >45%). The incidence and prevalence of primary diastolic heart failure increases with age and it may be as high as 50% in the elderly. Age, female gender, hypertension, coronary artery disease, diabetes, and increased body mass index are risk factors for diastolic heart failure. Hemodynamic consequences such as increased pulmonary venous pressure, post-capillary pulmonary hypertension, and secondary right heart failure as well as decreased cardiac output are similar to those of systolic left ventricular failure, although the nature of primary left ventricular dysfunction is different. Diagnosis of primary diastolic heart failure depends on the presence of preserved left ventricular ejection fraction. Assessment of diastolic dysfunction is preferable but not mandatory. It is to be noted that increased levels of B-type natriuretic peptide does not distinguish between diastolic and systolic heart failure. Echocardiographic studies are recommended to exclude hypertrophic cardiomyopathy, infiltrative heart disease, primary valvular heart disease, and constrictive pericarditis. Myocardial stress imaging is frequently required to exclude ischemic heart disease. The prognosis of diastolic heart failure is variable; it is related to age, severity of heart failure, and associated comorbid diseases such as coronary artery disease. The prognosis of severe diastolic heart failure is similar to that of systolic heart failure. However, cautious use of diuretics and/or nitrates may cause hypotension and low output state. Heart rate control is essential to improving ventricular filling. Pharmacologic agents such as angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and calcium channel blockers are used in selected patients to decrease left ventricular hypertrophy. To decrease myocardial fibrosis, aldosterone antagonists have a potential therapeutic role. However, prospective controlled studies will be required to establish their efficacy in primary diastolic heart failure.     

Management issues for patients with coronary artery disease and heart failure

Despite recent favorable trends in survival, heart failure remains a highly fatal disease. Improvements in the prevention of early death from coronary artery disease, along with an aging population, have resulted in an increased prevalence for heart failure in the United States. In the management of patients with heart failure secondary to coronary artery disease, the relative efficacy of invasive therapies such as coronary revascularization, surgical left ventricle remodeling, internal cardiac defibrillator implantation, cardioverter resynchronization therapy, mechanical ventricular assist, and cardiac transplantation need to be considered. Clinical studies examining these important treatment options are reviewed in order to better define the optimal management strategy for this challenging population of patients.     

The Challenge of Antiplatelet Therapy in Patients with Atrial Fibrillation and Heart Failure

Antiplatelet therapy is the cornerstone of secondary prevention in cardiovascular disease. This review focuses on the role of antiplatelet therapy in atrial fibrillation (AF) and heart failure (HF). Aspirin has a limited role in stroke prevention among most patients with AF, being of limited efficacy and not any safer than warfarin, especially in the elderly. For HF patients with AF, cardioembolism is a major cause of stroke, and antiplatelet alone would be insufficient thromboprophylaxis. Aspirin plus clopidogrel rather than aspirin alone is preferred for those AF patients who have refused any form of oral anticoagulation. For AF patients undergoing percutaneous coronary intervention, triple antithrombotic therapy (aspirin, clopidogrel, and warfarin) is recommended for the initial period (1–6 months) based on the stent type, followed by vitamin K antagonists (VKA) and clopidogrel or, alternatively VKA and aspirin for up to 12 months. In AF patients with stable vascular disease, VKA monotherapy would suffice.     

Prevention and treatment of ischemic heart disease in patients with diabetes mellitus

The incidence of cardiovascular diseases among diabetic patients is so high that diabetes mellitus is currently defined as a cardiovascular disease equivalent. Furthermore, diabetic patients who develop acute coronary syndromes have a poorer short-term and long-term prognosis, so primary and secondary preventive measures are critically important in this population subgroup.There is substantial evidence that pharmacological therapy for primary and secondary cardiovascular prevention is more effective in diabetic patients than in non-diabetics. This article reviews the evidence of the efficacy of pharmacological prevention therapies in diabetic patients in favor of an aggressive pharmacological preventive strategy. Every diabetic patient without known cardiovascular disease should be treated with angiotensin-converting enzyme inhibitors and statins. High-risk patients should also receive low-dose aspirin.Compared with non-diabetics, diabetic patients who develop acute coronary events benefit more from the addition of intensive antithrombotic therapy to aspirin treatment. Diabetic patients presenting with non-ST segment elevation syndromes have better outcomes when treated with clopidogrel or glycoprotein IIb/IIIa inhibitors, and diabetics presenting with ST-segment elevation or left bundle-branch block have a greater survival benefit when given thrombolytic therapy compared with non-diabetic patients.Unless formal contraindications are present, diabetic patients with ischemic heart disease, particularly those with previous myocardial infarction, should always be treated with aspirin, betablockers, angiotensin converting enzyme inhibitors, and statins, regardless of lipid levels, left ventricular systolic function or the presence of congestive heart failure.     

Prevention of heart failure

In light of the increasing prevalence, morbidity, and mortality of heart failure, preventative strategies are urgently needed. Risk factors include coronary artery disease, renal insufficiency, diabetes, and smoking. Essential strategies for prevention of heart failure are modification of risk factors for its development, and detection and treatment of asymptomatic left ventricular dysfunction (ALVD). In patients with ALVD, angiotensin-converting enzyme (ACE) inhibitor and β-blocker therapy can prevent progression to symptomatic heart failure. Additional recently identified preventative strategies include ACE inhibitor therapy for all coronary artery disease and diabetic patients, clopidogrel therapy in acute coronary syndromes, and avoidance of calcium channel blockers and a-blockers as first-line antihypertensive therapy.     

Update: orale Thrombozyteninhibitoren in der Kardiologie

The antithrombotic therapy in patients with atherosclerotic vascular disease is subject of several new therapeutic approaches. Simultaneous treatment with acetylsalicylic acid (ASS) and a thienopyridin (clopidogrel) represents the standard of care for patients with acute coronary syndrome and following coronary stenting recommended by many guidelines. Without true evidence this drug combination is used for the prevention of arterial thrombosis in many other vascular interventions (e.g. carotid or aortic stenting). The main problems of this dual antiplatelet therapy are the slow onset of action and the high interindividual variation in the degree of platelet inhibition. The thienopyridin prasugrel is a more potent platelet inhibitor with a more rapid onset of action and smaller interindividual variations in platelet inhibition. The therapeutic superiority of prasugrel was proven in patients with acute coronary syndrome undergoing coronary interventions. As a higher rate of bleeding complications was seen in patient subgroups further clinical studies with prasugrel are ongoing. Newer developments are focusing on ticagrelor, a new ADP-receptor antagonist, which has been proven superior to clopidogrel in clinical studies and triple therapy utilizing ASS, clopidogrel, and one of the new highly specific antithrombotics (e.g. factors Xa-antagonists or direct thrombin inhibitors).     

Cardiac resynchronization therapy for patients with congenital heart disease: technical challenges

Cardiac resynchronization therapy (CRT) is a commonly used procedure to help patients with drug refractory heart failure (HF) symptoms. More patients with congenital heart disease (CHD) survive to adulthood with the improvements that have occurred as a result of surgical and medical care of these patients. However, patients with CHD may develop ventricular dysfunction and HF and thus be considered for CRT. In this review, we discuss the unique features of CRT in the adult CHD population. We examine the existing data on utilization of CRT in patients with HF and CHD and specifically discuss the limitations in terms of benefit as well as data availability. Finally, we review the specific coronary sinus anatomy and technical considerations for placing a left ventricular lead in patients with CHD.     

Concordance between clopidogrel use and prescribing guidelines

BACKGROUND: Clopidogrel is an antiplatelet drug increasingly used in the secondary prevention of atherosclerotic vascular events. Compared with aspirin, clopidogrel has marginal additional efficacy and similar safety, but carries a substantial price premium. It remains unclear whether its use is cost-effective. AIMS: (i) To determine concordance between clopidogrel use and the Pharmaceutical Benefits Scheme and local hospital prescribing guidelines and (ii) to determine the intended duration of clopidogrel therapy and ascertain whether this is supported by other published reports. METHODS: Cross-sectional evaluation by patient interview and chart review of appropriateness of clopidogrel prescribing was carried out for 100 consecutive patients attending a 700 bed metropolitan, primary care and tertiary referral hospital. RESULTS: Clopidogrel was predominantly used for secondary prevention of ischaemic heart disease (60%) and following percutaneous coronary intervention (34%). A significant proportion of patients (29%) received clopidogrel outside the prescribing guidelines. Many patients were intended to receive indefinite therapy for secondary prevention of ischaemic vascular events. Concomitant aspirin therapy was not prescribed in 23% of patients, for 78% of whom it was inappropriate. CONCLUSIONS: There is a lack of concordance between clopidogrel use and prescribing guidelines. In the majority of patients (71%), clopidogrel is used for valid indications but there is considerable leakage of use beyond prescribing guidelines. Concomitant aspirin therapy is often not prescribed in the absence of clinically relevant contraindications. Moreover, treatment is continued in many patients beyond what is supported by current published data.     

Delayed and indirect effects of antiarrhythmic drugs in reducing sudden cardiac death

In the USA, two-thirds of sudden cardiac deaths (SCDs) are caused by sustained ventricular tachycardia and ventricular fibrillation. Implantable cardioverter defibrillator (ICD) therapy has been demonstrated to decrease mortality caused by these arrhythmias, when used both for primary and secondary prevention. However, ICD use is expensive, has proarrhythmic effects and does not prevent ventricular arrhythmias. Antiarrhythmic drugs (AADs) can be used for acute or chronic therapy to prevent ventricular arrhythmias and SCD. Most commonly, AADs are often used in patients with an ICD who have recurrent ICD shocks due to ventricular arrhythmias. Class I AADs are used in patients with a structurally normal heart and are contraindicated in patients with structural heart disease. β-blockers have been demonstrated to be beneficial in preventing mortality and malignant tachyarrhythmias in postmyocardial infarction and congestive heart failure patients, and in patients who have an ICD. Amiodarone has a neutral effect on mortality, while other class III drugs may increase mortality in certain subgroups of patients. Dronedarone, a new class III drug, may reduce mortality, but sufficient data are not available to allow for its use in the prevention of malignant tachyarrhythmias. Few drugs that are not classified as AADs can also prevent arrhythmias, via their beneficial effects on cardiovascular remodeling. These non-ADDs have delayed and indirect effects, which are mediated by the renin-angiotensin-aldosterone system and lipid metabolism - n-3 polyunsaturated fatty acids (fish oil), and statins, and can thus can reduce the likelihood of future malignant ventricular arrhythmias in patients with coronary artery disease or congestive heart failure. The role of chronic drug therapy alone for primary and secondary prevention of SCD is less than desirable because of proarrhythmic and adverse side effects. The non-ADDs are well tolerated and have no proarrhythmic actions, thus their benefit could outweigh risks, although currently there are no concrete data to suggest this.     

40例心脏移植术后受体心脏病理诊断与术前临床诊断的对比分析

目的通过比较40例心脏移植前、后诊断的异同来评价终末期心力衰竭患者术前诊断的准确性。方法40例患者术前全部经过询问病史,体格检查,心电图、超声心动图检查。凡有心绞痛症状,超声心动图证实存在节段性室壁运动异常或存在明确的危险因素等条件之一,且病情允许的患者在术前作冠状动脉造影。若≥1支冠状动脉主支的横断面面积减少75％以上被认为是有意义的冠状动脉病变。术前诊断为冠心病的患者全部行双核素检查,评价存活心肌。所有心脏移植术取下的心脏均被称重,测量室壁厚度,并经大体检查和组织学检查。结果心脏移植术前诊断为原发性扩张型心肌病（IDC）占45．0％,酒精性心肌病17．5％,冠心病占17．5％,肥厚型心肌病7．5％。高血压病、瓣膜病、致心律失常性右室心肌病、克山病和心肌致密化不全各1例,各占2．5％。术前诊断为冠心病者,受体心脏均有严重冠状动脉病变。术前诊断为IDC的18例和酒精性心肌病的7例患者,受体心脏病理检查共有8例（占32％）可见严重的冠状动脉病变。术前诊断为高血压心脏病和主动脉瓣换瓣术后心力衰竭的患者各1例,也可见冠状动脉严重病变。术前诊断为IDC和克山病者,6例受体心脏病理诊断为致心律失常性右室心肌病。术前诊断为IDC者1例,在移植取下心脏后被病理诊断为巨细胞心肌炎。结论早期正确诊断心力衰竭的病因,可决定患者不同的治疗方法（血管重建而不是心脏移植）,且能判断移植患者的预后。本研究的结果提示：无论临床表现如何,所有怀疑IDC的患者均应尽早作冠状动脉造影,并尽可能查明其病因。     

Nutrition and coronary heart disease

There is increasing evidence for the protective effect of a diet low in total and saturated fat and high in fresh fruit and vegetables in the primary and secondary prevention of coronary heart disease (CHD). This review describes recent evidence and international nutritional/dietary guidelines that outline both the effects of dietary change on coronary risk and the implications for current advice offered in clinical practice. Given the considerable body of evidence, it is concluded that comprehensive dietary management should be central to the routine primary and secondary prevention of CHD.