External validity of ST elevation myocardial infarction trials: the Zwolle studies.

BACKGROUND: Guidelines are mainly based upon results of randomised controlled clinical trials. However, due to low external validity of these trials, their results can not reasonably be applied to all patients in routine practice. In our hospital, all patients with ST-elevation myocardial infarction (STEMI) are eligible for inclusion in one of our ongoing trials or registries. To asses differences between patients enrolled versus not-enrolled in a trial or registry, we evaluated all patients with a discharge diagnose of STEMI during the study period. METHODS: Retrospectively, individual patient data from all patients with a discharge diagnosis of STEMI between Jan 2001 and Dec 2001 were evaluated. Follow-up data were obtained until Dec 2004. RESULTS: A total of 583 patients were discharged with a diagnosis of STEMI. About 455 (78%) patients were enrolled in one of the ongoing clinical trials or registry and 128 were not. Not-enrolled patients were significantly older; more often had a history of previous MI and had higher risk profiles. Multivariate analysis revealed that higher age was the only independent predictor for non enrollment. Not-enrolled patients were more often treated conservatively and had a higher mortality rate (36% vs. 6%, P < 0.001). After multivariate analysis, non-enrollment (OR: 95% CI) 4.02 (1.98-8.16), age 1.07 (1.04-1.12), and diabetes 2.39 (1.17-4.89) were the only independent predictors of long term mortality. CONCLUSIONS: This study shows important differences in baseline characteristics, treatment, and prognosis between patients with STEMI who were enrolled or not in a trial. To better reflect daily clinical practice, guidelines should also consider results of observational studies of unselected patients.     

Treatment algorithms and critical pathways for acute coronary syndromes

Although numerous clinical trials have identified many advances in the treatment of patients with acute coronary syndromes (ACS), registries of clinical practice have identified that in clinical practice a large proportion of patients do not receive guideline-recommended therapies. In addition to development and dissemination of national guidelines, there is a need for specific tools to ensure that the guideline recommendations are implemented on a patient-by-patient basis. Better adherence to practice guidelines has been found to be associated with improved outcomes. Critical pathways and/or the process of Continuous Quality Improvement (CQI) are means of trying to improve care. Critical pathways are standardized protocols that aim to optimize and streamline patient care, which usually involve standardized order sets, (or computerized ones), and/or simple pocket cards, reminders, or checklists of the appropriate therapies. Another key part of an overall CQI effort is to monitor data on performance-i.e. utilization of guideline recommended therapies. Several well-conducted studies, showing that particular use of critical pathways, can lead to improve quality of care.     

Clinical disease registries in acute myocardial infarction

Disease registries,containing systematic records of cases,have for nearly 100 years been valuable in exploring and understanding various aspects of cardiology. This is particularly true for myocardial infarction,where such registries have provided both epidemiological and clinical information that was not readily available from randomised controlled trials in highlyselected populations. Registries,whether mandated or voluntary,prospective or retrospective in their analysis,have at their core a common study population and common data definitions. In this review we highlight how registries have diversified to offer information on epidemiology,risk modelling,quality assurance/improvement and original research-through data mining,transnational comparisons and the facilitation of enrolment in,and follow-up during registry-based randomised clinical trials.     

The risks and benefits of drug-eluting stents in the setting of STEMI

Primary percutaneous coronary intervention (PCI) represents the treatment of choice in patients with ST-segment elevation myocardial infarction (STEMI). In randomized trials excluding STEMI patients, using drug-eluting stents (DES) significantly reduced angiographic restenosis and target vessel revascularization compared with bare metal stents (BMS); however, concerns exist regarding an increased follow-up incidence of stent thrombosis after DES implantation. This complication, which is associated with higher mortality and morbidity rates, may be more frequent among STEMI patients receiving DES versus BMS. Various registries, randomized trials, and two recent meta-analyses on patients undergoing primary PCI have shown that using DES is safe and is associated with significantly reduced rates of restenosis and repeat intervention without an increased risk of myocardial infarction or stent thrombosis at intermediate-term follow-up. However, large trials with hard clinical end points and longer follow-up are needed before routine DES use can be recommended in patients undergoing primary PCI.     

Aktuelle Umsetzung der leitlinienkonformen Therapie des akuten ST-Hebungsinfarkts in Deutschland

Treatment of acute ST elevation myocardial infarction (STEMI) is based on early reperfusion therapy (primary PCI [percutaneous coronary intervention], thrombolysis) and adjunctive medical therapy. Primary PCI is recommended as the therapy of first choice in the German guidelines, if the delay by a transfer to primary PCI versus thrombolysis is 相似文献   

Reperfusion strategies for acute myocardial infarction in the elderly: benefits and risks

The optimal reperfusion strategy in elderly patients with ST-segment elevation myocardial infarction (STEMI) remains a topic of debate. This lack of consensus stems from the exclusion or under-representation of the elderly in clinical trials. This review evaluates the available literature pertaining to reperfusion therapy for the treatment of STEMI in the elderly. We identified all published studies evaluating the effectiveness of thrombolytic therapy, primary percutaneous coronary intervention (PCI), or adjunctive therapies to reperfusion by conducting an electronic search of MEDLINE through December 2003. Meta-analysis of clinical trials suggests a survival benefit of thrombolytic therapy in the elderly with STEMI, whereas some observational studies have raised concerns about the lack of short-term benefit or possibility of harm with thrombolysis. However, most observational studies demonstrate improved intermediate-term survival with thrombolysis. In contrast, multiple clinical trials and observational studies indicate improved survival and low risk of stroke with primary PCI compared with thrombolysis in elderly patients with STEMI. Information on the efficacy of newer antithrombotic agents as adjunct to thrombolysis or primary PCI is scarce. Available data suggest an increased risk of intracerebral bleeding with the combination of a fibrin-specific agent and a glycoprotein IIb/IIIa receptor antagonist in patients >75 years of age. Clearly targeted large-scale clinical trials are needed to evaluate the relative merits of available reperfusion strategies as well as newer antithrombotic adjunctive therapies in the elderly with STEMI.     

Current management of acute coronary syndromes in Australia: observations from the acute coronary syndromes prospective audit

Background: Acute coronary syndromes (ACS) management is now well informed by guidelines extrapolated from clinical trials. However, most of these data have been acquired outside the local context. We sought to describe the current patterns of ACS care in Australia. Methods: The Acute Coronary Syndrome Prospective Audit study is a prospective multi‐centre registry of ST‐segment elevation myocardial infarction (STEMI), high‐risk non‐ST‐segment elevation ACS (NSTEACS‐HR) and intermediate‐risk non‐ST‐segment elevation ACS (NSTEACS‐IR) patients, involving 39 metropolitan, regional and rural sites. Data included hospital characteristics, geographic and demographic factors, risk stratification, in‐hospital management including invasive services, and clinical outcomes. Results: A cohort of 3402 patients was enrolled; the median age was 65.5 years. Female and non‐metropolitan patients comprised 35.5% and 23.9% of the population, respectively. At enrolment, 756 (22.2%) were STEMI patients, 1948 (57.3%) were high‐risk NSTEACS patients and 698 (20.5%) were intermediate‐risk NSTEACS patients. Evidence‐based therapies and invasive management use were highest among suspected STEMI patients compared with other strata (angiography: STEMI 89%, NSTEACS‐HR 54%, NSTEACS‐IR 34%, P < 0.001) (percutaneous coronary intervention: STEMI 68.1%, NSTEACS‐HR 22.2%, NSTEACS‐IR 8.1%, P < 0.001). In hospital mortality was low (STEMI 4.0%, NSTEACS‐HR 1.8%, NSTEACS‐IR 0.1%, P < 0.001), as was recurrent MI (STEMI 2.4%, NSTEACS‐HR: 2.8%, NSTEACS‐IR 1.2%, P = 0.052). Conclusion: There appears to be an ‘evidence‐practice gap’ in the management of ACS, but this is not matched by an increased risk of in‐hospital clinical events. Objective evaluation of local clinical care is a key initial step in developing quality improvement initiatives and this study provides a basis for the improvement in ACS management in Australia.     

Validation of the Thrombolysis In Myocardial Infarction (TIMI) risk index for predicting early mortality in a population-based cohort of STEMI and non-STEMI patients

BACKGROUND: The Thrombolysis In Myocardial Infarction (TIMI) risk index for the prediction of 30-day mortality was developed and validated in patients with ST-segment elevation myocardial infarction (STEMI) who were being treated with thrombolytics in randomized clinical trials. When tested in clinical registries of patients with STEMI, the index performed poorly in an older (65 years and older) Medicare population, but it was a good predictor of early death among the more representative population on the National Registry of Myocardial Infarction-3 and -4 databases. It has not been tested in a population outside the United States or among non-STEMI patients. METHODS: The TIMI risk index was applied to the Enhanced Feedback for Effective Cardiac Treatment (EFFECT) study cohort of 11,510 acute MI patients from Ontario. The model's discriminatory capacity and calibration were tested in all patients and in subgroups determined by age, sex, diagnosis and reperfusion status. RESULTS: The TIMI risk index was strongly associated with 30-day mortality for both STEMI and non-STEMI patients. The C statistic was 0.82 for STEMI and 0.80 for non-STEMI patients, with overlapping 95% CI. The discriminatory capacity was somewhat lower for patients older than 65 years of age (0.74). The model was well calibrated. CONCLUSIONS: The TIMI risk index is a simple, valid and moderately accurate tool for the stratification of risk for early death in STEMI and non-STEMI patients in the community setting. Its routine clinical use is warranted.     

Influence of guideline adherence on outcome in a randomised controlled trial on the efficacy of methotrexate with folate supplementation in rheumatoid arthritis

OBJECTIVE: To study the influence of rheumatologists' adherence to a methotrexate guideline on efficacy and toxicity in the treatment of rheumatoid arthritis. METHODS: In a 48 week randomised controlled trial of methotrexate, comparing folates with placebo, rheumatologists were advised on methotrexate dosage using a guideline reflecting daily practice. The influence of guideline non-adherence on outcome was analysed using generalised estimating equations and survival analysis. RESULTS: In 51% of the 411 study patients the guidelines were always followed. Non-adherence resulted in lower doses of methotrexate in 25% of cases, and higher doses in 24%. The reduction in the disease activity score was significantly greater (mean -0.4; p = 0.0085) in the adherent group than in the "low dose" group; the "high dose" group did not differ from the adherent group. Dropout caused by severe adverse events did not differ between the three groups. CONCLUSIONS: There is an indication that adherence to guidelines on methotrexate dosage may benefit patients with rheumatoid arthritis by improving disease activity without increasing toxicity. For definite proof, a randomised controlled trial comparing guideline supported dosing with usual care is needed.     

Advances in Transcatheter Valve Therapies

The surgical treatment for valvular heart disease is well established with excellent long-term outcomes in appropriately selected patients. For patients at elevated risk for surgical intervention, options have traditionally been limited to medical therapy with disappointing results. The advent of transcatheter techniques of valvular repair or replacement has revolutionized treatment options for these patients at significantly elevated risk for surgery. In both the aortic and mitral realms, landmark clinical trials and real-world registries have begun to define the roles of these therapies, and the development of multidisciplinary heart teams have helped optimize patient treatment pathways and outcomes. Transcatheter treatment of aortic stenosis and mitral regurgitation has emerged as an approved option for properly selected patients, and guidelines have evolved to include these therapies. Further procedural refinement, device development, and clinical trials will continue to evolve this field.     

Karotisstenose

Carotid stenosis amenable to surgical or interventional revascularization accounts for 5–12% of all new strokes. Duplex sonography, due to its high sensitivity and specificity is the first and most important step in establishing the diagnosis. Several randomised trials have proven the superiority of carotid endarterectomy (CEA) over medical treatment of symptomatic and also asymptomatic stenoses. For a growing number of patients carotid artery stenting (CAS) can be an alternative. The safety of CAS has improved in recent years due to technical developments, especially cerebral protection systems. According to large registries and also randomised trials the complication rate is comparable to CEA, at least for high surgical risk patients. Results of further randomised trials remain awaited before CAS will also be recommended for low risk patients and patients with asymptomatic stenoses.     

Telemedicine and remote management of patients with heart failure

Advances in telecommunication technologies have created new opportunities to provide telemedical care as an adjunct to medical management of patients with heart failure. Meta-analyses suggest that telemedicine can reduce morbidity and mortality in such patients; however, two prospective clinical trials not included in the analyses do not support these findings. Therefore, the effectiveness of telemedicine in heart failure is not established. Telemedicine approaches range from computer-based support systems to programmes led by nurses and physicians. Standardisation and appropriate classification of telemedical systems are needed to enable accurate interpretation of clinical trials. Here we propose a classification of four generations of telemedicine in heart failure. Not all approaches are the same and not every patient with heart failure will need telemedicine. Crisis prevention and treatment, and stabilisation and self-empowerment of patients are focuses of telemedicine in heart failure. The profile of patients who can potentially benefit from telemedicine is unknown and should be investigated in adequately powered randomised clinical trials. We are optimistic that telemedicine is an efficient approach and will become an important feature of management in heart failure.     

From guidelines to clinical practice: the impact of hospital and geographical characteristics on temporal trends in the management of acute coronary syndromes. The Global Registry of Acute Coronary Events (GRACE).

AIMS: The extent to which hospital and geographic characteristics influence the time course of uptake of evidence from key clinical trials and practice guidelines is unknown. The gap between evidence and practice is well recognized but the factors influencing this disjunction, and the extent to which such factors are modifiable, remain uncertain. METHODS AND RESULTS: Using chronological data from the GRACE registry (n=12666, July 1999 to December 2001), we test the hypothesis that hospital and geographic characteristics influence the time course of uptake of evidence-based guideline recommendations for acute coronary syndromes (ACS) with and without ST elevation. Certain therapies were widely adopted in both ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients (aspirin >94% of all patients; beta-blockers 85-95%) and changed only modestly over time. Significant increases in the use of low-molecular-weight heparins and glycoprotein IIb/IIIa inhibitors occurred in STEMI and NSTEMI patients in advance of published practice guidelines (September/November 2000) with marked geographical differences. The highest use of LMWH was in Europe in NSTEMI (86.8%) and the lowest in the USA (24.0%). Contrasting geographical variations were seen in the use of percutaneous coronary intervention (PCI) in NSTEMI: 39.5% USA, 34.6% Europe, 33.5% Argentina/Brazil, 25.0% Australia/New Zealand/Canada (July-December 2001). Theuse of PCI was more than five times greater in hospitals with an on-site catheterization laboratory compared to centres without these facilities, and geographic differences remained after correction for available facilities. CONCLUSIONS: Hospital and geographical factors appear to have a marked influence on the uptake of evidence-based therapies in ACS management. The presentation and publication of major international guidelines was not associated with a measurable change in the temporal pattern of practice. In contrast, antithrombotic and interventional therapies changed markedly over time and were profoundly influenced by hospital and geographic characteristics.     

Similarities and Differences in Patient Characteristics Between Heart Failure Registries Versus Clinical Trials

Acute and chronic heart failure results in significant morbidity and mortality to patients and is a major concern for the healthcare systems. Various randomized controlled trials have demonstrated an improvement in morbidity and mortality for patients with heart failure. However, the findings of these trials are often applicable to a limited population. Several large-scale registries are now shedding insight as to the treatment, outcomes, and follow-up of patients in a real-life clinical setting. The objective of this review is to examine some of the heart failure therapies, such as cardiac resynchronization therapy, implantable cardioverter defibrillators and medications, in the context of randomized trials versus clinical registries. This review will also identify how registries are improving patient outcomes and how they are uncovering differences and gaps in treatment in non-randomized trial settings.     

Thrombusaspiration bei Patienten mit akutem Myokardinfarkt

Recent advances in percutaneous coronary intervention and antiplatelet therapy as well as faster door-to-balloon times have markedly improved the therapy of patients with acute myocardial infarction. However, impaired myocardial perfusion despite revascularization of the infarcted vessel remains an ongoing problem with high prognostic relevance. In initial clinical trials thrombus aspiration in addition to conventional percutaneous coronary intervention demonstrated benefits regarding coronary flow and myocardial perfusion and was therefore recommended in practice guidelines. These improvements in surrogate endpoints did not translate into a favorable clinical outcome in recent large-scale multicenter randomized trials investigating the routine use of thrombus aspiration in patients with acute myocardial infarction. Furthermore, an increased risk of stroke after thrombus aspiration raises safety concerns. Therefore, thrombus aspiration has been downgraded in the recent guideline updates. The current article reviews the evidence from clinical trials and the recommendations in practice guidelines regarding thrombus aspiration in acute myocardial infarction.     

Diabetes Mellitus and Atrial Remodeling: Mechanisms and Potential Upstream Therapies

Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, and its prevalence has increasing substantially over the last decades. Recent data suggest that there is an increased risk of AF among the patients with diabetes mellitus (DM). However, the potential molecular mechanisms regarding DM‐related AF and diabetic atrial remodeling are not fully understood. In this comprehensive review, we would like to summarize the potential relationship between diabetes and atrial remodeling, including structural, electrical, and autonomic remodeling. Also, some upstream therapies, such as thiazolidinediones, probucol, ACEI/ARBs, may play an important role in the prevention and treatment of AF. Therefore, large prospective randomized, controlled trials and further experimental studies should be challengingly continued.     

Role of HDL in Those with Diabetes

Low levels of high-density lipoprotein cholesterol (HDL-C) have been associated with an increased risk of coronary heart disease in prospective population studies and clinical trials of high-risk patients treated with a low to moderate intensity statin. As a result, therapeutic targets were developed to increase concentrations of HDL-C. Subsequently, clinical trials of high-intensity statins have not supported this previously well-established association. In trials of high-intensity statin therapy, low HDL particle concentration (HDL-P) has been associated with an increased risk of future cardiovascular events. Therefore, strategies that increase HDL-C without expanding the pool of HDL-P with its rich proteome/lipidome do not seem to be an effective strategy. In this review, we discuss potential mechanisms of action for the anti-atherogenic effect of HDL and the impact of current and emerging therapies on the functional capacity of HDL-P. Finally, we discuss emerging therapies that increase the concentration and functional properties of HDL.     

Antithrombotic drug development for atrial fibrillation: proceedings, Washington, DC, July 25-27, 2005

In July 2005, leaders from academia, government, and industry convened in Washington, DC, to discuss key issues in the development of antithrombotic treatments for atrial fibrillation (AF). In addition to summarizing available data on the relative benefits and risks of currently available therapies in diverse clinical practice settings, we reviewed designs of ongoing trials and registries, focusing on areas of methodological controversy and uncertainty. Participants in this meeting described the growing burden of AF, summarized the data showing effectiveness of warfarin for prevention of stroke in AF, and noted that warfarin is both underused and poorly monitored and adjusted in general practice. There was consensus that there is an important unmet clinical need for better treatment of patients with AF at risk of stroke, including alternatives to warfarin that address its limitations. Comparative noninferiority trials to develop alternatives to warfarin must include warfarin management that is at least as good as that provided in historical trials. There was agreement that noninferiority trials can be done based on historical warfarin trials, and that placebo-controlled trials focused on patients not receiving warfarin in general practice can provide important information as well. Statistical principles for noninferiority in this setting were discussed, and a standard approach was proposed. A majority of clinical trial representatives suggested that large, simple, open-label trials would provide the most meaningful information relevant to future practice, but regulators cautioned that, in such a simple trial, one needs to ensure that the control group does at least as well as the historical controls for the noninferiority design to be interpretable. With this summary document, we hope to provide a helpful resource for future drug development for AF.     

Specialized centers and systems for heart attack care

Evidence from randomized controlled clinical trials and registries suggest that primary percutaneous coronary intervention provides superior clinical outcomes when compared with fibrinolytic therapy for the treatment of ST segment elevation myocardial infarction (STEMI). However, the delivery of expert and timely primary percutaneous coronary intervention to the majority of patients with STEMI is extremely challenging. This objective has fueled the concept of regional centers of excellence for the care of patients with STEMI as well as regional STEMI networks similar to those currently available for trauma or stroke victims. This article reviews the rationale behind, as well as the issues inherent to, the development of systems of care for STEMI patients.     

Mortality rates in patients with ST-elevation vs. non-ST-elevation acute myocardial infarction: observations from an unselected cohort.

AIMS: Acute myocardial infarction (AMI) is categorized, according to the presenting electrocardiogram, into non-ST-elevation myocardial infarction (non-STEMI), ST-elevation myocardial infarction (STEMI), or bundle branch block myocardial infarction (BBBMI). Data on the prognostic significance of these categories mainly originate from voluntary based registries or large-scale clinical trials and may be hampered by selection and information bias. The aim of this historical cohort study was to evaluate the prognostic significance of different categories of AMI in an unselected cohort. METHODS AND RESULTS: From 1 November 1999 to 31 October 2001, patient records were reviewed from all admissions to hospitals serving a study region with 139,000 inhabitants. An Endpoint Committee determined whether patients fulfilled the European Society of Cardiology criteria of AMI. A total of 654 patients with AMI were identified. The proportion having non-STEMI, STEMI, and BBBMI was 54, 39 and 6%, and the associated 1 year mortality was 31, 21, and 55%, respectively (log rank 54, P<0.001). The more favourable outcome observed in patients with STEMI remained significant according to multivariable analysis (P=0.044). CONCLUSION: In an unselected cohort of patients admitted with AMI, the mortality was considerably higher than expected from voluntary-based registries and large-scale clinical trials. The most favourable outcome is observed in patients with STEMI.