Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: rationale and design of the LEGACY study

BackgroundEarly aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI.MethodsThe LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT.ConclusionsThe LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS.Cardiolog

Ischemic events and bleeding complications after primary percutaneous coronary intervention

Met de introductie van primaire percutane coronaire interventie en verbeteringen in de antistollingsbehandeling is de prognose van patiënten met een acuut hartinfarct in de afgelopen decennia substantieel verbeterd. Desondanks komt circa 10% van de patiënten binnen een jaar te overlijden. Daarnaast wordt een deel van de patiënten getroffen door een recidief infarct, waarvan een deel veroorzaakt wordt door stent thrombose. Ter preventie van recidief ischemische uitkomsten zoals recidief infarcten, stent thromboses of beroertes, worden patiënten met een hartinfarct rondom de primaire PCI behandeld met heparine en gedurende 1 jaar met dubbele plaatjes aggregatieremmers behandeld. De keerzijde van deze behandeling is het ontstaan van bloedingscomplicaties, die soms fulminant kunnen verlopen. In deel 1 van het proefschrift wordt onderzoek gedaan naar de prognostische waarde van periprocedurele aPTTs (een stollingstijd die gebruikt wordt om heparine behandeling te monitoren). Sterk verlengde aPTTs zijn geassocieerd met een hoog risico op bloedingen terwijl lage aPTTs niet geassocieerd zijn met recidief ischemische uitkomsten. Dit suggereert dat nabehandeling met heparine na een geslaagde PPCI niet routinematig moet worden toegepast. Tevens worden in deel 1 risicofactoren beschreven voor het ontwikkelen van een verlengde aPTT. In deel 2 wordt als onderdeel van de HORIZONS AMI studie onderzoek gedaan naar nieuwe biomarkers als voorspeller voor het ontwikkelen van een bloedingscomplicatie. Tenslotte wordt in het derde gedeelte onderzoek gedaan naar de prognostische waarde van bloedingscomplicaties, en wordt de prognostische waarde van bloedingscomplicaties vergeleken met de prognostische waarde van recidief infarcten

Optimal duration of dual antiplatelet therapy for coronary artery disease

The optimal duration of dual antiplatelet therapy (DAPT) for stable coronary artery disease and acute coronary syndrome is a complex decision. We review current literature on standard duration DAPT versus short duration DAPT (6 months or shorter) or extended duration DAPT (>12 months) after percutaneous coronary intervention with drug-eluting stent placement, and prolonged treatment after 12 months in acute coronary syndrome. Current guideline recommendations are summarised, including the use of risk scores for ischaemic and bleeding risk assessment. Because of the limitations of current risk scores, we propose multiple patient-related and procedure-related factors for the ischaemic and bleeding risk assessment aiding in personalised DAPT duration

Guideline adherence for antithrombotic therapy in acute coronary syndrome: an overview in Dutch hospitals

OBJECTIVE: To assess current Dutch antithrombotic treatment strategies for acute coronary syndrome (ACS) in light of the current European Society of Cardiology (ESC) guidelines. METHODS: For every Dutch hospital with a coronary care unit (CCU) (n = 93) a single cardiologist was interviewed concerning heparin, thienopyridine and GP IIb/IIIa inhibitor (GPI) treatment. In each hospital, we randomly approached one cardiologist assuming equal policy among physicians employed at the same hospital. RESULTS: The response rate was 90%. In 59% of hospitals, treatment of ST-elevation myocardial infarction (STEMI) occurred according to the 2008 ESC STEMI guideline, with unfractionated heparin. In contrast, although not recommended, low-molecular-weight heparin (LMWH) was used in 39% (enoxaparin 19%, dalteparin 12%, nadroparin 8%). In non-STEMI, low-molecular-weight-heparins (LMWHs) were used in 97% of all hospitals. Fondaparinux, agent of choice in a noninvasive strategy for the treatment of non-STEMI, was applied in only 2% of hospitals. Although recommended by the ESC, dose adjustment of LMWH therapy for patients with renal failure is not applied in 71% of hospitals. Likewise, LMWH dose adjustment is not applied for patients aged over 75 years in 92% of hospitals. CONCLUSION: To a great extent treatment of ACS in the Netherlands occurs according to ESC guidelines. Additional benefit may be achieved by routine dose adjustment of LMWH for patients with renal insufficiency and aged >75 years, since these patients are at high risk of bleeding complications secondary to antithrombotic treatment. Periodical evaluation of real-life practice may improve guideline adherence and potentially improve clinical outcome. (Neth Heart J 2010;18:291-9.

Patient-tailored antithrombotic therapy following percutaneous coronary intervention

Dual antiplatelet therapy has long been the standard of care in preventing coronary and cerebrovascular thrombotic events in patients with chronic coronary syndrome and acute coronary syndrome undergoing percutaneous coronary intervention, but choosing the optimal treatment duration and composition has become a major challenge. Numerous studies have shown that certain patients benefit from either shortened or extended treatment duration. Furthermore, trials evaluating novel antithrombotic strategies, such as P2Y(12) inhibitor monotherapy, low-dose factor Xa inhibitors on top of antiplatelet therapy, and platelet function- or genotype-guided (de-)escalation of treatment, have shown promising results. Current guidelines recommend risk stratification for tailoring treatment duration and composition. Although several risk stratification methods evaluating ischaemic and bleeding risk are available to clinicians, such as the use of risk scores, platelet function testing, and genotyping, risk stratification has not been broadly adopted in clinical practice. Multiple risk scores have been developed to determine the optimal treatment duration, but external validation studies have yielded conflicting results in terms of calibration and discrimination and there is limited evidence that their adoption improves clinical outcomes. Likewise, platelet function testing and genotyping can provide useful prognostic insights, but trials evaluating treatment strategies guided by these stratification methods have produced mixed results. This review critically appraises the currently available antithrombotic strategies and provides a viewpoint on the use of different risk stratification methods alongside clinical judgement in current clinical practice.[GRAPHICS

P2Y(12)-inhibitor monotherapy after coronary stenting: are all P2Y(12)-inhibitors equal?

Introduction: P2Y(12)-inhibitor monotherapy following 1-3 months of dual antiplatelet therapy (DAPT) reduces (major) bleeding without an apparent increase in ischemic events and has therefore emerged as an alternative to 6-12 months of DAPT following percutaneous coronary intervention (PCI). However, there are important differences between the available P2Y(12)-inhibitors (clopidogrel, prasugrel, and ticagrelor) as agents of choice for P2Y(12)-inhibitor monotherapy.Areas covered: This review critically appraises the evidence for P2Y(12)-inhibitor monotherapy after PCI using either clopidogrel, prasugrel, or ticagrelor. Furthermore, we discuss ongoing trials and future directions for research.Expert opinion: P2Y(12)-inhibitor monotherapy following 1-3 months of DAPT is an alternative to 6-12 months of DAPT following PCI. Ticagrelor may be considered the current preferred option due to its reliable effect on platelet reactivity and its predominant use in clinical trials. Prasugrel could serve as a useful substitute for those not tolerating ticagrelor, but more research into prasugrel monotherapy is warranted. Alternatively, clopidogrel can be used, although there are concerns of high platelet reactivity, especially when genotyping and/or platelet function testing are not used. Future research will need to address the minimal duration of DAPT before switching to P2Y(12)-inhibitor monotherapy and what the optimal antithrombotic therapy beyond 12 months is

Primary percutaneous coronary intervention for ST elevation myocardial infarction in octogenarians: trends and outcomes

Objective The general population is gradually ageing in the western world. Therefore, the number of octogenarians undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) is increasing. We aim to provide insight into temporal trends in the annual proportions of octogenarians among STEMI patients undergoing primary PCI and their clinical characteristics and outcomes over an 11-year observational period. Design Single-centre observational study. Patients Between 1997 and 2007, 4506 STEMI patients were treated with primary PCI at the authors' institution. Patients aged over 80 years were identified. Main outcome measures Temporal trends in the annual proportion of octogenarian STEMI patients and their baseline characteristics, 30-day and 1-year mortality were analysed. Results A total of 379 octogenarians (8.4% of the total population) was treated with primary PCI between 1997 and 2007. Over time, the annual proportion of octogenarians gradually increased from four of 113 (3.5%) in 1997 to 51 of 579 (8.8%) in 2007 (p for trend <0.01). In the total cohort of 379 patients, 30-day mortality was 21% (81 patients) and 1-year mortality was 28% (107 patients). There was no improvement in survival among octogenarian STEMI patients over the 11-year study period. Conclusion The annual proportion of octogenarian STEMI patients increased significantly over the 11-year study period. Mortality among these high-risk patients was high and did not improve during the study period. Unfortunately, little is known about the optimal treatment of the elderly as they are underrepresented in many randomised clinical trials. Further studies into the optimal STEMI management strategy for the elderly are warrante

Prevalence and impact of a chronic total occlusion in a non-infarct-related artery on long-term mortality in diabetic patients with ST elevation myocardial infarction

Background Recently, a chronic total occlusion (CTO) in a non-infarct-related artery (non-IRA) and not multivessel disease (MVD) alone was identified as an independent predictor of mortality after ST elevation myocardial infarction (STEMI). Patients with diabetes mellitus (DM) constitute a patient group with a high prevalence of MVD and high mortality after STEMI. The prevalence of CTO in a non-IRA was studied and its impact on long-term mortality in STEMI patients with DM was investigated. Methods Between 1997 and 2007 4506 patients with STEMI were admitted and treated with primary percutaneous coronary intervention (PCI). Patients with DM were identified. The patients were categorised as having single vessel disease (SVD), MVD without CTO and CTO based on the angiogram before PCI. Results A total of 539 patients (12%) had DM. MVD with or without a CTO was present in 33% of non-diabetic patients and in 51% of diabetic patients. The prevalence of a CTO in a non-IRA was 21% in STEMI patients with DM and 12% in STEMI patients without DM (p <0.01). Kaplan-Meier estimates for 5-year mortality in STEMI patients with DM were 25%, 21% and 47% in patients with SVD, MVD without a CTO and MVD with a CTO in a non-IRA, respectively. A CTO in a non-IRA was an independent predictor of 5-year mortality (HR 2.2, 95% CI 1.3 to 3.5, p <0.01). Conclusion The prevalence of a CTO in a non-IRA was increased in STEMI patients with DM. The presence of a CTO in a non-IRA was a strong and independent predictor of 5-year mortality. These results suggest that, particularly in the high-risk subgroup of STEMI patients with DM, MVD has prognostic implications only if a concurrent CTO is presen