Platelet glycoprotein IIb/IIIa receptor blockers in clinical practice

I n this thesis, platelet glycoprotein (GP) IIb/IIIa receptor blockers are discussed for use in patients with acute coronary syndromes without persistent ST-segment elevation but also for use in patients with overt myocardial infarction. Furthermore, the role of intervention, and more specifically, the role of timing of percutaneous coronary intervention is descnOed in patients 'With acute coronary syndromes without persistent ST-segment elevation incorporating use of platelet GP IIb/IIIa receptor antagonists

Which options fit best? Operationalizing the socio-ecological niche concept

Article Purchased; Published: 1st August 2016The large diversity of farms and farming systems in sub-Saharan Africa calls for agricultural improvement options that are adapted to the context in which smallholder farmers operate. The socio-ecological niche concept incorporates the agro-ecological, socio-cultural, economic and institutional dimensions and the multiple levels of this context in order to identify which options fit best. In this paper, we illustrate how farming systems analysis, following the DEED cycle of Describe, Explain, Explore and Design, and embedding co-learning amongst researchers, farmers and other stakeholders, helps to operationalize the socio-ecological niche concept. Examples illustrate how farm typologies, detailed farm characterization and on-farm experimental work, in combination with modelling and participatory approaches inform the matching of options to the context at regional, village, farm and field level. Recommendation domains at these gradually finer levels form the basis for gradually more detailed baskets of options from which farmers and other stakeholders may choose, test and adjust to their specific needs. Tailored options identified through the DEED cycle proof to be more relevant, feasible and performant as compared to blanket recommendations in terms of both researcher and farmer-identified criteria. As part of DEED, on-farm experiments are particularly useful in revealing constraints and risks faced by farmers. We show that targeting options to the niches in which they perform best, helps to reduce this risk. Whereas the conclusions of our work about the potential for improving smallholders’ livelihoods are often sobering, farming systems analysis allows substantiating the limitations of technological options, thus highlighting the need for enabling policies and institutions that may improve the larger-scale context and increase the uptake potential of options

Which options fit best? Operationalizing the socio-ecological niche concept

The large diversity of farms and farming systems in sub-Saharan Africa calls for agricultural improvement options that are adapted to the context in which smallholder farmers operate. The socio-ecological niche concept incorporates the agro-ecological, socio-cultural, economic and institutional dimensions and the multiple levels of this context in order to identify which options fit best. In this paper, we illustrate how farming systems analysis, following the DEED cycle of Describe, Explain, Explore and Design, and embedding co-learning amongst researchers, farmers and other stakeholders, helps to operationalize the socio-ecological niche concept. Examples illustrate how farm typologies, detailed farm characterization and on-farm experimental work, in combination with modelling and participatory approaches inform the matching of options to the context at regional, village, farm and field level. Recommendation domains at these gradually finer levels form the basis for gradually more detailed baskets of options from which farmers and other stakeholders may choose, test and adjust to their specific needs. Tailored options identified through the DEED cycle proof to be more relevant, feasible and performant as compared to blanket recommendations in terms of both researcher and farmer-identified criteria. As part of DEED, on-farm experiments are particularly useful in revealing constraints and risks faced by farmers. We show that targeting options to the niches in which they perform best, helps to reduce this risk. Whereas the conclusions of our work about the potential for improving smallholders' livelihoods are often sobering, farming systems analysis allows substantiating the limitations of technological options, thus highlighting the need for enabling policies and institutions that may improve the larger-scale context and increase the uptake potential of options

Impact of percutaneous coronary intervention timing on 5-year outcome in patients with non-ST-segment elevation acute coronary syndromes. The ‘wait a day’ approach might be safer

Background The OPTIMA trial was a randomised multicentre trial exploring the influence of the timing of percutaneous coronary intervention (PCI) on patient outcomes in an intermediate to high risk non-ST-elevation acute coronary syndrome (NSTE-ACS) population. In order to decide the best treatment strategy for patients presenting with NSTEACS, long-term outcomes are essential. Methods Five-year follow-up data from 133 of the 142 patients could be retrieved (94 %). The primary endpoint was a composite of death and spontaneous myocardial infarction (MI). Spontaneous MI was defined as MI occurring more than 30 days after randomisation. Secondary endpoints were the individual outcomes of death, spontaneous MI or re-PCI. Results No significant difference with respect to the primary endpoint was observed (17.8 vs. 10.1 %; HR 1.55, 95 % CI: 0.73–4.22, p = 0.21). There was no significant difference in mortality rate. However, spontaneous MI was significantly more common in the group receiving immediate PCI (11.0 vs. 1.4 %; HR 4.46, 95 % CI: 1.21–16.50, p = 0.02). We did not find a significant difference between the groups with respect to re-PCI rate. Conclusion There was no difference in the composite of death and spontaneous MI. The trial suggests an increased long-term risk of spontaneous MI for patients treated with immediate PCI

Cohort profile of BIOMArCS: The BIOMarker study to identify the Acute risk of a Coronary Syndrome-a prospective multicentre biomarker study conducted in the Netherlands

__Purpose:__ Progression of stable coronary artery disease (CAD) towards acute coronary syndrome (ACS) is a dynamic and heterogeneous process with many intertwined constituents, in which a plaque destabilising sequence could lead to ACS within short time frames. Current CAD risk assessment models, however, are not designed to identify increased vulnerability for the occurrence of coronary events within a precise, short time frame at the individual patient level. The BIOMarker study to identify the Acute risk of a Coronary Syndrome (BIOMArCS) was designed to evaluate whether repeated measurements of multiple biomarkers can predict such 'vulnerable periods'. __Participants:__ BIOMArCS is a multicentre, prospective, observational study of 844 patients presenting with ACS, either with or without ST-elevation and at least one additional cardiovascular risk factor. __Methods and analysis:__ We hypothesised that patterns of circulating biomarkers that reflect the various pathophysiological components of CAD, such as distorted lipid metabolism, vascular inflammation, endothelial dysfunction, increased thrombogenicity and ischaemia, diverge in the days to weeks before a coronary event. Divergent biomarker patterns, identified by serial biomarker measurements during 1-year follow-up might then indicate 'vulnerable periods' during which patients with CAD are at high short-Term risk of developing an ACS. Venepuncture was performed every fortnight during the first half-year and monthly thereafter. As prespecified, patient enrolment was terminated after the primary end point of cardiovascular death or hospital admission for nonfatal ACS had occurred in 50 patients. A case-cohort design will explore differences in temporal patterns of circulating biomarkers prior to the repeat ACS

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved