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Sökning: WFRF:(Fox Keith A. A.) > Linköpings universitet

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1.
  • Holmes, Michael V., et al. (författare)
  • Secretory Phospholipase A(2)-IIA and Cardiovascular Disease
  • 2013
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:21, s. 1966-1976
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives This study sought to investigate the role of secretory phospholipase A(2) (sPLA(2))-IIA in cardiovascular disease. less thanbrgreater than less thanbrgreater thanBackground Higher circulating levels of sPLA(2)-IIA mass or sPLA(2) enzyme activity have been associated with increased risk of cardiovascular events. However, it is not clear if this association is causal. A recent phase III clinical trial of an sPLA(2) inhibitor (varespladib) was stopped prematurely for lack of efficacy. less thanbrgreater than less thanbrgreater thanMethods We conducted a Mendelian randomization meta-analysis of 19 general population studies (8,021 incident, 7,513 prevalent major vascular events [MVE] in 74,683 individuals) and 10 acute coronary syndrome (ACS) cohorts (2,520 recurrent MVE in 18,355 individuals) using rs11573156, a variant in PLA2G2A encoding the sPLA(2)-IIA isoenzyme, as an instrumental variable. less thanbrgreater than less thanbrgreater thanResults PLA2G2A rs11573156 C allele associated with lower circulating sPLA(2)-IIA mass (38% to 44%) and sPLA(2) enzyme activity (3% to 23%) per C allele. The odds ratio (OR) for MVE per rs11573156 C allele was 1.02 (95% confidence interval [CI]: 0.98 to 1.06) in general populations and 0.96 (95% CI: 0.90 to 1.03) in ACS cohorts. In the general population studies, the OR derived from the genetic instrumental variable analysis for MVE for a 1-log unit lower sPLA(2)-IIA mass was 1.04 (95% CI: 0.96 to 1.13), and differed from the non-genetic observational estimate (OR: 0.69; 95% CI: 0.61 to 0.79). In the ACS cohorts, both the genetic instrumental variable and observational ORs showed a null association with MVE. Instrumental variable analysis failed to show associations between sPLA2 enzyme activity and MVE. less thanbrgreater than less thanbrgreater thanConclusions Reducing sPLA(2)-IIA mass is unlikely to be a useful therapeutic goal for preventing cardiovascular events.
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2.
  • O'Donoghue, Michelle, et al. (författare)
  • Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction : a meta-analysis
  • 2008
  • Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 300:1, s. 71-80
  • Forskningsöversikt (refereegranskat)abstract
    • CONTEXT: Although an invasive strategy is frequently used in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), data from some trials suggest that this strategy may not benefit women. OBJECTIVE: To conduct a meta-analysis of randomized trials to compare the effects of an invasive vs conservative strategy in women and men with NSTE ACS. DATA SOURCES: Trials were identified through a computerized literature search of the MEDLINE and Cochrane databases (1970-April 2008) using the search terms invasive strategy, conservative strategy, selective invasive strategy, acute coronary syndromes, non-ST-elevation myocardial infarction, and unstable angina. STUDY SELECTION: Randomized clinical trials comparing an invasive vs conservative treatment strategy in patients with NSTE ACS. DATA EXTRACTION: The principal investigators for each trial provided the sex-specific incidences of death, myocardial infarction (MI), and rehospitalization with ACS through 12 months of follow-up. DATA SYNTHESIS: Data were combined across 8 trials (3075 women and 7075 men). The odds ratio (OR) for the composite of death, MI, or ACS for invasive vs conservative strategy in women was 0.81 (95% confidence interval [CI], 0.65-1.01; 21.1% vs 25.0%) and in men was 0.73 (95% CI, 0.55-0.98; 21.2% vs 26.3%) without significant heterogeneity between sexes (P for interaction = .26). Among biomarker-positive women, an invasive strategy was associated with a 33% lower odds of death, MI, or ACS (OR, 0.67; 95% CI, 0.50-0.88) and a nonsignificant 23% lower odds of death or MI (OR, 0.77; 95% CI, 0.47-1.25). In contrast, an invasive strategy was not associated with a significant reduction in the triple composite end point in biomarker-negative women (OR, 0.94; 95% CI, 0.61-1.44; P for interaction = .36) and was associated with a nonsignificant 35% higher odds of death or MI (OR, 1.35; 95% CI, 0.78-2.35; P for interaction = .08). Among men, the OR for death, MI, or ACS was 0.56 (95% CI, 0.46-0.67) if biomarker-positive and 0.72 (95% CI, 0.51-1.01) if biomarker-negative (P for interaction = .09). CONCLUSIONS: In NSTE ACS, an invasive strategy has a comparable benefit in men and high-risk women for reducing the composite end point of death, MI, or rehospitalization with ACS. In contrast, our data provide evidence supporting the new guideline recommendation for a conservative strategy in low-risk women.
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3.
  • O'Donoghue, Michelle L., et al. (författare)
  • An Invasive or Conservative Strategy in Patients With Diabetes Mellitus and Non-ST-Segment Elevation Acute Coronary Syndromes A Collaborative Meta-Analysis of Randomized Trials
  • 2012
  • Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:2, s. 106-111
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives The purpose of this study was to conduct a meta-analysis to examine an invasive or conservative strategy in diabetic versus nondiabetic patients. Background Diabetic patients are at increased risk of cardiovascular events after an acute coronary syndrome, yet it remains unknown whether they derive enhanced benefit from an invasive strategy.Methods Randomized trials comparing an invasive versus conservative treatment strategy were identified. The prevalence of cardiovascular events through 12 months was reported for each trial, stratified by diabetes mellitus status and randomized treatment strategy. Relative risk (RR) ratios and absolute risk reductions were combined using random-effects models.Results Data were combined across 9 trials comprising 9,904 subjects of whom 1,789 (18.1%) had diabetes mellitus. The RRs for death, nonfatal myocardial infarction (MI), or rehospitalization with an acute coronary syndrome for an invasive versus conservative strategy were similar between diabetic patients (RR: 0.87; 95% confidence interval [CI]: 0.73 to 1.03) and nondiabetic patients (RR: 0.86; 95% CI: 0.70 to 1.06; p interaction = 0.83). An invasive strategy reduced nonfatal MI in diabetic patients (RR: 0.71; 95% CI: 0.55 to 0.92), but not in nondiabetic patients (RR: 0.98; 95% CI: 0.74 to 1.29; p interaction = 0.09). The absolute risk reduction in MI with an invasive strategy was greater in diabetic than nondiabetic patients (absolute risk reduction: 3.7% vs. 0.1%; p interaction = 0.02). There were no differences in death or stroke between groups (p interactions 0.68 and 0.20, respectively).Conclusions An early invasive strategy yielded similar RR reductions in overall cardiovascular events in diabetic and nondiabetic patients. However, an invasive strategy appeared to reduce recurrent nonfatal MI to a greater extent in diabetic patients. These data support the updated guidelines that recommend an invasive strategy for patients with diabetes mellitus and non-ST-segment elevation acute coronary syndromes.
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4.
  • Schiele, Francois, et al. (författare)
  • 2020 Update of the quality indicators for acute myocardial infarction: a position paper of the Association for Acute Cardiovascular Care: the study group for quality indicators from the ACVC and the NSTE-ACS guideline group
  • 2021
  • Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 2048-8726 .- 2048-8734. ; 10:2, s. 224-233
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims Quality indicators (QIs) are tools to improve the delivery of evidence-base medicine. In 2017, the European Society of Cardiology (ESC) Association for Acute Cardiovascular Care (ACVC) developed a set of QIs for acute myocardial infarction (AMI), which have been evaluated at national and international levels and across different populations. However, an update of these QIs is needed in light of the accumulated experience and the changes in the supporting evidence. Methods and results The ESC methodology for the QI development was used to update the 2017 ACVC QIs. We identified key domains of AMI care, conducted a literature review, developed a list of candidate QIs, and used a modified Delphi method to select the final set of indicators. The same seven domains of AMI care identified by the 2017 Study Group were retained for this update. For each domain, main and secondary QIs were developed reflecting the essential and complementary aspects of care, respectively. Overall, 26 QIs are proposed in this document, compared to 20 in the 2017 set. New QIs are proposed in this document (e.g. the centre use of high-sensitivity troponin), some were retained or modified (e.g. the in-hospital risk assessment), and others were retired in accordance with the changes in evidence [e.g. the proportion of patients with non-ST segment elevation myocardial infarction (NSTEMI) treated with fondaparinux] and the feasibility assessments (e.g. the proportion of patients with NSTEMI whom risk assessment is performed using the GRACE and CRUSADE risk scores). Conclusion Updated QIs for the management of AMI were developed according to contemporary knowledge and accumulated experience. These QIs may be applied to evaluate and improve the quality of AMI care.
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5.
  • Alfredsson, Joakim, et al. (författare)
  • Impact of an invasive strategy on 5 years outcome in men and women with non-ST-segment elevation acute coronary syndromes
  • 2014
  • Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 168:4, s. 522-529
  • Tidskriftsartikel (refereegranskat)abstract
    • Background A routine invasive (RI) strategy in non-ST-segment elevation acute coronary syndromes (NSTE ACS) has been associated with better outcome compared with a selective invasive (SI) strategy in men, but results in women have yielded disparate results. The aim of this study was to assess gender differences in long-term outcome with an SI compared with an RI strategy in NSTE ACS. Methods Individual patient data were obtained from the FRISC II trial, ICTUS trial, and RITA 3 trial for a collaborative meta-analysis. Results Men treated with an RI strategy had significantly lower rate of the primary outcome 5-year cardiovascular (CV) death/myocardial infarction (MI) compared with men treated with an SI strategy (15.6% vs 19.8%, P = .001); risk-adjusted hazards ratio (HR) 0.73 (95% CI 0.63-0.86). In contrast, there was little impact of an RI compared with an SI strategy on the primary outcome among women (16.5% vs 15.1%, P = .324); risk-adjusted HR 1.13 (95% CI 0.89-1.43), interaction P = .01. For the individual components of the primary outcome, a similar pattern was seen with lower rate of MI (adjusted HR 0.69, 95% CI 0.57-0.83) and CV death (adjusted HR 0.71, 95% CI 0.56-0.89) in men but without obvious difference in women in MI (adjusted HR 1.13, 95% CI 0.85-1.50) or CV death (adjusted HR 0.97, 95% CI 0.68-1.39). Conclusions In this meta-analysis comparing an SI and RI strategy, benefit from an RI strategy during long-term follow-up was confirmed in men. Conversely, in women, there was no evidence of benefit.
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6.
  • Alfredsson, Joakim, et al. (författare)
  • Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes
  • 2017
  • Ingår i: Heart. - : BMJ PUBLISHING GROUP. - 1355-6037 .- 1468-201X. ; 103:15, s. 1168-1176
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives Dual antiplatelet therapy (DAPT) with aspirin + a P2Y12 inhibitor is recommended for at least 12 months for patients with acute coronary syndrome (ACS), with shorter durations considered for patients with increased bleeding risk. However, there are no decision support tools available to predict an individual patients bleeding risk during DAPT treatment in the post-ACS setting. Methods To develop a longitudinal bleeding risk prediction model, we analysed 9240 patients with unstable angina/non-ST segment elevation myocardial infarction (NSTEMI) from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial, who were managed without revascularisation and treated with DAPT for a median of 14.8 months. Results We identified 10 significant baseline predictors of non-coronary artery bypass grafting (CABG)-related Global Use of Strategies to Open Occluded Arteries (GUSTO) severe/life-threatening/moderate bleeding: age, sex, weight, NSTEMI (vs unstable angina), angiography performed before randomisation, prior peptic ulcer disease, creatinine, systolic blood pressure, haemoglobin and treatment with beta-blocker. The five significant baseline predictors of Thrombolysis In Myocardial Infarction (TIMI) major or minor bleeding included age, sex, angiography performed before randomisation, creatinine and haemoglobin. The models showed good predictive accuracy with Therneaus C-indices: 0.78 (SE=0.024) for the GUSTO model and 0.67 (SE=0.023) for the TIMI model. Internal validation with bootstrapping gave similar C-indices of 0.77 and 0.65, respectively. External validation demonstrated an attenuated C-index for the GUSTO model (0.69) but not the TIMI model (0.68). Conclusions Longitudinal bleeding risks during treatment with DAPT in patients with ACS can be reliably predicted using selected baseline characteristics. The TRILOGY ACS bleeding models can inform riskbenefit considerations regarding the duration of DAPT following ACS.
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7.
  • Henriksson, Martin, et al. (författare)
  • The cost-effectiveness of an early interventional strategy in non-ST-elevation acute coronary syndrome based on the RITA 3 trial
  • 2008
  • Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 94, s. 717-723
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Evidence suggests that an early interventional strategy for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) can improve health outcomes but also increase costs when compared with a conservative strategy. Objective: The aim of this study was to assess the cost-effectiveness of an early interventional strategy in different risk groups from a UK health-service perspective. Design: Decision-analytic model based on randomised clinical trial data. Main outcome measures: Costs in UK Sterling at 2003/2004 prices and quality-adjusted life years (QALYs) combined into an incremental cost-effectiveness ratio. Methods: Data from the third Randomised Intervention Trial of unstable Angina (RITA 3) was employed to estimate rates of cardiovascular death and myocardial infarction, costs and health-related quality of life. Cost-effectiveness was estimated over patients’ lifetimes within the decision-analytic model. Results: The mean incremental cost per QALY gained for an early interventional strategy was approximately £55 000, £22 000 and £12 000 for patients at low, intermediate and high risk, respectively. The early interventional strategy is approximately 1%, 35% and 95% likely to be cost-effective for patients at low, intermediate and high risk, respectively, at a threshold of £20 000 per QALY. The cost-effectiveness of early intervention in low-risk patients is sensitive to assumptions about the duration of the treatment effect. Conclusion: An early interventional strategy in patients presenting with NSTE-ACS is likely to be considered cost-effective for patients at high and intermediate risk, but this is less likely to be the case for patients at low risk.
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