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- Alfredsson, Joakim, et al.
(author)
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Predicting the risk of bleeding during dual antiplatelet therapy after acute coronary syndromes
- 2017
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In: Heart. - : BMJ PUBLISHING GROUP. - 1355-6037 .- 1468-201X. ; 103:15, s. 1168-1176
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Journal article (peer-reviewed)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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| 2. |
- Venetsanos, Dimitrios, et al.
(author)
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Sex-related response to bivalirudin and unfractionated heparin in patients with acute myocardial infarction undergoing percutaneous coronary intervention : A subgroup analysis of the VALIDATE-SWEDEHEART trial
- 2019
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In: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 8:6, s. 502-509
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Journal article (peer-reviewed)abstract
- AIMS: Our aim was to study the impact of sex on anticoagulant treatment outcomes during percutaneous coronary intervention in acute myocardial infarction patients.METHODS: This study was a prespecified analysis of the Bivalirudin versus Heparin in ST-Segment and Non ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated according to Recommended Therapies Registry Trial (VALIDATE-SWEDEHEART) trial, in which patients with myocardial infarction were randomised to bivalirudin or unfractionated heparin during percutaneous coronary intervention. The primary outcome was the composite of death, myocardial infarction or major bleeding at 180 days.RESULTS: There was a lower risk of the primary outcome in women assigned to bivalirudin than to unfractionated heparin (13.6% vs 17.1%, hazard ratio 0.78, 95% confidence interval (0.60-1.00)) with no significant difference in men (11.8% vs 11.2%, hazard ratio 1.06 (0.89-1.26), p for interaction 0.05). The observed difference was primarily due to lower risk of major bleeding (Bleeding Academic Research Consortium definition 2, 3 or 5) associated with bivalirudin in women (8.9% vs 11.8%, hazard ratio 0.74 (0.54-1.01)) but not in men (8.5% vs 7.3%, hazard ratio 1.16 (0.94-1.43) in men, p for interaction 0.02). Conversely, no significant difference in the risk of Bleeding Academic Research Consortium 3 or 5 bleeding, associated with bivalirudin, was found in women 4.5% vs 5.4% (hazard ratio 0.84 (0.54-1.31)) or men 2.9% vs 2.1% (hazard ratio 1.36 (0.93-1.99)). Bleeding Academic Research Consortium 2 bleeding occurred significantly less often in women assigned to bivalirudin than to unfractionated heparin. The risk of death or myocardial infarction did not significantly differ between randomised treatments in men or women.CONCLUSION: In women, bivalirudin was associated with a lower risk of adverse outcomes, compared to unfractionated heparin, primarily due to a significant reduction in Bleeding Academic Research Consortium 2 bleeds.
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| 3. |
- Alfredsson, Joakim, et al.
(author)
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Large early variation of residual platelet reactivity in Acute Coronary Syndrome patients treated with clopidogrel : Results from Assessing Platelet Activity in Coronary Heart Disease (APACHE).
- 2015
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In: Thrombosis Research. - : Pergamon Press. - 0049-3848 .- 1879-2472. ; 136:2, s. 335-340
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Journal article (peer-reviewed)abstract
- INTRODUCTION: There is a large inter-individual variation in response to clopidogrel treatment and previous studies have indicated higher risk of thrombotic events in patients with high residual platelet reactivity (HRPR), but the optimal time-point for testing is not established. The aim of this study was to investigate the optimal time-point for aggregometry testing and the risk of major adverse cardiac events associated with HRPR.METHOD AND RESULTS: We included 125 patients with ACS (73 with STEMI, and 71 received abciximab). The prevalence of HRPR varied substantially over time. The rate of HRPR in patients treated and not treated with abciximab were 43% vs 67% (p=0.01) before, 2% vs 23% (p=0.001) 6-8h after, 8% vs 9% (p=0.749) 3days after, and 23% vs 12% (p=0.138) 7-9 days after loading dose of clopidogrel. We found HRPR in 18% of the patients but only four ischemic events during 6months follow-up, with no significant difference between HRPR patients compared to the rest of the population. There were 3 TIMI major bleedings, all of which occurred in the low residual platelet reactivity (LRPR) group.CONCLUSION: There is a large variation in platelet reactivity over time, also depending on adjunctive therapy, which has a large impact on optimal time-point for assessment. We found HRPR in almost 1 in 5 patients, but very few MACE, and not significantly higher in HRPR patients. In a contemporary ACS population, with low risk for stent thrombosis, the predictive value of HRPR for ischemic events will probably be low.
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| 4. |
- Hofmann, R., et al.
(author)
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Supplemental oxygen therapy does not affect the systemic inflammatory response to acute myocardial infarction
- 2018
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In: Journal of Internal Medicine. - : WILEY. - 0954-6820 .- 1365-2796. ; 283:4, s. 334-345
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Journal article (peer-reviewed)abstract
- Background. Oxygen therapy has been used routinely in normoxemic patients with suspected acute myocardial infarction (AMI) despite limited evidence supporting a beneficial effect. AMI is associated with a systemic inflammation. Here, we hypothesized that the inflammatory response to AMI is potentiated by oxygen therapy. Methods. The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) multicentre trial randomized patients with suspected AMI to receive oxygen at 6 L min(-1) for 6-12 h or ambient air. For this prespecified subgroup analysis, we recruited patients with confirmed AMI from two sites for evaluation of inflammatory biomarkers at randomization and 5-7 h later. Ninety-two inflammatory biomarkers were analysed using proximity extension assay technology, to evaluate the effect of oxygen on the systemic inflammatory response to AMI. Results. Plasma from 144 AMI patients was analysed whereof 76 (53%) were randomized to oxygen and 68 (47%) to air. Eight biomarkers showed a significant increase, whereas 13 were decreased 5-7 h after randomization. The inflammatory response did not differ between the two treatment groups neither did plasma troponin T levels. After adjustment for increase in troponin T over time, age and sex, the release of inflammation-related biomarkers was still similar in the groups. Conclusions. In a randomized controlled setting of normoxemic patients with AMI, the use of supplemental oxygen did not have any significant impact on the early release of systemic inflammatory markers.
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| 5. |
- Szymanowski, Aleksander, et al.
(author)
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Soluble markers of apoptosis in myocardial infarction patients during acute phase and 6-month follow up
- 2015
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Other publication (other academic/artistic)abstract
- ObjectivesThe aim of the study was to investigate circulating markers of apoptosis in the acute phase and at follow8up in patients with ST8elevation myocardial infarction (STEMI) or non8ST8elevation myocardial infarction (NSTEMI).BackgroundMyocardial cell death during acute MI results from necrosis, apoptosis and autophagy. An elevated rate of apoptosis can continue for several days after the acute event, contributing to an increased final infarct size. Moreover, a lower but still increased apoptosis can continue for months resulting in left ventricular (LV) dysfunction and heart failure. Few studies have analysed markers of apoptosis longitudinally in MI patients. Also, it is not known whether STEMI and NSTEMI patients differ in regard to these markers. MethodsThis study is a prespecified substudy of the APACHE trial. We included 61 STEMI and 40 NSTEMI patients. Blood samples for analysis of soluble tumor necrosis factor receptor (sTNFR) 1, sTNFR2, sFas, sFas ligand (sFasL) and IL86 were collected at baseline prior to PCI, at 3 days and at 6 months. High sensitivity troponin T (hsTnT) was measured at 688 hours and echocardiography was performed at 283 days after admission to hospital.ResultsSTEMI compared to NSTEMI patients showed very similar temporal patterns for each of the markers of apoptosis analyzed. Levels of sTNFRs increased from baseline to day 3 and the absolute increase as well as day 3 levels correlated significantly with TnT. At 6 months, sTNFR1 had returned to baseline whereas levels of sTNFR2 were still elevated. Soluble Fas and sFasL did not change from baseline to day 3, and both markers were significantly lower in the acute phase compared to 6 months. Indeed, sFas at day 3 correlated negatively with TnT. At all time points, plasma sTNFRs were significantly higher in patients with reduced LV function, whereas no such associations with sFas or sFasL was observed. ConclusionsThe TNF and Fas/FasL pathways of apoptosis, as reflected by soluble markers, show markedly different temporal changes after an acute MI, indicating diverse roles of these two systems. STEMI compared to NSTEMI patients showed very similar temporal patterns for all the analyzed markers, suggesting apoptosis to be equally involved in myocardial damage of either infarct type.
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