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Sökning: WFRF:(Wallentin Lars C. 1943 ) > (2015-2019) > (2018)

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1.
  • Szummer, Karolina, et al. (författare)
  • Relations between implementation of new treatments and improved outcomes in patients with non-ST-elevation myocardial infarction during the last 20 years : experiences from SWEDEHEART registry 1995 to 2014
  • 2018
  • Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 39:42, s. 3766-3776
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims We assessed the changes in short- and long-term outcomes and their relation to implementation of new evidence- based treatments in all patients with non-ST-elevation myocardial infarction (NSTEMI) in Sweden over 20 years. Methods and results Cases with NSTEMI (n = 205 693) between 1995 and 2014 were included from the nationwide Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry. During 20 years in-hospital invasive procedures increased from 1.9% to 73.2%, percutaneous coronary intervention or coronary artery bypass grafting 6.5% to 58.1%, dual antiplatelet medication 0% to 72.7%, statins 13.3% to 85.6%, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blocker 36.8% to 75.5%. The standardized 1-year mortality ratio compared with a control population decreased from 5.53 [95% confidence interval (CI) 5.30-5.75] to 3.03 (95% CI 2.89-3.19). If patients admitted the first 2 years were modelled to receive the same invasive treatments as the last 2 years the expected mortality/ myocardial infarction (MI) rate would be reduced from 33.0% to 25.0%. After adjusting for differences in baseline characteristics, the change of 1-year cardiovascular death/MI corresponded to a linearly decreasing odds ratio trend of 0.930 (95% CI 0.926-0.935) per 2-year period. This trend was substantially attenuated [0.970 (95% CI 0.964-0.975)] after adjusting for changes in coronary interventions, and almost eliminated [0.988 (95% CI 0.982-0.994)] after also adjusting for changes in discharge medications. Conclusion In NSTEMI patients during the last 20 years, there has been a substantial improvement in long-term survival and re- duction in the risk of new cardiovascular events. These improvements seem mainly explained by the gradual uptake and widespread use of in-hospital coronary interventions and evidence-based long-term medications.
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2.
  • Hagström, Emil, et al. (författare)
  • Psychosocial stress and major cardiovascular events in patients with stable coronary heart disease
  • 2018
  • Ingår i: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 283:1, s. 83-92
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Assess the risk of ischaemic events associated with psychosocial stress in patients with stable coronary heart disease (CHD).METHODS: Psychosocial stress was assessed by a questionnaire in 14 577 patients (median age 65.0, IQR 59, 71; 81.6% males) with stable CHD on optimal secondary preventive therapy in the prospective randomized STABILITY clinical trial. Adjusted Cox regression models were used to assess associations between individual stressors, baseline cardiovascular risk factors and outcomes.RESULTS: After 3.7 years of follow-up, depressive symptoms, loss of interest and financial stress were associated with increased risk (hazard ratio, 95% confidence interval) of CV death (1.21, 1.09-1.34; 1.15, 1.05-1.27; and 1.19, 1.08-1.30, respectively) and the primary composite end-point of CV death, nonfatal MI or nonfatal stroke (1.21, 1.13-1.30; 1.19, 1.11-1.27; and 1.17, 1.10-1.24, respectively). Living alone was related to higher risk of CV death (1.68, 1.38-2.05) and the primary composite end-point (1.28, 1.11-1.48), whereas being married as compared with being widowed, was associated with lower risk of CV death (0.64, 0.49-0.82) and the primary composite end-point (0.81, 0.67-0.97).CONCLUSIONS: Psychosocial stress, such as depressive symptoms, loss of interest, living alone and financial stress, were associated with increased CV mortality in patients with stable CHD despite optimal medical secondary prevention treatment. Secondary prevention of CHD should therefore focus also on psychosocial issues both in clinical management and in future clinical trials.
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3.
  • Held, Claes, 1956-, et al. (författare)
  • Characterization of cardiovascular clinical events and impact of event adjudication on the treatment effect of darapladib versus placebo in patients with stable coronary heart disease : Insights from the STABILITY trial
  • 2018
  • Ingår i: American Heart Journal. - 0002-8703 .- 1097-6744. ; 208, s. 65-73
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Clinical Endpoint Classification (CEC) in clinical trials allows FOR standardized, systematic, blinded, and unbiased adjudication of investigator-reported events. We quantified the agreement rates in the STABILITY trial on 15,828 patients with stable coronary heart disease.METHODS: Investigators were instructed to report all potential events. Each reported event was reviewed independently by 2 reviewers according to prespecified processes and prespecified end point definitions. Concordance between reported and adjudicated cardiovascular (CV) events was evaluated, as well as event classification influence on final study results.RESULTS: In total, CEC reviewed 7,096 events: 1,064 deaths (696 CV deaths), 958 myocardial infarctions (MI), 433 strokes, 182 transient ischemic attacks, 2,052 coronary revascularizations, 1,407 hospitalizations for unstable angina, and 967 hospitalizations for heart failure. In total, 71.8% events were confirmed by CEC. Concordance was high (>80%) for cause of death and nonfatal MI and lower for hospitalization for unstable angina (25%) and heart failure (50%). For the primary outcome (composite of CV death, MI, and stroke), investigators reported 2,086 events with 82.5% confirmed by CEC. The STABILITY trial treatment effect of darapladib versus placebo on the primary outcome was consistent using investigator-reported events (hazard ratio 0.96 [95% CI 0.87-1.06]) or adjudicated events (hazard ratio 0.94 [95% CI 0.85-1.03]).CONCLUSIONS: The primary outcome results of the STABILITY trial were consistent whether using investigator-reported or CEC-adjudicated events. The proportion of investigator-reported events confirmed by CEC varied by type of event. These results should help improve event identification in clinical trials to optimize ascertainment and adjudication.
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4.
  • Kolb, Jennifer M., et al. (författare)
  • Locations and Mucosal Lesions Responsible for Major Gastrointestinal Bleeding in Patients on Warfarin or Dabigatran
  • 2018
  • Ingår i: Digestive Diseases and Sciences. - : SPRINGER. - 0163-2116 .- 1573-2568. ; 63:7, s. 1878-1889
  • Tidskriftsartikel (refereegranskat)abstract
    • Different oral anticoagulants may be associated with gastrointestinal bleeding (GIB) from different locations or mucosal lesions. We aimed to test this hypothesis. Two blinded gastroenterologists independently analyzed source documents from the randomized evaluation of long-term anticoagulant therapy (RE-LY) trial of dabigatran 150 mg BID (D150), dabigatran 110 mg BID (D110) versus warfarin in non-valvular atrial fibrillation (NVAF). Major GIB events (total n = 546) and life-threatening GIB events (n = 258) were more common with D150 versus warfarin (RR 1.57 [1.28-1.92] and RR 1.62 [1.20-2.18], respectively) and similar for D110 compared to warfarin (RR 1.11 [0.89-1.38] and RR 1.16 [0.84-1.61], respectively). Fatal bleeding was similarly rare across treatment groups. Lower GI major bleeding and life-threatening bleeding were more common with D150 compared to warfarin (RR 2.23 [1.47, 3.38] and RR 2.64 [1.36, 5.13], respectively) and with D110 compared to warfarin (RR 1.78 [1.16, 2.75] and RR 2.00 [1.00, 4.00], respectively). MGIB from colonic angiodysplasia was increased with dabigatran versus warfarin (P < 0.01 for both dose comparisons). Subacute and chronic MGIB events were more common with D150 than with warfarin (RR 1.72 [1.06, 2.78] and RR 1.66 [1.12, 2.45], respectively), as were hematochezia or melena (RR 1.67 [1.18, 2.36] and RR 1.72 [1.20, 2.47], respectively). In a chronic NVAF population, D150 but not D110 is associated with increased major and life-threatening GI bleeding in comparison with warfarin. At both dabigatran doses, increased bleeding from the colorectum, in particular from angiodysplasia, is seen.
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5.
  • Manichaikul, Ani, et al. (författare)
  • Lp-PLA(2), scavenger receptor class B type I gene (SCARB1) rs10846744 variant, and cardiovascular disease
  • 2018
  • Ingår i: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 13:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background We previously reported association of SCARB1 SNP rs10846744 with common carotid IMT (cIMT) and cardiovascular disease (CVD) events. Since rs10846744 has been reported in association with Lp-PLA(2) mass and activity, we hypothesized that inflammatory pathways might mediate the association of rs10846744 with atherosclerosis. Methods We first examined association of rs10846744 in CVD in multiple large-scale consortium-based genome-wide association studies. We further examined 27 parameters of interest, including Lp-PLA(2) mass and activity, inflammatory markers, and plasma phospholipid fatty acids, and fatty acid ratios in participants from the Multi-Ethnic Study of Atherosclerosis (MESA), as potential mediators in the pathway linking rs10846744 with cIMT and incident CVD. Finally, we examined the association of rs10846744 with Lp-PLA(2) activity, cardiovascular outcomes, and interaction with the Lp-PLA(2) inhibitor, darapladib, in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy (STABILITY) and Stabilization of Plaque using Darapladib-Thrombolysis in Myocardial Infarction 52 (SOLID-TIMI 52) studies. Results SCARB1 rs10846744 was associated with coronary artery disease events in CARDIo-GRAMplusC4D (odds ratio 1.05; 95% CI [1.02, 1.07]; P= 1.4x10(-4)). In combined analysis across race/ethnic groups in MESA, rs10846744 was associated with Lp-PLA(2 )mass (P= 0.04) and activity (P = 0.001), homocysteine (P = 0.03), LDL particle number (P = 0.01), docosahexaenoic acid [DHA] (P = 0.01), docosapentaenoic acid [DPA] (P = 0.04), DPA/eicosapentaenoic acid [EPA] ratio (P= 0.002), and DHA/EPA ratio (P= 0.008). Lp-PLA(2) activity was identified as a mediator of rs10846744 with cIMT in a basic model (P = 8x10(-5)), but not after adjustment for CVD risk factors. There was no interaction or modifier effect of the Lp-PLA(2) inhibitor darapladib assignment on the relationship between rs10846744 and major CVD events in either STABILITY or SOLID-TIMI 52. Summary SCARB1 rs10846744 is significantly associated with Lp-PLA(2) activity, atherosclerosis, and CVD events, but Lp-PLA(2) activity is not a mediator in the association of rs10846744 with cIMT in MESA.
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6.
  • Parker, William A E, et al. (författare)
  • Equilibrative nucleoside transporter 1 gene polymorphisms and clinical outcomes following acute coronary syndromes : findings from the PLATelet inhibition and patient Outcomes (PLATO) study
  • 2018
  • Ingår i: Platelets. - 0953-7104 .- 1369-1635. ; 30:5, s. 579-588
  • Tidskriftsartikel (refereegranskat)abstract
    • In the PLATelet inhibition and patient Outcomes (PLATO) study, the P2Y12 inhibitors ticagrelor and clopidogrel were compared in the treatment of acute coronary syndromes (ACS). Ticagrelor was shown to reduce occurrence of the primary end point - a composite of death from vascular causes, myocardial infarction, or stroke - compared to clopidogrel. Ticagrelor's pleiotropic effects on reuptake of adenosine via inhibition of equilibrative nucleoside transporter 1 (ENT1) have been hypothesized to contribute to this. Several polymorphisms of ENT1 are known to exist. We explored the interaction between ENT1 polymorphisms and clinical outcomes in ACS patients participating in the PLATO genetic substudy. Using genotyping data obtained in a genome-wide association study, the gene region encoding ENT1 was assessed and 94 polymorphisms were identified. After quality control filtering, data from 9943 participants were included. Subjects were divided into discovery (phase 1, n = 3970) and replication (phase 2, n = 5973) cohorts. Cox-regression analysis of the relationship between variants and seven efficacy and safety outcomes was performed in discovery, replication, and combined cohorts. Treatment-marker interactions were also determined. Although 35 variants were found with associations to the investigated outcomes reaching p < 0.05 in the discovery cohort, only one of these was replicated in phase 2 of the analysis and also reached the predetermined level of statistical significance in the combined data, taking into account the number of tests performed: the rare polymorphism rs141034817, with a frequency of 0.2%, was significantly associated with bleeding. Thirty-three treatment-marker interactions were found with a significance level of p < 0.05 in phase 1, but none was replicated in phase 2. We found no significant interaction between ENT1 genotype and clinical outcomes in ACS patients treated with ticagrelor or clopidogrel, apart from the association between a rare polymorphism and bleeding that requires further study. If ticagrelor's pleiotropic effects on adenosine uptake are clinically relevant, these do not appear to be significantly affected by variation in the ENT1 gene.
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7.
  • Scirica, Benjamin M., et al. (författare)
  • Safety of ticagrelor in patients with baseline conduction abnormalities : A PLATO (Study of Platelet Inhibition and Patient Outcomes) analysis
  • 2018
  • Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 202, s. 54-60
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Although bradyarrhythmias have been observed with ticagrelor and its use with advanced atrioventricular block is not recommended, questions arise regarding its use in patients with mild conduction abnormalities. The objectives were to compare rates of clinically relevant arrhythmias in relation to any mild baseline conduction abnormality in patients with acute coronary syndrome randomized to ticagrelor versus clopidogrel. Methods: We included all subjects in the electrocardiographic (ECG) substudy of the Platelet Inhibition and Patient Outcomes trial, excluding those with missing baseline ECG or with a pacemaker at baseline (N = 15,460). Conduction abnormality was defined as sinus bradycardia, first-degree atrioventricular block, hemiblock, or bundle-branch block. The primary arrhythmic outcome was the composite of any symptomatic brady-or tachyarrhythmia, permanent pacemaker placement, or cardiac arrest through 12 months. Results: Patients with baseline conduction abnormalities (n = 4,256, 27.5%) were older and more likely to experience the primary arrhythmic outcome. There were no differences by ticagrelor versus clopidogrel in the composite arrhythmic end point in those with baseline conduction disease (1-year cumulative incidence rate: 17% for both study arms; hazard ratio: 0.99 [0.86-1.15]) or without baseline conduction disease (1-year cumulative incidence rate: clopidogrel 12.8% vs ticagrelor 12.4%; hazard ratio: 0.98 (0.88-1.09). There were also no statistically significant differences between ticagrelor and clopidogrel in the rates of bradycardic (or any individual arrhythmic) events in patients with baseline conduction abnormalities. Conclusions: Ticagrelor compared to clopidogrel did not increase arrhythmic events even in subjects with acute coronary syndrome who present with mild conduction abnormalities on their baseline ECG. (C) 2018 Published by Elsevier Inc.
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8.
  • Sherwood, Matthew W, et al. (författare)
  • Apixaban following acute coronary syndromes in patients with prior stroke : Insights from the APPRAISE-2 trial
  • 2018
  • Ingår i: American Heart Journal. - 0002-8703 .- 1097-6744. ; 197, s. 1-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND PURPOSE: Patients with prior stroke are at greater risk for recurrent cardiovascular events post-acute coronary syndromes (ACS) and may have a different risk/benefit profile with antithrombotic therapy than patients without prior stroke.METHODS: We studied 7391 patients with ACS from APPRAISE-2, stratified by the presence or absence of prior stroke. Baseline characteristics and outcomes of cardiovascular death, myocardial infarction (MI), or stroke were compared between groups. Interactions between prior stroke, treatment assignment (apixaban vs placebo), and outcomes were tested before and after multivariable adjustment with Cox proportional hazards models.RESULTS: A total of 902 patients (12%) had prior stroke. Those with prior stroke were older (69 vs 67 years), had more hypertension (91% vs 77%), peripheral vascular disease (22% vs18%), and impaired renal function (38% vs 30%) but less diabetes (44% vs 48%) than those without prior stroke. Patients with prior stroke vs no prior stroke had higher unadjusted rates of cardiovascular death (4.8% vs 4.0%), MI (11.2% vs 7.1%), and ischemic stroke (3.2% vs 0.9%). Patients with prior stroke assigned to apixaban had similar rates of the composite of cardiovascular death, MI, or stroke compared with those assigned to placebo (HR 1.39; 95% CI 0.92-2.08). Patients without prior stroke assigned to apixaban had similar rates of cardiovascular death, MI, or ischemic stroke compared with those assigned to placebo (HR 0.87; 95% CI 0.73-1.04; P-interaction=.041). Median follow-up was 240 days.CONCLUSIONS: Patients with prior stroke are at higher risk for recurrent cardiovascular events post-ACS and had a differential risk/benefit profile with oral anticoagulation.
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9.
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10.
  • Tricoci, Pierluigi, et al. (författare)
  • Effects of genetic variation in protease activated receptor 4 after an acute coronary syndrome : Analysis from the TRACER trial
  • 2018
  • Ingår i: Blood Cells, Molecules & Diseases. - 1079-9796 .- 1096-0961. ; 72, s. 37-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Variation in platelet response to thrombin may affect the safety and efficacy of PAR antagonism. The Thr120 variant of the common single nucleotide polymorphism (SNP) rs773902 in the protease-activated receptor (PAR) 4 gene is associated with higher platelet aggregation compared to the Ala120 variant. We investigated the relationship between the rs773902 SNP with major bleeding and ischemic events, safety, and efficacy of PAR1 inhibition in 6177 NSTE ACS patients in the TRACER trial. There was a lower rate of GUSTO moderate/severe bleeding in patients with the Thr120 variant. The difference was driven by a lower rate in the smaller homozygous group (recessive model, HR 0.13 [0.02-0.92] P= 0.042). No significant differences were observed in the ischemic outcomes. The excess in bleeding observed with PAR1 inhibition was attenuated in patients with the Thr120 variant, but the interactions were not statistically significant. In summary, lower major bleeding rates were observed in the overall TRACER cohort with the hyperreactive PAR4 Thr120 variant. The increase in bleeding with vorapaxar was attenuated with the Thr120 variant, but we could not demonstrate an interaction with PAR1 inhibition. These findings warrant further exploration, including those of African ancestry where the A allele (Thr120) frequency is similar to 65%.
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