| 1. |
|
|
| 2. |
- Werdan, K., et al.
(författare)
-
Curriculum Kardiologie 2., aktualisierte Auflage
- 2020
-
Ingår i: KARDIOLOGE. - : SPRINGER HEIDELBERG. - 1864-9718 .- 1864-9726. ; 14:6, s. 505-536
-
Tidskriftsartikel (refereegranskat)abstract
- The updated second edition of the "Curriculum cardiology", first edition 2013, aims to show which competences a cardiologist should nowadays master. It is very pleasing that in this second edition representatives of the Young German Cardiac Society (Young DGK) have contributed as authors. The increasing specialization within cardiology should, however, only represent one side of the coin: there must also still be a common foundation of cardiology, embedded in the discipline "internal medicine". This foundation includes the basis of theoretical knowledge, practical skills (competence levels I-III) and an occupational and professional attitude of the (prospective) cardiologist. New additions to the advanced training since the first edition of the curriculum in 2013 are, for example a chapter on digital cardiology, the further training in psychocardiology, which was newly introduced into the model further training regulations and finally also the explicit formulation of shared decision making in the interests of cardiac patients. The curriculum should give the prospective cardiologist the possibility to structure the further training as efficiently as possible and ultimately to retain and expand that which has been learned in the sense of a "professional lifelong" qualification. The curriculum also aims to reach the trainers and the Medical Councils and demonstrate which contents and skills should be mediated in the further training to become a cardiologist from the perspective of the German Cardiac Society (DGK).
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Franchi, Francesco, et al.
(författare)
-
Impact of Diabetes Mellitus and Chronic Kidney Disease on Cardiovascular Outcomes and Platelet P2Y12 Receptor Antagonist Effects in Patients With Acute Coronary Syndromes : Insights From the PLATO Trial
- 2019
-
Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:6
-
Tidskriftsartikel (refereegranskat)abstract
- Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P<0.001). Patients with DM+/CKD- and DM-/CKD+ had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups (P-interaction=0.264), but with an increased absolute risk reduction in DM+/CKD+. The effects on major bleeding were also consistent across subgroups (P-interaction=0.288). Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Neumann, J. T., et al.
(författare)
-
Application of High-Sensitivity Troponin in Suspected Myocardial Infarction
- 2019
-
Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 380:26, s. 2529-2540
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundData regarding high-sensitivity troponin concentrations in patients presenting to the emergency department with symptoms suggestive of myocardial infarction may be useful in determining the probability of myocardial infarction and subsequent 30-day outcomes. MethodsIn 15 international cohorts of patients presenting to the emergency department with symptoms suggestive of myocardial infarction, we determined the concentrations of high-sensitivity troponin I or high-sensitivity troponin T at presentation and after early or late serial sampling. The diagnostic and prognostic performance of multiple high-sensitivity troponin cutoff combinations was assessed with the use of a derivation-validation design. A risk-assessment tool that was based on these data was developed to estimate the risk of index myocardial infarction and of subsequent myocardial infarction or death at 30 days. ResultsAmong 22,651 patients (9604 in the derivation data set and 13,047 in the validation data set), the prevalence of myocardial infarction was 15.3%. Lower high-sensitivity troponin concentrations at presentation and smaller absolute changes during serial sampling were associated with a lower likelihood of myocardial infarction and a lower short-term risk of cardiovascular events. For example, high-sensitivity troponin I concentrations of less than 6 ng per liter and an absolute change of less than 4 ng per liter after 45 to 120 minutes (early serial sampling) resulted in a negative predictive value of 99.5% for myocardial infarction, with an associated 30-day risk of subsequent myocardial infarction or death of 0.2%; a total of 56.5% of the patients would be classified as being at low risk. These findings were confirmed in an external validation data set. ConclusionsA risk-assessment tool, which we developed to integrate the high-sensitivity troponin I or troponin T concentration at emergency department presentation, its dynamic change during serial sampling, and the time between the obtaining of samples, was used to estimate the probability of myocardial infarction on emergency department presentation and 30-day outcomes.
|
|
| 15. |
- Saenger, A. K., et al.
(författare)
-
Multicenter analytical evaluation of a high-sensitivity troponin T assay
- 2011
-
Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 412:9-10, s. 748-754
-
Tidskriftsartikel (refereegranskat)abstract
- Background: High-sensitivity cardiac troponin assays are being introduced clinically for earlier diagnosis of acute myocardial infarction (AMI). We evaluated the analytical performance of a high-sensitivity cardiac troponin T assay (hscTnT. Roche Diagnostics) in a multicenter, international trial. Methods: Three US and 5 European sites evaluated hscTnT on the Modular (R) Analytics E170, cobas (R) 6000, Elecsys 2010, and cobas (R) e 411. Precision, accuracy, reportable range, an inter-laboratory comparison trial, and the 99th percentile of a reference population were assessed. Results: Total imprecision (CVs) were 4.6-36.8% between 3.4 and 10.3 ng/L hscTnT. Assay linearity was up to 10,000 ng/L and the limit of blank and detection were 3 and 5 ng/L, respectively. The 99th percentile reference limit was 14.2 ng/L (n = 533). No significant differences between specimen types, assay incubation time, or reagent lots existed. A substantial positive bias (76%) exists between the 4th generation and hscTnT assays at the low end of the measuring range (< 50 ng/L). hscTnT serum pool concentrations were within 2SD limits of the mean of means in the comparison trial, indicating comparable results across multiple platforms and laboratories. Conclusion: The Roche hscTnT assay conforms to guideline precision requirements and will likely identify additional patients with myocardial injury suspicious for AMI.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Cornel, Jan H., et al.
(författare)
-
Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes-Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
- 2012
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 164:3, s. 334-342
-
Tidskriftsartikel (refereegranskat)abstract
- Background Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits.Methods Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses.Results Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P = .50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P = .61).Conclusions In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.
|
|
| 19. |
- Ducrocq, Gregory, et al.
(författare)
-
Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes
- 2017
-
Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 186, s. 91-99
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality.Methods: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events.Results: A total of 822 patients (4.4%) had >= 1 spontaneous ischemic event; 485 patients (2.6%), >= 1 spontaneous PLATO major bleed, 282 (1.5%), >= 1 spontaneous TIMI major bleed; and 207 (1.1%), >= 1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% Cls) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05)Conclusions: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.
|
|
| 20. |
- Eggers, Kai M., 1962-, et al.
(författare)
-
Temporal biomarker concentration patterns during the early course of acute coronary syndrome
- 2024
-
Ingår i: Clinical Chemistry and Laboratory Medicine. - : Walter de Gruyter. - 1434-6621 .- 1437-4331. ; 62:6, s. 1167-1176
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: Biomarker concentrations and their changes during acute coronary syndrome (ACS) provide clinically useful information on pathophysiological processes, e.g. myocardial necrosis, hemodynamic stress and inflammation. However, current evidence on temporal biomarker patterns early during ACS is limited, and studies investigating multiple biomarkers are lacking.Methods: We measured concentrations of high-sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI), NT-terminal pro-B-type natriuretic peptide, C-reactive protein, and growth-differentiation factor-15 (GDF-15) in plasma samples obtained at randomization in ACS patients from the PLATelet inhibition and patient Outcomes (PLATO) trial. Linear regressions with interaction analyses were used to investigate the associations of biomarker concentrations with the time from symptom onset and to model temporal biomarker concentration patterns.Results: The study population consisted of 16,944 patients (median age 62 years; 71.3 % males) with 6,853 (40.3 %) having ST-elevation myocardial infarction (STEMI) and 10,141 (59.7 %) having non-ST-elevation ACS (NSTE-ACS). Concentrations of all biomarkers were associated with time from symptom onset (pinteraction<0.001), apart for GDF-15 (pinteraction=0.092). Concentration increases were more pronounced in STEMI compared to NSTE-ACS. Temporal biomarker patterns for hs-cTnT and hs-cTnI were different depending on sex whereas biomarker patterns for the other biomarkers were similar in cohorts defined by age and sex.Conclusions: Temporal concentration patterns differ for various biomarkers early during ACS, reflecting the variability in the activation and duration of different pathophysiological processes, and the amount of injured myocardium. Our data emphasize that the time elapsed from symptom onset should be considered for the interpretation of biomarker results in ACS.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
- Frohlich, H, et al.
(författare)
-
Epidemiology and long-term outcome in outpatients with chronic heart failure in Northwestern Europe
- 2019
-
Ingår i: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 105:16, s. 1252-1259
-
Tidskriftsartikel (refereegranskat)abstract
- To describe the epidemiology, long-term outcomes and temporal trends in mortality in ambulatory patients with chronic heart failure (HF) with reduced (HFrEF), mid-range (HFmrEF) or preserved ejection fraction (HFpEF) from three European countries.MethodsWe identified 10 312 patients from the Norwegian HF Registry and the HF registries of the universities of Heidelberg, Germany, and Hull, UK. Patients were classified according to baseline left ventricular ejection fraction (LVEF) and time of enrolment (period 1: 1995–2005 vs period 2: 2006–2015). Predictors of mortality were analysed by use of univariable and multivariable Cox regression analyses.ResultsAmong 10 312 patients with stable HF, 7080 (68.7%), 2086 (20.2%) and 1146 (11.1%) were classified as having HFrEF, HFmrEF or HFpEF, respectively. A total of 4617 (44.8%) patients were included in period 1, and 5695 (55.2%) patients were included in period 2. Baseline characteristics significantly differed with respect to type of HF and time of enrolment. During a median follow-up of 66 (33–105) months, 5297 patients (51.4%) died. In multivariable analyses, survival was independent of LVEF category (p>0.05), while mortality was lower in period 2 as compared with period 1 (HR 0.81, 95% CI 0.72 to 0.91, p<0.001). Significant predictors of all-cause mortality regardless of HF category were increasing age, New York Heart Association functional class, N-terminal pro-brain natriuretic peptide and use of loop diuretics.ConclusionAmbulatory patients with HF stratified by LVEF represent different phenotypes. However, after adjusting for a wide range of covariates, long-term survival is independent of LVEF category. Outcome significantly improved during the last two decades irrespective from type of HF.
|
|
| 26. |
|
|
| 27. |
- Haas, Jan, et al.
(författare)
-
Atlas of the clinical genetics of human dilated cardiomyopathy
- 2015
-
Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 36:18, s. 1123-U43
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: We were able to show that targeted Next-Generation Sequencing is well suited to be applied in clinical routine diagnostics, substantiating the ongoing paradigm shift from low- to high-throughput genomics in medicine. By means of our atlas of the genetics of human DCM, we aspire to soon be able to apply our findings to the individual patient with cardiomyopathy in daily clinical practice. Numerous genes are known to cause dilated cardiomyopathy (DCM). However, until now technological limitations have hindered elucidation of the contribution of all clinically relevant disease genes to DCM phenotypes in larger cohorts. We now utilized next-generation sequencing to overcome these limitations and screened all DCM disease genes in a large cohort. Methods and results: In this multi-centre, multi-national study, we have enrolled 639 patients with sporadic or familial DCM. To all samples, we applied a standardized protocol for ultra-high coverage next-generation sequencing of 84 genes, leading to 99.1% coverage of the target region with at least 50-fold and a mean read depth of 2415. In this well characterized cohort, we find the highest number of known cardiomyopathy mutations in plakophilin-2, myosin-binding protein C-3, and desmoplakin. When we include yet unknown but predicted disease variants, we find titin, plakophilin-2, myosin-binding protein-C 3, desmoplakin, ryanodine receptor 2, desmocollin-2, desmoglein-2, and SCN5A variants among the most commonly mutated genes. The overlap between DCM, hypertrophic cardiomyopathy (HCM), and channelopathy causing mutations is considerably high. Of note, we find that >38% of patients have compound or combined mutations and 12.8% have three or even more mutations. When comparing patients recruited in the eight participating European countries we find remarkably little differences in mutation frequencies and affected genes. Conclusion: This is to our knowledge, the first study that comprehensively investigated the genetics of DCM in a large-scale cohort and across a broad gene panel of the known DCM genes. Our results underline the high analytical quality and feasibility of Next-Generation Sequencing in clinical genetic diagnostics and provide a sound database of the genetic causes of DCM.
|
|
| 28. |
- Hilbel, T., et al.
(författare)
-
Performance and productivity benefits using multi-core processors for the analysis of digital long-term ECG recordings
- 2008
-
Ingår i: Computers in Cardiology, 2008. ; , s. 1069-1072
-
Konferensbidrag (refereegranskat)abstract
- Modern Holter recorders allow the acquisition of 12 lead ECGs with a sampling rate of IKHz or higher and a resolution of 16 bits over more than 24h. While large volumes of data can be easily stored on flash memory cards the analysis of these biosignals requires considerable calculation power and network bandwidth. In general, processing time is important when hundreds of digital recordings from large study groups need to be analyzed The objective of the following investigation is to address the question: Can performance and productivity benefits in ECG analysis be achieved using multi-core processor technology? Because these processors have two or more processing cores they can perform parallel processing. The results show that segmentation of Holter data and running the same program multiple times simultaneously can dramatically speedup the computing performance.
|
|
| 29. |
|
|
| 30. |
- Hjort, Marcus, 1988-, et al.
(författare)
-
Biomarker Concentrations and Their Temporal Changes in Patients With Myocardial Infarction and Nonobstructive Compared With Obstructive Coronary Arteries : Results From the PLATO Trial
- 2023
-
Ingår i: Journal of the American Heart Association. - : American heart association. - 2047-9980. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The pathobiology of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is often uncertain. Investigating biomarker concentrations and their changes may offer novel pathophysiological insights.Methods and Results: In this post hoc study of the PLATO (Platelet Inhibition and Patient Outcomes) trial, concentrations of hs‐cTnT (high‐sensitivity cardiac troponin T), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), hs‐CRP (high‐sensitivity C‐reactive protein), and GDF‐15 (growth differentiation factor 15) were measured in patients with MINOCA at baseline (n=554) and at 1‐month follow‐up (n=107). For comparisons, biomarkers were also measured in patients with MI with obstructive (stenosis ≥50%) coronary artery disease (baseline: n=11 106; follow‐up: n=2755]). Adjusted linear regression models were used to compare concentrations and their short‐ and long‐term changes. The adjusted geometric mean ratios (GMRs) in patients with MINOCA (median age, 61 years; 50.4% women) indicated lower hs‐cTnT (GMR, 0.77 [95% CI, 0.68–0.88]) but higher hs‐CRP (GMR, 1.21 [95% CI, 1.08–1.37]) and GDF‐15 concentrations (GMR, 1.06 [95% CI, 1.02–1.11]) at baseline compared with patients with MI with obstructive coronary artery disease, whereas NT‐proBNP concentrations were similar. Temporal decreases in hs‐cTnT, NT‐proBNP, and hs‐CRP concentrations until 1‐month follow‐up were more pronounced in patients with MINOCA. At follow‐up, patients with MINOCA had lower concentrations of hs‐cTnT (GMR, 0.71 [95% CI, 0.60–0.84]), NT‐proBNP (GMR, 0.45 [95% CI, 0.36–0.56]), and hs‐CRP (GMR, 0.68 [95% CI, 0.53–0.86]). One‐month GDF‐15 concentrations were similar between both groups with MI.Conclusions: Biomarker concentrations suggest greater initial inflammatory activity, similar degree of myocardial dysfunction, and less pronounced myocardial injury during the acute phase of MINOCA compared with MI with obstructive coronary artery disease but also faster myocardial recovery.CLINICAL TRAIL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
|
|
| 31. |
|
|
| 32. |
- James, Stefan K., et al.
(författare)
-
Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management : substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial
- 2011
-
Ingår i: The BMJ. - : BMJ. - 1756-1833. ; 342, s. d3527-
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate efficacy and safety outcomes in patients in the PLATelet inhibition and patient Outcomes (PLATO) trial who at randomisation were planned for a non-invasive treatment strategy. Design Pre-specified analysis of pre-randomisation defined subgroup of prospective randomised clinical trial. Setting 862 centres in 43 countries. Participants 5216 (28%) of 18 624 patients admitted to hospital for acute coronary syndrome who were specified as planned for non-invasive management. Interventions Randomised treatment with ticagrelor (n=2601) versus clopidogrel (2615). Main outcome measurements Primary composite end point of cardiovascular death, myocardial infarction, and stroke; their individual components; and PLATO defined major bleeding during one year. Results 2183 (41.9%) patients had coronary angiography during their initial hospital admission, 1065 (20.4%) had percutaneous coronary intervention, and 208 (4.0%) had coronary artery bypass surgery. Cumulatively, 3143 (60.3%) patients had been managed non-invasively by the end of follow-up. The incidence of the primary end point was lower with ticagrelor than with clopidogrel (12.0% (n=295) v 14.3% (346); hazard ratio 0.85, 95% confidence interval 0.73 to 1.00; P=0.04). Overall mortality was also lower (6.1% (147) v 8.2% (195); 0.75, 0.61 to 0.93; P=0.01). The incidence of total major bleeding (11.9% (272) v 10.3% (238); 1.17, 0.98 to 1.39; P=0.08) and non-coronary artery bypass grafting related major bleeding (4.0% (90) v 3.1% (71); 1.30, 0.95 to 1.77; P=0.10) was numerically higher with ticagrelor than with clopidogrel. Conclusions In patients with acute coronary syndrome initially intended for non-invasive management, the benefits of ticagrelor over clopidogrel were consistent with those from the overall PLATO results, indicating the broad benefits of P2Y12 inhibition with ticagrelor regardless of intended management strategy.
|
|
| 33. |
- James, Stefan, et al.
(författare)
-
Ticagrelor Versus Clopidogrel in Acute Coronary Syndromes in Relation to Renal Function Results From the Platelet Inhibition and Patient Outcomes (PLATO) Trial
- 2010
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 122:11, s. 1056-1067
-
Tidskriftsartikel (refereegranskat)abstract
- Background-Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates. Methods and Results-Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n = 3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n = 11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant. Conclusions-In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding.
|
|
| 34. |
|
|
| 35. |
|
|
| 36. |
- Mueller-Hennessen, Matthias, et al.
(författare)
-
Combined testing of copeptin and high-sensitivity cardiac troponin T at presentation in comparison to other algorithms for rapid rule-out of acute myocardial infarction
- 2019
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 276, s. 261-267
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to directly compare the diagnostic and prognostic performance of a dual maker strategy (DMS) with combined testing of copeptin and high-sensitivity (hs) cardiac troponin T (cTnT) at time of presentation with other algorithms for rapid rule-out of acute myocardial infarction (AMI).METHODS: 922 patients presenting to the emergency department with suspected AMI and available baseline copeptin measurements qualified for the present TRAPID-AMI substudy. Diagnostic measures using the DMS (copeptin <10, <14 or < 20 pmol/L and hs-cTnT≤14 ng/L), the 1 h-algorithm (hs-cTnT<12 ng/L and change <3 ng/L at 1 h), as well as the hs-cTnT limit-of-blank (LoB, <3 ng/L) and -detection (LoD, <5 ng/L) were compared. Outcomes were assessed as combined end-points of death and myocardial re-infarction.RESULTS: True-negative rule-out using the DMS could be achieved in 50.9%-62.3% of all patients compared to 35.0%, 45.3% and 64.5% using LoB, LoD or the 1 h-algorithm, respectively. The DMS showed NPVs of 98.1%-98.3% compared to 99.2% for the 1 h-algorithm, 99.4% for the LoB and 99.3% for the LoD. Sensitivities were 93.5%-94.8%, as well as 96.8%, 98.7% and 98.1%, respectively. Addition of clinical low-risk criteria such as a HEART-score ≤ 3 to the DMS resulted in NPVs and sensitivities of 100% with a true-negative rule-out to 33.8%-41.6%. Rates of the combined end-point of death/MI within 30 days ranged between 0.2% and 0.3% for all fast-rule-out protocols.CONCLUSION: Depending on the applied copeptin cut-off and addition of clinical low-risk criteria, the DMS might be an alternative to the hs-cTn-only-based algorithms for rapid AMI rule-out with comparable diagnostic measures and outcomes.
|
|
| 37. |
- Mueller-Hennessen, Matthias, et al.
(författare)
-
Diagnostic and prognostic implications using age- and gender-specific cut-offs for high-sensitivity cardiac troponin T - Sub-analysis from the TRAPID-AMI study
- 2016
-
Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 209, s. 26-33
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: To evaluate the impact of age-and gender-specific cut-offs for high-sensitivity cardiac troponin T (hs-cTnT) compared to the general 99th percentile hs-cTnT cut-off on diagnosis and prognosis of acute myocardial infarction (AMI).Methods: 1282 unselected patients presenting to the emergency department with suspected AMI were enrolled as part of the TRAPID-AMI study. In the present sub-analysis, reclassification of AMI diagnosis was performed by comparing the general hs-cTnT cut-off of 14 ng/L to previously proposed age-and gender-dependent hs-cTnT 99th percentile cut-offs (28 ng/L for >= 65 years, 9 ng/L for female and 15.5 ng/L for male patients). Patients were further clinically adjudicated into acute coronary syndrome (ACS) and non-ACS.Results: For patients >= 65 years, application of age-specified cut-offs resulted in a decrease of AMI from 29.8% to 18.3% in the entire cohort (n = 557) and 54.7% to 40.9% in the ACS subcohort (n = 225). Using gender-specific cut-offs, AMI-rate increased from 16.6% to 22.6% (entire cohort, n = 477) and 62.6% to 71.7% (ACS subcohort, n = 99) in women, whereas in men, rates decreased from 23.1% to 21.1% (entire cohort, n = 805) and 48.8% to 45.9% (ACS, n = 281), respectively. Age-specified cut-offs significantly reclassified patients for outcomes of 1-month and 3-month mortality in the entire and ACS cohort (14.2% net reclassification improvement, p < 0.001, respectively). Contrary, no significant differences in outcomes could be found using gender-specific cut-offs.Conclusions: While influence of gender-specific hs-cTnT cut-offs on diagnostic and prognostic reclassification was only modest in patients with suspected AMI, age-specific cut-offs showed a significant impact and may be considered for further validation.
|
|
| 38. |
|
|
| 39. |
- Tager, T, et al.
(författare)
-
Comparative efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) for cardiovascular outcomes in type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials
- 2021
-
Ingår i: Heart failure reviews. - : Springer Science and Business Media LLC. - 1573-7322 .- 1382-4147. ; 26:6, s. 1421-1435
-
Tidskriftsartikel (refereegranskat)abstract
- Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with type 2 diabetes mellitus (T2D). The comparative efficacy of individual SGLT2i remains unclear. We searched PubMed, www.clinicaltrials.gov and the Cochrane Central Register of Controlled Trials for randomised controlled trials exploring the use of canagliflozin, dapagliflozin, empagliflozin or ertugliflozin in patients with T2D. Comparators included placebo or any other active treatment. The primary endpoint was all-cause mortality. Secondary endpoints were cardiovascular mortality and worsening heart failure (HF). Evidence was synthesised using network meta-analysis (NMA). Sixty-four trials reporting on 74,874 patients were included. The overall quality of evidence was high. When compared with placebo, empagliflozin and canagliflozin improved all three endpoints, whereas dapagliflozin improved worsening HF. When compared with other SGLT2i, empagliflozin was superior for all-cause and cardiovascular mortality reduction. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Ertugliflozin had no effect on any of the three endpoints investigated. Sensitivity analyses including extension periods of trials or excluding studies with a treatment duration of < 52 weeks confirmed the main results. Similar results were obtained when restricting mortality analyses to patients included in cardiovascular outcome trials (n = 38,719). Empagliflozin and canagliflozin improved survival with empagliflozin being superior to the other SGLT2i. Empagliflozin, canagliflozin and dapagliflozin had similar effects on improving worsening HF. Prospective head-to-head comparisons would be needed to confirm these results.
|
|
| 40. |
|
|
| 41. |
- Wallentin, Lars, et al.
(författare)
-
Biomarkers in Relation to the Effects of Ticagrelor in Comparison With Clopidogrel in Non-ST-Elevation Acute Coronary Syndrome Patients Managed With or Without In-Hospital Revascularization A Substudy From the Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) Trial
- 2014
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 129:3, s. 293-303
-
Tidskriftsartikel (refereegranskat)abstract
- Background Risk stratification and the use of specific biomarkers have been proposed for tailoring treatment in patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). We investigated the prognostic importance of high-sensitivity troponin T (hs-TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP), and growth differentiation factor-15 (GDF-15) in relation to randomized treatment (ticagrelor versus clopidogrel) and management strategy (with or without revascularization) in the NSTE-ACS subgroup of the Platelet Inhibition and Patient Outcomes (PLATO) trial. Methods and Results Of 18 624 patients in the PLATO trial, 9946 had an entry diagnosis of NSTE-ACS and baseline blood samples available. During index hospitalization, 5357 were revascularized, and 4589 were managed without revascularization. Hs-TnT, NT-proBNP, and GDF-15 were determined and assessed according to predefined cutoff levels. Median follow-up was 9.1 months. Increasing levels of hs-TnT were associated with increasing risk of cardiovascular death, myocardial infarction, and stroke in medically managed patients (P<0.001), but not in those managed invasively. NT-proBNP and GDF-15 levels were associated with the same events independent of management strategy. Ticagrelor versus clopidogrel reduced the rate of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS and hs-TnT 14.0 ng/L in both invasively and noninvasively managed patients; in patients with hs-TnT <14.0 ng/L, there was no difference between ticagrelor and clopidogrel in the noninvasive group Conclusions Hs-TnT, NT-proBNP, and GDF-15 are predictors of cardiovascular death, myocardial infarction, and stroke in patients with NSTE-ACS managed noninvasively, and NT-proBNP and GDF-15 also in those managed invasively. Elevated hs-TnT predicts substantial benefit of ticagrelor over clopidogrel both in invasively and noninvasively managed patients, but no apparent benefit was seen at normal hs-TnT. Clinical Trial Registration URL:http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
|
|
| 42. |
- Wallentin, Lars, et al.
(författare)
-
Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes : a genetic substudy of the PLATO trial
- 2010
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 376:9749, s. 1320-1328
-
Tidskriftsartikel (refereegranskat)abstract
- Background In the PLATO trial of ticagrelor versus clopidogrel for treatment of acute coronary syndromes, ticagrelor reduced the composite outcome of cardiovascular death, myocardial infarction, and stroke, but increased events of major bleeding related to non-coronary artery bypass graft (CABG). CYP2C19 and ABCB1 genotypes are known to influence the effects of clopidogrel. In this substudy, we investigated the effects of these genotypes on outcomes between and within treatment groups. Methods DNA samples obtained from patients in the PLATO trial were genotyped for CYP2C19 loss-of-function alleles (*2, *3, *4, *5, *6, *7, and *8), the CYP2C19 gain-of-function allele *17, and the ABCB1 single nucleotide polymorphism 3435C -> T. For the CYP2C19 genotype, patients were stratified by the presence or absence of any loss-of-function allele, and for the ABCB1 genotype, patients were stratified by predicted gene expression (high, intermediate, or low). The primary efficacy endpoint was the composite of cardiovascular death, myocardial infarction, or stroke after up to 12 months' treatment with ticagrelor or clopidogrel. Findings 10 285 patients provided samples for genetic analysis. The primary outcome occurred less often with ticagrelor versus clopidogrel, irrespective of CYP2C19 genotype: 8.6% versus 11.2% (hazard ratio 0.77, 95% CI 0.60-0.99, p=0.0380) in patients with any loss-of-function allele; and 8.8% versus 10.0% (0.86, 0.74-1.01, p=0.0608) in those without any loss-of-function allele (interaction p=0.46). For the ABCB1 genotype, event rates for the primary outcome were also consistently lower in the ticagrelor than in the clopidogrel group for all genotype groups (interaction p=0.39; 8.8% vs 11.9%; 0.71, 0.55-0.92 for the high-expression genotype). In the clopidogrel group, the event rate at 30 days was higher in patients with than in those without any loss-of-function CYP2C19 alleles (5.7% vs 3.8%, p=0.028), leading to earlier separation of event rates between treatment groups in patients with loss-of-function alleles. Patients on clopidogrel who had any gain-of-function CYP2C19 allele had a higher frequency of major bleeding (11.9%) than did those without any gain-of-function or loss-of-function alleles (9.5%; p=0.022), but interaction between treatment and genotype groups was not significant for any type of major bleeding. Interpretation Ticagrelor is a more efficacious treatment for acute coronary syndromes than is dopidogrel, irrespective of CYP2C19 and ABCB1 polymorphisms. Use of ticagrelor instead of clopidogrel eliminates the need for presently recommended genetic testing before dual antiplatelet treatment.
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
- Åkerblom, Axel, et al.
(författare)
-
Outcome and causes of renal deterioration evaluated by serial cystatin C measurements in acute coronary syndrome patients : Results from the PLATelet inhibition and patient Outcomes (PLATO) study
- 2012
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 164:5, s. 728-734
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To investigate if ticagrelor treatment and other clinical characteristics were associated with increased cystatin C concentrations and if a deterioration in estimated renal function was associated with worse outcome in patients with acute coronary syndromes (ACS). Methods: Plasma cystatin C concentrations were determined within 24 hours of admission (baseline), at discharge, 1 month, and 6 months in the PLATO trial. The changes over time in relation to randomized treatment were analyzed by analysis of covariance. C-statistics and the relative Integrated Discrimination Improvement of the cystatin C concentrations regarding the primary outcome (cardiovascular death or myocardial infarction) was evaluated by multivariable analysis including background characteristics and biomarkers: N-terminal-pro-B-type natriuretic peptide and Troponin I. Results: Mean cystatin C concentrations in 2133 ticagrelor- and 2162 clopidogrel-treated patients were at baseline (0.86 mg/L and 0.86 mg/L), discharge (1.01 mg/L and 0.98 mg/L) (P <.0005), 1 month (1.00 mg/L and 0.98 mg/L) (P =.12), and 6 months (1.00 mg/L and 0.99 mg/L) (P =.17), respectively. Age, heart failure, and type of ACS were major determinants of the cystatin C concentration. c Statistics and the relative Integrated Discrimination Improvement of the primary outcome for the baseline cystatin C concentration were 0.687 and 5.2%, compared to 0.684 and 4.5% at discharge (n = 4034) and 0.693 and 5.1% at one month (n = 3096), respectively. Conclusions: Mean cystatin C concentrations increased in ACS patients, most importantly determined by age. The initial greater increase in ticagrelor-treated patients was not sustained over time. Risk prediction did not improve with serial measurements of renal markers.
|
|
| 46. |
|
|
