| 131. |
- 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.
|
|
| 132. |
- Wood, David A., et al.
(författare)
-
Timing of Staged Nonculprit Artery Revascularization in Patients With ST-Segment Elevation Myocardial Infarction COMPLETE Trial
- 2019
-
Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 74:22, s. 2713-2723
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The COMPLETE (Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease After Early PCI for STEMI) trial demonstrated that staged nonculprit lesion percutaneous coronary intervention (PCI) reduced major cardiovascular (CV) events in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). OBJECTIVES The purpose of this study was to determine the effect of nonculprit-lesion PCI timing on major CV outcomes and also the time course of the benefit of complete revascularization. METHODS Following culprit-lesion PCI, 4,041 patients with STEMI and multivessel CAD were randomized to staged nonculprit-lesion PCI or culprit-lesion only PCI. Randomization was stratified according to investigator-planned timing of nonculprit-lesion PCI: during or after the index hospitalization. The first coprimary outcome was the composite of CV death or myocardial infarction (MI). In pre-specified analyses, hazard ratios (HRs) were calculated for each time stratum. Landmark analyses of the entire population were performed within 45 days and after 45 days. RESULTS For nonculprit-lesion PCI planned during the index hospitalization (actual time: median 1 day), CV death or MI was reduced with complete revascularization compared with culprit-lesion only PCI (HR: 0.77; 95% confidence interval [CI]: 0.59 to 1.00). For nonculprit lesion PCI planned to occur after hospital discharge (actual time: median 23 days), CV death or MI was also reduced with complete revascularization (HR: 0.69; 95% CI: 0.49 to 0.97; interaction p = 0.62). Landmark analyses demonstrated an HR of 0.86 (95% CI: 0.59 to 1.24) during the first 45 days and 0.69 (95% CI: 0.54 to 0.89) from 45 days to the end of follow-up for intended nonculprit lesion PCI versus culprit lesion only PCI. CONCLUSIONS Among STEMI patients with multivessel disease, the benefit of complete revascularization over culprit-lesion only PCI was consistent irrespective of the investigator-determined timing of nonculprit-lesion intervention. The benefit of complete revascularization on hard clinical outcomes emerged mainly over the long term. (C) 2019 by the American College of Cardiology Foundation.
|
|
| 133. |
- Åkerblom, Axel, 1977-, et al.
(författare)
-
Cystatin C- and Creatinine-based Estimates of Renal Function and Their Value for Risk Prediction in Patients with Acute Coronary Syndrome : Results from the PLATelet Inhibition and Patient Outcomes (PLATO) Study
- 2013
-
Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 59:9, s. 1369-1375
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The estimated glomerular filtration rate (eGFR) independently predicts cardiovascular (CV) death or myocardial infarction (MI), and can be estimated by creatinine and cystatin C concentrations. We evaluated two different cystatin C assays, alone or combined with creatinine, in patients with acute coronary syndromes.Methods: Plasma cystatin C, measured with assays from Gentian and Roche, and serum creatinine was analyzed in 16279 patients from the PLATelet inhibition and patient Outcomes trial. Pearson’s correlation and agreement (Bland–Altman) between methods was evaluated. Prognostic value in relation to CV death or MI during one year of follow up was evaluated by multivariable logistic regression analysis including clinical variables and biomarkers, c-statistics and relative Integrated Discrimination Improvement (IDI).Results: Median cystatin C concentrations (interquartile intervals) were 0.83 (0.68 - 1.01) mg/L (Gentian) and 0.94 (0.80 - 1.14) mg/L (Roche). Overall correlation was 0.86 (95% confidence interval 0.85-0.86). The level of agreement was ±0.39mg/L (±2 standard deviations) (n=16279).The area under curve (AUC) in the multivariable risk prediction model with cystatin C (Gentian, Roche) or Chronic Kidney Disease - Epidemiology (CKD-EPI) added was 0.6914, 0.6913 and 0.6932. Corresponding relative IDIs were 2.96%, 3.86% and 4.68%, respectively (n=13050). Addition of eGFR by the combined creatinine-cystatin C equation yielded AUC of 0.6923(Gentian) and 0.6924(Roche) with relative IDIs of 3.54% and 3.24% respectively.Conclusions: Despite differences in cystatin C concentrations, overall correlation between the Gentian and Roche assays was good while agreement was moderate. The combined creatinine-cystatin C equation did not outperform risk prediction compared to CKD-EPI.
|
|
| 134. |
- Åkerblom, Axel, 1977-, et al.
(författare)
-
Cystatin C and Estimated Glomerular Filtration Rate as Predictors for Adverse Outcome in Patients with ST-Elevation and Non-ST-Elevation Acute Coronary Syndromes : Results from the Platelet Inhibition and Patient Outcomes Study
- 2012
-
Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 58:1, s. 190-199
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:We evaluated the predictive ability of cystatin C and creatinine-based estimations of glomerular filtration rate (eGFR), including the Chronic Kidney Disease-Epidemiology (CKD-EPI) equation, in acute coronary syndrome (ACS) patients with (STE-ACS) or without (NSTE-ACS) ST elevation in a large contemporary ACS population.METHODS:Concentrations of cystatin C and creatinine, as well as eGFR at randomization, were measured in 16 401 patients in the Platelet Inhibition and Patient Outcomes (PLATO) study and evaluated as predictors of the composite end point of cardiovascular death or myocardial infarction within 1 year. Two Cox proportional hazards models were used, the first adjusting for clinical characteristics and the second for clinical characteristics plus the biomarkers N-terminal pro-B-type natriuretic peptide, troponin I, and C-reactive protein.RESULTS:The median cystatin C value was 0.83 mg/L. Increasing quartiles of cystatin C were strongly associated with poor outcome (6.9%, 7.1%, 9.5%, and 16.2%). The fully adjusted hazard ratios per SD of cystatin C in the NSTE-ACS and STE-ACS populations were 1.12 (95% CI 1.04-1.20) (n = 8053) and 1.06 (95% CI 0.97-1.17) (n = 5278), respectively. There was no significant relationship of cystatin C with type of ACS (STE or NSTE). c Statistics ranged from 0.6923 (cystatin C) to 0.6941 (CKD-EPI).CONCLUSIONS:Cystatin C concentration contributes independently in predicting the risk of cardiovascular death or myocardial infarction in NSTE-ACS, with no interaction by type of ACS. CKD-EPI exhibited the largest predictive value of all renal markers. Nevertheless, the additive predictive value of cystatin C or creatinine-based eGFR measures in the unselected ACS patient is small.
|
|
| 135. |
|
|
| 136. |
- Åkerblom, Axel, et al.
(författare)
-
Interleukin-18 in patients with acute coronary syndromes.
- 2019
-
Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 42:12, s. 1202-1209
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We aimed to assess associations between circulating IL-18 concentrations and cardiovascular outcomes in patients with acute coronary syndromes (ACS).HYPOTHESIS AND METHODS: Plasma IL-18 concentrations were measured at admission, discharge, 1 month, and 6 months in patients with ACS in the PLATelet inhibition and patient Outcomes (PLATO) trial. Associations with outcomes were evaluated with Cox regression models on the composite of CV death, spontaneous myocardial infarction (sMI), or stroke; and on CV death or sMI separately, including adjustment for clinical risk factors and biomarkers (cTnT-hs, NT-proBNP, cystatin C, CRP-hs, and GDF-15).RESULTS: Median IL-18 concentrations at baseline, discharge, 1 month, and 6 months were 237, 283, 305, and 320 ng/L (n = 16 636). Male sex, obesity, diabetes, and plasma levels of cystatin C, GDF-15, and CRP-hs were independently associated with higher IL-18 levels. Higher baseline IL-18 levels were associated with the composite endpoint and with CV death (hazard ratio [HR] 1.05, 95% confidence interval [95% CI] 1.02-1.07 and HR 1.10, 95% CI 1.06-1.14, respectively, per 25% increase of IL-18 levels). Associations remained significant after adjustment for clinical variables but became non-significant after adjustment for all biomarkers (HR 1.01, 95% CI 0.98-1.04 and HR 1.04, 95% CI 1.00-1.08, respectively). There were no associations with sMI.CONCLUSIONS: In ACS patients, IL-18 concentrations increased after the acute event and remained increased for 6 months. Baseline IL-18 levels were significantly associated with CV mortality, independent of clinical characteristics and indicators of renal/cardiac dysfunction but this association was attenuated after adjustment for multiple biomarkers.
|
|
| 137. |
- Åkerblom, Axel, 1977-, et al.
(författare)
-
Polymorphism of the cystatin C gene in patients with acute coronary syndromes : Results from the PLATelet Inhibition and Patient Outcomes (PLATO) Study
- 2014
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 168:1, s. 96-102
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose: Plasma cystatin C is independently associated with cardiovascular (CV) risk in non-ST-elevation acute coronary syndromes (NSTE-ACS). The effect of genetic variability on cystatin C concentrations and outcome is unclear.Methods: Plasma cystatin C concentrations were measured in blood, obtained within 24 hours of admission, in 16279 ACS patients from the PLATelet inhibition and patient Outcomes trial. 9978 patients were genome-wide genotyped with up to 2.5 million SNPs. The first occurrence of CV death or myocardial infarction (MI) within one year was evaluated by multivariable (clinical variables and biomarkers) Cox regression analysis and c-statistics both overall (all ACS) and in NSTE-ACS.Results: We observed SNPs association with cystatin C levels (up to p=7.82 x 10-16). The most significant SNP (rs6048952) was adjacent the CST3 gene with additive effect on cystatin C concentrations: 0.85mg/L, 0.80mg/L and 0.73mg/L for the A/A, A/G and G/G genotypes respectively. Multivariable c-statistics regarding the combined endpoint (CV death or MI) was 0.6619. Adding cystatin C concentrations or genetically adjusted cystatin C levels, exhibited c-statistics of 0.6705 and 0.6703, respectively.The overall hazard ratio for rs6048952 was 0.93 (95%CI 0.82-1.04) regarding the CV death or MI while 0.85 (95%CI 0.70-1.03) regarding CV death in all ACS patients. In the NSTE-ACS subgroup, the hazard ratio for rs6048952 was 0.72 (95%CI 0.54-0.95).Conclusions: Genetic polymorphism, independently of kidney function, affects cystatin C concentrations, but does not appear to influence ischemic outcome in an overall ACS population. However, genetic variation appears to affect cardiovascular mortality in moderate-to-high risk NSTE-ACS patients.
|
|
| 138. |
- Åkerblom, Axel, 1977-, et al.
(författare)
-
Prevalence and relevance of abnormal glucose metabolism in acute coronary syndromes : insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
- 2019
-
Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer. - 0929-5305 .- 1573-742X. ; 48:4, s. 563-569
-
Tidskriftsartikel (refereegranskat)abstract
- Diabetes mellitus (DM) and abnormal glucose metabolism are associated with cardiovascular (CV) disease. We investigated the prevalence and prognostic importance of dysglycaemia in patients with acute coronary syndromes (ACS) in the PLATelet inhibition and patient Outcomes (PLATO) trial. Diabetes was defined as known diabetes or HbA1c >= 6.5% or non-fasting glucose >= 11.1 mmol/L on admission, prediabetes as HbA1c >= 5.7% but < 6.5%, and no diabetes as HbA1c < 5.7%. The primary endpoint was the composite of CV death, spontaneous myocardial infarction type 1 (sMI) or stroke at 12 months. Multivariable Cox regression models, adjusting for baseline characteristics, and biomarkers NT-proBNP and troponin I, were used to explore the association between glycaemia and outcome. On admission, 16,007 (86.1%) patients had HbA1c and/or glucose levels available and were subdivided into DM 38.5% (6160) (1501 patients had no previous DM diagnosis), prediabetes 38.8% (6210), and no DM 22.7% (3637). Kaplan Meier event rates at 12 months for CV death, sMI or stroke per subgroups were 14.5% (832), 9.0% (522), and 8.5% (293), respectively with multivariable adjusted HRs, versus no diabetes, for diabetes: 1.71 (1.50-1.95) and for prediabetes 1.03 (0.90-1.19). Corresponding event rates for CV death were 6.9% (391), 3.4% (195) and 3.0% (102), respectively, with adjusted HRs for patients with DM of: 1.92 (1.42-2.60) and for prediabetes 1.02 (0.79-1.32). Abnormal glucose metabolism is common in ACS patients, but only patients with definite DM have an increased CV risk, indicating that prediabetes is not immediately associated with worse CV outcomes.
|
|
| 139. |
- Åkerblom, Axel, 1977-, et al.
(författare)
-
Ticagrelor in patients with heart failure after acute coronary syndromes - Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
- 2019
-
Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 213, s. 57-65
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Heart failure (HF) following acute coronary syndromes (ACS) is associated with worse prognosis; however, the efficacy and safety of ticagrelor in patients with HF and if ticagrelor influences the risk of new-onset HF are unknown.Methods: We examined the efficacy and safety of ticagrelor compared to clopidogrel in patients with ACS in the randomized PLATelet inhibition and patient Outcomes (PLATO) trial subdivided by strata: (1) previous HF and/or clinical signs of HF on admission or (2) no HF on admission. The primary outcome was the combination of cardiovascular death, myocardial infarction, or stroke evaluated by multivariable Cox regression models. The safety outcome was major bleeding. New-onset HF was defined as an HF event after discharge in patients without previous HF.Results: Data were available in 18,556 patients, whom 2,862 (15.4%) patients had HF, including 1,584 (8.5%) patients with previous HF. Patients randomized to ticagrelor had lower risk of the composite end point regardless of HF status: hazard ratio (HR) 0.87 (95% CI: 0.73-1.03) in patients with HF and HR 0.84 (95% CI: 0.75-0.93) in patients with no HF (P = .76). Corresponding HR for major bleeding were HR 1.08 (95% CI: 0.87-1.34) and HR 1.03 (95% CI: 0.94-1.14) (P = .71). There was no difference in new-onset HF at 12 months between patients randomized to ticagrelor (4.1%, n = 278) or clopidogrel (4.0%, n = 276).Conclusions: In patients with ACS, ticagrelor is more efficacious in protecting against new ischemic events and mortality than clopidogrel irrespective of the presence of HF. There is no difference between ticagrelor or clopidogrel treatment in new-onset HF post-ACS.
|
|
