| 1. |
- Fabris, Enrico, et al.
(författare)
-
Clinical impact and predictors of complete ST segment resolution after primary percutaneous coronary intervention : A subanalysis of the ATLANTIC Trial
- 2019
-
Ingår i: European Heart Journal. - : Sage Publications. - 2048-8726 .- 2048-8734. ; 8:3, s. 208-217
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In the ATLANTIC (Administration of Ticagrelor in the catheterization laboratory or in the Ambulance for New ST elevation myocardial Infarction to open the Coronary artery) trial the early use of aspirin, anticoagulation, and ticagrelor coupled with very short medical contact-to-balloon times represent good indicators of optimal treatment of ST-elevation myocardial infarction and an ideal setting to explore which factors may influence coronary reperfusion beyond a well-established pre-hospital system.METHODS: This study sought to evaluate predictors of complete ST-segment resolution after percutaneous coronary intervention in ST-elevation myocardial infarction patients enrolled in the ATLANTIC trial. ST-segment analysis was performed on electrocardiograms recorded at the time of inclusion (pre-hospital electrocardiogram), and one hour after percutaneous coronary intervention (post-percutaneous coronary intervention electrocardiogram) by an independent core laboratory. Complete ST-segment resolution was defined as ≥70% ST-segment resolution.RESULTS: Complete ST-segment resolution occurred post-percutaneous coronary intervention in 54.9% ( n=800/1456) of patients and predicted lower 30-day composite major adverse cardiovascular and cerebrovascular events (odds ratio 0.35, 95% confidence interval 0.19-0.65; p<0.01), definite stent thrombosis (odds ratio 0.18, 95% confidence interval 0.02-0.88; p=0.03), and total mortality (odds ratio 0.43, 95% confidence interval 0.19-0.97; p=0.04). In multivariate analysis, independent negative predictors of complete ST-segment resolution were the time from symptoms to pre-hospital electrocardiogram (odds ratio 0.91, 95% confidence interval 0.85-0.98; p<0.01) and diabetes mellitus (odds ratio 0.6, 95% confidence interval 0.44-0.83; p<0.01); pre-hospital ticagrelor treatment showed a favorable trend for complete ST-segment resolution (odds ratio 1.22, 95% confidence interval 0.99-1.51; p=0.06).CONCLUSIONS: This study confirmed that post-percutaneous coronary intervention complete ST-segment resolution is a valid surrogate marker for cardiovascular clinical outcomes. In the current era of ST-elevation myocardial infarction reperfusion, patients' delay and diabetes mellitus are independent predictors of poor reperfusion and need specific attention in the future.
|
|
| 2. |
- 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.
|
|
| 3. |
- Kessler, Thorsten, et al.
(författare)
-
Association of the coronary artery disease risk gene GUCY1A3 with ischaemic events after coronary intervention
- 2019
-
Ingår i: Cardiovascular Research. - : OXFORD UNIV PRESS. - 0008-6363 .- 1755-3245. ; 115:10, s. 1512-1518
-
Tidskriftsartikel (refereegranskat)abstract
- Aim A common genetic variant at the GUCY1A3 coronary artery disease locus has been shown to influence platelet aggregation. The risk of ischaemic events including stent thrombosis varies with the efficacy of aspirin to inhibit platelet reactivity. This study sought to investigate whether homozygous GUCY1A3 (rs7692387) risk allele carriers display higher on-aspirin platelet reactivity and risk of ischaemic events early after coronary intervention. Methods and results The association of GUCY1A3 genotype and on-aspirin platelet reactivity was analysed in the genetics substudy of the ISAR-ASPI registry (n = 1678) using impedance aggregometry. The clinical outcome cardiovascular death or stent thrombosis within 30 days after stenting was investigated in a meta-analysis of substudies of the ISAR-ASPI registry, the PLATO trial (n = 3236), and the Utrecht Coronary Biobank (n = 1003) comprising a total 5917 patients. Homozygous GUCY1A3 risk allele carriers (GG) displayed increased on-aspirin platelet reactivity compared with non-risk allele (AA/AG) carriers [150 (interquartile range 91-209) vs. 134 (85-194) AU.min, P < 0.01]. More homozygous risk allele carriers, compared with non-risk allele carriers, were assigned to the high-risk group for ischaemic events (>203AU.min; 29.5 vs. 24.2%, P = 0.02). Homozygous risk allele carriers were also at higher risk for cardiovascular death or stent thrombosis (hazard ratio 1.70, 95% confidence interval 1.08-2.68; P = 0.02). Bleeding risk was not altered. Conclusion We conclude that homozygous GUCY1A3 risk allele carriers are at increased risk of cardiovascular death or stent thrombosis within 30 days after coronary stenting, likely due to higher on-aspirin platelet reactivity. Whether GUCY1A3 genotype helps to tailor antiplatelet treatment remains to be investigated.
|
|
| 4. |
- Lip, Gregory Y.H., et al.
(författare)
-
2018 Joint European consensus document on the management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous cardiovascular interventions : a joint consensus document of the European Heart Rhythm Association (EHRA), European Society of Cardiology Working Group on Thrombosis, European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA)
- 2019
-
Ingår i: Europace. - : Oxford University Press (OUP). - 1099-5129 .- 1532-2092. ; 21:2, s. 192-
-
Tidskriftsartikel (refereegranskat)abstract
- In 2014, a joint consensus document dealing with the management of antithrombotic therapy in atrial fibrillation (AF) patients presenting with acute coronary syndrome (ACS) and/or undergoing percutaneous coronary or valve interventions was published, which represented an effort of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Since publication of this document, additional data from observational cohorts, randomized controlled trials, and percutaneous interventions as well as new guidelines have been published. Moreover, new drugs and devices/interventions are also available, with an increasing evidence base. The approach to managing AF has also evolved towards a more integrated or holistic approach. In recognizing these advances since the last consensus document, EHRA, WG Thrombosis, EAPCI, and ACCA, with additional contributions from HRS, APHRS, Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA), proposed a focused update, to include the new data, with the remit of comprehensively reviewing the available evidence and publishing a focused update consensus document on the management of antithrombotic therapy in AF patients presenting with ACS and/or undergoing percutaneous coronary or valve interventions, and providing up-to-date consensus recommendations for use in clinical practice.
|
|
| 5. |
- Andersen, Thomas, et al.
(författare)
-
C-X-C Ligand 16 Is an Independent Predictor of Cardiovascular Death and Morbidity in Acute Coronary Syndromes
- 2019
-
Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 39:11, s. 2402-2410
-
Tidskriftsartikel (refereegranskat)abstract
- Objective:The chemokine CXCL16 (C-X-C motif ligand 16) is a scavenger receptor for OxLDL (oxidized low-density lipoproteins) and involved in inflammation at sites of atherosclerosis. This study aimed to investigate the association of CXCL16 with clinical outcome in patients with acute coronary syndrome.Approach and Results:Serial measurements of CXCL16 were performed in a subgroup of 5142 patients randomized in the PLATO trial (Platelet Inhibition and Patient Outcome). Associations between CXCL16 and a composite of cardiovascular death, spontaneous myocardial infarction or stroke, and the individual components were assessed by multivariable Cox regression analyses. The hazard ratio per 50% increase in admission levels of CXCL16 analyzed as continuous variable was 1.64 (95% CI, 1.44-1.88), P<0.0001. This association remained statistically significant after adjustment for randomized treatment, clinical variables, CRP (C-reactive protein), leukocytes, cystatin C, NT-proBNP (N-terminal pro-brain natriuretic peptide), troponin T, GDF-15 (growth differentiation factor 15), and other biomarkers; hazard ratio 1.23 (1.05-1.45), P=0.0126. The admission level of CXCL16 was independently associated with cardiovascular death (1.50 [1.17-1.92], P=0.0014) but not with ischemic events alone, in fully adjusted analyses. No statistically independent association was found between CXCL16 measured at 1 month, or change in CXCL16 from admission to 1 month, and clinical outcomes.Conclusions:In patients with acute coronary syndrome, admission level of CXCL16 is independently related to adverse clinical outcomes, mainly driven by an association to cardiovascular death. Thus, CXCL16 measurement may enhance risk stratification in patients with this condition.
|
|
| 6. |
- Dellborg, Mikael, 1954, et al.
(författare)
-
Efficacy and safety with ticagrelor in patients with prior myocardial infarction in the approved European label: insights from PEGASUS-TIMI 54.
- 2019
-
Ingår i: European heart journal. Cardiovascular pharmacotherapy. - : Oxford University Press (OUP). - 2055-6845 .- 2055-6837. ; 5:4, s. 200-206
-
Tidskriftsartikel (refereegranskat)abstract
- In PEGASUS-TIMI 54, ticagrelor significantly reduced the risk of the composite of major adverse cardiovascular (CV) events by 15-16% in stable patients with a prior myocardial infarction (MI) 1-3years earlier. We report the efficacy and safety in the subpopulation recommended for treatment in the European (EU) label, i.e. treatment with 60mg b.i.d. initiated up to 2years from the MI, or within 1 year after stopping previous adenosine diphosphate receptor inhibitor treatment.Of the 21162 patients enrolled in PEGASUS-TIMI 54, 10779 patients were included in the primary analysis for this study, randomized to ticagrelor 60mg (n=5388) or matching placebo (n=5391). The cumulative proportions of patients with events at 36months were calculated by the Kaplan-Meier (KM) method. The composite of CV death, MI, or stroke occurred less frequently in the ticagrelor group (7.9% KM rate vs. 9.6%), hazard ratio (HR) 0.80 [95% confidence interval (CI) 0.70-0.91; P=0.001]. Ticagrelor also reduced the risk of all-cause mortality, HR 0.80 (0.67-0.96; P=0.018). Thrombolysis in myocardial infarction major bleeding was more frequent in the ticagrelor group 2.5% vs. 1.1%; HR 2.36 (1.65-3.39; P<0.001). The corresponding HR for fatal or intracranial bleeding was 1.17 (0.68-2.01; P=0.58).In PEGASUS-TIMI 54, treatment with ticagrelor 60mg as recommended in the EU label, was associated with a relative risk reduction of 20% in CV death, MI, or stroke. Thrombolysis in myocardial infarction major bleeding was increased, but fatal or intracranial bleeding was similar to placebo. There appears to be a favourable benefit-risk ratio for long-term ticagrelor 60mg in this population.http://www.clinicaltrials.gov NCT01225562.
|
|
| 7. |
- Fabris, Enrico, et al.
(författare)
-
Pre-hospital administration of ticagrelor in diabetic patients with ST-elevation myocardial infarction undergoing primary angioplasty : A sub-analysis of the ATLANTIC trial
- 2019
-
Ingår i: Catheterization and cardiovascular interventions. - : John Wiley & Sons. - 1522-1946 .- 1522-726X. ; 93:7, s. E369-E377
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated, in the contemporary era of ST-elevation myocardial infarction (STEMI) treatment, the influence of diabetes mellitus (DM) on cardiovascular outcomes, and whether pre-hospital administration of ticagrelor may affect these outcomes in a subgroup of STEMI patients with DM.BACKGROUND: DM patients have high platelet reactivity and a prothrombotic condition which highlight the importance of an effective antithrombotic regimen in this high-risk population.METHODS: In toal 1,630 STEMI patients enrolled in the ATLANTIC trial who underwent primary percutaneous coronary intervention (PCI) were included. Multivariate analysis was used to explore the association of DM with outcomes and potential treatment-by-diabetes interaction was tested.RESULTS: A total of 214/1,630 (13.1%) patients had DM. DM was an independent predictor of poor myocardial reperfusion as reflected by less frequent ST-segment elevation resolution (≥70%) after PCI (OR 0.59, 95% CI 0.43-0.82, P < 0.01) and was an independent predictor of the composite 30-day outcomes of death/new myocardial infarction (MI)/urgent revascularization/definite stent thrombosis (ST) (OR 2.80, 95% CI 1.62-4.85, P < 0.01), new MI or definite acute ST (OR 2.46, 95% CI 1.08-5.61, P = 0.03), and definite ST (OR 10.00, 95% CI 3.54-28.22, P < 0.01). No significant interaction between pre-hospital ticagrelor vs in-hospital ticagrelor administration and DM was present for the clinical, electrocardiographic and angiographic outcomes as well as for thrombolysis in myocardial infarction major bleeding.CONCLUSIONS: DM remains independently associated with poor myocardial reperfusion and worse 30-day clinical outcomes. No significant interaction was found between pre-hospital vs in-hospital ticagrelor administration and DM status. Further approaches for the treatment of DM patients are needed.CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.
|
|
| 8. |
- Lapostolle, Frédéric, et al.
(författare)
-
Morphine and Ticagrelor Interaction in Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction : ATLANTIC-Morphine
- 2019
-
Ingår i: American Journal of Cardiovascular Drugs. - Auckland, New Zealand : Adis International Ltd.. - 1175-3277 .- 1179-187X. ; 19, s. 173-183
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Morphine adversely impacts the action of oral adenosine diphosphate (ADP)-receptor blockers in ST-segment elevation myocardial infarction (STEMI) patients, and is possibly associated with differing patient characteristics. This retrospective analysis investigated whether interaction between morphine use and pre-percutaneous coronary intervention (pre-PCI) ST-segment elevation resolution in STEMI patients in the ATLANTIC study was associated with differences in patient characteristics and management.METHODS: ATLANTIC was an international, multicenter, randomized study of treatment in the acute ambulance/hospital setting where STEMI patients received ticagrelor 180 mg ± morphine. Patient characteristics, cardiovascular history, risk factors, management, and outcomes were recorded.RESULTS: Opioids (97.6% morphine) were used in 921 out of 1862 patients (49.5%). There were no significant differences in age, sex or cardiovascular history, but more morphine-treated patients had anterior myocardial infarction and left-main disease. Time from chest pain to electrocardiogram and ticagrelor loading was shorter with morphine (both p = 0.01) but not total ischemic time. Morphine-treated patients more frequently received glycoprotein IIb/IIIa inhibitors (p = 0.002), thromboaspiration and stent implantation (both p < 0.001). No significant difference between the two groups was found regarding pre-PCI ≥ 70% ST-segment elevation resolution, death, myocardial infarction, stroke, urgent revascularization and definitive acute stent thrombosis. More morphine-treated patients had an absence of pre-PCI Thrombolysis in Myocardial Infarction (TIMI) 3 flow (85.8% vs. 79.7%; p = 0.001) and more had TIMI major bleeding (1.1% vs. 0.1%; p = 0.02).CONCLUSIONS: Morphine-treatment was associated with increased GP IIb/IIIa inhibitor use, less pre-PCI TIMI 3 flow, and more bleeding. Judicious morphine use is advised with non-opioid analgesics preferred for non-severe acute pain.TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01347580.
|
|
| 9. |
- Lopes, Renato D., et al.
(författare)
-
Antithrombotic Therapy after Acute Coronary Syndrome or PCI in Atrial Fibrillation
- 2019
-
Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 380:16, s. 1509-1524
-
Tidskriftsartikel (refereegranskat)abstract
- Background Appropriate antithrombotic regimens for patients with atrial fibrillation who have an acute coronary syndrome or have undergone percutaneous coronary intervention (PCI) are unclear. Methods In an international trial with a two-by-two factorial design, we randomly assigned patients with atrial fibrillation who had an acute coronary syndrome or had undergone PCI and were planning to take a P2Y(12) inhibitor to receive apixaban or a vitamin K antagonist and to receive aspirin or matching placebo for 6 months. The primary outcome was major or clinically relevant nonmajor bleeding. Secondary outcomes included death or hospitalization and a composite of ischemic events. Results Enrollment included 4614 patients from 33 countries. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. Major or clinically relevant nonmajor bleeding was noted in 10.5% of the patients receiving apixaban, as compared with 14.7% of those receiving a vitamin K antagonist (hazard ratio, 0.69; 95% confidence interval [CI], 0.58 to 0.81; P<0.001 for both noninferiority and superiority), and in 16.1% of the patients receiving aspirin, as compared with 9.0% of those receiving placebo (hazard ratio, 1.89; 95% CI, 1.59 to 2.24; P<0.001). Patients in the apixaban group had a lower incidence of death or hospitalization than those in the vitamin K antagonist group (23.5% vs. 27.4%; hazard ratio, 0.83; 95% CI, 0.74 to 0.93; P=0.002) and a similar incidence of ischemic events. Patients in the aspirin group had an incidence of death or hospitalization and of ischemic events that was similar to that in the placebo group. Conclusions In patients with atrial fibrillation and a recent acute coronary syndrome or PCI treated with a P2Y(12) inhibitor, an antithrombotic regimen that included apixaban, without aspirin, resulted in less bleeding and fewer hospitalizations without significant differences in the incidence of ischemic events than regimens that included a vitamin K antagonist, aspirin, or both.
|
|
| 10. |
- 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
- 2019
-
Ingår i: Platelets. - : Informa UK Limited. - 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.
|
|
