| 1. |
- Bassand, Jean-Pierre, et al.
(författare)
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Guía de Práctica Clínica para el diagnóstico y tratamiento del síndrome coronario agudo sin elevación del segmento ST
- 2007
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Ingår i: Revista Española de Cardiología. - 0300-8932 .- 1579-2242. ; 60:10, s. 1070-1080
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Tidskriftsartikel (refereegranskat)abstract
- El contenido de estas Guías de Práctica Clínica de la Sociedad Europea de Cardiología (ESC) ha sido publicado para uso exclusivamente personal y educativo. No está autorizado su uso comercial. No se permite la traducción o reproducción en ningún formato de las Guías de la ESC ni de ninguna de sus partes sin un permiso escrito de la ESC. El permiso puede obtenerse enviando una solicitud por escrito a Oxford University Press, la editorial del European Heart Journal, y parte autorizada para gestionar esos permisos en representación de la ESC.
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| 2. |
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| 3. |
- Cannon, Christopher P., et al.
(författare)
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Comparison of ticagrelor with clopidogrel in patients with a planned invasive strategy for acute coronary syndromes (PLATO) : a randomised double-blind study
- 2010
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Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 375:9711, s. 283-293
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Variation in and irreversibility of platelet inhibition with clopidogrel has led to controversy about its optimum dose and timing of administration in patients with acute coronary syndromes. We compared ticagrelor, a more potent reversible P2Y12 inhibitor with clopidogrel in such patients. METHODS: At randomisation, an invasive strategy was planned for 13 408 (72.0%) of 18 624 patients hospitalised for acute coronary syndromes (with or without ST elevation). In a double-blind, double-dummy study, patients were randomly assigned in a one-to-one ratio to ticagrelor and placebo (180 mg loading dose followed by 90 mg twice a day), or to clopidogrel and placebo (300-600 mg loading dose or continuation with maintenance dose followed by 75 mg per day) for 6-12 months. All patients were given aspirin. The primary composite endpoint was cardiovascular death, myocardial infarction, or stroke. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00391872. FINDINGS: 6732 patients were assigned to ticagrelor and 6676 to clopidogrel. The primary composite endpoint occurred in fewer patients in the ticagrelor group than in the clopidogrel group (569 [event rate at 360 days 9.0%] vs 668 [10.7%], hazard ratio 0.84, 95% CI 0.75-0.94; p=0.0025). There was no difference between clopidogrel and ticagrelor groups in the rates of total major bleeding (691 [11.6%] vs 689 [11.5%], 0.99 [0.89-1.10]; p=0.8803) or severe bleeding, as defined according to the Global Use of Strategies To Open occluded coronary arteries, (198 [3.2%] vs 185 [2.9%], 0.91 [0.74-1.12]; p=0.3785). INTERPRETATION: Ticagrelor seems to be a better option than clopidogrel for patients with acute coronary syndromes for whom an early invasive strategy is planned.
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| 4. |
- Franchi, Francesco, et al.
(författare)
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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
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 8:6
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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.
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| 5. |
- Kohli, Payal, et al.
(författare)
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Reduction in First and Recurrent Cardiovascular Events with Ticagrelor Compared with Clopidogrel in the PLATO Study
- 2013
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 127:6, s. 673-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:We sought to evaluate the effect of potent platelet inhibition following acute coronary syndrome on total (i.e. first and recurrent) occurrences of any of the primary outcome events (e.g. cardiovascular death, myocardial infarction, and stroke) as well as on other ischemic events, such as urgent revascularization, (severe) recurrent ischemia (SRI/RI), transient ischemic attacks (TIA) and arterial thrombotic events (ATE).METHODS AND RESULTS:In the PLATelet inhibition and patient Outcomes (PLATO) study, 18,624 patients presenting with acute coronary syndromes randomly received ticagrelor (N=9333) or clopidogrel (N=9291). Cox proportional hazard models were used to calculate time to first event and hazard ratios. Total events were compared using a Poisson regression model and time to second event or death was calculated with the Wei Lin Weissfeld method. Patients randomized to ticagrelor had 1057 total primary endpoint events vs. 1225 for patients on clopidogrel (rate ratio=0.86, 95% CI 0.79-0.93, p=0.003). The number of additional events was numerically lower for ticagrelor (189 vs. 205, p=0.40), resulting in a hazard for time to second event/death of 0.80 (95% CI 0.70-0.90, p<0.001) and a number needed to treat of 54. For CVD/MI/Stroke/SRI/RI/TIA/ATE, total events were fewer with ticagrelor (2030 vs. 2290, rate ratio 0.88, 95% CI 0.82-0.95, p<0.001), with fewer recurrent events with ticagrelor (740 vs. 834, p=0.01) and a highly significant concurrent reduction in hazard for time to second event or death of 0.83 (95% CI 0.75-0.91, p<0.001). Recurrent PLATO major or TIMI major non-CABG bleeding events were infrequent and not different between the two therapies (p=0.96 and 0.38, respectively).CONCLUSIONS: In PLATO, treatment with ticagrelor compared with clopidogrel resulted in a reduction in total events, including first and subsequent recurrent cardiovascular events, when compared to clopidogrel. These types of analyses demonstrate an even greater absolute benefit of ticagrelor over clopidogrel than previously reported.CLINICAL TRIAL REGISTRATION INFORMATION:http://www.clinicaltrials.gov. Identifier: NCT00391872.
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| 6. |
- Mahaffey, Kenneth W., et al.
(författare)
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Ticagrelor Effects on Myocardial Infarction and the Impact of Event Adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) Trial
- 2014
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 63:15, s. 1493-1499
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study sought to report the treatment effect of ticagrelor on myocardial infarction (MI) and the strategy for and impact of event adjudication in the PLATO (Platelet Inhibition and Patient Outcomes) trial. Background In PLATO, ticagrelor reduced cardiovascular death, MI, or stroke in patients with acute coronary syndromes (ACS). Methods A CIinical events committee (CEC) prospectively defined and adjudicated all suspected MI events, on the basis of events reported by investigators and by triggers on biomarkers. Treatment comparisons used CEC-adjudicated data, and per protocol, exCIuded silent MI. Results Overall, 1,299 (610 ticagrelor, 689 CIopidogrel) MIs reported by the CEC occurred during the trial. Of these, 1,097 (504 ticagrelor, 593 CIopidogrel) contributed to the primary composite endpoint. Site investigators reported 1,198 (580 ticagrelor, 618 CIopidogrel) MIs. Ticagrelor significantly reduced overall MI rates (12-month CEC-adjudicated Kaplan-Meier rates: 5.8% ticagrelor, 6.9% CIopidogrel; hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.75 to 0.95). Nonprocedural MI (HR: 0.86; 95% CI: 0.74 to 1.01) and MI related to percutaneous coronary intervention or stent thrombosis tended to be lower with ticagrelor. MIs related to coronary artery bypass graft surgery were few, but numerical excess was observed in patients assigned ticagrelor. Analyses of overall MIs using investigator-reported data showed similar results but did not reach statistical significance (HR: 0.88; 95% CI: 0.78 to 1.00). ConCIusions In patients with ACS, ticagrelor significantly reduced the incidence of MI compared with CIopidogrel, with consistent results across most MI subtypes. CEC procedures identified more MI endpoints compared with site investigators. (A Comparison of Ticagrelor [AZD6140] and CIopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872)
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| 7. |
- Patel, Riyaz S., et al.
(författare)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 8. |
- Patel, Riyaz S., et al.
(författare)
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Subsequent Event Risk in Individuals With Established Coronary Heart Disease : Design and Rationale of the GENIUS-CHD Consortium
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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| 9. |
- Steg, Philippe Gabriel, et al.
(författare)
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Ticagrelor Versus Clopidogrel in Patients With ST-Elevation Acute Coronary Syndromes Intended for Reperfusion With Primary Percutaneous Coronary Intervention A Platelet Inhibition and Patient Outcomes (PLATO) Trial Subgroup Analysis
- 2010
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 122:21, s. 2131-2141
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Tidskriftsartikel (refereegranskat)abstract
- Background-Aspirin and clopidogrel are recommended for patients with acute coronary syndromes (ACS) or undergoing coronary stenting. Ticagrelor, a reversible oral P2Y12-receptor antagonist, provides faster, greater, and more consistent platelet inhibition than clopidogrel and may be useful for patients with acute ST-segment elevation (STE) ACS and planned primary percutaneous coronary intervention. Methods and Result-Platelet Inhibition and Patient Outcomes (PLATO), a randomized, double-blind trial, compared ticagrelor with clopidogrel for the prevention of vascular events in 18 624 ACS patients. This report concerns the 7544 ACS patients with STE or left bundle-branch block allocated to either ticagrelor 180-mg loading dose followed by 90 mg twice daily or clopidogrel 300-mg loading dose (with provision for 300 mg clopidogrel at percutaneous coronary intervention) followed by 75 mg daily for 6 to 12 months. The reduction of the primary end point (myocardial infarction, stroke, or cardiovascular death) with ticagrelor versus clopidogrel (10.8% versus 9.4%; hazard ratio [HR], 0.87; 95% confidence interval, 0.75 to 1.01; P=0.07) was consistent with the overall PLATO results. There was no interaction between presentation with STE/left bundle-branch block and randomized treatment (interaction P=0.29). Ticagrelor reduced several secondary end points, including myocardial infarction alone (HR, 0.80; P=0.03), total mortality (HR, 0.82; P=0.05), and definite stent thrombosis (HR, 0.66; P=0.03). The risk of stroke, low in both groups, was higher with ticagrelor (1.7% versus 1.0%; HR, 1.63; 95% confidence interval, 1.07 to 2.48; P=0.02). Ticagrelor did not affect major bleeding (HR, 0.98; P=0.76). Conclusion-In patients with STE-ACS and planned primary percutaneous coronary intervention, the effects of ticagrelor were consistent with those observed in the overall PLATO trial.
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