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- Armstrong, Paul W., et al.
(författare)
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Quantitative ST-depression in Acute Coronary Syndromes : the PLATO Electrocardiographic Substudy
- 2013
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Ingår i: American Journal of Medicine. - : Elsevier BV. - 0002-9343 .- 1555-7162. ; 126:8, s. 723-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We evaluated whether electrocardiogram (ECG) characteristics were aligned with clinical outcomes and the effect of ticagrelor within the diverse spectrum of non-ST-elevation acute coronary syndrome patients enrolled in the PLATelet inhibition and patient Outcomes (PLATO) trial. METHODS: There were 8884 PLATO patients who had baseline ECGs assessed by a core laboratory; of these, 4935 had an ECG at hospital discharge that also was assessed. Associations with study treatment on vascular death or myocardial infarction within 1 year were examined. RESULTS: At baseline, most patients had either no or <= 0.5 mm of ST-segment depression (57%); 26% had 1.0 mm, and 17% had more extensive depression (>1.0 mm). Across the baseline ST-segment depression strata, there was a consistent treatment benefit with ticagrelor versus clopidogrel on vascular death/myocardial infarction. The extent of residual ST-segment depression at discharge was similar in the treatment groups, and the treatment effect did not differ by the extent of discharge ST-segment depression. There was a progressive increase in vascular death/myocardial infarction with increasing extent of baseline ST-segment depression (1.0 mm [vs no/0.5 mm]: hazard ratio [HR] 1.22; 95% confidence interval [CI], 1.03-1.45; > 1.0 mm: HR 1.49; 95% CI, 1.24-1.78; P < .001) and at discharge (HR 1.28; 95% CI, 1.02-1.61; HR 2.13; 95% CI, 1.54-2.95; P <. 001). CONCLUSION: The treatment effect of ticagrelor among non-ST-segment-elevation acute coronary syndrome patients was consistently expressed across all baseline ST-segment depression strata. There was no indication of an anti-ischemic benefit of ticagrelor as reflected on the discharge ECG. Our data affirm the independent prognostic relationship of both baseline and hospital discharge ST-segment depression on outcomes within 1 year in non-ST-segment-elevation acute coronary syndrome patients.
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| 4. |
- Kunadian, Vijay, et al.
(författare)
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Angiographic Outcomes in the PLATO Trial (Platelet Inhibition and Patient Outcomes)
- 2013
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Ingår i: JACC-CARDIOVASCULAR INTERVENTIONS. - : Elsevier BV. - 1936-8798. ; 6:7, s. 671-683
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The PLATO (Platelet Inhibition and Patient Outcomes) angiographic substudy sought to compare the efficacy of ticagrelor versus clopidogrel with respect to angiographic outcomes before and after PCI in the setting of acute coronary syndrome. Background Greater platelet inhibition has been associated with improved angiographic outcomes before and after percutaneous coronary intervention (PCI). Therefore, it was hypothesized that treatment with ticagrelor, which achieves more rapid, higher, and more consistent platelet inhibition, would be associated with improved angiographic outcomes when compared with those of clopidogrel treatment. Methods The angiographic cohort consists of 2,616 patients drawn from the 18,624-patient PLATO trial. Clopidogrel naive or pre-treated patients were randomized to 180 mg of ticagrelor or 300 mg of clopidogrel (75 mg for clopidogrel pre-treated patients). PCI patients were administered, as per treatment group: 1) an additional 90 mg of ticagrelor if >24 h following the initial loading dose; or 2) an optional further 300 mg of clopidogrel or placebo (total 600 mg) prior to PCI. The substudy primary endpoint was the incidence of post-PCI TIMI (Thrombolysis In Myocardial Infarction) myocardial perfusion grade 3 (TMPG 3) among patients who received a study drug prior to PCI. Results In total, 21.3% of patients were pretreated with clopidogrel prior to randomization. There was a short time interval between randomization and PCI (median: 0.68 [interquartile range (IQR): 0.30 to 2.21] h) among all patients. Post-PCI TMPG 3 was similar between the ticagrelor and clopidogrel groups (47.1% vs. 46.9%; p = 0.96). Likewise, the following pre-PCI outcomes were similar in the ticagrelor and clopidogrel groups, respectively: TMPG 3 (30.5% vs. 31.2%), TIMI flow grade 3 (37.1% vs. 39.3%), corrected TIMI frame count (median: 100 vs. 71 frames), TIMI thrombus grade 0 (24.1% vs. 27.6%), minimum lumen diameter (median: 0.3 [IQR: 0.0 to 0.6] vs. 0.3 [IQR: 0.0 to 0.6] mm) and percentage of diameter stenosis (median: 89 [IQR: 78 to 100] vs. 89 [IQR: 77 to 100]). Conclusions Neither coronary flow nor myocardial perfusion, evaluated on coronary angiograms performed before or following PCI procedures within a few hours after the start of oral antiplatelet treatment in the setting of acute coronary syndromes, demonstrated a difference with ticagrelor versus clopidogrel. (A Comparison of Ticagrelor [AZD6140] and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872)
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| 5. |
- Steg, P. Gabriel, et al.
(författare)
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Stent Thrombosis With Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes : An Analysis From the Prospective, Randomized PLATO Trial
- 2013
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 128:10, s. 1055-1065
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Tidskriftsartikel (refereegranskat)abstract
- Background We aimed to describe the effects of ticagrelor versus clopidogrel on stent thrombosis in the Platelet Inhibition and Patient Outcomes (PLATO) trial. Methods and Results Of 18624 patients hospitalized for acute coronary syndromes, 11289 (61%) had at least 1 intracoronary stent. Ticagrelor reduced stent thrombosis compared with clopidogrel across all definitions: definite, 1.37% (n=71) versus 1.93% (n=105; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.50-0.90; P=0.0091); definite or probable, 2.21% (n=118) versus 2.87% (n=157; HR, 0.75; 95% CI, 0.59-0.95; P=0.017); and definite, probable, and possible, 2.94% (n=154) versus 3.77 (n=201; HR, 0.77; 95% CI, 0.62-0.95). The reduction in definite stent thrombosis was consistent regardless of acute coronary syndrome type, presence of diabetes mellitus, stent type (drug-eluting or bare metal stent), CYP2C19 genetic status, loading dose of aspirin, dose of clopidogrel before randomization, and use of glycoprotein IIb/IIIa inhibitors at randomization. The reduction in stent thrombosis with ticagrelor was numerically greater for late (>30 days; HR, 0.48; 95% CI, 0.24-0.96) and subacute (4 hours-30 days; HR, 0.60; 95% CI, 0.39-0.93) compared with acute (<24 hours; HR, 0.94; 95% CI, 0.43-2.05) stent thrombosis or for patients compliant to therapy (ie, taking blinded study treatment 80% of the time) compared with less compliant patients. Randomization to ticagrelor was a strong independent inverse predictor of definite stent thrombosis (HR, 0.65; 95% CI, 0.48-0.88). Conclusion Ticagrelor compared with clopidogrel reduces the incidence of stent thrombosis in patients with acute coronary syndromes, with consistent benefit across a broad range of patient, stent, and treatment characteristics. Clinical Trial Registration URL: . Unique identifier: NCT00391872.
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| 9. |
- 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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| 10. |
- Levin, Lars-Åke, et al.
(författare)
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Health-Related Quality of Life of Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes-Results from the PLATO Trial
- 2013
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Ingår i: Value in Health. - : Wiley-Blackwell: No OnlineOpen / Elsevier. - 1098-3015 .- 1524-4733. ; 16:4, s. 574-580
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to compare the effects of ticagrelor versus clopidogrel on health-related quality of life in the PLATelet inhibition and patient Outcomes (PLATO) trial. Background: The PLATO trial showed that ticagrelor was superior to clopidogrel for the prevention of cardiovascular death, myocardial infarction, or stroke in a broad population of patients with acute coronary syndromes. Methods: HRQOL in the PLATO study was measured at hospital discharge, 6-month visit, and end of treatment (anticipated at 12 months) by using the EuroQol five-dimensional (EQ-5D) questionnaire. All patients who had an EQ-5D questionnaire assessment at discharge from the index hospitalization (n = 15,212) were included in the study. Patients who died prior to the end-of-treatment visit were assigned an EQ-5D questionnaire value of 0. Results: The EQ-5D questionnaire value at discharge among 7631 patients assigned to ticagrelor was 0.847 and among 7581 patients assigned to clopidogrel was 0.846 (P = 0.71). At 12 months, the mean EQ-5D questionnaire value was 0.840 for ticagrelor and 0.832 for clopidogrel (P = 0.046). Excluding patients who died resulted in mean EQ-5D questionnaire values of 0.864 among ticagrelor patients and 0.863 among clopidogrel patients (P = 0.69). Conclusions: In patients hospitalized with acute coronary syndromes with or without ST-segment elevation, treatment with ticagrelor was associated with a lower mortality but otherwise no difference in quality of life relative to treatment with clopidogrel. The improved survival and reduction in cardiovascular events with ticagrelor are therefore obtained with no loss in quality of life.
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