| 81. |
- 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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| 82. |
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| 83. |
- Tye, Sok Cin, et al.
(författare)
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Initiation of the SGLT2 inhibitor canagliflozin to prevent kidney and heart failure outcomes guided by HbA1c, albuminuria, and predicted risk of kidney failure
- 2022
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Ingår i: Cardiovascular Diabetology. - : Springer Nature. - 1475-2840. ; 21:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Sodium glucose co-transporter-2 (SGLT2) inhibitors reduce the risk of kidney and heart failure events independent of glycemic effects. We assessed whether initiation of the SGLT2 inhibitor canagliflozin guided by multivariable predicted risk based on clinical characteristics and novel biomarkers is more efficient to prevent clinical outcomes compared to a strategy guided by HbA1c or urinary-albumin-creatinine ratio (UACR) alone. Methods We performed a post-hoc analysis of the CANVAS trial including 3713 patients with available biomarker measurements. We compared the number of composite kidney (defined as a sustained 40% decline in eGFR, chronic dialysis, kidney transplantation, or kidney death) and composite heart failure outcomes (defined as heart failure hospitalization or cardiovascular (CV) death) prevented per 1000 patients treated for 5 years when canagliflozin was initiated in patients according to HbA1c >= 7.5%, UACR, or multivariable risk models consisting of: (1) clinical characteristics, or (2) clinical characteristics and novel biomarkers. Differences in the rates of events prevented between strategies were tested by Chi(2)-statistic. Results After a median follow-up of 6.1 years, 144 kidney events were recorded. The final clinical model included age, previous history of CV disease, systolic blood pressure, UACR, hemoglobin, body weight, albumin, estimated glomerular filtration rate, and randomized treatment assignment. The combined biomarkers model included all clinical characteristics, tumor necrosis factor receptor-1, kidney injury molecule-1, matrix metallopeptidase-7 and interleukin-6. Treating all patients with HbA1c >= 7.5% (n = 2809) would prevent 33.0 (95% CI 18.8 to 43.3 ) kidney events at a rate of 9.6 (95% CI 5.5 to 12.6) events prevented per 1000 patients treated for 5 years. The corresponding rates were 5.8 (95% CI 3.4 to 7.9), 16.6 (95% CI 9.5 to 22.0) (P < 0.001 versus HbA1c or UACR approach), and 17.5 (95% CI 10.0 to 23.0) (P < 0.001 versus HbA1c or UACR approach; P = 0.54 versus clinical model). Findings were similar for the heart failure outcome. Conclusion Initiation of canagliflozin based on an estimated risk-based approach prevented more kidney and heart failure outcomes compared to a strategy based on HbA1c or UACR alone. There was no apparent gain from adding novel biomarkers to the clinical risk model. These findings support the use of risk-based assessment using clinical markers to guide initiation of SGLT2 inhibitors in patients with type 2 diabetes.
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| 84. |
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| 85. |
- Wallentin, Lars, et al.
(författare)
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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
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 129:3, s. 293-303
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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.
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| 86. |
- Wallentin, Lars, et al.
(författare)
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Review of the accumulated PLATO documentation supports reliable and consistent superiority of ticagrelor over clopidogrel in patients with acute coronary syndrome Commentary on : DiNicolantonio JJ, Tomek A, Inactivations, deletions, non-adjudications, and downgrades of clinical endpoints on ticagrelor: Serious concerns over the reliability of the PLATO trial, International Journal of Cardiology, 2013
- 2014
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 170:3, s. E59-E62
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Tidskriftsartikel (refereegranskat)
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| 87. |
- Wallentin, Lars, 1943-, et al.
(författare)
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Ticagrelor versus clopidogrel in patients with acute coronary syndromes
- 2009
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 361:11, s. 1045-1057
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel. METHODS: In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation. RESULTS: At 12 months, the primary end point--a composite of death from vascular causes, myocardial infarction, or stroke--had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types. CONCLUSIONS: In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding.
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| 88. |
- Zhou, Zien, et al.
(författare)
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Canagliflozin and Stroke in Type 2 Diabetes Mellitus Results From the Randomized CANVAS Program Trials
- 2019
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Ingår i: Stroke. - : LIPPINCOTT WILLIAMS & WILKINS. - 0039-2499 .- 1524-4628. ; 50:2, s. 396-404
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose-This study reports the detailed effects of canagliflozin on stroke, stroke subtypes, and vascular outcomes in participants with and without cerebrovascular disease (stroke or transient ischemic attack) at baseline from the CANVAS (Canagliflozin Cardiovascular Assessment Study) Program. Methods-The CANVAS Program, comprising 2 similarly designed and conducted clinical trials, randomly assigned 10 142 participants with type 2 diabetes mellitus and high cardiovascular risk to canagliflozin or placebo. Its primary outcome was a composite of major adverse cardiovascular events. The main outcome of interest for this report was fatal or nonfatal stroke. Additional exploratory outcomes were stroke subtypes and other vascular outcomes defined according to standard criteria. Results-There were 1 958 (19%) participants with prior stroke or transient ischemic attack at baseline. These individuals were older, more frequently women, and had higher rates of heart failure, atrial fibrillation, and microvascular disease (all Pamp;lt;0.001) compared with those without such a history. There were 309 participants with stroke events during followup (123 had prior stroke or transient ischemic attack at baseline and 186 did not), at a rate of 7.93/1000 patient-years among those assigned canagliflozin and 9.62/1000 patient-years among placebo (hazard ratio, 0.87; 95% CI, 0.691.09). Analysis of stroke subtypes found no effect on ischemic stroke (n=253, hazard ratio, 0.95; 95% CI, 0.74-1.22), a significant reduction for hemorrhagic stroke (n=30, hazard ratio, 0.43; 95% CI, 0.20-0.89) and no effect on undetermined stroke (n=29, hazard ratio, 1.04; 95% CI, 0.48-2.22). Effects on other cardiovascular outcomes were comparable among participants with and without stroke or transient ischemic attack at baseline. Conclusions-There were too few events in the CANVAS Program to separately define the effects of canagliflozin on stroke, but benefit is more likely than harm. The observed possible protective effect for hemorrhagic stroke was based on small numbers but warrants further investigation.
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| 89. |
- Zimerman, Andre, et al.
(författare)
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Pooled analysis of adverse event collection from 4 acute coronary syndrome trials
- 2016
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 174, s. 60-67
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adverse event collection in randomized clinical trials establishes drug safety. Although costly and regulated, it is rarely studied.Methods: Adverse event data from 4 clinical trials (APPRAISE-2, PLATO, TRACER, TRILOGY ACS) comprising 48,118 participants with acute coronary syndromes were pooled to compare patterns and determinants of reporting. Events were classified as serious (SAE) or nonserious (AE) from hospital discharge to 1 year; study end points were excluded.Results: In total, 84,901 events were reported. Of those, 12,266 (14.4%) were SAEs and 72,635 (85.6%) were AEs. Of all participants, 7,823 (16.3%) had SAEs, 18,124 (37.7%) had only AEs, and 22,171 (46.1%) had neither. Nonserious adverse events were distributed across system organ classes: general disorders (11%), infection (10%), gastrointestinal (10%), respiratory (9%), cardiovascular (8.4%), and other (35%). Serious adverse events had a higher proportion of cardiovascular causes (14.0%). Event reporting was highest after hospital discharge, decreasing rapidly during the following 3 months. In a Cox proportional hazards model, chronic obstructive pulmonary disease (hazard ratio 1.58, 95% CI 1.44-1.74), heart failure (1.55, 1.40-1.70), older age, and female sex were independent predictors of more SAEs, whereas enrollment in Eastern Europe (0.63, 0.58-0.69) or Asia (0.84, 0.75-0.94) were independent predictors of fewer SAEs.Conclusions: Half of all participants reported adverse events in the year after acute coronary syndrome; most were AEs and occurred within 3 months. The high volume of events, as well as the variation in SAE reporting by characteristics and enrollment region, indicates that efforts to refine event collection in large trials are warranted.
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