| 11. |
- Cleland, John G F, et al.
(författare)
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Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure).
- 2009
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 54:20, s. 1850-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We investigated whether plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction and prognosis measured in CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), could be used to identify the severity of heart failure at which statins become ineffective. BACKGROUND: Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transition point at which treatment with a statin becomes futile. METHODS: In CORONA, patients with heart failure, reduced left ventricular ejection fraction, and ischemic heart disease were randomly assigned to 10 mg/day rosuvastatin or placebo. The primary composite outcome was cardiovascular death, nonfatal myocardial infarction, or stroke. RESULTS: Of 5,011 patients enrolled, NT-proBNP was measured in 3,664 (73%). The midtertile included values between 103 pmol/l (868 pg/ml) and 277 pmol/l (2,348 pg/ml). Log NT-proBNP was the strongest predictor (per log unit) of every outcome assessed but was strongest for death from worsening heart failure (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.71 to 2.30), was weaker for sudden death (HR: 1.69; 95% CI: 1.52 to 1.88), and was weakest for atherothrombotic events (HR: 1.24; 95% CI: 1.10 to 1.40). Patients in the lowest tertile of NT-proBNP had the best prognosis and, if assigned to rosuvastatin rather than placebo, had a greater reduction in the primary end point (HR: 0.65; 95% CI: 0.47 to 0.88) than patients in the other tertiles (heterogeneity test, p = 0.0192). This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin. CONCLUSIONS: Patients with heart failure due to ischemic heart disease who have NT-proBNP values <103 pmol/l (868 pg/ml) may benefit from rosuvastatin.
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| 12. |
- Cornel, Jan H., et al.
(författare)
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Glycoprotein IIb/IIIa Receptor Inhibitors in Combination With Vorapaxar, a Platelet Thrombin Receptor Antagonist, Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes (from the TRACER Trial)
- 2015
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 115:10, s. 1325-1332
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the interaction between protease-activated receptor-1 antagonist vorapaxar and concomitant glycoprotein (GP) IIb/IIIa receptor inhibitors in patients with non-ST-segment elevation acute coronary syndromes who underwent PCI. In Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome trial, 12,944 patients with non-ST-segment elevation acute coronary syndromes were randomized to vorapaxar or placebo. Administration of GP IIb/IIIa receptor inhibitors was allowed at the treating physician's discretion. We investigated whether use of GP IIb/IIIa receptor inhibitors modified vorapaxar's effect on non-coronary artery bypass grafting (CABG)-related bleeding at 7 days and ischemic events at 30 days. In total, 7,455 patients underwent PCI during index hospitalization. Of these, 2,023 patients (27.1%) received inhibitors and 5,432 (72.9%) did not. Vorapaxar was associated with a numerically higher rate of non-CABG-related moderate/severe Global Use of Strategies to Open Occluded Arteries (GUSTO) bleeding at 7 days compared with placebo in those who did (1.3% vs 1.0%) and did not (0.6% vs 0.4%) receive GP IIb/IIIa receptor inhibitors. Ischemic end point rates at 30 days were not significantly lower with vorapaxar versus placebo. Increased rates of non-CABG GUSTO moderate/severe bleeding were observed in patients who received GP IIb/IIIa receptor inhibitors versus those who did not (adjusted hazard ratio [HR] 1.77, 95% confidence interval [CI] 0.43 to 7.35 in placebo arm; adjusted HR 2.02, 95% CI 0.62 to 6.61 in vorapaxar arm) and in those who received vorapaxar versus placebo (adjusted HR 1.54, 95% CI 0.36 to 6.56 in the GP IIn/IIIa group; adjusted FIR 1.34, 95% CI 0.44 to 4.07 in the no-GP IIb/IIIa group). No interaction was found between vorapaxar and inhibitor use up to 7 days (P interaction = 0.89) nor at the end of the treatment (P interaction = 0.74); however, the event rate was low. Also, no interaction was observed for efficacy end points after PCI at 30 days or at the end of the treatment. In conclusion, GP IIb/IIIa receptor inhibitor use plus dual antiplatelet therapy in a population with non-ST-segment elevation myocardial infarction planned for PCI was frequent but did not interact with vorapaxar's efficacy or safety. Nonetheless, GP IIb/IIIa receptor inhibitors and vorapaxar were associated with increased bleeding risk, and their combined use may result in additive effects on bleeding rates.
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| 13. |
- Cornel, Jan H., et al.
(författare)
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Prior smoking status, clinical outcomes, and the comparison of ticagrelor with clopidogrel in acute coronary syndromes-Insights from the PLATelet inhibition and patient Outcomes (PLATO) trial
- 2012
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 164:3, s. 334-342
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Tidskriftsartikel (refereegranskat)abstract
- Background Habitual smoking has been associated with increased platelet reactivity, increased risk of thrombotic complications and greater efficacy of clopidogrel therapy over placebo. In the PLATO trial, ticagrelor compared to clopidogrel in patients with acute coronary syndromes (ACS) reduced the primary composite end point of vascular death, myocardial infarction and stroke, without increasing overall rates of major bleeding. We evaluated the results in relation to smoking habits.Methods Interactions between habitual smokers (n = 6678) and in ex/nonsmokers (n = 11,932) and the effects of randomized treatments on ischemic and bleeding outcomes were evaluated by Cox regression analyses.Results Habitual smokers had an overall lower risk profile and more often ST-elevation ACS. After adjustment for baseline imbalances, habitual smoking was associated with a higher incidence of definite stent thrombosis (adjusted HR, 1.44 [95% CI, 1.07-1.94]); there were no significant associations with other ischemic or bleeding end points. The effects of ticagrelor compared to clopidogrel were consistent for all outcomes regardless of smoking status. Thus, there was a similar reduction in the primary composite end point for habitual smokers (adjusted HR, 0.83 [95% CI, 0.68-1.00]) and ex/nonsmokers (adjusted HR, 0.89 [95% CI, 0.79-1.00]) (interaction P = .50), and in definite stent thrombosis for habitual smokers (adjusted HR, 0.59 [0.39-0.91]) and ex/nonsmokers (adjusted HR, 0.69 [95% CI, 0.45-1.07]) (interaction P = .61).Conclusions In patients hospitalized with ACS, habitual smoking is associated with a greater risk of subsequent stent thrombosis. The reduction of vascular death, myocardial infarction, stroke, and stent thrombosis by ticagrelor compared to clopidogrel is consistent regardless of smoking habits.
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| 14. |
- Cornel, Jan H., et al.
(författare)
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Relationship of Platelet Reactivity With Bleeding Outcomes During Long-Term Treatment With Dual Antiplatelet Therapy For Medically Managed Patients With Non-St-Segment Elevation Acute Coronary Syndromes
- 2016
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:11
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Tidskriftsartikel (refereegranskat)abstract
- Background--The relationship between "on-treatment" low platelet reactivity and longitudinal risks of major bleeding dual antiplatelet therapy following acute coronary syndromes remains uncertain, especially for patients who do not undergo percutaneous coronary intervention. Methods and Results--We analyzed 2428medicallymanaged acute coronary syndromes patients fromthe Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial who had serial platelet reactivity measurements (P2Y12 reaction units; PRUs) and were randomized to aspirin+prasugrel versus aspirin+clopidogrel for up to 30 months. Contal's method was used to determine whether a cut point for steady-state PRU values could distinguish high versus low bleeding risk using 2-level composites: Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe/life-threatening or moderate bleeding unrelated to coronary artery bypass grafting (CABG) and non-CABG Thrombolysis In Myocardial Infarction (TIMI) major orminor bleeding. Exploratory analyses used 3-level composites that incorporatedmild andminimalGUSTOand TIMI events.Continuousmeasures of PRUs (per 10-unit decrease)were not independently associatedwith the 2-levelGUSTO (adjusted hazard ratio [HR], 1.01; 95% CI, 0.96-1.06) or TIMI composites (1.02; 0.98-1.07). Furthermore, no PRU cut point could significantly distinguish bleeding risk using the 2-level composites.However, the PRUcut point of 75 differentiated bleeding riskwith the 3-level composites ofGUSTO(26.5% vs 12.6%; adjusted HR, 2.28; 95% CI, 1.77-2.94; P<0.001) and TIMI bleeding events (25.9% vs 12.2%; adjusted HR, 2.30; 95% CI, 1.78-2.97; P<0.001). Conclusions--Among medically managed non-ST-segment elevation acute coronary syndromes patients receiving prolonged dual antiplatelet therapy, PRU values were not significantly associated with the long-term risk of major bleeding events, suggesting that low on-treatment platelet reactivity does not independently predict serious bleeding risk.
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| 15. |
- Ducrocq, Gregory, et al.
(författare)
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Balancing the risk of spontaneous ischemic and major bleeding events in acute coronary syndromes
- 2017
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 186, s. 91-99
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Tidskriftsartikel (refereegranskat)abstract
- Background: Evaluation of antithrombotic treatments for acute coronary syndromes (ACS) requires balancing ischemic and bleeding risks to assess net benefit. We sought to compare the relative effects of ischemic and bleeding events on mortality.Methods: In the PLATelet inhibition and patient Outcomes (PLATO) trial, we compared spontaneous ischemic events (myocardial infarction or stroke) with spontaneous major bleeding events (PLATO major, Thrombolysis In Myocardial Infarction [TIMI] major, Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries [GUSTO] severe) with respect to risk of mortality using time-dependent Cox proportional hazards models. The comparison was performed using ratio of hazard ratios for mortality increase after ischemic vs bleeding events.Results: A total of 822 patients (4.4%) had >= 1 spontaneous ischemic event; 485 patients (2.6%), >= 1 spontaneous PLATO major bleed, 282 (1.5%), >= 1 spontaneous TIMI major bleed; and 207 (1.1%), >= 1 spontaneous severe GUSTO bleed. In patients who had both events, bleeding occurred first in most patients. Regardless of classification, major bleeding events were associated with increased short- and long-term mortality that were not significantly different from the increase associated with spontaneous ischemic events: ratio of hazard ratios (95% Cls) for short- and long-term mortality after spontaneous ischemic vs bleeding events: 1.46 (0.98-2.19) and 0.92 (0.52-1.62) (PLATO major); 1.26 (0.80-1.96) and 1.19 (0.58-2.24) (TIMI major), 0.72 (0.47-1.10) and 0.83 (0.38-1.79) (GUSTO severe) (all P > 0.05)Conclusions: In patients with ACS on dual antiplatelet therapy, spontaneous major bleeding events seem "prognostically equivalent" to spontaneous ischemic complications. This result allows quantitative comparisons between both actual and predicted bleeding and ischemic risks. Our findings help to better define net clinical benefit of antithrombotic treatments and more accurately estimate mortality after ischemic and bleeding events in patients with ACS.
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| 16. |
- 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 .- 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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| 17. |
- Giannitsis, Evangelos, et al.
(författare)
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Contra
- 2021
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Ingår i: European Heart Journal. - : Oxford University Press. - 0195-668X .- 1522-9645. ; 42:31, s. 2979-2985
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 18. |
- Gurbel, Paul A., et al.
(författare)
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Platelet Function During Extended Prasugrel and Clopidogrel Therapy for Patients With ACS Treated Without Revascularization The TRILOGY ACS Platelet Function Substudy
- 2012
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598. ; 308:17, s. 1785-1794
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Tidskriftsartikel (refereegranskat)abstract
- Context The relationship of platelet function testing measurements with outcomes in patients with acute coronary syndromes (ACS) initially managed medically without revascularization is unknown. Objective To characterize the differences and evaluate clinical outcomes associated with platelet reactivity among patients with ACS treated with clopidogrel or prasugrel. Design, Setting, and Patients Patients with medically managed unstable angina or non-ST-segment elevation myocardial infarction were enrolled in the TRILOGY ACS trial (2008 to 2011) comparing clopidogrel vs prasugrel. Of 9326 participants, 27.5% were included in a platelet function substudy: 1286 treated with prasugrel and 1278 treated with clopidogrel. Interventions Aspirin with either prasugrel (10 or 5 mg/d) or clopidogrel (75 mg/d); those 75 years or older and younger than 75 years but who weighed less than 60 kg received a 5-mg prasugrel maintenance dose. Main Outcome Measures Platelet reactivity, measured in P2Y(12) reaction units (PRUs), was performed at baseline, at 2 hours, and at 1, 3, 6, 12, 18, 24, and 30 months after randomization. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke through 30 months. Results Among participants younger than 75 years and weighing 60 kg or more, the median PRU values at 30 days were 64 (interquartile range [IQR], 33-128) in the prasugrel group vs 200 (IQR, 141-260) in the clopidogrel group (P<.001), a difference that persisted through all subsequent time points. For participants younger than 75 years and weighing less than 60 kg, the median 30-day PRU values were 139 (IQR, 86-203) for the prasugrel group vs 209 (IQR, 148-283) for the clopidogrel group (P<.001), and for participants 75 years or older, the median PRU values were 164 (IQR, 105-216) for the prasugrel group vs 222 (IQR, 148-268) for the clopidogrel group (P<.001). At 30 months the rate of the primary efficacy end point was 17.2% (160 events) in the prasugrel group vs 18.9% (180 events) in the clopidogrel group (P=.29). There were no significant differences in the continuous distributions of 30-day PRU values for participants with a primary efficacy end point event after 30 days (n=214) compared with participants without an event (n=1794; P=.07) and no significant relationship between the occurence of the primary efficacy end point and continuous PRU values (adjusted hazard ratio [HR] for increase of 60 PRUs, 1.03; 95% CI, 0.96-1.11; P=.44). Similar findings were observed with 30-day PRU cut points used to define high on-treatment platelet reactivity-PRU more than 208 (adjusted HR, 1.16; 95% CI, 0.89-1.52, P=.28) and PRU more than 230 (adjusted HR, 1.20; 95% CI, 0.90-1.61; P=.21). Conclusions Among patients with ACS without ST-segment elevation and initially managed without revascularization, prasugrel was associated with lower platelet reactivity than clopidogrel, irrespective of age, weight, and dose. Among those in the platelet substudy, no significant differences existed between prasugrel vs clopidogrel in the occurence of the primary efficacy end point through 30 months and no significant association existed between platelet reactivity and occurrence of ischemic outcomes.
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| 19. |
- Gurbel, Paul A., et al.
(författare)
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Translational platelet research in patients with coronary artery disease: hat are the rnalor knowledge gaps?
- 2012
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Ingår i: Thrombosis and Haemostasis. - 0340-6245. ; 108:1, s. 12-20
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Forskningsöversikt (refereegranskat)abstract
- Translational platelet function investigations performed in the percutaneous coronary intervention (PCI)-treated population receiving clopidogrel have identified high platelet reactivity to ADP (HPR) as a major risk factor for both acute as well as long-term ischaemic event occurrence, including stent thrombosis. Recent studies have highlighted the relation of single nucleotide polymorphisms of genes involved in clopidogrel absorption and metabolism to reduced pharmacokinetic and pharmacodynamic responses to clopidogrel. CYP2C19 loss-of-function (LoF) allele carriage has been associated with increased thrombotic risk in the PCI population. However, there is no information regarding the utility of platelet function testing to predict outcomes in patients with stable coronary artery disease and in medically managed patients with acute coronary syndromes. Additionally, few studies have included longitudinal assessment of platelet function to assess a potential time-dependent relation to ischaemic event occurrence and no phase-III antiplatelet-therapy trial has included a large enough platelet function sub-study to examine the relation between on-treatment platelet reactivity, bleeding, and ischaemic event occurrence. Therefore, futher studies are needed to delineate the role of platelet function testing across the spectrum of symptomatic coronary artery disease.
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| 20. |
- Hjort, Marcus, 1988-, et al.
(författare)
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Biomarker Concentrations and Their Temporal Changes in Patients With Myocardial Infarction and Nonobstructive Compared With Obstructive Coronary Arteries : Results From the PLATO Trial
- 2023
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Ingår i: Journal of the American Heart Association. - : American heart association. - 2047-9980 .- 2047-9980. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The pathobiology of myocardial infarction (MI) with nonobstructive coronary arteries (MINOCA) is often uncertain. Investigating biomarker concentrations and their changes may offer novel pathophysiological insights.Methods and Results: In this post hoc study of the PLATO (Platelet Inhibition and Patient Outcomes) trial, concentrations of hs‐cTnT (high‐sensitivity cardiac troponin T), NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), hs‐CRP (high‐sensitivity C‐reactive protein), and GDF‐15 (growth differentiation factor 15) were measured in patients with MINOCA at baseline (n=554) and at 1‐month follow‐up (n=107). For comparisons, biomarkers were also measured in patients with MI with obstructive (stenosis ≥50%) coronary artery disease (baseline: n=11 106; follow‐up: n=2755]). Adjusted linear regression models were used to compare concentrations and their short‐ and long‐term changes. The adjusted geometric mean ratios (GMRs) in patients with MINOCA (median age, 61 years; 50.4% women) indicated lower hs‐cTnT (GMR, 0.77 [95% CI, 0.68–0.88]) but higher hs‐CRP (GMR, 1.21 [95% CI, 1.08–1.37]) and GDF‐15 concentrations (GMR, 1.06 [95% CI, 1.02–1.11]) at baseline compared with patients with MI with obstructive coronary artery disease, whereas NT‐proBNP concentrations were similar. Temporal decreases in hs‐cTnT, NT‐proBNP, and hs‐CRP concentrations until 1‐month follow‐up were more pronounced in patients with MINOCA. At follow‐up, patients with MINOCA had lower concentrations of hs‐cTnT (GMR, 0.71 [95% CI, 0.60–0.84]), NT‐proBNP (GMR, 0.45 [95% CI, 0.36–0.56]), and hs‐CRP (GMR, 0.68 [95% CI, 0.53–0.86]). One‐month GDF‐15 concentrations were similar between both groups with MI.Conclusions: Biomarker concentrations suggest greater initial inflammatory activity, similar degree of myocardial dysfunction, and less pronounced myocardial injury during the acute phase of MINOCA compared with MI with obstructive coronary artery disease but also faster myocardial recovery.CLINICAL TRAIL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.
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