| 1. |
|
|
| 2. |
- James, Stefan K., et al.
(författare)
-
Ticagrelor versus clopidogrel in patients with acute coronary syndromes intended for non-invasive management : substudy from prospective randomised PLATelet inhibition and patient Outcomes (PLATO) trial
- 2011
-
Ingår i: The BMJ. - : BMJ. - 1756-1833. ; 342, s. d3527-
-
Tidskriftsartikel (refereegranskat)abstract
- Objective To evaluate efficacy and safety outcomes in patients in the PLATelet inhibition and patient Outcomes (PLATO) trial who at randomisation were planned for a non-invasive treatment strategy. Design Pre-specified analysis of pre-randomisation defined subgroup of prospective randomised clinical trial. Setting 862 centres in 43 countries. Participants 5216 (28%) of 18 624 patients admitted to hospital for acute coronary syndrome who were specified as planned for non-invasive management. Interventions Randomised treatment with ticagrelor (n=2601) versus clopidogrel (2615). Main outcome measurements Primary composite end point of cardiovascular death, myocardial infarction, and stroke; their individual components; and PLATO defined major bleeding during one year. Results 2183 (41.9%) patients had coronary angiography during their initial hospital admission, 1065 (20.4%) had percutaneous coronary intervention, and 208 (4.0%) had coronary artery bypass surgery. Cumulatively, 3143 (60.3%) patients had been managed non-invasively by the end of follow-up. The incidence of the primary end point was lower with ticagrelor than with clopidogrel (12.0% (n=295) v 14.3% (346); hazard ratio 0.85, 95% confidence interval 0.73 to 1.00; P=0.04). Overall mortality was also lower (6.1% (147) v 8.2% (195); 0.75, 0.61 to 0.93; P=0.01). The incidence of total major bleeding (11.9% (272) v 10.3% (238); 1.17, 0.98 to 1.39; P=0.08) and non-coronary artery bypass grafting related major bleeding (4.0% (90) v 3.1% (71); 1.30, 0.95 to 1.77; P=0.10) was numerically higher with ticagrelor than with clopidogrel. Conclusions In patients with acute coronary syndrome initially intended for non-invasive management, the benefits of ticagrelor over clopidogrel were consistent with those from the overall PLATO results, indicating the broad benefits of P2Y12 inhibition with ticagrelor regardless of intended management strategy.
|
|
| 3. |
- Scirica, Benjamin M., et al.
(författare)
-
The Incidence of Bradyarrhythmias and Clinical Bradyarrhythmic Events in Patients With Acute Coronary Syndromes Treated With Ticagrelor or Clopidogrel in the PLATO (Platelet Inhibition and Patient Outcomes) Trial Results of the Continuous Electrocardiographic Assessment Substudy
- 2011
-
Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 57:19, s. 1908-1916
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives The aim of this study was to determine whether ticagrelor increased the risk of ventricular pauses compared with clopidogrel and whether these pauses were associated with any clinical bradycardic events in patients presenting with acute coronary syndromes. Background Ticagrelor, an oral reversibly binding P2Y(12) inhibitor, provides more potent and consistent inhibition of platelet aggregation than clopidogrel but in a phase II study was associated with increased risk for ventricular pauses. A prospective continuous electrocardiographic (cECG) assessment was therefore performed within the PLATO (Platelet Inhibition and Patient Outcomes) study comparing ticagrelor and clopidogrel in patients hospitalized with acute coronary syndromes. Methods Patients in the cECG assessment had planned 7-day cECG recording initiated at the time of randomization (week 1), which was within 24 h of symptom onset, and then repeated at 1 month after randomization during the convalescent phase. The principal safety endpoint was the incidence of ventricular pauses lasting at least 3 s. Investigators also reported symptomatic bradycardic adverse events during the entire study duration (median 277 days). Results A total of 2,908 patients were included in the cECG assessment, of whom 2,866 (98.5%) had week 1 recordings, 1,991 (68.4%) had 1-month recordings, and 1,949 (67.0%) had both. During the first week after randomization, ventricular pauses >= 3 s occurred more frequently in patients receiving ticagrelor than clopidogrel (84 [5.8%] vs. 51 [3.6%]; relative risk: 1.61; p = 0.006). At 1 month, pauses >= 3 s occurred overall less frequently and were similar between treatments (2.1% vs. 1.7%). Most were ventricular pauses, and the greatest excess associated with ticagrelor were asymptomatic, sinoatrial nodal in origin (66%), and nocturnal. There were no differences between ticagrelor and clopidogrel in the incidence of clinically reported bradycardic adverse events, including syncope, pacemaker placement, and cardiac arrest. Conclusions In the PLATO cECG assessment, more patients treated with ticagrelor compared with clopidogrel had ventricular pauses, which were predominantly asymptomatic, sinoatrial nodal in origin, and nocturnal and occurred most frequently in the acute phase of acute coronary syndromes. There were no apparent clinical consequences related to the excess in ventricular pauses in patients assigned to ticagrelor. (A Comparison of AZD6140 and Clopidogrel in Patients With Acute Coronary Syndrome [PLATO]; NCT00391872) (J Am Coll Cardiol 2011; 57: 1908-16) .
|
|
| 4. |
- Storey, Robert F, et al.
(författare)
-
Lower mortality following pulmonary adverse events and sepsis with ticagrelor compared to clopidogrel in the PLATO study
- 2014
-
Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 25:7, s. 517-525
-
Tidskriftsartikel (refereegranskat)abstract
- In the PLATelet inhibition and patient Outcomes (PLATO) study of patients with acute coronary syndromes, ticagrelor reduced mortality compared to clopidogrel but the mechanisms for this mortality reduction remain uncertain. We analysed adverse events (AEs) consistent with either pulmonary infection or sepsis, and subsequent mortality, in 18,421 PLATO patients treated with ticagrelor or clopidogrel. AEs occurring within 7 days of last dose of study medication were defined as "on-treatment". Serial measurements of blood leukocyte counts, C-reactive protein and interleukin-6 were performed. Fewer on-treatment pulmonary AEs occurred in the ticagrelor compared to the clopidogrel group (275 vs. 331 respectively; p = 0.019), with fewer deaths following these AEs (33 vs. 71; p < 0.001), particularly in those who remained on study medication three days after AE onset (10 vs. 43; p < 0.001). There were fewer deaths attributed to sepsis in the ticagrelor group (7 vs. 23; p = 0.003). Leukocyte counts were lower in the clopidogrel group during treatment (p < 0.0001 at 1, 3 and 6 months) but not at 1 month post-discontinuation. C-reactive protein increased more at discharge in the ticagrelor group (28.0 ± 38.0 vs. 26.1 ± 36.6 mg/l; p < 0.001) and interleukin-6 remained higher during the first month of treatment with ticagrelor. We conclude that the mortality risk following pulmonary AEs and sepsis in acute coronary syndrome patients appears to be lower during ticagrelor compared to clopidogrel therapy. Further work should assess whether ticagrelor and clopidogrel have differential effects on immune signalling.
|
|
| 5. |
- Wallentin, Lars, et al.
(författare)
-
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
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 129:3, s. 293-303
-
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.
|
|
| 6. |
- White, Harvey, et al.
(författare)
-
Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease
- 2010
-
Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 160:4, s. 655-661.e2
-
Tidskriftsartikel (refereegranskat)abstract
- Background Elevated plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with increased risk of cardiovascular (CV) events. Direct inhibition of this proinflammatory enzyme with darapladib may benefit CV patients when given as an adjunct to standard of care, including lipid-lowering and antiplatelet therapies. Methods STABILITY is a randomized, placebo-controlled, double-blind, international, multicenter, event-driven trial. The study has randomized 15,828 patients with chronic coronary heart disease (CHD) receiving standard of care to darapladib enteric-coated (EC) tablets, 160 mg or placebo. Results The primary end point is the composite of major adverse cardiovascular events (MACE): CV death, nonfatal myocardial infarction, and nonfatal stroke. The key secondary end points will include major coronary events, total coronary events, individual components of MACE, and all-cause mortality. Prespecified substudies include 24-hour ambulatory blood pressure monitoring, albuminuria progression, changes in cognitive function, and pharmacokinetic and biomarker analyses. Health economic outcomes and characterization of baseline lifestyle risk factors also will be assessed. The study will continue until 1,500 primary end points have occurred to achieve 90% power to detect a 15.5% reduction in the primary end point. The median treatment duration is anticipated to be 2.75 years. Conclusions STABILITY will assess whether direct inhibition of Lp-PLA(2) with darapladib added to the standard of care confers clinical benefit to patients with CHD.
|
|
