08 Nov 10
Posted in Coronary artery disease at 2:22 by Laci
By C Cannon, R Harrington, S James, D Ardissino, R Becker, H Emanuelsson et al for the PLATelet inhibition and patient Outcomes (PLATO) investigators
Lancet 2010;375:283-93
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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04 Nov 10
Posted in Coronary artery disease at 0:02 by Laci
By L Wallentin, R Becker, A Budaj, C Cannon et al, for the PLATO Investigators
NEJM 2009; 361:1045-1057
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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02 Nov 10
Posted in Coronary artery disease at 0:17 by Laci
By G Montalescot and J Silvain
Circulation 2010;122:1049-1052
Reduced renal function is associated with a poorer prognosis and increased bleeding risk in patients with acute coronary syndromes and may therefore alter the risk-benefit ratio with antiplatelet therapies. In the Platelet Inhibition and Patient Outcomes (PLATO) trial, ticagrelor compared with clopidogrel reduced the primary composite end point of cardiovascular death, myocardial infarction, and stroke at 12 months but with similar major bleeding rates.
Methodes and results
Central laboratory serum creatinine levels were available in 15 202 (81.9%) acute coronary syndrome patients at baseline, and creatinine clearance, estimated by the Cockcroft Gault equation, was calculated. In patients with chronic kidney disease (creatinine clearance <60 mL/min; n=3237), ticagrelor versus clopidogrel significantly reduced the primary end point to 17.3% from 22.0% (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.65 to 0.90) with an absolute risk reduction greater than that of patients with normal renal function (n=11 965): 7.9% versus 8.9% (HR, 0.90; 95% CI, 0.79 to 1.02). In patients with chronic kidney disease, ticagrelor reduced total mortality (10.0% versus 14.0%; HR, 0.72; 95% CI, 0.58 to 0.89). Major bleeding rates, fatal bleedings, and non-coronary bypass-related major bleedings were not significantly different between the 2 randomized groups (15.1% versus 14.3%; HR, 1.07; 95% CI, 0.88 to 1.30; 0.34% versus 0.77%; HR, 0.48; 95% CI, 0.15 to 1.54; and 8.5% versus 7.3%; HR, 1.28; 95% CI, 0.97 to 1.68). The interactions between creatinine clearance and randomized treatment on any of the outcome variables were nonsignificant.
Conclusions
In acute coronary syndrome patients with chronic kidney disease, ticagrelor compared with clopidogrel significantly reduces ischemic end points and mortality without a significant increase in major bleeding but with numerically more non-procedure-related bleeding.
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26 Oct 10
Posted in Anesthesia at 20:57 by Laci
By T Cook, S Payne, E Skryabina, D Hurford, E Clow and A Georgiou
Anaesthesia 2010;65:1069-1079
The National Patient Safety Agency has issued a Patient Safety Alert with the aim of eliminating Luer connectors from equipment for lumbar puncture and subarachnoid injections by 1 April 2011, and from all neuraxial and regional anaesthesia equipment in 2013. B-link (UK) Ltd and InterVene Ltd have produced non-Luer connectors for neuraxial devices: the Neurax® and Spinalok® respectively. Using an adult spinal simulator, 59 experienced clinicians performed neuraxial procedures using these devices and reported on specific performance characteristics and overall usability. Cross-connectivity between non-Luer and Luer connectors was also examined. The median (IQR [range]) overall assessment scores (0–10 scale) of usability for the standard, Neurax and Spinalok systems were 8 (8–9 [7–10]), 6 (5–7 [0–8]) and 7 (6–8 [1–9]) for spinal procedures and 8 (8–9 [6–10]), 7 (5–8 [1–9]) and 4 (3–6 [0–9]) for epidural procedures, respectively. Both study systems scored significantly lower than standard equipment for overall performance of spinal and epidural procedures, although the performance of non-Luer devices was mostly rated ‘adequate’ or better. Both non-Luer connectors could cross-connect with one or more Luer connectors. Following feedback to the manufacturers, both systems have been modified and cross-connectivity apparently has been eliminated. Our results indicate that clinicians may not find non-Luer devices immediately ‘user-friendly’. More importantly, some cross-connectivity with Luer devices was possible. Our findings illustrate that introducing equipment that is fully compliant with the National Patient Safety Agency alert poses a significant challenge to manufacturers and clinicians. We conclude that before introducing any non-Luer device into widespread use, independent, formal evaluation should be carried out.
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