468 research outputs found

    Metabolism of ticagrelor in patients with acute coronary syndromes.

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    © The Author(s) 2018Ticagrelor is a state-of-the-art antiplatelet agent used for the treatment of patients with acute coronary syndromes (ACS). Unlike remaining oral P2Y12 receptor inhibitors ticagrelor does not require metabolic activation to exert its antiplatelet action. Still, ticagrelor is extensively metabolized by hepatic CYP3A enzymes, and AR-C124910XX is its only active metabolite. A post hoc analysis of patient-level (n = 117) pharmacokinetic data pooled from two prospective studies was performed to identify clinical characteristics affecting the degree of AR-C124910XX formation during the first six hours after 180 mg ticagrelor loading dose in the setting of ACS. Both linear and multiple regression analyses indicated that ACS patients presenting with ST-elevation myocardial infarction or suffering from diabetes mellitus are more likely to have decreased rate of ticagrelor metabolism during the acute phase of ACS. Administration of morphine during ACS was found to negatively influence transformation of ticagrelor into AR-C124910XX when assessed with linear regression analysis, but not with multiple regression analysis. On the other hand, smoking appears to increase the degree of ticagrelor transformation in ACS patients. Mechanisms underlying our findings and their clinical significance warrant further research.Peer reviewedFinal Published versio

    Use of glycoprotein IIb/IIIa antagonists to prevent stent thrombosis in morphine-treated patients with ST-elevation myocardial infarction

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    Morphine can delay absorption of P2Y12-inhibitors in ST-elevation myocardial infarction (STEMI) patients, which has the potential to expose these patients to increased stent thrombosis risk after primary percutaneous coronary intervention (PPCI). Limited evidence exists for pharmacotherapeutic strategies aiming to mitigate this risk. We evaluated the impact of guideline-driven ‘routine’ glycoprotein IIb/IIIa antagonist (GPI) use in morphine-treated patients undergoing PPCI. A total of 3224 consecutive STEMI patients undergoing PPCI at a large tertiary cardiac center between 2012 and 2017 were evaluated. GPI use and outcomes before and after introduction of a local guideline were compared, and rates of definite stent thrombosis were identified at 24 h and 30 days. GPI use increased from 42.4% to 69.9% after the introduction of the new guideline. Stent thrombosis occurred in 1.3% (26/1947) pre-guideline and 0.6% (7/1244) post-guideline (P = .037). Of the 33 stent thrombosis cases, 90% (27/30) had received morphine, of whom 85.2% (23/27) had not received adjunctive GPI. Complete records for assessing 30-day bleeding rates were only available in 374 patients and, in this subset, there was no significant difference in rates of GUSTO moderate or severe bleeding before vs. after introduction of the local guideline (1.7% vs 2.8%; P = .47) although, in both cohorts combined, any GUSTO bleeding was observed more frequently in GPI-treated patients (21.8%) compared to those not receiving a GPI (10.0%; P = .002). In conclusion, routine GPI use in morphine-treated STEMI patients undergoing PPCI appears to protect against stent thrombosis. Large-scale studies are needed to establish the overall risk-benefit of GPI therapy in morphine-treated PPCI patients and to assess alternative strategies for preventing acute stent thrombosis in these patients

    Survival of patients with HCV cirrhosis and sustained virologic response is similar to the general population.

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    Background & Aims: Life expectancy of patients with compensated hepatitis C virus (HCV) cirrhosis achieving sustained virologic response (SVR) is limited by liver events as compared to the general population. Thus, survival benefit of SVR remains to be measured. Methods: The study includes prospective surveillance data from three cohorts of Italian patients with compensated HCV cirrhosis who achieved SVR on an interferon-based (IFN) regimen, compared to simultaneously observed non-SVR, untreated and decompensated patients. Overall survival was calculated from the date of start of IFN to death. The number of deaths expected during the at-risk period was determined by applying age- and sex-specific mortality rates recorded in Italy for person-years adequate for the enrolment period. The standardized mortality ratio (SMR) determined the relative risk of death over that of the age and sex matched general population. Results: Overall, 28/181 patients followed-up for a median period of 9.6 years (range 1–25 years) died. The 10 and 20-year overall survival rates for the whole series were 90.9% (95% CI, 84.3–94.8) and 62.9% (95% CI, 45.9–75.9), respectively. The number of expected deaths in the corresponding age and sex matched general population was 28.1, corresponding to a SMR = 1.00 (95% CI, 0.72–1.35), with an SMR for non-SVR patients of 3.85 (95% CI, 3.43–4.30), for untreated of 3.01 (95% CI, 2.64–3.42) and for decompensated of 6.70 (95% CI, 5.39–8.22). Conclusions: Patients with compensated HCV cirrhosis achieving SVR by IFN obtain a main benefit levelling their survival curve to that of the general population. Wider applicability of IFN-free regimens will possibly make this achievement more generalizable

    Repositionable Versus Balloon-Expandable Devices for Transcatheter Aortic Valve Implantation in Patients With Aortic Stenosis.

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    The safety and effectiveness of the fully repositionable LOTUS valve system as compared with the balloon-expandable Edwards SAPIEN 3 prosthesis for the treatment of aortic stenosis has not been evaluated to date. All patients undergoing transcatheter aortic valve implantation with the Edwards SAPIEN 3 or the LOTUS valve system were included into the Swiss Transcatheter Aortic Valve Implantation Registry. An adjusted analysis was performed to compare the early clinical safety outcome according to the Valve Academic Research Consortium-2 definition. Between February 2014 and September 2015, 140 and 815 patients were treated with the LOTUS and the Edwards SAPIEN 3 valve, respectively. There was no difference in crude and adjusted analyses of the early safety outcome between patients treated with LOTUS (14.3%) and those treated with Edwards SAPIEN 3 (14.6%) (crude hazard ratio, 0.97; 95% CI, 0.61-1.56 [P=0.915]; adjusted hazard ratio, 1.03; 95% CI, 0.64-1.67 [P=0.909]). More than mild aortic regurgitation was <2% for both devices. A total of 34.3% of patients treated with LOTUS and 14.1% of patients treated with Edwards SAPIEN 3 required a permanent pacemaker (HR, 2.76; 95% CI, 1.97-3.87 [P<0.001]). The repositionable LOTUS valve system and the balloon-expandable Edwards SAPIEN 3 prosthesis appeared comparable in regard to the Valve Academic Research Consortium-2 early safety outcome, and the rates of more than mild aortic regurgitation were exceedingly low for both devices. The need for new permanent pacemaker implantation was more frequent among patients treated with the LOTUS valve

    Diabetes and baseline glucose are associated with inflammation, left ventricular function and short- and long-term outcome in acute coronary syndromes: role of the novel biomarker Cyr 61.

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    Hyperglycemia in the setting of an acute coronary syndrome (ACS) impacts short term outcomes, but little is known about longer term effects. We therefore designed this study to firstly determine the association between hyperglycemia and short term and longer term outcomes in patients presenting with ACS and secondly evaluate the prognostic role of diabetes, body mass index (BMI) and the novel biomarker Cyr61 on outcomes. The prospective Special Program University Medicine-Acute Coronary Syndrome (SPUM-ACS) cohort enrolled 2168 patients with ACS between December 2009 and October 2012, of which 2034 underwent PCI (93.8%). Patients were followed up for 12 months. Events were independently adjudicated by three experienced cardiologists. Participants were recruited from four tertiary hospitals in Switzerland: Zurich, Geneva, Lausanne and Bern. Participants presenting with acute coronary syndromes and who underwent coronary angiography were included in the analysis. Patients were grouped according to history of diabetes (or HbA1c greater than 6%), baseline blood sugar level (BSL; < 6, 6-11.1 and > 11.1 mmol/L) and body mass index (BMI). The primary outcome was major adverse cardiac events (MACE) which was a composite of myocardial infarction, stroke and all-cause death. Secondary outcomes included the individual components of the primary endpoint, revascularisations, bleeding events (BARC classification) and cerebrovascular events (ischaemic or haemorrhagic stroke or TIA). Patients with hyperglycemia, i.e. BSL ≄ 11.1 mmol/L, had higher levels of C-reactive protein (CRP), white blood cell count (WBC), creatinine kinase (CK), higher heart rates and lower left ventricular ejection fraction (LVEF) and increased N-terminal pro-brain natriuretic peptide. At 30 days and 12 months, those with BSL ≄ 11.1 mmol/L had more MACE and death compared to those with BSL < 6.0 mmol/L or 6.0-11.1 mmol/L (HR-ratio 4.78 and 6.6; p < 0.001). The novel biomarker Cyr61 strongly associated with high BSL and STEMI and was independently associated with 1 year outcomes (HR 2.22; 95% CI 1.33-3.72; Tertile 3 vs. Tertile 1). In this large, prospective, independently adjudicated cohort of in all comers ACS patients undergoing PCI, both a history of diabetes and elevated entry glucose was associated with inflammation and increased risk of MACE both at short and long-term. The mediators might involve increased sympathetic activation, inflammation and ischemia as reflected by elevated Cyr61 levels leading to larger levels of troponin and lower LVEF. Trial registration Clinical Trial Registration Number: NCT01000701. Registered October 23, 2009

    Performance of hospitals according to the ESC ACCA quality indicators and 30-day mortality for acute myocardial infarction: national cohort study using the United Kingdom Myocardial Ischaemia National Audit Project (MINAP) register

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    Aims To investigate the application of the European Society of Cardiology Acute Cardiovascular Care Association quality indicators (QI) for acute myocardial infarction for the study of hospital performance and 30-day mortality. Methods and results National cohort study (n = 118,075 patients, n = 211 hospitals, MINAP registry), 2012-13. Overall, 16 of the 20 QIs could be calculated. Eleven QIs had a significant inverse association with GRACE risk adjusted 30-day mortality (all P < 0.005). The association with the greatest magnitude was high attainment of the composite opportunity-based QI (80-100%) vs. zero attainment (odds ratio 0.04, 95% confidence interval 0.04-0.05, P < 0.001), increasing attainment from low (0.42, 0.37- 0.49, P < 0.001) to intermediate (0.15, 0.13-0.16, P < 0.001) was significantly associated with a reduced risk of 30-day mortality. A 1% increase in attainment of this QI was associated with a 3% reduction in 30-day mortality (0.97, 0.97-0.97, P < 0.001). The QI with the widest hospital variation was â€Čfondaparinux received among NSTEMIâ€Č (interquartile range 84.7%) and least variation â€Čcentre organisationâ€Č (0.0%), with seven QIs depicting minimal variation (<11%). GRACE risk score adjusted 30-day mortality varied by hospital (median 6.7%, interquartile range 5.4-7.9%). Conclusions Eleven QIs were significantly inversely associated with 30-day mortality. Increasing patient attainment of the composite quality indicator was the most powerful predictor; a 1% increase in attainment represented a 3% decrease in 30-day standardised mortality. The ESC QIs for acute myocardial infarction are applicable in a large health system and have the potential to improve care and reduce unwarranted variation in death from acute myocardial infarction

    Spontaneous recanalization of a completely occluded saphenous vein graft two months following acute myocardial infarction with persistent one year patency

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    Acute myocardial infarction resulting from saphenous vein graft occlusion occurs not infrequently in patients who have undergone coronary artery bypass graft surgery. In this case report, we present a novel case of spontaneous recanalization of a thrombotic graft occlusion in a patient who presented with a subacute myocardial infarction. The patient was treated medically with aspirin as the only anti-platelet agent. Interestingly, he presented 2 months later with new onset angina. Coronary angiography demonstrated complete resolution of thrombus but a severe focal stenosis in the distal anastomoses. Following drug eluting stent placement, a favorable clinical course has ensued and patency confirmed on follow up angiography at 1 year

    The RAPID-CTCA trial (Rapid Assessment of Potential Ischaemic Heart Disease with CTCA) - a multicentre parallel-group randomised trial to compare early computerised tomography coronary angiography versus standard care in patients presenting with suspected or confirmed acute coronary syndrome: study protocol for a randomised controlled trial.

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    BACKGROUND: Emergency department attendances with chest pain requiring assessment for acute coronary syndrome (ACS) are a major global health issue. Standard assessment includes history, examination, electrocardiogram (ECG) and serial troponin testing. Computerised tomography coronary angiography (CTCA) enables additional anatomical assessment of patients for coronary artery disease (CAD) but has only been studied in very low-risk patients. This trial aims to investigate the effect of early CTCA upon interventions, event rates and health care costs in patients with suspected/confirmed ACS who are at intermediate risk. METHODS/DESIGN: Participants will be recruited in about 35 tertiary and district general hospitals in the UK. Patients ≄18 years old with symptoms with suspected/confirmed ACS with at least one of the following will be included: (1) ECG abnormalities, e.g. ST-segment depression >0.5 mm; (2) history of ischaemic heart disease; (3) troponin elevation above the 99(th) centile of the normal reference range or increase in high-sensitivity troponin meeting European Society of Cardiology criteria for 'rule-in' of myocardial infarction (MI). The early use of ≄64-slice CTCA as part of routine assessment will be compared to standard care. The primary endpoint will be 1-year all-cause death or recurrent type 1 or type 4b MI at 1 year, measured as the time to such event. A number of secondary clinical, process and safety endpoints will be collected and analysed. Cost effectiveness will be estimated in terms of the lifetime incremental cost per quality-adjusted life year gained. We plan to recruit 2424 (2500 with ~3% drop-out) evaluable patients (1212 per arm) to have 90% power to detect a 20% versus 15% difference in 1-year death or recurrent type 1 MI or type 4b MI, two-sided p < 0.05. Analysis will be on an intention-to-treat basis. The relationship between intervention and the primary outcome will be analysed using Cox proportional hazard regression adjusted for study site (used to stratify the randomisation), age, baseline Global Registry of Acute Coronary Events score, previous CAD and baseline troponin level. The results will be expressed as a hazard ratio with the corresponding 95% confidence intervals and p value. DISCUSSION: The Rapid Assessment of Potential Ischaemic Heart Disease with CTCA (RAPID-CTCA) trial will recruit 2500 participants across about 35 hospital sites. It will be the first study to investigate the role of CTCA in the early assessment of patients with suspected or confirmed ACS who are at intermediate risk and including patients who have raised troponin measurements during initial assessment. TRIAL REGISTRATION: ISRCTN19102565 . Registered on 3 October 2014. ClinicalTrials.gov: NCT02284191

    Platelet inhibition with ticagrelor 60 mg versus 90 mg twice daily in the PEGASUS-TIMI 54 trial

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    Background The PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis In Myocardial Infarction 54) trial studied 2 doses of ticagrelor, 90 mg twice a day (bid) and 60 mg bid, for long-term prevention of ischemic events in patients with prior myocardial infarction. Both doses similarly reduced the rate of ischemic events versus placebo. The pharmacokinetics and pharmacodynamics of ticagrelor 60 mg bid have not been studied. Objectives In this study, the authors sought to study the pharmacokinetics and pharmacodynamics for ticagrelor 60 mg compared with 90 mg bid. Methods A total of 180 patients who received >4 weeks of study medication had blood sampling in the morning pre-maintenance dose and again 2 h post-dose. All patients received aspirin. Plasma levels of ticagrelor and its active metabolite AR-C124910XX were determined. P2Y12 inhibition was assessed by the VerifyNow P2Y12 assay (Accumetrics, Inc., San Diego, California) (P2Y12 reaction units [PRU]), light transmittance aggregometry (adenosine diphosphate 5 and 20 ÎŒmol/l and arachidonic acid), and vasodilator-stimulated phosphoprotein phosphorylation assays. VerifyNow Aspirin assays and serum thromboxane B2 measurements were performed. Results Mean pre- and post-dose plasma levels of ticagrelor were 35% and 38% lower, respectively, with 60 mg versus 90 mg. Both doses achieved high levels of platelet inhibition pre- and post-dose, with numerically slightly more variability with 60 mg: mean (SD) pre-dose PRU values were 59 ± 63 and 47 ± 43 for ticagrelor 60 and 90 mg, respectively (p = 0.34). High platelet reactivity, determined as PRU >208, was rare with the 60-mg pre-dose and was absent post-dose. Platelet reactivity pre- and post-dose, as measured by light transmittance aggregometry or vasodilator-stimulated phosphoprotein assays, was numerically but not significantly lower with 90 mg than with 60 mg. Aspirin response was not affected by either dose. Conclusions Ticagrelor 60 mg bid achieved high levels of peak and trough platelet inhibition in nearly all patients, similar to that with 90 mg bid, helping to explain the efficacy of the lower ticagrelor dose in PEGASUS-TIMI 54
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