57 research outputs found
Coronary Atheroma Regression With Evolocumab in Stable and Unstable Coronary Syndromes
No full textStephen J. Nicholls, Yu Kataoka, Steven E. Nissen, Francesco Prati, Stephan Windecker, Rishi Puri, Thomas Hucko, Daniel Aradi, Jean-Paul R. Herrman, Renicus S. Hermanides, Bei Wang, Huei Wang, Julie Butters, Giuseppe Di Giovanni, Stephen Jones, Gianluca Pompili, Kathy Wolski, Peter J. Psalti
Hyperglycemia, hypoglycemia, and glycemic complexity are associated with worse outcomes after surgery
No full textPurpose: The purpose of this study was to determine if glycemic complexity, along with hypoglycemia and hyperglycemia, was associated with worse outcomes after cardiac surgery. Materials and methods: We conducted a retrospective analysis of 970 patients who had insulin infusions designed to keep blood glucose levels between 80 and 110 mg-dL. Glycemic complexity was calculated using jackknifed approximate entropy. Logistic regression was used to adjust for confounders. Results: A total of 495 patients (51percent) developed complications, and 32 patients (3.3percent) died. Along with older age, comorbidities, and complicated surgeries, any hypoglycemia (glucose 71 mg-dL) and the number of glucose values greater than 140 mg-dL were independent predictors of complications. Increased risk of mortality, after adjusting for other risk factors, was associated with older age, longer perfusion time, receiving intraoperative transfusions, and greater jackknifed approximate entropy of the glucose time series. Conclusion: We found that hypoglycemia (glucose 71 mg-dL) and hyperglycemia (glucose 140 mg-dL) were associated with increased risk of complications, whereas greater complexity of the glucose time series was associated with mortality. © 2014 Elsevier Inc.Amir J, 2011, CELL IMMUNOL, V272, P45, DOI 10.1016-j.cellimm.2011.09.008; Bagshaw SM, 2009, CRIT CARE, V13, DOI 10.1186-cc7921; Cochran WG, 1967, SAMPLING TECHNIQUES, P154; Cueni-Villoz N, 2011, CRIT CARE MED, V39, P2225, DOI 10.1097-CCM.0b013e31822572c9; D'Ancona G, 2011, EUR J CARDIO-THORAC, V40, P360, DOI 10.1016-j.ejcts.2010.11.065; Egi M, 2010, MAYO CLIN PROC, V85, P217, DOI 10.4065-mcp.2009.0394; Engoren M, 2009, J APPL PHYSIOL, V106, P766, DOI 10.1152-japplphysiol.90575.2008; Finfer S, 2009, NEW ENGL J MED, V360, P1283, DOI 10.1056-NEJMoa0810625; Finney SJ, 2003, JAMA-J AM MED ASSOC, V290, P2041, DOI 10.1001-jama.290.15.2041; Hermanides J, 2010, CRIT CARE MED, V38, P838, DOI 10.1097-CCM.0b013e3181cc4be9; Hermanides J, 2010, CRIT CARE MED, V38, P1430, DOI 10.1097-CCM.0b013e3181de562c; Hollingdal M, 2000, DIABETES, V49, P1334, DOI 10.2337-diabetes.49.8.1334; Kemeny SF, 2011, J BIOMECH, V44, P1927, DOI 10.1016-j.jbiomech.2011.04.026; Krinsley JS, 2004, MAYO CLIN PROC, V79, P992; Krinsley James Stephen, 2009, J Diabetes Sci Technol, V3, P1292; Lazar HL, 2009, ANN THORAC SURG, V87, P663, DOI 10.1016-j.athoracsur.2008.11.011; Li J, 2006, PHYS REV E, V73, DOI 10.1103-PhysRevE.73.052902; Mackenzie IMJ, 2011, INTENS CARE MED, V37, P435, DOI 10.1007-s00134-010-2103-2; Meyfroidt G, 2011, INTENS CARE MED, V37, P1151, DOI 10.1007-s00134-011-2159-7; Meyfroidt G, 2010, CRIT CARE MED, V38, P1021, DOI 10.1097-CCM.0b013e3181cf710e; Pappada SM, 2011, DIABETES TECHNOL THE, V13, P135, DOI 10.1089-dia.2010.0104; Pincus SM, 2008, J PSYCHIATR RES, V42, P337, DOI 10.1016-j.jpsychires.2007.01.001; Suh SW, 2007, GLIA, V55, P1280, DOI 10.1002-glia.20440; Van den Berghe G, 2006, NEW ENGL J MED, V354, P449, DOI 10.1056-NEJMoa052521; Van den Berghe G, 2001, NEW ENGL J MED, V345, P1359, DOI 10.1056-NEJMoa011300; Wang X, 2009, THESIS U VIRGINIA; Wessel N, 2000, PHYS REV E, V61, P733, DOI 10.1103-PhysRevE.61.7330
Thin-Cap Fibroatheroma Rather Than Any Lipid Plaques Increases the Risk of Cardiovascular Events in Diabetic Patients: Insights from the COMBINE OCT-FFR Trial
No full textBackground: Autopsy studies have established that thin-cap fibroatheromas (TCFAs) are the most frequent cause of fatal coronary events. In living patients, optical coherence tomography (OCT) has sufficient resolution to accurately differentiate TCFA from thick-cap fibroatheroma (ThCFA) and not lipid rich plaque (non-LRP). However, the impact of OCT-detected plaque phenotype of nonischemic lesions on future adverse events remains unknown. Therefore, we studied the natural history of OCT-detected TCFA, ThCFA, and non-LRP in patients enrolled in the prospective multicenter COMBINE FFR-OCT trial (Combined Optical Coherence Tomography Morphologic and Fractional Flow Reserve Hemodynamic Assessment of Non-Culprit Lesions to Better Predict Adverse Event Outcomes in Diabetes Mellitus Patients). Methods: In the COMBINE FFR-OCT trial, patients with diabetes and ≥1 lesion with a fractional flow reserve >0.80 underwent OCT evaluation and were clinically followed for 18 months. A composite primary end point of cardiac death, target vessel-related myocardial infarction, target-lesion revascularization, and hospitalization for unstable angina was evaluated in relation to OCT-based plaque morphology. Results: A total of 390 patients (age 67.5±9 years; 63% male) with ≥1 nonischemic lesions underwent OCT evaluation: 284 (73%) had ≥1 LRP and 106 (27%) non-LRP lesions. Among LRP patients, 98 (34.5%) had ≥1 TCFA. The primary end point occurred in 7% of LRP patients compared with 1.9% of non-LRP patients (7.0% versus 1.9%; hazard ratio [HR], 3.9 [95% CI, 0.9-16.5]; P=0.068; log rank-P=0.049). However, within LRP patients, TCFA patients had a much higher risk for primary end point compared with ThCFA (13.3% versus 3.8%; HR, 3.8 [95% CI, 1.5-9.5]; P<0.01), and to non-LRP patients (13.3% versus 1.9%; HR, 7.7 [95% CI, 1.7-33.9]; P<0.01), whereas ThCFA patients had risk similar to non-LRP patients (3.8% versus 1.9%; HR, 2.0 [95% CI, 0.42-9.7]; P=0.38). Multivariable analyses identified TCFA as the strongest independent predictor of primary end point (HR, 6.79 [95% CI, 1.50-30.72]; P=0.013). Conclusions: Among diabetes patients with fractional flow reserve-negative lesions, patients carrying TCFA lesions represent only one-third of LRP patients and are associated with a high risk of future events while patients carrying LRP-ThCFA and non-LRP lesions portend benign outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02989740
Long-term outcomes of patients with normal fractional flow reserve and thin-cap fibroatheroma
No full textBACKGROUND: The long-term prognostic implications of fractional flow reserve (FFR)-negative lesions hosting vulnerable plaques remain unsettled. AIMS: The aim of this study was to evaluate the association of non-ischaemic lesions hosting optical coherence tomography (OCT)-detected thin-cap fibroatheromas (TCFA) with first and recurrent cardiovascular events during follow-up up to 5 years in a diabetes mellitus (DM) patient population. METHODS: COMBINE OCT-FFR is a prospective, international, double-blind, natural history study. Patients with DM and with ≥1 FFR-negative lesion were classified into 2 groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint (PE) is a composite of cardiac mortality, target vessel-related myocardial infarction (TV-MI), clinically driven target lesion revascularisation (TLR), or unstable angina (UA) requiring hospitalisation during follow-up up to 5 years. RESULTS: Among 390 DM patients (age 67.5±9 years; 37% female) with ≥1 FFR-negative lesion, 292 (74.9%) were TCFA-negative while 98 (25.1%) were TCFA-positive. The PE occurred more frequently in TCFA-positive than in TCFA-negative patients (21.4% vs 8.2%, hazard ratio [HR] 2.89, 95% confidence interval [CI]: 1.61-5.20; p<0.001; 6.42 vs 2.46 events per 100 patient-years, rate ratio [RR] 2.61, 95% CI: 1.38-4.90; p=0.002). Furthermore, when TV-MI, TLR, and UA were treated as recurrent components of the PE, TCFA-positive patients experienced a higher risk of recurrent events (HR 2.89, 95% CI; 1.74-4.80; p<0.001; 13.45 vs 2.87 events per 100 patient-years, RR 4.69, 95% CI: 2.86-7.83; p<0.001). A multivariable analysis identified the presence of TCFA as an independent predictor of the PE (HR 2.76, 95% CI: 1.53-4.97; p<0.001). CONCLUSIONS: OCT-detected TCFA-positive lesions, although not ischaemia-generating, are associated with an increased risk of adverse events during long-term follow-up. CLINICALTRIALS: gov: NCT02989740
Thin-cap fibroatheroma predicts clinical events in diabetic patients with normal fractional flow reserve: the COMBINE OCT-FFR trial
No full textAims The aim of this study was to understand the impact of optical coherence tomography (OCT)-detected thin-cap fibroatheroma (TCFA) on clinical outcomes of diabetes mellitus (DM) patients with fractional flow reserve (FFR)-negative lesions. Methods and results COMBINE OCT-FFR study was a prospective, double-blind, international, natural history study. After FFR assessment, and revascularization of FFR-positive lesions, patients with ≥1 FFR-negative lesions (target lesions) were classified in two groups based on the presence or absence of ≥1 TCFA lesion. The primary endpoint compared FFR-negative TCFA-positive patients with FFR-negative TCFA-negative patients for a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or unstable angina requiring hospitalization at 18 months. Among 550 patients enrolled, 390 (81%) patients had ≥1 FFR-negative lesions. Among FFR-negative patients, 98 (25%) were TCFA positive and 292 (75%) were TCFA negative. The incidence of the primary endpoint was 13.3% and 3.1% in TCFA-positive vs. TCFA-negative groups, respectively (hazard ratio 4.65; 95% confidence interval, 1.99-10.89; P < 0.001). The Cox regression multivariable analysis identified TCFA as the strongest predictor of major adverse clinical events (MACE) (hazard ratio 5.12; 95% confidence interval 2.12-12.34; P < 0.001). Conclusions Among DM patients with ≥1 FFR-negative lesions, TCFA-positive patients represented 25% of this population and were associated with a five-fold higher rate of MACE despite the absence of ischaemia. This discrepancy between the impact of vulnerable plaque and ischaemia on future adverse events may represent a paradigm shift for coronary artery disease risk stratification in DM patients
Clopidogrel Versus Ticagrelor or Prasugrel after Primary Percutaneous Coronary Intervention According to CYP2C19 Genotype: A POPular Genetics Subanalysis
No full textBackground: Guidelines favor ticagrelor or prasugrel over clopidogrel in patients with myocardial infarction. However, the POPular Genetics trial (Patient Outcome After Primary Percutaneous Coronary Intervention [PCI]) showed that in patients with primary PCI, a CYP2C19 genotype-guided strategy was associated with a lower bleeding risk without increasing thrombotic risk, compared with routine ticagrelor/prasugrel treatment. Nevertheless, optimal P2Y12 inhibitor treatment in specific CYP2C19 genetic subgroups is still a subject of debate. Methods: A prespecified subanalysis of the POPular Genetics trial was performed, using patients in whom CYP2C19∗2, ∗3, and ∗17 genotypes was determined. Two different analyses were planned. The first assessed the effect of the CYP2C19∗17 allele in clopidogrel-treated patients. The second compared the effect of clopidogrel in noncarriers of a loss-of-function allele with ticagrelor/prasugrel-treated patients, irrespective of CYP2C19 genotype. Main outcomes were a thrombotic outcome (cardiovascular death, myocardial infarction, stent thrombosis, and stroke) and a bleeding outcome (PLATO [Platelet Inhibition and Patient Outcomes] major and minor bleeding) after 12 months. Results: A total of 2429 patients were used for analyses. In the first analysis, the CYP2C19∗17 polymorphism was not found to have a significant influence on thrombotic (adjusted hazard ratio, 0.95 [95% CI, 0.45-2.02]) or bleeding outcomes (adjusted hazard ratio, 0.74 [95% CI, 0.48-1.18]). In the second analysis, clopidogrel was associated with a lower number of bleeding events compared with ticagrelor/prasugrel (9.9% versus 11.7%, adjusted hazard ratio, 0.74 [95% CI, 0.56-0.96]), without a significant increase in thrombotic events (3.4% versus 2.5%, adjusted hazard ratio, 1.14 [95% CI, 0.68-1.90]). Conclusions: In patients with primary PCI not carrying a CYP2C19 loss-of-function allele, the use of clopidogrel compared with ticagrelor or prasugrel was associated with lower bleeding rates, without an increase in thrombotic events. No effect on clinical outcomes was found for the CYP2C19∗17 polymorphism
Risk factors for domestic infestation by the Chagas disease vector, Triatoma dimidiata in Chiquimula, Guatemala.
No full textIn Guatemala prior to control initiatives, the main vectors of Trypanosoma cruzi, the causative agent of Chagas disease, were Rhodnius prolixus and Triatoma dimidiata. This study conducted in 2006 in the department of Chiquimula recorded a high level of T. dimidiata infestation and an absence of R. prolixus in all surveyed communities. In Guatemala, the presence of T. dimidiata as domestic, peridomestic and sylvatic populations results in control difficulties as houses are re-infested from the surrounding environment. Entomological surveys, the current method used to select houses in need of control efforts, are labour intensive and time consuming. A time- and cost-effective way to prioritize houses for evaluation and subsequent treatment is the stratification of houses based on the risk of triatomine infestation. In the present study, 17 anthropogenic risk factors were evaluated for associations with house infestation of T. dimidiata including: wall, floor and roof type. There was an increased likelihood of domestic infestation with T. dimidiata associated with the presence of dirt floors (18/29; OR 8.075, 95% CI 2.13-30.6), uncoated bajareque walls (12/17; OR 4.80, 95% CI 1.35-17.1) and triatomine-like faeces on walls (16/26; OR 3.89, 95% CI 1.19-12.7). These factors could be used to target control of T. dimidiata to communities with an increased risk of being infested
A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction
No full textBACKGROUND: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI).METHODS: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo.RESULTS: The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61]).CONCLUSIONS: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI
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