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Effect of Evolocumab on Complex Coronary Disease Requiring Revascularization.
Oyama, K, Furtado, RHM, Fagundes, A, Zelniker, TA, Tang, M, Kuder, J, Murphy, SA, Hamer, A, Wang, H, Keech, AC, et al
Journal of the American College of Cardiology. 2021;(3):259-267
Abstract
OBJECTIVES This study sought to evaluate the ability of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab to reduce the risk of complex coronary atherosclerosis requiring revascularization. BACKGROUND PCSK9 inhibitors induce plaque regression and reduce the risk of coronary revascularization overall. METHODS FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) was a randomized trial of the PCSK9 inhibitor evolocumab versus placebo in 27,564 patients with stable atherosclerotic cardiovascular disease on statin therapy followed for a median of 2.2 years. Clinical documentation of revascularization events was blindly reviewed to assess coronary anatomy and procedural characteristics. Complex revascularization was the composite of complex percutaneous coronary intervention (PCI) (as per previous analyses, ≥1 of: multivessel PCI, ≥3 stents, ≥3 lesions treated, bifurcation PCI, or total stent length >60 mm) or coronary artery bypass grafting surgery (CABG). RESULTS In this study, 1,724 patients underwent coronary revascularization, including 1,482 who underwent PCI, 296 who underwent CABG, and 54 who underwent both. Complex revascularization was performed in 632 (37%) patients. Evolocumab reduced the risk of any coronary revascularization by 22% (hazard ratio [HR]: 0.78; 95% CI: 0.71 to 0.86; p < 0.001), simple PCI by 22% (HR: 0.78; 95% CI: 0.70 to 0.88; p < 0.001), complex PCI by 33% (HR: 0.67; 95% CI: 0.54 to 0.84; p < 0.001), CABG by 24% (HR: 0.76; 95% CI: 0.60 to 0.96; p = 0.019), and complex revascularization by 29% (HR: 0.71; 95% CI: 0.61 to 0.84; p < 0.001). The magnitude of the risk reduction with evolocumab in complex revascularization tended to increase over time (20%, 36%, and 41% risk reductions in the first, second, and beyond second years). CONCLUSIONS Adding evolocumab to statin therapy significantly reduced the risk of developing complex coronary disease requiring revascularization, including complex PCI and CABG individually. (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk (FOURIER); NCT01764633.).
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Coronary Artery Spasm: New Insights.
Matta, A, Bouisset, F, Lhermusier, T, Campelo-Parada, F, Elbaz, M, Carrié, D, Roncalli, J
Journal of interventional cardiology. 2020;:5894586
Abstract
Coronary artery spasm (CAS) defined by a severe reversible diffuse or focal vasoconstriction is the most common diagnosis among INOCA (ischemia with no obstructive coronary artery disease) patients irrespective to racial, genetic, and geographic variations. However, the prevalence of CAS tends to decrease in correlation with the increasing use of medicines such as calcium channel blockers, angiotensin converting enzyme inhibitor, and statins, the controlling management of atherosclerotic risk factors, and the decreased habitude to perform a functional reactivity test in highly active cardiac catheterization centers. A wide spectrum of clinical manifestations from silent disease to sudden cardiac death was attributed to this complex entity with unclear pathophysiology. Multiple mechanisms such as the autonomic nervous system, endothelial dysfunction, chronic inflammation, oxidative stress, and smooth muscle hypercontractility are involved. Regardless of the limited benefits proffered by the newly emerged cardiac imaging modalities, the provocative test remains the cornerstone diagnostic tool for CAS. It allows to reproduce CAS and to evaluate reactivity to nitrates. Different invasive and noninvasive therapeutic approaches are approved for the management of CAS. Long-acting nondihydropyridine calcium channel blockers are recommended for first line therapy. Invasive strategies such as PCI (percutaneous coronary intervention) and CABG (coronary artery bypass graft) have shown benefits in CAS with significant atherosclerotic lesions. Combination therapies are proposed for refractory cases.
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Early and Mid-Term Vascular Responses to Optical Coherence Tomography-Guided Everolimus-Eluting Stent Implantation in Stable Coronary Artery Disease.
Shinke, T, Itoh, T, Ishida, M, Otake, H, Terashita, D, Fusazaki, T, Kikuchi, T, Okamura, T, Morita, T, Hayashi, T, et al
The Canadian journal of cardiology. 2019;(11):1513-1522
Abstract
BACKGROUND Analysis of pooled clinical data has shown the safety of 3 months of dual antiplatelet therapy with everolimus-eluting cobalt-chromium stents (Co-Cr EESs). This study evaluated early and mid-term vascular responses to Co-Cr EESs in patients with stable coronary artery disease. METHODS The Multicenter Comparison of Early and Late Vascular Responses to Everolimus-Eluting Cobalt-Chromium Stent and Platelet Aggregation Studies in Patients With Stable Angina Managed as Elective Case (MECHANISM-Elective) study (NCT02014818) is a multicenter optical coherence tomography (OCT) registry. Enrolled patients were evaluated by OCT immediately after everolimus-eluting stent implantation were prospectively allocated to 1 month (n = 50) or 3 months (n = 50) OCT follow-up and then received a 12-month OCT evaluation. The incidences of intrastent thrombus (IS-Th) and irregular protrusion (IRP) were also assessed. RESULTS The percentage of uncovered struts was 6.4% ± 10.3% at 1 month (P < 0.001 vs. postprocedure) and 0.5% ± 0.9% at 12 months (P < 0.001 vs. 1 month). The corresponding values in the 3-month cohort were 2.0% ± 2.5% (P < 0.001 vs. postprocedure) and 0.5% ± 1.5% (P < 0.001 vs. 3 months). The incidence of IS-Th was 32.7% at 1 month, 5.4% at 3 months, and 2.0% at 12 months. IRP was observed in 21.8% of patients post-EES but had totally resolved at 1, 3, and 12 months. CONCLUSION Early and mid-term vascular reactions after Co-Cr EES implantation in stable patients with coronary artery disease in the MECHANISM-Elective included dynamic resolution of IS-Th and IRP and rapid decrease in uncovered struts. Thus, EES may allow shortening of dual antiplatelet therapy duration less than 3 months in this patient subset.
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Relationship Between Optimism and Outcomes in Patients With Chronic Angina Pectoris.
Fanaroff, AC, Prather, K, Brucker, A, Wojdyla, D, Davidson-Ray, L, Mark, DB, Williams, RB, Barefoot, J, Weisz, G, Ben-Yehuda, O, et al
The American journal of cardiology. 2019;(9):1399-1405
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Abstract
Greater optimism regarding recovery from chronic illness is associated with improved quality of life and clinical outcomes. We performed a post-hoc analysis on the association between optimism and outcomes in Ranolazine in Patients with Incomplete Revascularization after Percutaneous Coronary Intervention (RIVER-PCI), a randomized trial in patients with chronic angina pectoris who had incomplete revascularization following percutaneous coronary intervention. At baseline, patients answered how much they agreed with the phrase, "I am optimistic about my future and returning to a normal lifestyle." We evaluated the association between baseline optimism and time to ischemia-driven hospitalization or revascularization using a Cox model, and the association between baseline optimism and change in frequency of angina pectoris using a mixed measures model. Of 2,389 patients, 782 (33.2%) were very optimistic ("strongly agree"), 1,000 (42.4%) were optimistic ("agree"), 451 (19.1%) were neutral ("undecided"), and 123 (5.2%) were not optimistic ("disagree" or "strongly disagree"). Very optimistic patients had a lower prevalence of co-morbidities and less severe angina at baseline than less optimistic patients. The rate of ischemia-driven revascularization or hospitalization was higher in neutral and not optimistic patients compared with very optimistic patients; this finding persisted after adjustment for co-morbidities and baseline angina frequency (hazard ratio 1.42, 95% confidence interval 1.14 to 1.77 for neutral vs very optimistic; hazard ratio 1.38, 95% confidence interval 0.98 to 1.94 for not optimistic vs very optimistic). Neutral and not optimistic patients also had less improvement in angina than very optimistic patients. In conclusion, in patients with angina, those with more self-reported optimism had better health status outcomes. Whether structured interventions targeting optimism improve outcomes in these patients warrants further study.
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Rationale and design of a trial to personalize risk assessment in familial coronary artery disease.
Marwick, TH, Whitmore, K, Nicholls, SJ, Stanton, T, Mitchell, G, Tonkin, A, Blizzard, C, Neil, A, Jones, C, Watts, GF, et al
American heart journal. 2018;:22-30
Abstract
BACKGROUND The lifetime risk of coronary artery disease (CAD) is doubled in people with a family history of premature disease, yet this risk is not captured in most 5- or 10-year risk assessment algorithms. Coronary artery calcium scoring (CCS) is a marker of subclinical CAD risk, which has been shown in observational studies to provide prognostic information that is incremental to clinical assessment; is relatively inexpensive; and is performed with a small radiation dose. However, the use of CCS in guiding prevention is not strongly supported by guidelines. Showing definitive evidence of the efficacy and cost-effectiveness of CCS is therefore of importance. STUDY DESIGN The proposed randomized controlled trial of the use of CCS will be targeted to 40- to 70-year-old first-degree relatives of patients with CAD onset <60 years old or second-degree relatives of patients with onset <50 years old. Control patients will undergo standard risk scoring and be blinded to CCS results. In the intervention group, primary prevention in patients undergoing CCS will be informed by this score. At 3 years, effectiveness will be assessed on change in plaque volume at computed tomography coronary angiography, the extent of which has been strongly linked to outcome. SUMMARY The CAUGHT-CAD trial will provide evidence to inform the guidelines regarding the place of CCS in decision making regarding primary prevention of patients with a family history of premature disease.
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High Triglycerides Are Associated With Increased Cardiovascular Events, Medical Costs, and Resource Use: A Real-World Administrative Claims Analysis of Statin-Treated Patients With High Residual Cardiovascular Risk.
Toth, PP, Granowitz, C, Hull, M, Liassou, D, Anderson, A, Philip, S
Journal of the American Heart Association. 2018;(15):e008740
Abstract
Background The American Heart Association recognizes high triglycerides as a cardiovascular risk factor. Methods and Results This retrospective observational administrative claims analysis (Optum Research Database) included statin-treated patients ≥45 years old with diabetes mellitus and/or atherosclerotic cardiovascular disease, triglycerides 2.26 to 5.64 mmol/L, and a propensity-matched comparator cohort with triglycerides <1.69 mmol/L and high-density lipoprotein cholesterol >1.04 mmol/L. In the high-triglycerides cohort versus comparators (both n=10 990, 49% women), mean age was 61.7 versus 62.2 years and follow-up was 41.3 versus 42.1 months, respectively. Multivariate analysis of composite major cardiovascular events demonstrated significantly increased risk in the high-triglycerides (n=13 411 patients) versus comparator (n=32 506 patients) cohorts (hazard ratio [ HR ], 1.35; 95% confidence interval [ CI ], 1.225-1.485; P<0.001), with significantly higher risk for nonfatal myocardial infarction ( HR , 1.35; 95% CI , 1.19-1.52; P<0.001), nonfatal stroke ( HR , 1.27; 95% CI , 1.14-1.42; P<0.001), and need for coronary revascularization ( HR , 1.51; 95% CI , 1.34-1.69; P<0.001), but not unstable angina or cardiovascular death. Increased cardiovascular risk in the high-triglycerides versus comparator cohort was maintained, even with addition of non-high-density lipoprotein cholesterol to the multivariate model and when analyzing high and low high-density lipoprotein cholesterol subgroups. Average total healthcare cost per patient per month (cost ratio, 1.15; 95% CI , 1.084-1.210; P<0.001) and rate of occurrence of inpatient hospital stay ( HR , 1.17; 95% CI , 1.113-1.223; P<0.001) were also significantly greater in the high-triglycerides cohort. Conclusions In this real-world analysis, patients with high cardiovascular risk and high triglycerides had worse composite cardiovascular and health economic outcomes than patients with well-managed triglycerides and high-density lipoprotein cholesterol >1.04 mmol/L.
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Cardioprotective efficacy of sevoflurane vs. propofol during induction and/or maintenance in patients undergoing coronary artery revascularization surgery without pump: A randomized trial.
Guerrero Orriach, JL, Galán Ortega, M, Ramirez Fernandez, A, Ramirez Aliaga, M, Moreno Cortes, MI, Ariza Villanueva, D, Florez Vela, A, Alcaide Torres, J, Santiago Fernandez, C, Matute Gonzalez, E, et al
International journal of cardiology. 2017;:73-80
Abstract
PURPOSE Pre and post-operative administration of sevoflurane in myocardial revascularization surgery provides enhanced cardioprotective effects exerted by pharmacologic pre- and post-conditioning, as compared to propofol. The identification of the enzymes involved in conditioning mechanisms is crucial to the understanding of the effects of sevoflurane in cardiac surgery patients. The impact of sevoflurane on another crucial target organ-the kidney-was also assessed. METHODS Ninety patients undergoing off-pump myocardial revascularization surgery were allocated to receive either intra- and postoperative sevoflurane (SS), intraoperative sevoflurane and postoperative propofol (SP), or intra- and postoperative propofol (PP)). Troponin I and hemodynamic parameters were monitored during the first 48 postoperative hours; blood and urine samples were collected at baseline and at 24h to determine Akt, ERK1/2, PKG, iNO, bradykinin receptor, caspase 3, NT proBNP and urinary NGAL. RESULTS The enzymes were overexpressed in the SS group, remained unchanged in the SP group, and decreased in the PP group. Renal function was best preserved in the SS group. CONCLUSIONS The overexpression of enzymes induced by intraoperative anesthesia and postoperative sedation with sevoflurane reduces myocardial damage and improves renal function in patients undergoing off-pump myocardial revascularization surgery.
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Oral glutamine reduces myocardial damage after coronary revascularization under cardiopulmonary bypass. A randomized clinical trial.
Chávez-Tostado, M, Carrillo-Llamas, F, Martínez-Gutiérrez, PE, Alvarado-Ramírez, A, López-Taylor, JG, Vásquez-Jiménez, JC, Fuentes-Orozco, C, Rendón-Félix, J, Irusteta-Jiménez, L, Calil-Romero, VC, et al
Nutricion hospitalaria. 2017;(2):277-283
Abstract
BACKGROUND Glutamine is the most abundant free amino acid in the body. It modulates immune cell function and is an important energy substrate for cells in critically ill patients. Reduction of injury cardiac markers had been observed in patients receiving intravenous glutamine and in a pilot study with oral glutamine. The aim of this study was to analyze the effect of preoperative oral supplementation of glutamine on postoperative serum levels of cardiac injury markers. METHODS A randomized clinical trial was performed in 28 Mexican patients with ischemic heart disease who underwent cardiopulmonary bypass with extracorporeal circulation. Patients were randomly assigned to receive oral glutamine (0.5 g/kg/day) or maltodextrin 3 days before surgery. Cardiac injury markers as troponin-I, creatine phosphokinase, and creatine phosphokinase-Mb were measured at 1, 12, and 24 hours postoperatively. RESULTS At 12 and 24 hours serum markers levels were significantly lower in the glutamine group compared with controls (p = 0.01 and p = 0.001, respectively) (p = 0.004 and p < 0.001, respectively). Overall, complications were significantly lower in the glutamine group (p = 0.01, RR = 0.54, 95% CI 0.31-0.93). Mortality was observed with 2 cases of multiple organ failure in control group and 1 case of pulmonary embolism in glutamine group (p = 0.50). CONCLUSION Preoperative oral glutamine standardized at a dose of 0.5 g/kg/day in our study group showed a significant reduction in postoperative myocardial damage. Lower cardiac injury markers levels, morbidity and mortality were observed in patients receiving glutamine.
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Increasing Cardiac Rehabilitation Participation From 20% to 70%: A Road Map From the Million Hearts Cardiac Rehabilitation Collaborative.
Ades, PA, Keteyian, SJ, Wright, JS, Hamm, LF, Lui, K, Newlin, K, Shepard, DS, Thomas, RJ
Mayo Clinic proceedings. 2017;(2):234-242
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Abstract
The primary aim of the Million Hearts initiative is to prevent 1 million cardiovascular events over 5 years. Concordant with the Million Hearts' focus on achieving more than 70% performance in the "ABCS" of aspirin for those at risk, blood pressure control, cholesterol management, and smoking cessation, we outline the cardiovascular events that would be prevented and a road map to achieve more than 70% participation in cardiac rehabilitation (CR)/secondary prevention programs by the year 2022. Cardiac rehabilitation is a class Ia recommendation of the American Heart Association and the American College of Cardiology after myocardial infarction or coronary revascularization, promotes the ABCS along with lifestyle counseling and exercise, and is associated with decreased total mortality, cardiac mortality, and rehospitalizations. However, current participation rates for CR in the United States generally range from only 20% to 30%. This road map focuses on interventions, such as electronic medical record-based prompts and staffing liaisons that increase referrals of appropriate patients to CR, increase enrollment of appropriate individuals into CR, and increase adherence to longer-term CR. We also calculate that increasing CR participation from 20% to 70% would save 25,000 lives and prevent 180,000 hospitalizations annually in the United States.
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Remnant Lipoprotein Cholesterol and Incident Coronary Heart Disease: The Jackson Heart and Framingham Offspring Cohort Studies.
Joshi, PH, Khokhar, AA, Massaro, JM, Lirette, ST, Griswold, ME, Martin, SS, Blaha, MJ, Kulkarni, KR, Correa, A, D'Agostino, RB, et al
Journal of the American Heart Association. 2016;(5)
Abstract
BACKGROUND Remnant lipoproteins (RLPs), the triglyceride-enriched precursors to low-density lipoprotein, are an emerging risk factor for coronary heart disease (CHD). We sought to determine the association of RLP cholesterol (RLP-C) levels with incident CHD in 2 diverse, prospective, longitudinal observational US cohorts. METHODS AND RESULTS We analyzed cholesterol levels from serum lipoprotein samples separated via density gradient ultracentrifugation in 4114 US black participants (mean age 53.8 years, 64% women) from the Jackson Heart Study and a random sample of 818 predominantly white participants (mean age 57.3 years, 52% women) from the Framingham Offspring Cohort Study. Multivariable-adjusted hazard ratios (HRs) for RLP-C (the sum of very low-density lipoprotein3 cholesterol and intermediate-density lipoprotein cholesterol) were derived to estimate associations with incident CHD events consisting of myocardial infarction, CHD death, and revascularizations for each cohort separately and as a combined population. There were 146 CHD events in the combined population. After adjustments for age, sex, body mass index, smoking, blood pressure, diabetes, and lipid-lowering therapy for the combined population, RLP-C (HR 1.23 per 1-SD increase, 95% CI 1.06-1.42, P<0.01) and intermediate-density lipoprotein cholesterol (HR 1.26 per 1-SD increase, 95% CI 1.08-1.47, P<0.01) predicted CHD during an 8-year follow-up. Associations were attenuated by high-density lipoprotein cholesterol and ultimately lost significance with inclusion of real low-density lipoprotein cholesterol, which excludes Lp(a) and IDL cholesterol fractions. Similar associations were seen in multivariable analyses within each cohort. CONCLUSION RLP-C levels are predictive of incident CHD in this diverse group of primary prevention subjects. Interventions aimed at reducing RLP-C to prevent CHD warrant further intensive investigation. CLINICAL TRIAL REGISTRATION URL: http://www.ClinicalTrials.gov. Unique identifier: NCT00415415.