Search

Background: The PEARL study showed that palbociclib plus endocrine therapy (palbociclib/ET) was not superior to capecitabine in improving progression-free survival in postmenopausal patients with metastatic breast cancer resistant to aromatase inhibitors, but was better tolerated. This analysis compared patient-reported outcomes., Patients and Methods: The PEARL quality of life (QoL) population comprised 537 patients, 268 randomised to palbociclib/ET (exemestane or fulvestrant) and 269 to capecitabine. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and QLQ-BR23 and EQ-5D-3L questionnaires. Changes from the baseline and time to deterioration (TTD) were analysed using linear mixed-effect and stratified Cox regression models, respectively., Results: Questionnaire completion rate was high and similar between treatment arms. Significant differences were observed in the mean change in global health status (GHS)/QoL scores from the baseline to cycle 3 (2.9 for palbociclib/ET vs. -2.1 for capecitabine (95% confidence interval [CI], 1.4-8.6; P = 0.007). The median TTD in GHS/QoL was 8.3 months for palbociclib/ET versus 5.3 months for capecitabine (adjusted hazard ratio, 0.70; 95% CI, 0.55-0.89; P = 0.003). Similar improvements for palbociclib/ET were also seen for other scales as physical, role, cognitive, social functioning, fatigue, nausea/vomiting and appetite loss. No differences were observed between the treatment arms in change from the baseline in any item of the EQ-5D-L3 questionnaire as per the overall index score and visual analogue scale., Conclusion: Patients receiving palbociclib/ET experienced a significant delay in deterioration of GHS/QoL and several functional and symptom scales compared with capecitabine, providing additional evidence that palbociclib/ET is better tolerated., Trial Registration Number: NCT02028507 (ClinTrials.gov)., Eudract Study Number: 2013-003170-27., Competing Interests: Conflict of interest statement Z.K. has participated in advisory boards of and received speaker fees or travel support from Pfizer, Roche, AstraZeneca and Novartis. M.G-G.- has received honoraria from Pfizer and Eisai and has participated in advisory boards of Genentech and Daiichi Sankyo. He has received travel support from Pfizer, Novartis, Daiichi Sankyo, Roche and Kern. M.R.B. has received speaker fees and advisory grants from Pfizer, Novartis and Lilly. E.Ca., who has a stock and other ownership interests from Lilly, has received travel and accommodation support from Roche, and her husband, who has participated in consulting and advisory board activities with Bristol Myers Squibb, Novartis, Celgene, Roche Pharma, Janssen, Amgen, Incyte, AbbVie and Pfizer, has received travel and accommodation support from Celgene, Novartis and Bristol Myers Squibb. His institution has received research funding from Celgene, Janssen, Bristol Myers Squibb, Novartis, Roche/Genentech, Amgen, Pfizer and AbbVie. GEICAM has received research funding from Roche/Genentech, Bristol Myers Squibb, Novartis, Pfizer, Celgene, AstraZeneca, Merck Sharp & Dohme, Pierre Fabre and Takeda. E.Ci. has received advisory board honoraria from Lilly, Novartis, MSD, AstraZeneca, Pfizer and Roche and speakers' honoraria from Roche, Lilly and Pfizer, and she has received travel and congress assistance support from Pfizer and Roche. M.Mu. has received travel and congress assistance support from Roche, Novartis, Pfizer and Eisai. B.B. has received advisory board honoraria from Roche, Novartis and MSD and speakers' honoraria from Roche, Novartis, MSD, Pfizer and Pierre Fabre, and she has received travel and congress assistance support from Pfizer. M.Marg. has received advisory board fees from Roche, Novartis, Pfizer and Eisai. Her institution, ICO-Badalona. B-ARGO (Badalona Applied Research Group in Oncology) Hospital Universitari Germans Trias i Pujol, Badalona, has received research funding from Roche, Pfizer, Novartis, Lilly, AstraZeneca, Eisai and Kern, and she has received travel and congress assistance support from Roche. A.A. has received advisory board fees from Bayer, Spain. E.A. has received advisory board fees from Roche, Novartis, Pfizer, Lilly, Bristol Myers Squibb, Genomic Health and Nanostring. He has received travel support from Celgene. His institution, Hospitales Regional y Virgen de la Victoria, Málaga, has received research funding from Roche, Pfizer, Sysmex, Merck Sharp & Dohme and Nanostring. J.d.l.H-R. has received speaker's honoraria from AstraZeneca, Pfizer, Novartis and Lilly. M.R. has received honoraria from Novartis, Roche and Pfizer. I.M.A-L. has received consulting or advisory board honoraria from AstraZeneca, Pfizer, Novartis, Palex and Roche; speakers' honoraria from AstraZeneca, Pfizer, Novartis, Roche and Eisai; travel and congress assistance support from AstraZeneca, Pfizer, Roche and Eisai and research funding from Pfizer, Novartis, AstraZeneca and Roche. E.G-Y. has received honoraria and travel support and has participated in advisory boards for Pfizer, Roche, Novartis and Eli Lilly. S.G-S. has received consulting or advisory board honoraria from Pfizer, MSD, GSK and Roche and speakers' honoraria from AstraZeneca, Pfizer and Novartis. C.A.R. has received consulting or advisory board honoraria from AstraZeneca, Pfizer, Novartis, SeaGen, DaiiChi Sankyo and Roche and speakers' honoraria from MSD, Pfizer, Novartis, Roche, Nanostring, Amgen and Eisai. S.S. has received consulting or advisory board or speakers' honoraria from Roche, Eisai, Daiichi Sankyo, AstraZeneca, MSD and Genomic Health. M.C. is employed by Pfizer and has the company's stock options. X.H. is employed by Pfizer and has the company's stock options. C.Z. has received consulting fees and speaker's honoraria from Roche, Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Imugene, Ariad, Pfizer, Merrimack, Merck KGaA, FibroGen, AstraZeneca, Tesaro, Gilead, Servier, Shire, Eli Lilly and Athenex. His institution, Central European Cancer Center, Wiener Privatklinik Hospital, has received fees from Bristol Myers Squibb, Merck Sharp & Dohme, Pfizer, AstraZeneca and Merck KGaA. M.Mart. has received consulting fees from AstraZeneca, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology and Pfizer; speakers' honoraria from AstraZeneca, Amgen, Roche/Genentech, Novartis, Daiichi Sankyo and Pfizer and contracted research fees from Roche, Novartis and PUMA. All remaining authors have declared no conflicts of interest. A complete list of the PEARL trial collaborators is provided in the Supplementary Appendix., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The risk for cardiovascular adverse events after acute myocardial infarction (AMI) remains high despite potent medical treatment including low-density lipoprotein cholesterol (LDL-C) lowering with statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies substantially reduce LDL-C when added to statin. Alirocumab, a monoclonal antibody to PCSK9, reduces major adverse cardiovascular events after AMI. The effects of alirocumab on coronary atherosclerosis including plaque burden, plaque composition and fibrous cap thickness in patients presenting with AMI remains unknown., Aims: To determine the effect of LDL-C lowering with alirocumab on top of high-intensity statin therapy on intravascular ultrasound (IVUS)-derived percent atheroma volume (PAV), near-infrared spectroscopy (NIRS)-derived maximum lipid core burden index within 4 mm (maxLCBI 4 mm ) and optical coherence tomography (OCT)-derived fibrous cap thickness (FCT) in patients with AMI., Methods: In this multicenter, double-blind, placebo-controlled trial, 300 patients with AMI (ST-elevation or non-ST-elevation myocardial infarction) were randomly assigned to receive either biweekly subcutaneous alirocumab (150 mg) or placebo beginning <24 hours after the acute event as add-on therapy to rosuvastatin 20 mg. Patients undergo serial IVUS, NIRS and OCT in the two non-infarct related arteries at baseline (at the time of treatment of the culprit lesion) and at 52 weeks. The primary endpoint, change in IVUS-derived PAV, and the powered secondary endpoints, change in NIRS-derived maxLCBI 4 mm , and OCT-derived minimal FCT, will be assessed 52 weeks post randomization., Summary: The PACMAN-AMI trial will determine the effect of alirocumab on top of high-intensity statin therapy on high-risk coronary plaque characteristics as assessed by serial, multimodality intracoronary imaging in patients presenting with AMI., Clinical Trial Registration: NCT03067844., (Copyright © 2021. Published by Elsevier Inc.)

Aims: Impaired left ventricular diastolic function leading to elevated left atrial pressures, particularly during exertion, is a key driver of symptoms and outcomes in heart failure with preserved ejection fraction (HFpEF). Insertion of an interatrial shunt device (IASD) to reduce left atrial pressure in HFpEF has been shown to be associated with short-term haemodynamic and symptomatic benefit. We aimed to investigate the potential effects of IASD placement on HFpEF survival and heart failure hospitalization (HFH)., Methods and Results: Heart failure with preserved ejection fraction patients participating in the Reduce Elevated Left Atrial Pressure in Patients with Heart Failure study (Corvia Medical) of an IASD were followed for a median duration of 739 days. The theoretical impact of IASD implantation on HFpEF mortality was investigated by comparing the observed survival of the study cohort with the survival predicted from baseline data using the Meta-analysis Global Group in Chronic Heart Failure heart failure risk survival score. Baseline and post-IASD implant parameters associated with HFH were also investigated. Based upon the individual baseline demographic and cardiovascular profile of the study cohort, the Meta-analysis Global Group in Chronic Heart Failure score-predicted mortality was 10.2/100 pt years. The observed mortality rate of the IASD-treated cohort was 3.4/100 pt years, representing a 33% lower rate (P = 0.02). By Kaplan-Meier analysis, the observed survival in IASD patients was greater than predicted (P = 0.014). Baseline parameters were not predictive of future HFH events; however, poorer exercise tolerance and a higher workload-corrected exercise pulmonary capillary wedge pressure at the 6 months post-IASD study were associated with HFH., Conclusions: The current study suggests IASD implantation may be associated with a reduction in mortality in HFpEF. Large-scale ongoing randomized studies are required to confirm the potential benefit of this therapy., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Guidelines summarize and evaluate all available evidence on a particular issue at the time of the writing process, with the aim of assisting health professionals in selecting the best management strategies for an individual patient with a given condition, taking into account the impact on outcome, as well as the risk-benefit ratio of particular diagnostic or therapeutic means. Guidelines and recommendations should help health professionals to make decisions in their daily practice. However, the final decisions concerning an individual patient must be made by the responsible health professional(s) in consultation with the patient and caregiver as appropriate., (Published on behalf of the European Society of Cardiology and European Respiratory Society. All rights reserved. © 2015 European Society of Cardiology & European Respiratory Society.)

Objective: Pulmonary endarterectomy is a curative surgical treatment option for the majority of patients with chronic thromboembolic pulmonary hypertension. The current surgical management and postoperative outcome of patients enrolled in an international registry on chronic thromboembolic pulmonary hypertension were investigated., Methods: The registry included newly diagnosed (≤6 months) consecutive patients with chronic thromboembolic pulmonary hypertension from February 2007 to January 2009., Results: A total of 679 patients were registered from 1 Canadian and 26 European centers, of whom 386 (56.8%) underwent surgery. The median age of patients undergoing surgery was 60 years, and 54.1% were male. Previous pulmonary embolism was confirmed for 79.8% of patients. Perioperative complications occurred in 189 patients (49.2%): infection (18.8%), persistent pulmonary hypertension (16.7%), neurologic (11.2%) or bleeding (10.2%) complications, pulmonary reperfusion edema (9.6%), pericardial effusion (8.3%), need for extracorporeal membrane oxygenation (3.1%), and in-hospital mortality due to perioperative complications (4.7%). Documented 1-year mortality was 7%. Preoperative exercise capacity was predictive of 1-year mortality. Postoperative pulmonary vascular resistance predicted in-hospital and 1-year mortality. In patients evaluated within 1 year after surgery, the median pulmonary vascular resistance had decreased from 698 to 235 dyn x s x cm(-5) (95% confidence limit, 640-874 and 211-255, respectively, n = 70) and the median 6-minute walk distance had increased from 362 to 459 m (95% confidence limit, 340-399 and 440-473, respectively, n = 168). New York Heart Association functional class improved with most patients progressing from class III/IV to class I/II., Conclusions: Pulmonary endarterectomy is associated with a low in-hospital mortality rate and improvements in hemodynamics and exercise capacity., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Combined intracoronary and intramyocardial administration might improve outcomes for bone-marrow-derived stem cell therapy for acute myocardial infarction (AMI). We compared the safety and feasibility of early and late delivery of stem cells with combined therapy approaches., Methods: Patients with left ventricular ejection fraction less than 45% after AMI were randomly assigned stem cell delivery via intramyocardial injection and intracoronary infusion 3-6 weeks or 3-4 months after AMI. Primary end points were changes in infarct size and left ventricular ejection fraction 3 months after therapy., Results: A total of 60 patients were treated. The mean changes in infarct size at 3 months were -3.5 +/- 5.1% (95% CI -5.5% to -1.5%, P = 0.001) in the early group and -3.9 +/- 5.6% (95% CI -6.1% to -1.6%, P = 0.002) in the late group, and changes in ejection fraction were 3.5 +/- 5.6% (95% CI 1.3-5.6%, P = 0.003) and 3.4 +/- 7.0% (95% CI 0.7-6.1%, P = 0.017), respectively. At 9-12 months after AMI, ejection fraction remained significantly higher than at baseline in both groups. In the early and late groups, a mean of 200.3 +/- 68.7 x 10(6) and 194.8 +/- 60.4 x 10(6) stem cells, respectively, were delivered to the myocardium, and 1.30 +/- 0.68 x 10(9) and 1.29 +/- 0.41 x 10(9) cells, respectively, were delivered into the artery. A high number of cells was required for significant improvements in the primary end points., Conclusions: Combined cardiac stem cell delivery induces a moderate but significant improvement in myocardial infarct size and left ventricular function.