23 results on '"Jering, K."'
Search Results
2. Trends in management and outcomes of pulmonary embolism with a multidisciplinary response team
- Author
-
Chopard, R, primary, Campia, U, additional, Morin, L, additional, Jering, K S, additional, Almarzook, Z I, additional, Snyder, J E, additional, Rizzo, S, additional, Waxman, A B, additional, Goldhaber, S Z, additional, and Piazza, G, additional
- Published
- 2022
- Full Text
- View/download PDF
3. Atrial fibrillation in patients with high-risk acute myocardial infarction – the PARADISE-MI trial
- Author
-
Cikes, M, primary, Jering, K, additional, Claggett, B, additional, Amir, O, additional, Cadena Bonfanti, A J, additional, Cho, M C, additional, Granger, C, additional, Gullestad, L M, additional, Kao, H L, additional, Morais, J, additional, Tanguay, J F, additional, Tokmakova, M, additional, Widimsky, P, additional, and Solomon, S D, additional
- Published
- 2022
- Full Text
- View/download PDF
4. Sacubitril/valsartan compared to ramipril in high risk post myocardial infarction patients stratified according use of mineralocorticoid receptor antagonists: insight from PARADISE MI trial
- Author
-
Schou, M, primary, Claggett, B, additional, Fernandez, A, additional, Filippatos, G, additional, Granger, C, additional, Jering, K, additional, Maggioni, A, additional, McCausland, F, additional, Nunez Villota, J, additional, Rouleau, J L, additional, Mody, F G, additional, Van Der Meer, P, additional, Vinereanu, D, additional, Zhou, Y, additional, and Kober, L, additional
- Published
- 2022
- Full Text
- View/download PDF
5. PARADISE-MI – event rates and treatment effect of sacubitril/valsartan v ramipril by the presence or absence of transient pulmonary congestion and/or LVEF less or greater than 40
- Author
-
Petrie, M, primary, Solomon, S, additional, Claggett, B L, additional, Jering, K, additional, Steg, G, additional, Granger, C, additional, Lewis, E, additional, Kober, L, additional, Mann, D, additional, Rouleau, J L, additional, McMurray, J J, additional, Maggioni, A, additional, Braunwald, E, additional, and Pfeffer, M A, additional
- Published
- 2022
- Full Text
- View/download PDF
6. Trajectory of pulmonary congestion by lung ultrasound in patients with acute myocardial infarction and association with cardiac structure and function
- Author
-
Platz, E, primary, Claggett, B, additional, Jering, K S, additional, Kovacs, A, additional, Cikes, M, additional, Winzer, E B, additional, Rad, A, additional, Lefkowitz, M, additional, Gong, J, additional, Kober, L, additional, McMurray, J J V, additional, Solomon, S D, additional, and Shah, A, additional
- Published
- 2022
- Full Text
- View/download PDF
7. Influence of glycaemic status on the risk of cardiovascular events after a myocardial infarction
- Author
-
Zhou, Y., Wijkman, M., Claggett, B., Jering, K., Yilmaz, M., Claeys, M., De Pasquale, C., Kerkar, P., Moccetti, T., Ntsekhe, M., Sim, D., Studencan, M., Tokmakova, M., Zaman, A., and Lewis, E.
- Published
- 2022
8. Antibody Responses to COVID-19 Vaccination in Left Ventricular Assist Devices
- Author
-
Jering, K., primary, Kim, A., additional, Frankel, K., additional, Coakley, L., additional, Weber, B., additional, Harris, C.E., additional, Ellis, E.J., additional, Givertz, M.M., additional, Mallidi, H.R., additional, Baden, L.R., additional, Mehra, M.R., additional, and Woolley, A.E., additional
- Published
- 2022
- Full Text
- View/download PDF
9. Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction
- Author
-
Pfeffer, MA, Claggett, B, Lewis, EF, Granger, CB, Kober, L, Maggioni, AP, Mann, DL, McMurray, JJV, Rouleau, JL, Solomon, SD, Steg, PG, Berwanger, O, Cikes, M, De Pasquale, CG, East, C, Fernandez, A, Jering, K, Landmesser, U, Mehran, R, Merkely, B, Mody, FV, Petrie, MC, Petrov, I, Schou, M, Senni, M, Sim, D, van der Meer, P, Lefkowitz, M, Zhou, Y, Gong, J, Braunwald, E, Sionis A., and PARADISE-MI Invest & Comm
- Abstract
Sacubitril-Valsartan in Acute Myocardial Infarction In a randomized trial, 5661 patients with acute myocardial infarction and a reduced left ventricular ejection fraction, pulmonary congestion, or both were assigned to receive either sacubitril-valsartan or ramipril. At a median of 22 months, there was no significant difference between the two groups in the incidence of death from cardiovascular causes or incident heart failure. Background In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. Methods We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. Results A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P=0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. Conclusions Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, .)
- Published
- 2021
10. Impact of Sacubitril/Valsartan Versus Ramipril on Total Heart Failure Events in the PARADISE-MI Trial
- Author
-
Otavio Berwanger, Ivo Petrov, Eugene Braunwald, Douglas L. Mann, Morten Schou, Yinong Zhou, Alberto Fernandez, Venugopal Menon, Gerasimos Filippatos, Ulf Landmesser, Lars Køber, Aldo P. Maggioni, Karola S. Jering, Christopher B. Granger, Eldrin F. Lewis, Jean-Lucien Rouleau, Marc A. Pfeffer, B Merkely, Brian Claggett, Peter van der Meer, David Sim, Martin Lefkowitz, Carmine G. De Pasquale, John J.V. McMurray, Mark C. Petrie, Philippe Gabriel Steg, Yi Wang, Michele Senni, Scott D. Solomon, Maja Čikeš, Cardiovascular Centre (CVC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), Pfeffer, M, Claggett, B, Lewis, E, Granger, C, Kober, L, Maggioni, A, Mann, D, Mcmurray, J, Rouleau, J, Solomon, S, Steg, P, Berwanger, O, Cikes, M, De Pasquale, C, Fernandez, A, Filippatos, G, Jering, K, Landmesser, U, Menon, V, Merkely, B, Petrie, M, Petrov, I, Schou, M, Senni, M, Sim, D, van der Meer, P, Lefkowitz, M, Zhou, Y, Wang, Y, and Braunwald, E
- Subjects
Ramipril ,medicine.medical_specialty ,business.industry ,Aminobutyrates ,Biphenyl Compounds ,heart failure ,ramipril ,medicine.disease ,Article ,Drug Combinations ,myocardial infarction ,Physiology (medical) ,Heart failure ,Internal medicine ,sacubitril/valsartan ,medicine ,Cardiology ,Humans ,Valsartan ,Cardiology and Cardiovascular Medicine ,business ,Antihypertensive Agents ,Sacubitril, Valsartan ,medicine.drug - Abstract
Ovo istraživačko pismo prikazuje detaljniju analizu kliničkih ishoda u kliničkom ispitivanju PARADISE- MI.
- Published
- 2022
11. Angiotensin receptor–neprilysin inhibition in acute myocardial infarction
- Author
-
Marc A, Pfeffer, Brian, Claggett, Eldrin F, Lewis, Christopher B, Granger, Lars, Køber, Aldo P, Maggioni, Douglas L, Mann, John J V, McMurray, Jean-Lucien, Rouleau, Scott D, Solomon, Philippe G, Steg, Otavio, Berwanger, Maja, Cikes, Carmine G, De Pasquale, Cara, East, Alberto, Fernandez, Karola, Jering, Ulf, Landmesser, Roxana, Mehran, Béla, Merkely, Freny, Vaghaiwalla Mody, Mark C, Petrie, Ivo, Petrov, Morten, Schou, Michele, Senni, David, Sim, Peter, van der Meer, Martin, Lefkowitz, Yinong, Zhou, Jianjian, Gong, Eugene, Braunwald, M, Zughaib, Pfeffer, M, Claggett, B, Lewis, E, Granger, C, Kober, L, Maggioni, A, Mann, D, Mcmurray, J, Rouleau, J, Solomon, S, Steg, P, Berwanger, O, Cikes, M, De Pasquale, C, East, C, Fernandez, A, Jering, K, Landmesser, U, Mehran, R, Merkely, B, Mody, F, Petrie, M, Petrov, I, Schou, M, Senni, M, Sim, D, van der Meer, P, Lefkowitz, M, Zhou, Y, Gong, J, Braunwald, E, Department of Arts and Culture Studies, Cardiology, Erasmus MC other, Department of Technology and Operations Management, Cardiovascular Centre (CVC), and Restoring Organ Function by Means of Regenerative Medicine (REGENERATE)
- Subjects
Male ,Ramipril ,medicine.medical_specialty ,alanine aminotransferase ,Myocardial Infarction ,heart failure ,Angiotensin-Converting Enzyme Inhibitors ,ramipril ,Sacubitril ,Angiotensin Receptor Antagonists ,Ventricular Dysfunction, Left ,Double-Blind Method ,aspartate aminotransferase ,Internal medicine ,dipeptidyl carboxypeptidase inhibitor ,medicine ,Humans ,Myocardial infarction ,610 Medicine & health ,Aged ,Proportional Hazards Models ,sacubitril plus valsartan ,Ejection fraction ,business.industry ,Aminobutyrates ,potassium ,Biphenyl Compounds ,Hazard ratio ,creatinine ,mineralocorticoid antagonist ,Stroke Volume ,General Medicine ,Middle Aged ,angiotensin receptor ,medicine.disease ,Hospitalization ,Drug Combinations ,Valsartan ,Cardiovascular Diseases ,Heart failure ,Cardiology ,Myocardial infarction complications ,Female ,Hypotension ,business ,medicine.drug - Abstract
Sacubitril-Valsartan in Acute Myocardial Infarction In a randomized trial, 5661 patients with acute myocardial infarction and a reduced left ventricular ejection fraction, pulmonary congestion, or both were assigned to receive either sacubitril-valsartan or ramipril. At a median of 22 months, there was no significant difference between the two groups in the incidence of death from cardiovascular causes or incident heart failure. Background In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking. Methods We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first. Results A total of 5661 patients underwent randomization ; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90 ; 95% confidence interval [CI], 0.78 to 1.04 ; P=0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91 ; 95% CI, 0.78 to 1.07) ; death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87 ; 95% CI, 0.71 to 1.08) ; and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88 ; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group. Conclusions Sacubitril- valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis ; PARADISE-MI ClinicalTrials.gov number, NCT02924727.)
- Published
- 2021
12. Impact of Aficamten on Echocardiographic Cardiac Structure and Function in Symptomatic Obstructive Hypertrophic Cardiomyopathy.
- Author
-
Hegde SM, Claggett BL, Wang X, Jering K, Prasad N, Roshanali F, Masri A, Nassif ME, Barriales-Villa R, Abraham TP, Cardim N, Coats CJ, Kramer CM, Maron MS, Michels M, Olivotto I, Saberi S, Jacoby DL, Heitner SB, Kupfer S, Meng L, Wohltman A, Malik FI, and Solomon SD
- Abstract
Background: Aficamten, a next-in-class cardiac myosin inhibitor, improved peak oxygen uptake (pVO
2 ) and lowered resting and Valsalva left ventricular outflow (LVOT) gradients in adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in SEQUOIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM), a phase 3, multicenter, randomized, double-blinded, placebo-controlled study., Objectives: The authors sought to evaluate the effect of aficamten on echocardiographic measures of cardiac structure and function in SEQUOIA-HCM., Methods: Serial echocardiograms were performed over 28 weeks in patients randomized to receive placebo or aficamten in up to 4 individually titrated escalating doses (5-20 mg daily) over 24 weeks based on Valsalva LVOT gradients and left ventricular ejection fraction (LVEF)., Results: Among 282 patients (mean age 59 ± 13 years; 41% female, 79% White, 19% Asian), mean LVEF was 75% ± 6% with resting and Valsalva LVOT gradients of 55 ± 30 mm Hg and 83 ± 32 mm Hg, respectively. Over 24 weeks, aficamten significantly lowered resting and Valsalva LVOT gradients, and improved left atrial volume index, lateral and septal e' velocities, and lateral and septal E/e' (all P ≤ 0.001). LV end-systolic volume increased and wall thickness decreased (all P ≤ 0.003). Aficamten resulted in a mild reversible decrease in LVEF (-4.8% [95% CI: -6.4 to -3.3]; P < 0.001) and absolute LV global circumferential strain (-3.7% [95% CI: 1.8-5.6]; P < 0.0010), whereas LV global longitudinal strain was unchanged. Several measures, including LVEF, LVOT gradients, and E/e' returned to baseline following washout. Among those treated with aficamten, improved pVO2 and reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) were associated with improvement in lateral e' velocity and septal and lateral E/e' (all P < 0.03), whereas improvement in Kansas City Cardiomyopathy Questionnaire Clinical Summary Scores (KCCQ-CSS) was associated with a decrease in both LVOT gradients (all P < 0.001)., Conclusions: Compared with placebo, patients receiving aficamten demonstrated significant improvement in LVOT gradients and measures of LV diastolic function, and several of these measures were associated with improvements in pVO2 , KCCQ-CSS, and NT-proBNP. A modest decrease in LVEF occurred yet remained within normal range. These findings suggest aficamten improved multiple structural and physiological parameters in oHCM without significant adverse changes in LV systolic function. (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM [SEQUOIA-HCM]; NCT05186818)., Competing Interests: Funding Support and Author Disclosures The SEQUOIA-HCM trial is funded by Cytokinetics, Incorporated. Representatives of Cytokinetics have been involved in the design and conduct of the study reported in this paper. Study design and data analysis was supported by the funder and aided by coauthors. Manuscript drafting was completed independently but reviewed by the funder. Dr Wang is supported by a ACC/Merck Research Fellowship. Dr Hegde’s and Dr Wang’s institutions have received fees for core lab services from Cytokinetics and Bristol Myers Squibb. Dr Masri has received research grants from Pfizer, Ionis, Attralus, and Cytokinetics; and has received fees from Cytokinetics, BMS, Eidos/BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, Akros, Prothena, BioMarin, AstraZeneca, and Tenaya. Dr Nassif has received research and grant support from AstraZeneca and Cytokinetics; and has received consulting/advisory fees from Vifor and Cytokinetics. Dr Barriales-Villa has received consultant/advisor fees from MyoKardia/Bristol Myers Squibb. Dr Cardim has received speaker fees from Cytokinetics and Bristol Myers Squibb. Dr Coats has received speaker fees from Alnylam and Pfizer; and has received advisory fees from Cytokinetics and Roche Diagnostics. Dr Kramer has received research grants from Cytokinetics, BMS, and Eli Lilly; and is a consultant for Eli Lilly. Dr Maron has received consultant/advisor fees from Imbria and Takeda; and has received steering committee fees for SEQUOIA-HCM from Cytokinetics, Incorporated. Dr Michels’ institution has received a research grant from Bristol Myers Squibb; has received consultant/ advisor fees from Cytokinetics and Bristol Myers Squibb/Myokardia and Alnylam; and has received speaker fees from Bristol Myers Squibb and Pfizer. Dr Olivotto has received research grants from Bristol Myers Squibb, Cytotinetics, Sanofi, Benzyme, Amicus, Bayer, Menarini International, Chiesi, and Boston Scientific; has received consulting fees from Bristol Myers Squibb, Amicus, Sanofi, and Genzyme; and has served as an Advisory Board member for Cytokinetics, Bristol Myers Squibb, Chiesi, and Rocket Pharma. Dr Saberi has received consultant/advisor fees from Bristol Myers Squibb; and has received research grants from Cytokinetics, Bristol Myers Squibb, Cytokinetics, Novartis, and Actelion Pharmaceuticals. Drs Jacoby, Heitner, Kupfer, Meng, and Malik, and Ms Wohltman are employees of and hold stock in Cytokinetics, Incorporated. Dr Solomon has received research grants from Alexion, Alnylam, Applied Therapeutics, AstraZeneca, Bellerophon, Bayer, BMS, Boston Scientific, Cytokinetics, Edgewise, Eidos/Bridgebio, Gossamer, GSK, Ionis, Lilly, NIH/NHLBI, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Tenaya, Theracos, and US2.AI; and has consulted for Abbott, Action, Akros, Alexion, Alnylam, Amgen, Arena, AstraZeneca, Bayer, BMS, Cardior, Cardurion, Corvia, Cytokinetics, GSK, Lilly, Novartis, Roche, Theracos, Quantum Genomics, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
13. Safety and Tolerability of Angiotensin Receptor-Neprilysin Inhibitor Initiation in High-Risk Acute Myocardial Infarction Relative to Care Setting: A Subgroup Analysis of the PARADISE-MI Trial.
- Author
-
De Pasquale CG, Claggett B, Jering K, McMurray JJV, Mann D, Miao ZM, Granger CB, Køber L, Maggioni AP, Rouleau JL, Solomon SD, Steg PG, van der Meer P, Braunwald E, and Pfeffer MA
- Subjects
- Humans, Male, Biphenyl Compounds, Female, Aged, Treatment Outcome, Tetrazoles therapeutic use, Tetrazoles adverse effects, Middle Aged, Drug Combinations, Risk Factors, Myocardial Infarction drug therapy, Angiotensin Receptor Antagonists adverse effects, Angiotensin Receptor Antagonists therapeutic use, Neprilysin antagonists & inhibitors, Aminobutyrates therapeutic use, Aminobutyrates adverse effects, Valsartan
- Abstract
Competing Interests: Dr De Pasquale reports research funding from AstraZeneca and Novartis; consulting fees or speaker honoraria from AstraZeneca, Novartis, Vifor, Boehringer Ingelheim, Bayer, Eli Lilly, and Roche. Dr Claggett reports statistical consulting at Alnylam, Cardurion, Corvia, CVRx, Cytokinetics, Intellia, and Rocket. Dr McMurray received support from British Heart Foundation Centre of Research Excellence grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund; has received payments through the Glasgow University from work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GlaxoSmithKline (GSK), KBP Biosciences, and Novartis; has received personal consulting fees from Alnylam Pharma, Bayer, Bristol Myers Squibb (BMS), George Clinical Pty Ltd, Ionis Pharma, Novartis, Regeneron Pharma, and River 2 Renal Corporation; has received personal lecture fees from Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma Ltd, Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica Health, Intas Pharma, J.B. Chemicals and Pharma Ltd, Lupin Pharma, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharma, The Corpus, Translation Research Group, and Translational Medicine Academy; and is a director of Global Clinical Trial Partners Ltd. Dr Granger reports consulting fees from Abbvie, Abiomed, Alnylam Pharmaceuticals, Anthos, Bayer Corporation, Boehringer Ingelheim, Boston Scientific Corporation, BMS, Cardionomics, CeleCor Therapeutics, Janssen Pharmaceutical, Merck, Novo Nordisk, Novartis Pharmaceutical Company, Pfizer, Philips, Reata, and NephroSynergy; salary funded by Duke; grants sponsored by Alnylam, Boehringer Ingelheim, BMS, Daiichi Sankyo, Food and Drug Administration, Janssen Pharmaceuticals, National Institutes of Health (NIH), Novartis Pharmaceutical Company, Pfizer, and Philips; and equity in Tenac.io. Dr Køber reports speaker honoraria from AstraZeneca, Bayer, Boehringer, Novartis, and Novo Nordisk. Dr Maggioni reports personal fees for participation in studies from AstraZeneca, Bayer, Novartis, and Sanofi, outside the present work. Dr Rouleau reports DMC membership with Novartis, BMS, Bayer, and AstraZeneca. Dr Solomon reports research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, BMS, Cytokinetics, Eidos, Gossamer, GSK, Ionis, Lilly, MyoKardia, NIH/National Heart, Lung, and Blood Institute (NHLBI), Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI; and consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, GSK, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Valo. Dr Steg reports research grants from Amarin and Sanofi; clinical trials (Steering Committee, CEC, DSMB) at Amarin, Amgen, AstraZeneca, Bayer, BMS, Idorsia, Janssen, Novartis, and Sanofi; consulting or speaking at Amarin, Amgen, BMS, Novartis, and Novo Nordisk; and senior associate editor at Circulation. Dr van der Meer is supported by a grant from the European Research Council (ERC CoG 101045236, DISSECT-HF). The UMCG, which employs Dr van der Meer, received consultancy fees and grants from Novartis, Pharmacosmos, Vifor Pharma, AstraZeneca, Pfizer, Pharma Nord, BridgeBio, Novo Nordisk, Daiichi Sankyo, Boehringer Ingelheim, and Ionis. Dr Braunwald has received research grants through his institution from AstraZeneca, Daiichi Sankyo, Merck, and Novartis; and has consultancies with Amgen, BMS, Boehringer Ingelheim/Lilly, Cardurion, and Verve. Dr Pfeffer reports research grant support (via institution) from Lexicon and Novartis; consultant at Alnylam, AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Lexicon, NHLBI CONNECTs (Master Protocol Committee), Novartis, Novo Nordisk, and Sanofi; and has equity in DalCor. The other authors report no conflicts.
- Published
- 2024
- Full Text
- View/download PDF
14. Heart Failure, Investigator-Reported Sleep Apnea and Dapagliflozin: A Patient-Level Pooled Meta-Analysis of DAPA-HF and DELIVER.
- Author
-
Butt JH, Jering K, DE Boer RA, Claggett BL, Desai AS, Hernandez AF, Inzucchi SE, Jhund PS, Køber L, Kosiborod MN, Lam CSP, Martinez FA, Ponikowski P, Sabatine MS, Shah SJ, Vaduganathan M, Langkilde AM, Bengtsson O, Petersson M, Sjöstrand M, Wilderäng U, Solomon SD, and McMurray JJV
- Subjects
- Humans, Glucosides therapeutic use, Quality of Life, Stroke Volume, Ventricular Function, Left, Randomized Controlled Trials as Topic, Benzhydryl Compounds, Heart Failure drug therapy, Heart Failure epidemiology
- Abstract
Background: Sleep apnea is more common in patients with heart failure (HF) than in the general population, but little is known about its association with clinical outcomes in various HF phenotypes or how it might modify the effect of HF therapy., Objectives: To examine the prevalence of sleep apnea, its association with outcomes and the effects of dapagliflozin in patients with HF with and without sleep apnea in a pooled analysis of 2 trials comparing dapagliflozin to placebo in HFrEF (DAPA-HF trial) and HFmrEF/HFpEF (DELIVER trial)., Methods: A history of sleep apnea was investigator-reported. The primary outcome was a composite of worsening HF or cardiovascular death., Results: The prevalence of sleep apnea was 5.7% and 7.8% in patients with HFrEF and HFmrEF/HFpEF, respectively. The primary outcome occurred at a rate of 16.0 in participants with sleep apnea compared to 10.6 per 100 person-years in those without (adjusted HR 1.29 [95%CI, 1.10-1.52]). Compared with placebo, dapagliflozin reduced the risk of the primary endpoint to the same extent in patients with (HR 0.78 [95% CI, 0.59-1.03]) and without sleep apnea (HR 0.79 [0.72-0.87]) [P
interaction = 0.93]. The beneficial effects of dapagliflozin on other clinical outcomes and symptom burden, physical function, and quality of life were consistent in participants with and without sleep apnea., Conclusions: In DAPA-HF and DELIVER, the true prevalence of sleep apnea was likely underestimated. An investigator-reported history of sleep apnea was associated with higher rates of worsening HF events. The benefits of dapagliflozin on clinical outcomes were consistent in patients with and without sleep apnea., Clinical Trial Registration: Unique identifiers: NCT01920711 CONDENSED ABSTRACT: In a pooled analysis of the DAPA-HF and DELIVER trials of more than 11,000 patients with heart failure (HF) across the range of ejection fractions, an investigator-reported history of sleep apnea was associated with higher rates of worsening HF events but not mortality. The beneficial effects of dapagliflozin on clinical outcomes were consistent in patients with and without sleep apnea. These findings provide further evidence for dapagliflozin as a new treatment option for patients with heart failure across the range of ejection fractions., Competing Interests: Disclosures JHB reports advisory board honoraria from AstraZeneca and Bayer, consultant honoraria from Novartis and AstraZeneca and travel grants from AstraZeneca. RADB has received research grants and/or fees from AstraZeneca, Abbott, Boehringer Ingelheim, Cardior Pharmaceuticals, Ionis Pharmaceuticals, Novo Nordisk, and Roche and has had speaker engagements with Abbott, AstraZeneca, Bayer, Bristol Myers Squibb, Novartis, and Roche. BLC has received consulting fees from Boehringer Ingelheim. ASD has received grants and personal fees from AstraZeneca during the conduct of the study, personal fees from Abbott, Biofourmis, Boston Scientific, Boehringer Ingelheim, Corvidia, DalCor Pharma, Relypsa, Regeneron, and Merck, grants and personal fees from Alnylam and Novartis, and personal fees from Amgen, outside the submitted work. AFH has received research support from American Regent, AstraZeneca, Boehringer Ingelheim, Merck, Novartis, and Verily and has served as a consultant or on the advisory boards of Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cytokinetics, Myokardia, Merck, Novartis, and Vifor. SEI has served on clinical trial committees or as a consultant to AstraZeneca, Boehringer Ingelheim, Novo Nordisk, Lexicon, Merck, Pfizer, vTv Therapeutics, Abbott, and Esperion and has given lectures sponsored by Astra-Zeneca and Boehringer Ingelheim. PSJ's employer, the University of Glasgow, has been remunerated by Astrazeneca for working on the DAPA-HF and DELIVER trials, and he has received personal fees from Novartis and Cytokinetics and grants from Boehringer Ingelheim. LK reports compensation from Novartis, Novo Nordisk and AstraZeneca for other services. MNK has received research grant support from AstraZeneca and Boehringer Ingelheim, has served as a consultant or on an advisory board for Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, and Vifor Pharma and has received other research support from AstraZeneca and honoraria from AstraZeneca, Boehringer Ingelheim and Novo Nordisk. CSPL is supported by a Clinician Scientist Award from the National Medical Research Council of Singapore, has received research support from AstraZeneca, Bayer, Boston Scientific, and Roche Diagnostics, has served as a consultant or on the advisory board/steering committee/executive committee for Actelion, Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Cytokinetics, Darma, Us2.ai, Janssen Research & Development, Medscape, Merck, Novartis, Novo Nordisk, Radcliffe Group, Roche Diagnostics, Sanofi, and WebMD Global and serves as the cofounder and nonexecutive director of Us2.ai. FAM has received personal fees from AstraZeneca. PP reports compensation from AstraZeneca, Boehringer Ingelheim, and Servier for consultant services, compensation from AstraZeneca and Pfizer for other services, compensation from Amgen and Vifor Pharma for consultant services; compensation from Novartis and Abbott Vascular for other services. MSS reports research grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Daiichi-Sankyo, Eisai, Intarcia, IONIS, Medicines Company, MedImmune, Merck, Novartis, Pfizer, and Quark Pharmaceuticals and consulting fees from Althera, Amgen, Anthos Therapeutics, AstraZeneca, Bristol-Myers Squibb, CVS Caremark, DalCor, Dr. Reddy's Laboratories, Fibrogen, IFM Therapeutics, Intarcia, MedImmune, Merck, Moderna, and Novo Nordisk. SJS has received either personal or institutional research support for DELIVER from AstraZeneca. MV has received research grant support or served on advisory boards for American Regent, Amgen, AstraZeneca, Bayer AG, Baxter Healthcare, Boehringer Ingelheim, Cytokinetics, Lexicon Pharmaceuticals, and Relypsa, has had speaker engagements with Novartis and Roche Diagnostics and participates on clinical endpoint committees for studies sponsored by Galmed and Novartis. AML, OB, MP, MS, and UWkilde are employees of and shareholders in AstraZeneca. SDS has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lilly, Mesoblast, MyoKardia, National Institutes of Health/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellPro-Thera, Moderna, American Regent, and Sarepta. JJVM has received payments through Glasgow University for work on clinical trials, consulting and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, BMS, Cardurion, Cytokinetics, Dal-Cor, GSK, Ionis, KBP Biosciences, Novartis, Pfizer, Theracos and lecture fees: the Corpus, Abbott, Hikma, Sun Pharmaceuticals, Medscape/Heart.Org, Radcliffe Cardiology, Servier Director, Global Clinical Trial Partners., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
15. Pulmonary Congestion and Left Ventricular Dysfunction After Myocardial Infarction: Insights From the PARADISE-MI Trial.
- Author
-
Petrie MC, Rouleau JL, Claggett B, Jering K, van der Meer P, Køber L, Miao ZM, Lewis E, Granger C, De Pasqulae CG, Mann D, Steg PG, Maggioni A, Amir O, Lefkowitz M, Braunwald E, Solomon SD, McMurray JJV, and Pfeffer MA
- Subjects
- Humans, Pulmonary Circulation, Pulmonary Edema, Myocardial Infarction complications, Ventricular Dysfunction, Left etiology
- Abstract
Competing Interests: Disclosures Dr Petrie reports receiving research funding from Boehringer Ingelheim, Roche, SQ Innovations, AstraZeneca, Novartis, Novo Nordisk, Medtronic, Boston Scientific, Pharmacosmos, 3R LifeSciences; participating in consultancy and clinical trial committees, outside the submitted work, for Boehringer Ingelheim, Novartis, Roche, Corvia, AstraZeneca, Novo Nordisk, Medtronic, AbbVie, Bayer, Takeda, Cardiorentis, Pharmacosmos, and Siemens. Dr Rouleau reports receiving consultant fees from Novartis, BMS, Bayer, and AstraZeneca. Dr Køber reports receiving speaker fees from Novartis, Novo, AstraZeneca, Boehringer, and Bayer. Dr De Pasquale reports receiving speaker honoraria and consulting fees from AstraZeneca, Novartis, Vifor, Otsuka, St Jude, Boehringer Ingelheim, Bayer, Lilly, Roche, Servier, and American Regent. Dr Mann reports receiving consulting fees from Bristol Myers Squibb and NovoNordisk. Dr Steg reports receiving research grants from Amarin, Bayer, Sanofi, and Servier; serving on clinical trials (Steering Committee, Clinical Endpoint Committee, Data Safety Monitoring Board) for Amarin, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Idorsia, Novartis, Pfizer, Sanofi, and Servier; and receiving consultant or speaker fees from Amarin, Amgen, BMS/MyoKardia, Novartis, Novo Nordisk, and Regeneron. He is Senior Associate Editor at Circulation. Dr Maggioni reports receiving personal fees outside of the present work for participation in committees of studies supported by Bayer, Novartis, Astra Zeneca, and Fresenius. Dr Lefkowitz is an employee of Novartis Pharmaceutical Corporation. Dr Braunwald reports receiving research grants from AstraZeneca (to Brigham and Womens Hospital), Daiichi Sankyo, Merck, and Novartis; and consulting fees from Amgen, Bristol Myers Squibb (MyoKardia), Boehringer-Ingelheim/Lilly, Cardurion, and Verve. Dr McMurray reports receiving payments through Glasgow University from work on clinical trials, consulting, and other activities from Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK, KBP Biosciences, and Novartis; personal consultancy fees from Alnylam Pharma., Bayer, Bristol Myers Squibb, George Clinical PTY Ltd, Ionis Pharma, Novartis, Regeneron Pharma, and River 2 Renal Corporation; and personal lecture fees Abbott, Alkem Metabolics, AstraZeneca, Blue Ocean Scientific Solutions Ltd, Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma Ltd, Eris Lifesciences, European Academy of Continuing Medical Education, Hikma Pharmaceuticals, Imagica Health, Intas Pharma, JB Chemicals & Pharma Ltd, Lupin Pharma, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharma, The Corpus, Translation Research Group, and Translational Medicine Academy. He is a director of Global Clinical Trial Partners Ltd. The other authors have nothing to disclose.
- Published
- 2024
- Full Text
- View/download PDF
16. Sacubitril/valsartan compared to ramipril in high-risk post-myocardial infarction patients stratified according to use of mineralocorticoid receptor antagonists: Insight from the PARADISE MI trial.
- Author
-
Schou M, Claggett B, Miao ZM, Fernandez A, Filippatos G, Granger C, Jering K, Maggioni AP, McCausland F, Villota JN, Rouleau JL, Mody FV, van der Meer P, Vinereanu D, McGrath M, Zhou Y, Mann DL, Solomon SD, Steg PG, Braunwald E, McMurray JJV, Pfeffer MA, and Køber L
- Subjects
- Humans, Ramipril therapeutic use, Ramipril pharmacology, Mineralocorticoid Receptor Antagonists therapeutic use, Mineralocorticoid Receptor Antagonists pharmacology, Prospective Studies, Tetrazoles therapeutic use, Tetrazoles pharmacology, Angiotensin Receptor Antagonists adverse effects, Valsartan therapeutic use, Biphenyl Compounds therapeutic use, Aminobutyrates adverse effects, Drug Combinations, Stroke Volume, Heart Failure, Hyperkalemia drug therapy, Hypotension chemically induced, Myocardial Infarction complications, Myocardial Infarction drug therapy
- Abstract
Aim: It is unknown whether safety and clinical endpoints by use of sacubitril/valsartan (an angiotensin receptor-neprilysin inhibitor [ARNI]) are affected by mineralocorticoid receptor antagonists (MRA) in high-risk myocardial infarction (MI) patients. The aim of this study was to examine whether MRA modifies safety and clinical endpoints by use of sacubitril/valsartan in patients with a MI and left ventricular systolic dysfunction (LVSD) and/or pulmonary congestion., Methods and Results: Patients (n = 5661) included in the PARADISE MI trial (Prospective ARNI vs. ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After MI) were stratified according to MRA. Primary outcomes in this substudy were worsening heart failure or cardiovascular death. Safety was defined as symptomatic hypotension, hyperkalaemia >5.5 mmol/L, or permanent drug discontinuation. A total of 2338 patients (41%) were treated with MRA. Safety of ARNI compared to ramipril was not altered significantly by ± MRA, and both groups had similar increase in symptomatic hypotension with ARNI. In patients taking MRA, the risk of hyperkalaemia or permanent drug discontinuation was not significantly altered by ARNI (p > 0.05 for all comparisons). The effect of ARNI compared with ramipril was similar in those who were and were not taking MRA (hazard ratio [HR]
MRA 0.96, 95% confidence interval [CI] 0.77-1.19 and HRMRA- 0.87, 95% CI 0.71-1.05, for the primary endpoint; p = 0.51 for interaction [Clinical Endpoint Committee adjudicated]); similar findings were observed if investigator-reported endpoints were evaluated (p = 0.61 for interaction)., Conclusions: Use of a MRA did not modify safety or clinical endpoints related to initiation of ARNI compared to ramipril in the post-MI setting in patients with LVSD and/or congestion., (© 2023 European Society of Cardiology.)- Published
- 2024
- Full Text
- View/download PDF
17. Sacubitril/valsartan and loop diuretic requirement in heart failure with preserved ejection fraction in the PARAGON-HF trial.
- Author
-
Chatur S, Claggett BL, Vardeny O, Jering K, Desai AS, Pfeffer MA, Lefkowitz M, McMurray JJV, Solomon SD, and Vaduganathan M
- Subjects
- Humans, Sodium Potassium Chloride Symporter Inhibitors therapeutic use, Stroke Volume, Tetrazoles therapeutic use, Angiotensin Receptor Antagonists, Valsartan therapeutic use, Aminobutyrates therapeutic use, Biphenyl Compounds therapeutic use, Furosemide therapeutic use, Drug Combinations, Diuretics therapeutic use, Heart Failure drug therapy, Heart Failure chemically induced
- Abstract
Aims: As sacubitril/valsartan may potentiate early natriuresis, expert consensus documents recommend diuretic dose reduction on first initiation. However, there are limited data on the effects of sacubitril/valsartan on the background of varying diuretic regimens or on diuretic requirements over time in heart failure (HF) with preserved ejection fraction (HFpEF)., Methods and Results: In this post hoc analysis of PARAGON-HF, of the 4796 patients, background diuretic therapy was distributed as follows: 341 (7%) on no diuretic, 698 (15%) on non-loop diuretic, and 3757 (78%) were on loop diuretics (1255, 1589, and 913 were on <40, 40 and >40 mg furosemide equivalent doses, respectively). The primary composite outcome of total HF hospitalizations and cardiovascular death was analysed using semiparametric proportional rates methods. The cumulative incidence of the primary composite outcome (first events) was lowest in patients on no diuretic and highest in those on >40 mg of loop diuretic (p < 0.001). The effects of sacubitril/valsartan (vs. valsartan) on the primary composite outcome (recurrent events) did not significantly vary by baseline diuretic use (p
interaction = 0.65). Treatment effects on safety outcomes were similar across diuretic categories. Sacubitril/valsartan reduced new loop diuretic initiations over the course of the trial (hazard ratio 0.83; 95% confidence interval 0.68-1.00, p = 0.055), with similar mean loop diuretic dose and rates of diuretic discontinuation between treatment groups in follow-up. Patients randomized to sacubitril/valsartan experienced a slight early reduction in diuretic initiation or dose escalation at 30 days after initiation (net reduction 1.7%, p = 0.02), but these differences were not sustained beyond this timepoint., Conclusions: Patients with HFpEF on higher baseline diuretic doses were at heightened risk of HF events, but similarly benefited from sacubitril/valsartan with a consistent safety profile across a range of diuretic doses. Initiation of sacubitril/valsartan was associated with modestly lower new loop diuretic requirement in follow-up., (© 2022 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)- Published
- 2023
- Full Text
- View/download PDF
18. The Effects of Angiotensin Receptor-Neprilysin Inhibition on Major Coronary Events in Patients With Acute Myocardial Infarction: Insights From the PARADISE-MI Trial.
- Author
-
Mehran R, Steg PG, Pfeffer MA, Jering K, Claggett B, Lewis EF, Granger C, Køber L, Maggioni A, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Ducrocq G, Berwanger O, De Pasquale CG, Landmesser U, Petrie M, Leng DSK, van der Meer P, Lefkowitz M, Zhou Y, and Braunwald E
- Subjects
- Humans, Aminobutyrates therapeutic use, Angiotensin Receptor Antagonists therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Angiotensins, Biphenyl Compounds, Neprilysin antagonists & inhibitors, Prospective Studies, Ramipril therapeutic use, Receptors, Angiotensin, Stroke Volume, Tetrazoles therapeutic use, Valsartan therapeutic use, Heart Failure complications, Heart Failure diagnosis, Heart Failure drug therapy, Myocardial Infarction drug therapy, Ventricular Dysfunction, Left complications
- Abstract
Background: In patients who survive an acute myocardial infarction (AMI), angiotensin-converting enzyme inhibitors decrease the risk of subsequent major cardiovascular events. Whether angiotensin-receptor blockade and neprilysin inhibition with sacubitril/valsartan reduce major coronary events more effectively than angiotensin-converting enzyme inhibitors in high-risk patients with recent AMI remains unknown. We aimed to compare the effects of sacubitril/valsartan on coronary outcomes in patients with AMI., Methods: We conducted a prespecified analysis of the PARADISE-MI trial (Prospective ARNI vs ACE Inhibitors Trial to Determine Superiority in Reducing Heart Failure Events After MI), which compared sacubitril/valsartan (97/103 mg twice daily) with ramipril (5 mg twice daily) for reducing heart failure events after myocardial infarction in 5661 patients with AMI complicated by left ventricular systolic dysfunction, pulmonary congestion, or both. In the present analysis, the prespecified composite coronary outcome was the first occurrence of death from coronary heart disease, nonfatal myocardial infarction, hospitalization for angina, or postrandomization coronary revascularization., Results: Patients were randomly assigned at a median of 4.4 [3.0-5.8] days after index AMI (ST-segment-elevation myocardial infarction 76%, non-ST-segment-elevation myocardial infarction 24%), by which time 89% of patients had undergone coronary reperfusion. Compared with ramipril, sacubitril/valsartan decreased the risk of coronary outcomes (hazard ratio, 0.86 [95% CI, 0.74-0.99], P =0.04) over a median follow-up of 22 months. Rates of the components of the composite outcomes were lower in patients on sacubitril/valsartan but were not individually significantly different., Conclusions: In survivors of an AMI with left ventricular systolic dysfunction and pulmonary congestion, sacubitril/valsartan-compared with ramipril-reduced the risk of a prespecified major coronary composite outcome. Dedicated studies are necessary to confirm this finding and elucidate its mechanism., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02924727.
- Published
- 2022
- Full Text
- View/download PDF
19. Impact of Sacubitril/Valsartan Compared With Ramipril on Cardiac Structure and Function After Acute Myocardial Infarction: The PARADISE-MI Echocardiographic Substudy.
- Author
-
Shah AM, Claggett B, Prasad N, Li G, Volquez M, Jering K, Cikes M, Kovacs A, Mullens W, Nicolau JC, Køber L, van der Meer P, Jhund PS, Ibram G, Lefkowitz M, Zhou Y, Solomon SD, and Pfeffer MA
- Subjects
- Aged, Aminobutyrates adverse effects, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Biphenyl Compounds therapeutic use, Drug Combinations, Echocardiography, Female, Humans, Hypertrophy, Left Ventricular drug therapy, Male, Middle Aged, Neprilysin, Prospective Studies, Ramipril pharmacology, Ramipril therapeutic use, Receptors, Angiotensin therapeutic use, Stroke Volume physiology, Tetrazoles adverse effects, Valsartan therapeutic use, Heart Failure chemically induced, Heart Failure diagnostic imaging, Heart Failure drug therapy, Myocardial Infarction diagnostic imaging, Myocardial Infarction drug therapy
- Abstract
Background: Angiotensin-converting enzyme inhibitors attenuate left ventricular (LV) enlargement after acute myocardial infarction (AMI). Preclinical data suggest similar benefits with combined angiotensin receptor neprilysin inhibition, but human data are conflicting. The PARADISE-MI Echo Study (Prospective ARNI Versus ACE Inhibitor Trial to Determine Superiority in Reducing Heart Failure Events After Myocardial Infarction) tested the effect of sacubitril/valsartan compared with ramipril on LV function and adverse remodeling after high risk-AMI., Methods: In a prespecified substudy, 544 PARADISE-MI participants were enrolled in the Echo Study to undergo protocol echocardiography at randomization and after 8 months. Patients were randomized within 0.5 to 7 days of presentation with their index AMI to receive a target dose of sacubitril/valsartan 200 mg or ramipril 5 mg twice daily. Echocardiographic measures were performed at a core laboratory by investigators blinded to treatment assignment. The effect of treatment on change in echo measures was assessed with ANCOVA with adjustment for baseline value and enrollment region. The primary end points were change in LV ejection fraction (LVEF) and left atrial volume (LAV), and prespecified secondary end points included changes in LV end-diastolic and end-systolic volumes., Results: Mean age was 64±12 years; 26% were women; mean LVEF was 42±12%; and LAV was 49±17 mL. Of 544 enrolled patients, 457 (84%) had a follow-up echo at 8 months (228 taking sacubitril/valsartan, 229 taking ramipril). There was no significant difference in change in LVEF ( P =0.79) or LAV ( P =0.62) by treatment group. Patients randomized to sacubitril/valsartan demonstrated less increase in LV end-diastolic volume ( P =0.025) and greater decline in LV mass index ( P =0.037), increase in tissue Doppler e'
lat ( P =0.005), decrease in E/e'lat ( P =0.045), and decrease in tricuspid regurgitation peak velocity ( P =0.024) than patients randomized to ramipril. These differences remained significant after adjustment for differences in baseline characteristics. Baseline LVEF, LV end-diastolic volume, LV end-systolic volume, LV mass index, LAV, and Doppler-based diastolic indices were associated with risk of cardiovascular death or incident heart failure., Conclusions: Treatment with sacubitril/valsartan compared with ramipril after AMI did not result in changes in LVEF or LAV at 8 months. Patients randomized to sacubitril/valsartan had less LV enlargement and greater improvement in filling pressure. Measures of LV size, systolic function, and diastolic properties were predictive of cardiovascular death and incident heart failure after AMI in this contemporary, well-treated cohort., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02924727.- Published
- 2022
- Full Text
- View/download PDF
20. Impact of Sacubitril/Valsartan Versus Ramipril on Total Heart Failure Events in the PARADISE-MI Trial.
- Author
-
Pfeffer MA, Claggett B, Lewis EF, Granger CB, Køber L, Maggioni AP, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, Berwanger O, Cikes M, De Pasquale CG, Fernandez A, Filippatos G, Jering K, Landmesser U, Menon V, Merkely B, Petrie MC, Petrov I, Schou M, Senni M, Sim D, van der Meer P, Lefkowitz M, Zhou Y, Wang Y, and Braunwald E
- Subjects
- Aminobutyrates pharmacology, Antihypertensive Agents pharmacology, Biphenyl Compounds pharmacology, Drug Combinations, Humans, Ramipril pharmacology, Valsartan pharmacology, Aminobutyrates therapeutic use, Antihypertensive Agents therapeutic use, Biphenyl Compounds therapeutic use, Heart Failure drug therapy, Ramipril therapeutic use, Valsartan therapeutic use
- Published
- 2022
- Full Text
- View/download PDF
21. Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction.
- Author
-
Pfeffer MA, Claggett B, Lewis EF, Granger CB, Køber L, Maggioni AP, Mann DL, McMurray JJV, Rouleau JL, Solomon SD, Steg PG, Berwanger O, Cikes M, De Pasquale CG, East C, Fernandez A, Jering K, Landmesser U, Mehran R, Merkely B, Vaghaiwalla Mody F, Petrie MC, Petrov I, Schou M, Senni M, Sim D, van der Meer P, Lefkowitz M, Zhou Y, Gong J, and Braunwald E
- Subjects
- Aged, Aminobutyrates adverse effects, Angiotensin Receptor Antagonists adverse effects, Angiotensin-Converting Enzyme Inhibitors adverse effects, Biphenyl Compounds adverse effects, Cardiovascular Diseases mortality, Double-Blind Method, Drug Combinations, Female, Hospitalization statistics & numerical data, Humans, Hypotension chemically induced, Male, Middle Aged, Myocardial Infarction complications, Myocardial Infarction mortality, Proportional Hazards Models, Ramipril adverse effects, Stroke Volume, Valsartan adverse effects, Ventricular Dysfunction, Left etiology, Aminobutyrates therapeutic use, Angiotensin Receptor Antagonists therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Biphenyl Compounds therapeutic use, Heart Failure prevention & control, Myocardial Infarction drug therapy, Ramipril therapeutic use, Valsartan therapeutic use
- Abstract
Background: In patients with symptomatic heart failure, sacubitril-valsartan has been found to reduce the risk of hospitalization and death from cardiovascular causes more effectively than an angiotensin-converting-enzyme inhibitor. Trials comparing the effects of these drugs in patients with acute myocardial infarction have been lacking., Methods: We randomly assigned patients with myocardial infarction complicated by a reduced left ventricular ejection fraction, pulmonary congestion, or both to receive either sacubitril-valsartan (97 mg of sacubitril and 103 mg of valsartan twice daily) or ramipril (5 mg twice daily) in addition to recommended therapy. The primary outcome was death from cardiovascular causes or incident heart failure (outpatient symptomatic heart failure or heart failure leading to hospitalization), whichever occurred first., Results: A total of 5661 patients underwent randomization; 2830 were assigned to receive sacubitril-valsartan and 2831 to receive ramipril. Over a median of 22 months, a primary-outcome event occurred in 338 patients (11.9%) in the sacubitril-valsartan group and in 373 patients (13.2%) in the ramipril group (hazard ratio, 0.90; 95% confidence interval [CI], 0.78 to 1.04; P = 0.17). Death from cardiovascular causes or hospitalization for heart failure occurred in 308 patients (10.9%) in the sacubitril-valsartan group and in 335 patients (11.8%) in the ramipril group (hazard ratio, 0.91; 95% CI, 0.78 to 1.07); death from cardiovascular causes in 168 (5.9%) and 191 (6.7%), respectively (hazard ratio, 0.87; 95% CI, 0.71 to 1.08); and death from any cause in 213 (7.5%) and 242 (8.5%), respectively (hazard ratio, 0.88; 95% CI, 0.73 to 1.05). Treatment was discontinued because of an adverse event in 357 patients (12.6%) in the sacubitril-valsartan group and 379 patients (13.4%) in the ramipril group., Conclusions: Sacubitril-valsartan was not associated with a significantly lower incidence of death from cardiovascular causes or incident heart failure than ramipril among patients with acute myocardial infarction. (Funded by Novartis; PARADISE-MI ClinicalTrials.gov number, NCT02924727.)., (Copyright © 2021 Massachusetts Medical Society.)
- Published
- 2021
- Full Text
- View/download PDF
22. Burden of Heart Failure Signs and Symptoms, Prognosis, and Response to Therapy: The PARAGON-HF Trial.
- Author
-
Jering K, Claggett B, Redfield MM, Shah SJ, Anand IS, Martinez F, Sabarwal SV, Seferović PM, Kerr Saraiva JF, Katova T, Lefkowitz MP, Pfeffer MA, McMurray JJV, and Solomon SD
- Subjects
- Angiotensin Receptor Antagonists therapeutic use, Angiotensin-Converting Enzyme Inhibitors, Female, Humans, Prognosis, Prospective Studies, Stroke Volume, Heart Failure drug therapy, Heart Failure epidemiology
- Abstract
Objectives: This study investigated the prognostic importance of heart failure (HF) signs and symptoms in patients with heart failure and preserved ejection fraction (HFpEF), and the effect of sacubitril/valsartan on HF signs and symptoms., Background: In patients with HFpEF, worsening of HF symptoms, as a marker of cardiac decompensation, is frequently the reason for hospitalization. In this heterogenous disease entity, the prognostic value of HF signs and symptoms with regard to cardiovascular (CV) outcomes is poorly defined., Methods: The authors examined the association between baseline HF signs and symptoms (rest dyspnea, exertional dyspnea, paroxysmal nocturnal dyspnea, orthopnea, fatigue, edema, jugular venous distension, rales, and third heart sound) as well as burden of these HF signs and symptoms (classified as ≤2 and ≥3 HF signs and symptoms) and the primary composite of total HF hospitalizations and CV death, its components, and all-cause death in 4,725 patients enrolled in PARAGON-HF (Prospective Comparison of ARNI With ARB Global Outcomes in HFpEF) with available signs and symptoms at randomization. Response to sacubitril/valsartan on the basis of the presence of signs and symptoms was evaluated. Effects of sacubitril/valsartan on signs and symptoms over time were assessed using binary repeated-measures logistic regression., Results: Patients with high (≥3) burden of HF signs and symptoms (n = 1,772 [38%]) were more commonly women, had slightly lower left ventricular ejection fractions, higher body mass index, and more advanced New York Heart Association functional class compared with patients with low (≤2) burden (n = 2,953 [62%]) (p < 0.001 for all). Levels of N-terminal pro-B-type natriuretic peptide did not differ significantly between groups (p = 0.14). Greater burden of signs and symptoms was associated with higher risk for total HF hospitalizations and CV death (rate ratio [RR]: 1.50; 95% confidence interval [CI]: 1.30 to 1.74) and all-cause death (RR: 1.41; 95% CI: 1.21 to 1.65). Among individual signs and symptoms, orthopnea (RR: 1.29; 95% CI: 1.04 to 1.61) and rales (RR: 1.52; 95% CI: 1.10 to 2.10) were most predictive of the primary endpoint. Treatment response to sacubitril/valsartan was not significantly modified by burden of HF signs and symptoms (p for interaction = 0.08), though patients with orthopnea appeared to derive greater benefit from sacubitril/valsartan (RR: 0.67; 95% CI: 0.49 to 0.90) than those without orthopnea (RR: 0.97; 95% CI: 0.82 to 1.14; p for interaction = 0.04). Compared with valsartan, sacubitril/valsartan did not significantly decrease overall burden of HF signs and symptoms over time (odds ratio: 0.84; 95% CI: 0.67 to 1.07) but did reduce exertional dyspnea (odds ratio: 0.76; 95% CI: 0.63 to 0.93)., Conclusions: High burden of HF signs and symptoms, particularly the presence of orthopnea and rales, portends a higher risk for adverse CV events in patients with HF with preserved ejection fraction. Sacubitril/valsartan did not significantly decrease the burden of HF signs and symptoms over time but did reduce exertional dyspnea relative to valsartan. (Efficacy and Safety of LCZ696 Compared to Valsartan, on Morbidity and Mortality in Heart Failure Patients With Preserved Ejection Fraction [PARAGON-HF]; NCT01920711)., Competing Interests: Funding Support and Author Disclosures PARAGON-HF was funded by Novartis. Dr. Jering is supported by the National Institutes of Health (training grant 5-T32 HL007604). Dr. Claggett has been a consultant for Amgen, AO Biome, Biogen, Boehringer Ingelheim, Corvia, Gilead, Myokardia, and Novartis. Dr. Redfield has served as an unpaid consultant for Novartis. Dr. Shah has received research grants from Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received consulting fees from Abbott, Actelion, AstraZeneca, Amgen, Axon Therapies, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Cardiora, CVRx, Cytokinetics, Eisai, GlaxoSmithKline, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Sanofi, Shifamed, Tenax, and United Therapeutics. Dr. Anand has received fees for serving as U.S. national leader of a trial for AstraZeneca; receives fees for serving on steering committees for ARCA Biopharma, Amgen, LivaNova, and Novartis; has received fees for serving on an endpoint committee for Boehringer Ingelheim; has received fees for serving as chair of a data and safety monitoring board for Boston Scientific; and has received advisory board fees from Zensun. Dr. Martinez has received personal fees from AstraZeneca, Novartis, and Boehringer Ingelheim as honoraria. Drs. Sabarwal and Lefkowitz are salaried employees of Novartis. Dr. Seferović has received honoraria for lectures for Medtronic, Abbott, Servier, AstraZeneca, and Respicardia; has consultancy agreements with and has received honoraria for lectures from Boehringer Ingelheim and Novartis; and has a consultancy agreement with Vifor Pharma. Dr. Saraiva has received lecture fees from Amgen, Merck Sharpe & Dohme, and Pfizer; has received lecture fees, fees for serving on advisory boards, consulting fees, and fees for serving as a national leader of clinical trials from AstraZeneca, Boehringer Ingelheim, Novartis, and Novo Nordisk; and has received lecture fees and fees for serving on advisory boards from Eli Lilly and Servier. Dr. Katova has received lecture fees, fees for serving on an advisory board, and travel support from Novartis; and receives lecture fees, consulting fees, and fees for serving on an advisory board from AstraZeneca. Dr. Pfeffer has received consulting fees from AstraZeneca, DalCor, GlaxoSmithKline, Novo Nordisk, Sanofi, Jazz, MyoKardia, Servier, Takeda, and Corvidia. Dr. McMurray’s employer, Glasgow University, has received funding for his work on clinical trials, consulting, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardurion, Cytokinetics, DalCor, GlaxoSmithKline, Novartis, Pfizer, and Theracos; and has received personal lecture fees from Abbott, Hickma Pharmaceuticals, Sun Pharmaceuticals, and Servier. Dr. Solomon has received research grants from Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol-Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GlaxoSmithKline, Ionis, Lone Star Heart, Mesoblast, MyoKardia, the National Heart, Lung, and Blood Institute, Neurotronik, Novartis, Respicardia, Sanofi-Pasteur, and Theracos; and has consulted for Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Bristol-Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi Sankyo, Gilead, GlaxoSmithKline, Ironwood, Merck, Myokardia, Novartis, Roche, Takeda, Theracos, Quantum Genetics, Cardurion, AoBiome, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, and Moderna. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
23. Parenteral nutrition as an unexpected and preventable source of mercury exposure in preterm infants.
- Author
-
Jering K, Aschner M, Beller A, Hamm EL, Langdon M, and Maitre NL
- Subjects
- Female, Humans, Infant, Infant, Newborn, Infant, Premature, Male, Mercury Poisoning prevention & control, Prospective Studies, Mercury analysis, Mercury Poisoning etiology, Parenteral Nutrition, Parenteral Nutrition Solutions chemistry
- Abstract
Perinatal mercury exposure has neurodevelopmental consequences, which may be worse in preterm infants. In our cohort (N = 60), maternal and infant prenatal exposures were low, but infant levels increased during hospitalization and correlated only with duration of parenteral nutrition. A non-negligible exposure resulted from the nutrition preparation on equipment shared with adult preparations., (Copyright © 2015 Elsevier Inc. All rights reserved.)
- Published
- 2015
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.