Eldrin F. Lewis, MD, MPH

All Publications

• Angiotensin Receptor-Neprilysin Inhibition in Acute Myocardial Infarction. The New England journal of medicine Pfeffer, M. A., Claggett, B., Lewis, E. F., Granger, C. B., Kober, L., Maggioni, A. P., Mann, D. L., McMurray, J. J., Rouleau, J., Solomon, S. D., Steg, P. G., Berwanger, O., Cikes, M., De Pasquale, C. G., East, C., Fernandez, A., Jering, K., Landmesser, U., Mehran, R., Merkely, B., Vaghaiwalla Mody, F., Petrie, M. C., Petrov, I., Schou, M., Senni, M., Sim, D., van der Meer, P., Lefkowitz, M., Zhou, Y., Gong, J., Braunwald, E., PARADISE-MI Investigators and Committees, Pfeffer, M., Braunwald, E., Granger, C. B., Kober, L., Mann, D. L., Maggioni, A. P., McMurray, J. J., Rouleau, J. L., Solomon, S. D., Steg, P. G., Dargie, H., Foley, R., Francis, G. S., Komajda, M., Pocock, S., Lewis, E., Barkoudah, E., Brahimi, A., Correa-Gaviria, S., Cunningham, J., Finn, P., Hartley, H., Jering, K., McCausland, F. R., McGrath, M. M., Vaduganathan, M., Duong, C., Mercier, R., Roach, A., Saunders-Correa, B., Wivagg, A., Charytan, D., Joseph, J., Kaplan, A. P., Busse, P., Zuraw, B., Claggett, B., Fernandez, A., Barrionuevo, M., Albisu, J., Avaca, H., Brasca, D., Cartasegna, L., Casas, M., Costabel, J., de la Fuente, R., Duronto, E., Ferre Pacora, F., Guetta, J., Hominal, M., Hrabar, A., Luquez, H., Macin, S., Muntaner, J., Nani, S., Pizarro, R., Poy, C., Prado, A., Schiavi, L., Wenetz, L., Zapata, G., Zivano, D., De Pasquale, C., Amerena, J., Atherton, J., Lam, K., McKenzie, S., Roberts-Thomson, P., von Lewinski, D., Auer, J., Ebner, C., Hoppe, U., Mortl, D., Schober, A., Zaruba, M., Claeys, M., Cools, F., Gabriel, L., Janssens, S., Mullens, W., Van der Stighelen, H., Vanduynhoven, P., Berwanger, O., Arantes, F., Kormann, A., Maia, L., Manenti, E., Neuenschwander, F., Nicolau, J., Pimentel Filho, P., Precoma, D., Rassi, S., Rossi, P., Saraiva, J., Silva, R., Petrov, I., Atanasov, A., Dimitrov, C., Dimov, B., Gatzov, P., Jorgova Makedonska, J., Konteva, M., Markov, D., Mazhdrakov, G., Milanova, M., Panayotov, P., Raev, D., Stavreva, E., Stoyanov, M., Tisheva Gospodinova, S., Tokmakova, M., Tzekova, M., Tanguay, J., Gosselin, G., Mielniczuk, L., Moe, G., Robinson, S., Rodes-Cabau, J., Sia, Y., Welsh, R., Han, Y., Bai, F., Chen, J., Chen, H., Dong, Y., Fu, L., Gao, W., Gong, H., Huang, W., Li, Y., Li, X., Liu, S., Liu, F., Peng, D., Shen, A., Su, G., Sun, Y., Sun, J., Xu, B., Kong, X., Yao, Z., Yu, Z., Yuan, Z., Yuan, J., Zhou, Y., Cadena Bonfanti, A. J., Arana, C., Botero, R., Chavarriaga, J., Garcia, R., Gomez, E., Cikes, M., Gabor, M., Milicic, D., Trbusic, M., Widimsky, P., Belohlavek, J., Coufal, Z., Hromadka, M., Kala, P., Kettner, J., Motovska, Z., Podpera, I., Polasek, R., Schou, M., Due Vestergaard, L., Egstrup, K., Hollingdal, M., Koeber, L., Taskiran, M., Vraa, S., Vikman, S., Jaaskelainen, P., Nyman, K., Steg, G., Angoulvant, D., Barone-Rochette, G., Coste, P., Dubreuil, O., Elbaz, M., Henry, P., Mewton, N., Puymirat, E., Rosamel, Y., Landmesser, U., Bott, M., Brachmann, J., Cuneo, A., Dahl, J., Felix, S., Gutersohn, A., Haude, M., Horacek, T., Huegl, B., Jung, W., Kadel, C., Leschke, M., Lutz, M., Menck, N., Minden, H., Mittag, M., Nordbeck, P., Pfister, R., Pulz, J., Rassaf, T., Schwefer, M., Schwimmbeck, P., von Scheidt, W., Wienbergen, H., Winzer, E., Wolf, D., Yueksel, D., Zeh, W., Zeiher, A., Zeymer, U., Filippatos, G., Giamouzis, G., Karavidas, A., Milkas, A., Paraskevaidis, I., Patsilinakos, S., Tsioufis, K., Tziakas, D., Merkely, B., Andreka, P., Edes, I., Forster, T., Horvath, I., Kiss, R., Lupkovics, G., Noori, E., Tomcsanyi, J., Kerkar, P., Abdullakutty, J., Agarwal, D., Bhalani, N., Bhatia, T., Chanana, B., Chopada, M., Deshmukh, P., Hiremath, S., Karna, S., Mehta, A., Mittal, S., Premchand, R., Rathnavel, S., Ravikanth, A., Shah, U., Amir, O., Arbel, Y., Eisen, A., Halabi, M., Katz, A., Kinany, W., Zukerman, R., Senni, M., Barilla, F., Calabro, P., Camporotondo, R., Cannarile, P., D'Aiello, I., Ferrante, G., Fucili, A., Indolfi, C., Marenzi, G., Metra, M., Oliva, F., Pedone, C., Piovaccari, G., Prati, F., Sinagra, G., Taddei, F., Carrillo-Calvillo, J., Baleon, F., Bazzoni, A., de Los Rios, M., Leon, S., Rodriguez, J., Virgen, L., van der Meer, P., Al-Windy, N., De Nooijer, C., En Hartog, F., Dirksen, M., Elvan, A., Hamer, B., Jansen, A., Keijzers, M., Linssen, G., Magro, M., Manintveld, O., Nierop, P., Roemer, T., Schaap, J., Swart, H., Symersky, T., Troquay, R., van de Wal, R., van Heerebeek, L., Westendorp, I., Zoet, S., Gullestad, L., Al-Ani, R., Manhenke, C., Lema, J., Nunez, P., Rodriguez, A., Roldan, Y., Sanabria, E., Anonuevo, J., Abola, M., Sison, J., Tirador, L., Opolski, G., Blaszczak, P., Gil, R., Sobkowicz, B., Suckiel, M., Morais, J., Almeida, F., Azevedo, P., Brito, D., Ferreira, J., Lourenco, C., Marques, N., Moreira, J., Oliveira, L., Pereira, H., Pernencar, S., Cho, M., Jeong, M., Shim, W., Yoo, B., Vinereanu, D., Babes, K., Benedek, I., Chioncel, O., Ciobotaru, G., Dorobantu, M., Giuca, A., Iancu, A., Ionac, A., Militaru, C., Popescu, A., Rusu, R., Serban, L., Sinescu, C., Spiridon, M., Stanciulescu, G., Teodorescu, I., Teodoru, M., Todea, B., Tomescu, M., Barbarash, O., Agafina, A., Baranov, E., Berns, S., Boldueva, S., Kashtalap, V., Khaisheva, L., Khirmanov, V., Klein, G., Kobalava, Z., Kosmacheva, E., Kostenko, V., Lipchenko, A., Lomakin, N., Nosov, V., Petrov, A., Pevzner, D., Reznik, E., Ryabov, V., Scheglova, L., Shogenov, Z., Shvarts, Y., Timofeev, A., Yakovlev, A., Zykov, M., Sim Kheng Leng, D., D, S., Liew, M., Studencan, M., Blasko, P., Hudec, M., Jankajova, M., Slanina, M., Stevlik, J., Tomasovic, B., Ntsekhe, M., Corbett, C., Dawood, S., Gould, T., van Zyl, L., Nunez Villota, J., Bayon, J., Bueno, H., Crespo, M., Garcia, C., Garcia, E., Garcia, J., Gomez, J., Miro, V., Pascual, D., Pena, G., Reyes, A., Sionis, A., Christersson, C., Aladellie, L., Frick, M., Lonnberg, I., Mokhtari, A., Skoglund, K., Toernerud, M., Utter, F., Moccetti, T., Hunziker, L., Suter, T., Kobza, R., Maeder, M., Kao, H., Su, C. H., Chiang, C. Y., Tsao, H. M., Wen, M. S., Lo, P. H., Sung, S. H., Wu, Y. W., Kiatchoosakun, S., Ariyachaipanich, A., Kuanprasert, S., Sriratanasathavorn, C., Birhan Yilmaz, M., Akin, M., Badak, O., Cavusoglu, Y., Celik, O., Celik, A., Gecmen, C., Keles, T., Kutlu, M., Sahin, T., Turgut, O., Yigit, Z., Petrie, M., Zaman, A., Austin, D., Dixon, L., Glover, J., Hall, A., Jhund, P., Lee, K., Moriarty, A., O'Kane, P., Ryding, A., Squire, I., Trevelyan, J., Venugopal, V., East, C., Mehran, R., Mody, F., Ahmad, H., Alviar, C., Amidon, T., Ariani, M., Arora, V., Barman, N., Baron, S., Barringhaus, K., Bass, K., Bernstein, M., Bhagwat, R., Birchem, J., Blair, G., Blick, D., Cavender, M., Cebe, J., Chen, M., Cohn, J., Colfer, H., Dib, N., Duffy, B., Erickson, B., Fischer, S., Fung, G., Ghazi, F., Go, J., Graham, B., Gudipati, C., Guynes, R., Haddad, T., Hage, F., Hamzeh, I., Harris, B., Harrison, R., Hawa, Z., Heilman, K., Hinchman, D., Horwitz, P., Huth, M., Iteld, B., Jaffrani, N., Jain, A., Kang, G., Khant, R., Kono, A., Kozak, M., Kumar, V., Landers, D., Laney, P., Lombardo, D., Maheshwari, A., McGinty, J., McMillan, E., Mikdadi, G., Miller, G., Moustakakis, E., Nader, S., Nelson, W., O'Brien, T., Olson, C., Ooi, H., Prasanna, V., Prashad, R., Rees, A., Rennyson, S., Rogers, C., Schultz, J., Shah, R., Sharma, S., Singh, N., Sizemore, B., Soverow, J., Steuter, J., Suh, D., Tolerico, P., Tran, H., Treasure, C., Wallace, E., Wang, J., Wang, L., Wiseman, A., Zughaib, M. 2021; 385 (20): 1845-1855

  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.).

  View details for DOI 10.1056/NEJMoa2104508

  View details for PubMedID 34758252

• Association of Hyper-Polypharmacy With Clinical Outcomes in Heart Failure With Preserved Ejection Fraction. Circulation. Heart failure Minamisawa, M., Claggett, B., Suzuki, K., Hegde, S. M., Shah, A. M., Desai, A. S., Lewis, E. F., Shah, S. J., Sweitzer, N. K., Fang, J. C., Anand, I. S., O'Meara, E., Rouleau, J., Pitt, B., Pfeffer, M. A., Solomon, S. D., Vardeny, O. 2021: CIRCHEARTFAILURE120008293

  Abstract

  BACKGROUND: Polypharmacy is associated with a poor prognosis in the elderly, however, information on the association of polypharmacy with cardiovascular outcomes in heart failure with preserved ejection fraction is sparse. This study sought to investigate the relationship between polypharmacy and adverse cardiovascular events in patients with heart failure with preserved ejection fraction.METHODS: Baseline total number of medications was determined in 1758 patients with heart failure with preserved ejection fraction enrolled in the Americas regions of the TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist), by 3 categories: nonpolypharmacy (<5 medications), polypharmacy (5-9), and hyper-polypharmacy (≥10). We examined the relationship of polypharmacy status with the primary outcome (cardiovascular death, HF hospitalization, or aborted cardiac arrest), hospitalizations for any reason, and serious adverse events.RESULTS: The proportion of patients taking 5 or more medications was 92.5% (inclusive of polypharmacy [38.7%] and hyper-polypharmacy [53.8%]). Over a 2.9-year median follow-up, compared with patients with polypharmacy, hyper-polypharmacy was associated with an increased risk for the primary outcome, hospitalization for any reason and any serious adverse events in the univariable analysis, but not significantly associated with mortality. After multivariable adjustment for demographic and comorbidities, hyper-polypharmacy remained significantly associated with an increased risk for hospitalization for any reason (hazard ratio, 1.22 [95% CI, 1.05-1.41]; P=0.009) and any serious adverse events (hazard ratio, 1.23 [95% CI, 1.07-1.42]; P=0.005), whereas the primary outcome was no longer statistically significant.CONCLUSIONS: Hyper-polypharmacy was common and associated with an elevated risk of hospitalization for any reason and any serious adverse events in patients with heart failure with preserved ejection fraction. There were no significant associations between polypharmacy status and mortality.

  View details for DOI 10.1161/CIRCHEARTFAILURE.120.008293

  View details for PubMedID 34674539

• Association of Myocardial Blood Flow Reserve With Adverse Left Ventricular Remodeling in Patients With Aortic Stenosis: The Microvascular Disease in Aortic Stenosis (MIDAS) Study. JAMA cardiology Zhou, W., Sun, Y., Divakaran, S., Bajaj, N. S., Gupta, A., Chandra, A., Morgan, V., Barrett, L., Martell, L., Bibbo, C. F., Hainer, J., Lewis, E. F., Taqueti, V. R., Dorbala, S., Blankstein, R., Slomka, P., Shah, P. B., Kaneko, T., Adler, D. S., O'Gara, P., Di Carli, M. F. 2021

  Abstract

  Importance: Impaired myocardial flow reserve (MFR) and stress myocardial blood flow (MBF) on positron emission tomography (PET) myocardial perfusion imaging may identify adverse myocardial characteristics, including myocardial stress and injury in aortic stenosis (AS).Objective: To investigate whether MFR and stress MBF are associated with LV structure and function derangements, and whether these parameters improve after aortic valve replacement (AVR).Design, Setting, and Participants: In this single-center prospective observational study in Boston, Massachusetts, from 2018 to 2020, patients with predominantly moderate to severe AS underwent ammonia N13 PET myocardial perfusion imaging for myocardial blood flow (MBF) quantification, resting transthoracic echocardiography (TTE) for assessment of myocardial structure and function, and measurement of circulating biomarkers for myocardial injury and wall stress. Evaluation of health status and functional capacity was also performed. A subset of patients underwent repeated assessment 6 months after AVR. A control group included patients without AS matched for age, sex, and summed stress score who underwent symptom-prompted ammonia N13 PET and TTE within 90 days.Exposures: MBF and MFR quantified on ammonia N13 PET myocardial perfusion imaging.Main Outcomes and Measures: LV structure and function parameters, including echocardiographic global longitudinal strain (GLS), circulating high-sensitivity troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-pro BNP), health status, and functional capacity.Results: There were 34 patients with AS (1 mild, 9 moderate, and 24 severe) and 34 matched control individuals. MFR was independently associated with GLS and LV ejection fraction, (beta,-0.31; P=.03; beta, 0.41; P=.002, respectively). Stress MBF was associated with hs-cTnT (unadjusted beta, -0.48; P=.005) and log NT-pro BNP (unadjusted beta, -0.37; P=.045). The combination of low stress MBF and high hs-cTnT was associated with higher interventricular septal thickness in diastole, relative wall thickness, and worse GLS compared with high stress MBF and low hs-cTnT (12.4 mm vs 10.0 mm; P=.008; 0.62 vs 0.46; P=.02; and -13.47 vs -17.11; P=.006, respectively). In 9 patients studied 6 months after AVR, mean (SD) MFR improved from 1.73 (0.57) to 2.11 (0.50) (P=.008).Conclusions and Relevance: In this study, in AS, MFR and stress MBF were associated with adverse myocardial characteristics, including markers of myocardial injury and wall stress, suggesting that MFR may be an early sensitive marker for myocardial decompensation.

  View details for DOI 10.1001/jamacardio.2021.3396

  View details for PubMedID 34524397

• A fourth pillar for all in the treatment of heart failure. European heart journal Lewis, E. F. 2021

  View details for DOI 10.1093/eurheartj/ehab612

  View details for PubMedID 34516624

• Effect of a Hospital and Postdischarge Quality Improvement Intervention on Clinical Outcomes and Quality of Care for Patients With Heart Failure With Reduced Ejection Fraction: The CONNECT-HF Randomized Clinical Trial. JAMA DeVore, A. D., Granger, B. B., Fonarow, G. C., Al-Khalidi, H. R., Albert, N. M., Lewis, E. F., Butler, J., Pina, I. L., Allen, L. A., Yancy, C. W., Cooper, L. B., Felker, G. M., Kaltenbach, L. A., McRae, A. T., Lanfear, D. E., Harrison, R. W., Disch, M., Ariely, D., Miller, J. M., Granger, C. B., Hernandez, A. F. 2021; 326 (4): 314-323

  Abstract

  Importance: Adoption of guideline-directed medical therapy for patients with heart failure is variable. Interventions to improve guideline-directed medical therapy have failed to consistently achieve target metrics, and limited data exist to inform efforts to improve heart failure quality of care.Objective: To evaluate the effect of a hospital and postdischarge quality improvement intervention compared with usual care on heart failure outcomes and care.Design, Setting, and Participants: This cluster randomized clinical trial was conducted at 161 US hospitals and included 5647 patients (2675 intervention vs 2972 usual care) followed up after a hospital discharge for acute heart failure with reduced ejection fraction (HFrEF). The trial was performed from 2017 to 2020, and the date of final follow-up was August 31, 2020.Interventions: Hospitals (n=82) randomized to a hospital and postdischarge quality improvement intervention received regular education of clinicians by a trained group of heart failure and quality improvement experts and audit and feedback on heart failure process measures (eg, use of guideline-directed medical therapy for HFrEF) and outcomes. Hospitals (n=79) randomized to usual care received access to a generalized heart failure education website.Main Outcomes and Measures: The coprimary outcomes were a composite of first heart failure rehospitalization or all-cause mortality and change in an opportunity-based composite score for heart failure quality (percentage of recommendations followed).Results: Among 5647 patients (mean age, 63 years; 33% women; 38% Black; 87% chronic heart failure; 49% recent heart failure hospitalization), vital status was known for 5636 (99.8%). Heart failure rehospitalization or all-cause mortality occurred in 38.6% in the intervention group vs 39.2% in usual care (adjusted hazard ratio, 0.92 [95% CI, 0.81 to 1.05). The baseline quality-of-care score was 42.1% vs 45.5%, respectively, and the change from baseline to follow-up was 2.3% vs -1.0% (difference, 3.3% [95% CI, -0.8% to 7.3%]), with no significant difference between the 2 groups in the odds of achieving a higher composite quality score at last follow-up (adjusted odds ratio, 1.06 [95% CI, 0.93 to 1.21]).Conclusions and Relevance: Among patients with HFrEF in hospitals randomized to a hospital and postdischarge quality improvement intervention vs usual care, there was no significant difference in time to first heart failure rehospitalization or death, or in change in a composite heart failure quality-of-care score.Trial Registration: ClinicalTrials.gov Identifier: NCT03035474.

  View details for DOI 10.1001/jama.2021.8844

  View details for PubMedID 34313687

• Disparity in the Setting of Incident Heart Failure Diagnosis. Circulation. Heart failure Sandhu, A. T., Tisdale, R. L., Rodriguez, F., Stafford, R. S., Maron, D. J., Hernandez-Boussard, T., Lewis, E., Heidenreich, P. A. 2021: CIRCHEARTFAILURE121008538

  Abstract

  BACKGROUND: Early heart failure (HF) recognition can reduce morbidity, yet HF is often initially diagnosed only after a patient clinically worsens. We sought to identify characteristics that predict diagnosis in the acute care setting versus the outpatient setting.METHODS: We estimated the proportion of incident HF diagnosed in the acute care setting (inpatient hospital or emergency department) versus outpatient setting based on diagnostic codes from a claims database covering commercial insurance and Medicare Advantage between 2003 and 2019. After excluding new-onset HF potentially caused by a concurrent acute cause (eg, acute myocardial infarction), we identified demographic, clinical, and socioeconomic predictors of diagnosis setting. Patients were linked to their primary care clinicians to evaluate diagnosis setting variation across clinicians.RESULTS: Of 959 438 patients with new HF, 38% were diagnosed in acute care. Of these, 46% had potential HF symptoms in the prior 6 months. Over time, the relative odds of acute care diagnosis increased by 3.2% annually after adjustment for patient characteristics (95% CI, 3.1%-3.3%). Acute care diagnosis setting was more likely for women compared with men (adjusted odds ratio, 1.11 [95% CI, 1.10-1.12]) and for Black patients compared with White patients (adjusted odds ratio, 1.18 [95% CI, 1.16-1.19]). The proportion of acute care diagnosis varied substantially (interquartile range: 24%-39%) among clinicians after adjusting for patient-level risk factors.CONCLUSIONS: A large proportion of first HF diagnoses occur in the acute care setting, particularly among women and Black patients, yet many had potential HF symptoms in the months before acute care visits. These results raise concerns that many HF diagnoses are missed in the outpatient setting. Earlier diagnosis could allow for timelier high-value interventions, addressing disparities and reducing the progression of HF.

  View details for DOI 10.1161/CIRCHEARTFAILURE.121.008538

  View details for PubMedID 34311559

• Safety and Efficacy of Vadadustat for Anemia in Patients Undergoing Dialysis. The New England journal of medicine Eckardt, K., Agarwal, R., Aswad, A., Awad, A., Block, G. A., Bacci, M. R., Farag, Y. M., Fishbane, S., Hubert, H., Jardine, A., Khawaja, Z., Koury, M. J., Maroni, B. J., Matsushita, K., McCullough, P. A., Lewis, E. F., Luo, W., Parfrey, P. S., Pergola, P., Sarnak, M. J., Spinowitz, B., Tumlin, J., Vargo, D. L., Walters, K. A., Winkelmayer, W. C., Wittes, J., Zwiech, R., Chertow, G. M. 2021; 384 (17): 1601–12

  Abstract

  BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, a class of compounds that stimulate endogenous erythropoietin production.METHODS: We conducted two randomized, open-label, noninferiority phase 3 trials to evaluate the safety and efficacy of vadadustat, as compared with darbepoetin alfa, in patients with anemia and incident or prevalent dialysis-dependent chronic kidney disease (DD-CKD). The primary safety end point, assessed in a time-to-event analysis, was the first occurrence of a major adverse cardiovascular event (MACE, a composite of death from any cause, a nonfatal myocardial infarction, or a nonfatal stroke), pooled across the trials (noninferiority margin, 1.25). A key secondary safety end point was the first occurrence of a MACE plus hospitalization for either heart failure or a thromboembolic event. The primary and key secondary efficacy end points were the mean change in hemoglobin from baseline to weeks 24 to 36 and from baseline to weeks 40 to 52, respectively, in each trial (noninferiority margin, -0.75 g per deciliter).RESULTS: A total of 3923 patients were randomly assigned in a 1:1 ratio to receive vadadustat or darbepoetin alfa: 369 in the incident DD-CKD trial and 3554 in the prevalent DD-CKD trial. In the pooled analysis, a first MACE occurred in 355 patients (18.2%) in the vadadustat group and in 377 patients (19.3%) in the darbepoetin alfa group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.11). The mean differences between the groups in the change in hemoglobin concentration were -0.31 g per deciliter (95% CI, -0.53 to -0.10) at weeks 24 to 36 and -0.07 g per deciliter (95% CI, -0.34 to 0.19) at weeks 40 to 52 in the incident DD-CKD trial and -0.17 g per deciliter (95% CI, -0.23 to -0.10) and -0.18 g per deciliter (95% CI, -0.25 to -0.12), respectively, in the prevalent DD-CKD trial. The incidence of serious adverse events in the vadadustat group was 49.7% in the incident DD-CKD trial and 55.0% in the prevalent DD-CKD trial, and the incidences in the darbepoetin alfa group were 56.5% and 58.3%, respectively.CONCLUSIONS: Among patients with anemia and CKD who were undergoing dialysis, vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and correction and maintenance of hemoglobin concentrations. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; INNO2VATE ClinicalTrials.gov numbers, NCT02865850 and NCT02892149.).

  View details for DOI 10.1056/NEJMoa2025956

  View details for PubMedID 33913638

• Vadadustat in Patients with Anemia and Non-Dialysis-Dependent CKD. The New England journal of medicine Chertow, G. M., Pergola, P. E., Farag, Y. M., Agarwal, R., Arnold, S., Bako, G., Block, G. A., Burke, S., Castillo, F. P., Jardine, A. G., Khawaja, Z., Koury, M. J., Lewis, E. F., Lin, T., Luo, W., Maroni, B. J., Matsushita, K., McCullough, P. A., Parfrey, P. S., Roy-Chaudhury, P., Sarnak, M. J., Sharma, A., Spinowitz, B., Tseng, C., Tumlin, J., Vargo, D. L., Walters, K. A., Winkelmayer, W. C., Wittes, J., Eckardt, K., PRO2TECT Study Group, Porto, A., Glenny, J., Alvarisqueta, A., Vallejos, A., Cusumano, C., Chacon, C., Garcia, C., Goycoa, C., Stoppa, D., Otreras, F., Gorosito, G., Beresan, H., MacKinnon, I., Resk, J., Santos, J., Bittar, J., Schiavi, L., Rista, L., Maurich, M., Mansilla, M., Pelagagge, M., Garcia, N., Penalba, N., Ramallo, P., Calella, P., Leon de la Fuente, R., Visco, V., Irish, A., McMahon, L., Mathew, M., Suranyi, M., Boudville, N., Phoon, R., Ford, S., McDonald, S., Ludvik, B., Wiesholzer, M., Costa E Forti, A., Sousa, A., Goncalves, B., Teles Barretto, C., Fraga, C., Rinaldi Dos Santos, D., Miltersteiner, D., D'Avila, D., Contieri, F., Veronese, F., Neto, G., Sander, G., de Lourdes Noronha, I., Rodrigues Bacci, M., Gomes Bastos, M., Mara da Silva, M., Canziani, M., Paschoalin, N., Simoes Pires von Eye, O., Macedo de Souza, P., Silva, P., Armani, R., Barbieri, D., Paschoalin, R., Montenegro, R. J., Franco, R., Pecoits Filho, R., Yamada, S., Duro Garcia, V., Vasileva, A., Angelova, A., Kostadinova, A., Kundurdziev, A., Bogov, B., Kostadinova, D., Popov, I., Ashikova, K., Nikolova-Dimitrova, M., Petrova-Obretenova, P., Rangelov, R., Boyadzhieva, S., Vasilev, S., Bakardzhiev, T., Staykova, T., Atanasova, V., Hristov, V., Iliev, V., Simeonov, V., Todorova, V., Hristozov, V., Ting, R., Boltansky Brenner, A., Schneider Contreras, H., Garcia Lozada, H., Rueda Hernandez, J., Terront Lozano, M., Parikova, A., Dusilova Sulkova, S., Tesar, V., Mariat, C., Thervet, E., Fessi, H., Kazes, I., Lang, P., Rosenberger, C., Draganova, D., Toussaint, K., Krueger, T., Ladanyi, A., Palinkas, A., Csiky, B., Literati-Nagy, B., Pall, D., Magyar, K., Major, L., Zsom, M., Molnar, M., Keresztesi, S., Zolyomi, S., Szabo, T., Szelestei, T., Nemeth, Z., Szigeti, Z., Beberashvili, I., Hassan, K., Assady, S., Yagil, Y., Naticchia, A., Gambaro, G., Esposito, C., Aucella, F., Garibotto, G., Nicola, L. D., Vecchio, L. D., Zacchia, M., Ondei, P., David, S., Yang, C., Koh, E., Song, H., Chin, H., Joo, K., Han, S., Jo, S., Han, S., Yoo, S., An, W., Kim, Y., Kim, T., Kim, Y., Ching, C., Ong, L., Mohd, R., Lim, S., Leguizamo Dimas, A., Calvo Vargas, C., Tellez Chavez, E., Pelayo Orozco, E., Flores Lozano, F., Murguia Martin, F., Quintana Pina, F., Sanchez Mijangos, J., Tamayo Y Orozco, J., Herrara Jimenez, L., Nevarez Ruiz, L., Islas Guerrero, M., Vazquez Contreras, P., Austria Garcia, P., Banda Elizondo, R., Orozco Castellanos, R., Monreal Puente, R., Avila Pardo, S., Irizar Santana, S., Irigoyen Monroy, V., Limas Juarez, A., Pescador Martinez, Y., Achim, C., Bogeanu, C., David, C., Peride, I., Bako, G., Petrica, L., Vishnevsky, A., Smirnov, A., Pichkov, D., Reznik, E., Vaskina, E., Tsyba, L., Rossovskaya, M., Fomina, N., Barysheva, O., Kostitsina, O., Lesnyak, O., Sigitova, O., Ageeva, T., Marasaev, V., Tirmenstajn-Jankovic, B., Maksic, D., Maric, I., Velickovic-Radovanovic, R., Damjanovic, T., Dimkovic, N., Lazarevic, T., Lezaic, V., Krajnakova, A., Bobak, L., Vojtko, M., Muranda, A., Rayner, B., Malan, D., Engelbrecht, J., van Zyl, L., Van Jaarsveld, M., Mollentze, W., Sarvan, M., Nortje, M., Makanda, M. B., Ayoob, N., Chelin, N., Welkovics, N., Naiker, P., Moodley, R., Arnold, S., Govind, U., Naidoo, V., Galan Serrano, A., Garcia Carro, C., Hernandez Marrero, D., Gonzalez Martinez, F., Sanjuan, J., Ballarin Castan, J., Molas Coten, J., Torras Ambros, J., Hernandez-Jaras, J., Santos, J. P., Baro Salvador, M., Munar Vila, M., Slon Roblero, M., Yildiz, A., Kalender, B., Duranay, M., Tuglular, S., Ursol, G., Dudar, I., Rudyk, I., Vyshnyvetskyy, I., Kolesnyk, M., Tryshchuk, N., Pyvovarova, N., Sydor, N., Legun, O., Levchenko, O., Lyulko, O., Godlevska, O., Matushchak, O., Abrahamovych, O., Yatsyshyn, R., Kolupayev, S., Kostynenko, T., Vizir, V., Maslovskyi, V., Stus, V., Mostovoy, Y., Mikhail, A., Vilar, E., Yaqoob, M., Wilkie, M., El Kossi, M., Kalra, P., Shah, S., Nossuli, A. K., Jamal, A., Buridi, A., Murillo, A., Khan, A., Ijaz, A., Aswad, A., Awad, A., Sawhney, A., Esquenazi, A., Velar, A., Sprague, A., O'Shaughnessy, A., Agarwal, A., Parikh, S., Terrelonge, A., Dhandayuthapani, A., Chauhan, R., Silva, A., Mehta, A., Chaudhry, A., Bailey, A., Buerkert, J., Jones, A., Turk, T., Torres Consuegra, A., Sachdeva, B., Mehta, B., Thajudeen, B., Roy-Chaudhury, P., Spinowitz, B., Voinescu, C. G., Leon-Forero, C., Martinez, C., Ortiz-Butcher, C., Hernandez, C., Montoya, M., Arora, C., Sun, C., Argyropoulos, C., Galphin, C., Gadegbeku, C., Kovesdy, C., Christiano, C., Checketts, D., Arfaania, D., Goldfarb, D., Scott, D., Tietjen, D., Whittman, D., Price, D., Rizos, D., Dev, D., Belo, D., Brandon, D., Lanier, D., Hopkins, E., Linfert, D., Shemin, D., Gonzalez, E., Cosby, J., Rodriguez-Araya, E., Brown, E., Galindo-Ramos, E., Al-Saghir, F., Bangash, F., Castillo, F., Cid, J., Trespalacios, F., Finkelstein, F., Varghese, F., Vaz, G., Ramamurthy, G., Garcia Saez, G., Fadda, G., Hon, G., Nassar, G., Bueso, G., Diaz, G., Varallo, G., Pitone, J., Alvarez, G., Hernandez, G., Hadi, G., De La Calle, G., Krishna, G., Allen, G. J., Greenwood, G., Stewart, D., Toka, H., Boghara, H., Kumar, H., Niegos, F., Brar, H., Hubert, H., Szerlip, H., Farooq, H., Gonzalez, H., Martinez, L., Cosma, I., Drakakis, J., Shirazian, S., Reich, J., Tumlin, J., Colomar, J., Kumar, J., Moya, J., Rimmer, J., Navarro, J., Li, J., Meyer, J., Topf, J., Pullman, J., Alvarez-Moreno, J., Loredo, J., Posada, J., Fernandez, J., Gandhi, K., Servilla, K., Mootoo, K., Hendon, K., Choi, K., Bashir, K., Shah, K., Lalwani, T., Chaudhary, K., Thomas, K. V., Kooienga, L., Block, G., Forgosh, L., Spry, L., Adan, L., Glaser, L., Schneider, L., Seney, F., Lewy Alterbaum, L., Diaz-Secades, L., Perez, G., Garcia-Mayol, L., Bodell, M., Martinson, M., Sahani, M., Montero, M., Sanchez, M., Chang, M., Guillen, M., Henriquez, M., Lawrence, M., Vernace, M., Chan, M., Anger, M., Levey, S., Chang, I., Fredericks, M., Germain, M., Hassman, M., Levine, M., Patel, M., Issa, M., Dhillon, M., Moustafa, M., Siddiqui, N., Vo, N., Shahid, N., Atray, N., Khosla, N., Chronos, N., Stankus, N., Daboul, N., Frontela, O., Mendez, J., Ayodeji, O., Adler, O., Pergola, P., Kalirao, P., Peters, P., Santos, P., Van Buren, P., Lazowski, P., Ranjan, P., Krish, P., Suchinda, P., Gonzalez, R., Grillo, R., Abdullah, R., Zabaneh, R., Alappan, R., Yalavarthy, R., Patak, R., Berenji, R., Guadiz, R., Mendez, R., Sastre, R., Gaona, R., John, R., Sothinathan, R., Darwish, R., O'Donovan, R., Sandler, R., Szewc, R., Manllo-Karim, R., Gupta, R., Afsari, R., Raina, R., Benjamin, S., Kronfli, S., Sonbol, S., Butt, S., Sader, S., Kantor, S., Anand, S., Sharma, S., Dua, S., Kharait, S., Mandayam, S., Sitar, S., Zeig, S., Handelsman, S., Clarke, S., Joshi, S., Lalla-Reddy, S., Lee, S., Mustafa, E., Boone, T., Hart, T., Pillai, U., Subramanian, V., Prasad, V., Din, Z. 2021; 384 (17): 1589–1600

  Abstract

  BACKGROUND: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production.METHODS: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52.RESULTS: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter.CONCLUSIONS: Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PRO2TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.).

  View details for DOI 10.1056/NEJMoa2035938

  View details for PubMedID 33913637

• Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI): Design and Baseline Characteristics. European journal of heart failure Jering, K. S., Claggett, B., Pfeffer, M. A., Granger, C., Kober, L., Lewis, E. F., Maggioni, A. P., Mann, D., McMurray, J. J., Rouleau, J., Solomon, S. D., Steg, P. G., van der Meer, P., Wernsing, M., Carter, K., Guo, W., Zhou, Y., Lefkowitz, M., Gong, J., Wang, Y., Merkely, B., Macin, S. M., Shah, U., Nicolau, J. C., Braunwald, E. 2021

  Abstract

  AIMS: Patients surviving an acute myocardial infarction (AMI) are at risk of developing symptomatic heart failure (HF) or premature death. We hypothesized that sacubitril/valsartan, effective in the treatment of chronic HF, prevents development of HF and reduces cardiovascular death following high-risk AMI compared to a proven ACE inhibitor. This paper describes the study design and baseline characteristics of patients enrolled in the Prospective ARNI versus ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI) trial.METHODS AND RESULTS: PARADISE-MI, a multinational (41 countries), double-blind, active-controlled trial, randomized patients within 0.5-7days of presentation with index AMI to sacubitril/valsartan or ramipril. Transient pulmonary congestion and/or LVEF ≤40% and at least one additional factor augmenting risk of HF or death (age ≥70years, eGFR <60ml/min/1.73m2 , diabetes, prior MI, atrial fibrillation, LVEF <30%, Killip class ≥III, STEMI without reperfusion) were required for inclusion. PARADISE-MI was event-driven targeting 708 primary endpoints [cardiovascular (CV) death, HF hospitalization or outpatient development of HF]. Randomization of 5669 patients occurred 4.3 ±1.8days from presentation with index AMI. The mean age was 64 ±12years, 24% were women. The majority (76%) qualified with ST-segment elevation MI; acute percutaneous coronary intervention was performed in 88% and thrombolysis in 6%. LVEF was 37 ±9% and 58% were Killip class ≥2.CONCLUSIONS: Baseline therapies in PARADISE-MI reflect advances in contemporary evidence-based care. With enrollment complete PARADISE-MI is poised to determine whether sacubitril/valsartan is more effective than a proven ACE inhibitor in preventing development of HF and CV death following AMI.

  View details for DOI 10.1002/ejhf.2191

  View details for PubMedID 33847047

• Sex differences in congestive markers in patients hospitalized for acute heart failure. ESC heart failure Espersen, C., Campbell, R. T., Claggett, B., Lewis, E. F., Groarke, J. D., Docherty, K. F., Lee, M. M., Lindner, M., Biering-Sorensen, T., Solomon, S. D., McMurray, J. J., Platz, E. 2021

  Abstract

  AIMS: We sought to examine sex differences in congestion in patients hospitalized for acute heart failure (AHF). Understanding congestive patterns in women and men with AHF may provide insights into sex differences in the presentation and prognosis of AHF patients.METHODS AND RESULTS: In a prospective, two-site study in adults hospitalized for AHF, four-zone lung ultrasound (LUS) was performed at the time of echocardiography at baseline (LUS1) and, in a subset, pre-discharge (LUS2). B-lines on LUS and echocardiographic images were analysed offline, blinded to clinical information and outcomes. Among 349 patients with LUS1 data (median age 74, 59% male, and 87% White), women had higher left ventricular ejection fraction (mean 43% vs. 36%, P<0.001), higher tricuspid annular plane systolic excursion (mean 17 vs. 15mm, P=0.021), and higher measures of filling pressures (median E/e' 20 vs. 16, P<0.001). B-line number on LUS1 (median 6 vs. 6, P=0.69) and admission N-terminal pro-B-type natriuretic peptide levels (median 3932 vs. 3483pg/mL, P=0.77) were similar in women and men. In 121 patients with both LUS1 and LUS2 data, there was a similar and significant decrease in B-lines from baseline to discharge in both women and men. The risk of the composite 90day outcome increased with higher B-line number on four-zone LUS2: unadjusted hazard ratio for each B-line tertile was 1.86 (95% confidence interval 1.08-3.20, P=0.025) in women and 1.65 (95% confidence interval 1.03-2.64, P=0.037) in men (interaction P=0.72).CONCLUSIONS: Among patients with AHF, echocardiographic markers differed between women and men at baseline, whereas B-line number on LUS did not. The dynamic changes in B-lines during a hospitalization for AHF were similar in women and men.

  View details for DOI 10.1002/ehf2.13300

  View details for PubMedID 33709520

• Heart Failure Admission Service Triage (H-FAST) Study: Racialized Differences in Perceived Patient Self-Advocacy as a Driver of Admission Inequities. Cureus Cleveland Manchanda, E. C., Marsh, R. H., Osuagwu, C., Decopain Michel, J., Dugas, J. N., Wilson, M., Morse, M., Lewis, E., Wispelwey, B. P. 2021; 13 (2): e13381

  Abstract

  Background Racial inequities in mortality and readmission for heart failure (HF) are well documented. Inequitable access to specialized cardiology care during admissions may contribute to inequity, and the drivers of this inequity are poorly understood. Methodology This prospective observational study explored proposed drivers of racial inequities in cardiology admissions among Black, Latinx, and white adults presenting to the emergency department (ED) with symptoms of HF. Surveys of ED providers examined perceptions of patient self-advocacy, outreach to other clinicians (e.g., outpatient cardiologist), diagnostic uncertainty, and other active co-morbid conditions. Service census, bed availability, prior admission service, and other structural factors were explored through the electronic medical record. Results Complete data were available for 61/135 patients admitted with HF during the study period, which halted early due to coronavirus disease 2019. No significant differences emerged in admission to cardiology versus medicine based on age, sex, insurance status, education level, or perceived race/ethnicity. White patients were perceived as advocating for admission to cardiology more frequently (18.9 vs. 5.6%) and more strenuously than Black patients (p = 0.097). ED clinicians more often reported having spoken with the patient's outpatient cardiologist for whites than for Black or Latinx patients (24.3 vs. 16.7%, p = 0.069). Conclusions Theorized drivers of racial inequities in admission service did not reach statistical significance, possibly due to underpowering, the Hawthorne effect, or clinician behavior change based on knowledge of previously identified inequities. The observed trend towards racialdifferences in coordination of care between ED and outpatient providers, as well as in either actual or perceived self-advocacy by patients, may beas-yet undemonstrated components of structural racism driving HF care inequities.

  View details for DOI 10.7759/cureus.13381

  View details for PubMedID 33628703

• Evaluation of Quality of Care for US Veterans With Recent-Onset Heart Failure With Reduced Ejection Fraction. JAMA cardiology Sandhu, A. T., Kohsaka, S., Turakhia, M. P., Lewis, E. F., Heidenreich, P. A. 2021

  Abstract

  Multiple guideline-recommended therapies for heart failure with reduced ejection fraction (HFrEF) are available and promoted by performance measures. However, contemporary data on the use of these therapies are limited.To evaluate trends in guideline-directed medical therapy, implantable cardioverter-defibrillator (ICD) use, and risk-adjusted mortality among patients with recent-onset HFrEF.This cohort study analyzed claims and electronic health record data of patients with recent-onset HFrEF diagnosed at US Department of Veterans Affairs (VA) health care system facilities from July 1, 2013, through June 30, 2019. Veterans who had a history of heart transplant or used a ventricular assist device were among the patients who were excluded.Guideline-directed medical therapy (any β-blocker, guideline-recommended β-blocker [bisoprolol, carvedilol, or metoprolol succinate], angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, angiotensin receptor-neprilysin inhibitor, mineralocorticoid receptor antagonist, and hydralazine plus nitrate) and ICD.Treatment rates for guideline-directed medical therapies and ICDs were calculated within 6 months of the index HFrEF date using medication fills, procedural codes for implantation and monitoring, and diagnosis codes. Risk-adjusted mortality was calculated after adjusting for baseline patient characteristics. For both treatment rates and risk-adjusted mortality, we evaluated the change over 3 periods (period 1: July 1, 2013, to June 30, 2015; period 2: July 1, 2015, to June 30, 2017; and period 3: July 1, 2017, to June 30, 2019) and variation across VA facilities.The final cohort comprised 144 074 eligible patients with incident HFrEF that was diagnosed between July 1, 2013, and June 30, 2019. The cohort had a mean (SD) age of 71.0 (11.4) years and was mostly composed of men (140 765 [97.7%]). Overall, changes in medical therapy rates were minimal over time, with the use of a guideline-recommended β-blocker increasing from 64.2% in 2013 to 72.0% in 2019. Rates for mineralocorticoid receptor antagonist therapy increased from 23.9% in 2013 to 26.9% in 2019, and rates for hydralazine plus nitrate therapy remained stable at 24.2% over the study period. Rates for angiotensin receptor-neprilysin inhibitor therapy increased since its introduction in 2015 but only to 22.6% in 2019. Among patients with an ICD indication, early use rates decreased over time. Substantial variation in medical therapy rates persisted across VA facilities. Risk-adjusted mortality decreased over the study period from 19.9% (95% CI, 19.6%-20.2%) in July 1, 2013, to June 30, 2015, to 18.4% (95% CI, 18.0%-18.7%) in July 1, 2017, to June 30, 2019 (OR, 0.96 per additional year; 95% CI, 0.96-0.97).This study found only marginal improvement between 2013 and 2019 in the guideline-recommended therapy and mortality rates among patients with recent-onset HFrEF. New approaches to increase the uptake of evidence-based HFrEF treatment are urgently needed and could lead to larger reductions in mortality.

  View details for DOI 10.1001/jamacardio.2021.4585

  View details for PubMedID 34757380

• A-lines and B-lines in patients with acute heart failure. European heart journal. Acute cardiovascular care Johannessen, Ø., Claggett, B., Lewis, E. F., Groarke, J. D., Swamy, V., Lindner, M., Solomon, S. D., Platz, E. 2021; 10 (8): 909-917

  Abstract

  Lung ultrasound (LUS) relies on detecting artefacts, including A-lines and B-lines, when assessing dyspnoeic patients. A-lines are horizontal artefacts and characterize normal lung, whereas multiple vertical B-lines are associated with increased lung density. We sought to assess the prevalence of A-lines and B-lines in patients with acute heart failure (AHF) and examine their clinical correlates and their relationship with outcomes.In a prospective cohort study of adults with AHF, eight-zone LUS and echocardiography were performed early during the hospitalization and pre-discharge at an imaging depth of 18 cm. A- and B-lines were analysed separately off-line, blinded to clinical and outcome data. Of 164 patients [median age 71 years, 61% men, mean ejection fraction (EF) 40%], the sum of A-lines at baseline ranged from 0 to 19 and B-line number from 0 to 36. One hundred and fifty-six patients (95%) had co-existing A-lines and B-lines at baseline. Lower body mass index and lower chest wall thickness were associated with a higher number of A-lines (P trend < 0.001 for both). In contrast to B-lines, there was no significant change in the number of A-lines from baseline to discharge (median 6 vs. 5, P = 0.80). While B-lines were associated with 90-day HF readmission or death, A-lines were not [HR 1.67, 95% confidence interval (CI) 1.11-2.51 vs. HR 0.97, 95% CI 0.65-1.43].A-lines and B-lines on LUS co-exist in the vast majority of hospitalized patients with AHF. In contrast to B-lines, A-lines were not associated with adverse outcomes.

  View details for DOI 10.1093/ehjacc/zuab046

  View details for PubMedID 34160009

• Impact of Sacubitril/Valsartan Versus Ramipril on Total Heart Failure Events in the PARADISE-MI Trial. Circulation Pfeffer, M. A., Claggett, B., Lewis, E. F., Granger, C. B., Køber, L., Maggioni, A. P., Mann, D., McMurray, J. J., Rouleau, J. L., Solomon, S. D., Steg, P. G., Berwanger, O., Cikes, M., De Pasquale, C. G., Fernandez, A., Filippatos, G., Jering, K., Landmesser, U., Menon, V., Prof Merkely, B., Petrie, M. C., Petrov, I., Schou, M., Senni, M., Sim, D., van der Meer, P., Lefkowitz, M., Zhou, Y., Wang, Y., Braunwald, E. 2021

  View details for DOI 10.1161/CIRCULATIONAHA.121.057429

  View details for PubMedID 34797725

• Underrepresentation of Ethnic and Racial Minorities in Atrial Fibrillation Clinical Trials. Circulation. Arrhythmia and electrophysiology Nunes, J. C., Rice, E. N., Stafford, R. S., Lewis, E. F., Wang, P. J. 2021: CIRCEP121010452

  View details for DOI 10.1161/CIRCEP.121.010452

  View details for PubMedID 34789014

• A Randomized Trial of Strategies Using Darbepoetin Alfa To Avoid Transfusions in CKD. Journal of the American Society of Nephrology : JASN Toto, R., Petersen, J., Berns, J. S., Lewis, E. F., Tran, Q., Weir, M. R. 2020

  Abstract

  BACKGROUND: Exposure to high doses or a high cumulative dose of erythropoiesis-stimulating agents (ESAs) may contribute to cardiovascular events in patients with CKD and anemia. Whether using a low fixed ESA dose versus dosing based on a hemoglobin-based, titration-dose algorithm in such patients might reduce risks associated with high ESA doses and decrease the cumulative exposure-while reducing the need for red blood cell transfusions-is unknown.METHODS: In this phase-3, randomized trial involving 756 adults with stage-3 to -5 CKD and anemia, we evaluated incidence of red blood cell transfusions for participants randomized to receive darbepoetin given as a fixed dose (0.45 g/kg every 4 weeks) versus administered according to a hemoglobin-based, titration-dose algorithm, for up to 2 years. Participants received transfusions as deemed necessary by the treating physician.RESULTS: There were 379 patients randomized to the fixed-dose group, and 377 to the titration-dose group. The percentage of participants transfused did not differ (24.1% and 24.4% for the fixed-dose and titration-dose group, respectively), with similar time to first transfusion. The titration-dose group achieved significantly higher median hemoglobin (9.9 g/dl) compared with the fixed-dose group (9.4 g/dl). The fixed-dose group had a significantly lower median cumulative dose of darbepoetin (median monthly dose of 30.9 g) compared with the titration-dose group (53.6 g median monthly dose). The FD and TD group received a median (Q1, Q3) cumulative dose per 4 weeks of darbepoetin of 30.9 (21.8, 40.0) g and 53.6 (31.1, 89.9) g, respectively; the median of the difference between treatment groups was -22.1 (95% CI, -26.1 to -18.1) g.CONCLUSIONS: These findings indicate no evidence of difference in incidence of red blood cell transfusion for a titration-dose strategy versus a fixed-dose strategy for darbepoetin. This suggests that a low fixed dose of darbepoetin may be used as an alternative to a dose-titration approach to minimize transfusions, with less cumulative dosing.

  View details for DOI 10.1681/ASN.2020050556

  View details for PubMedID 33288629

• Cardiovascular Safety and Efficacy of Vadadust for the Treatment of Anemia in Non-Dialysis Dependent CKD: Design and Baseline Characteristics. American heart journal Chertow, G. M., Pergola, P. E., Agarwal, R., Block, G. A., Farag, Y. M., Jardine, A. G., Koury, M. J., Luo, W., Khawaja, Z., Lewis, E. F., Matsushita, K., McCullough, P. A., Parfrey, P. S., Wittes, J., Walters, K. A., Tseng, C., Lin, T., Sarnak, M. J., Vargo, D. L., Winkelmayer, W. C., Eckardt, K. 2020

  Abstract

  Current clinical practice guidelines for anemia management in non-dialysis dependent chronic kidney disease (NDD-CKD) recommend the use of erythropoiesis-stimulating agents (ESAs) as standard of care. Vadadustat, an investigational oral hypoxia-inducible factor prolyl hydroxylase inhibitor, stimulates endogenous erythropoietin production. The PRO2TECT program comprises two global, Phase 3, randomized, open-label, active-controlled, sponsor-blind clinical trials to evaluate safety and efficacy of vadadustat vs darbepoetin alfa in adult patients with anemia associated with NDD-CKD. Patients recruited into the ESA-untreated NDD-CKD trial (N=1751) had hemoglobin <10 g/dL and had not received an ESA within 8 weeks prior to inclusion in the study. Patients recruited into the ESA-treated NDD-CKD trial (N=1725) had hemoglobin between 8-11 g/dL (US) or 9-12 g/dL (non-US) and were actively treated with an ESA for anemia associated with CKD. Trial periods in both trials include 1) correction/conversion (weeks 0-23); 2) maintenance (weeks 24-52); 3) long-term treatment (week 53 to end of treatment); and 4) safety follow-up (end-of-treatment to 4 weeks later). The primary safety endpoint is time to first adjudicated major adverse cardiovascular event, defined as all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke, pooled across both trials. The primary efficacy endpoint in each trial is change in hemoglobin from baseline to primary evaluation period (weeks 24-36), comparing vadadustat vs darbepoetin alfa treatment groups. Demographics and baseline characteristics were similar among patients in both trials and broadly representative of the NDD-CKD population. These trials will help to evaluate the safety and efficacy of vadadustat for management of anemia associated with NDD-CKD.

  View details for DOI 10.1016/j.ahj.2020.10.068

  View details for PubMedID 33129989

• Blood pressure and mortality in patients with type 2 diabetes and a recent coronary event in the ELIXA trial. Cardiovascular diabetology Wijkman, M. O., Claggett, B., Diaz, R., Gerstein, H. C., Kober, L., Lewis, E., Maggioni, A. P., Wolsk, E., Aguilar, D., Bentley-Lewis, R., McMurray, J. J., Probstfield, J., Riddle, M., Tardif, J., Solomon, S. D., Pfeffer, M. A. 2020; 19 (1): 175

  Abstract

  BACKGROUND: The relationship between blood pressure and mortality in type 2 diabetes (T2DM) is controversial, with concern for increased risk associated with excessively lowered blood pressure.METHODS: We evaluated whether prior cardiovascular disease (CVD) altered the relationship between baseline blood pressure and all-cause mortality in 5852 patients with T2DM and a recent acute coronary syndrome (ACS) who participated in the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial. Risk of death was assessed in Cox models adjusted for age, sex, race, heart rate, BMI, smoking, diabetes duration, insulin use, HbA1c, eGFR, brain natriuretic peptide (BNP), urine albumin/creatinine ratio, treatment allocation and prior coronary revascularization.RESULTS: Although overall there was no significant association between systolic blood pressure (SBP) and mortality (hazard ratio per 10mmHg lower SBP 1.05 (95% CI 0.99-1.12) P=0.10), lower SBP was significantly associated with higher risk of death (hazard ratio per 10mmHg lower SBP 1.13 (95% CI 1.04-1.22) P=0.002) in 2325 patients with additional CVD (index ACS+at least one of the following prior to randomization: myocardial infarction other than the index ACS, stroke or heart failure). In 3527 patients with only the index ACS no significant association was observed (hazard ratio per 10mmHg lower SBP 0.95 (0.86-1.04) P=0.26; P for interaction 0.005).CONCLUSIONS: The association between blood pressure and mortality was modified by additional CVD history in patients with type 2 diabetes and a recent coronary event. When blood pressures measured after an acute coronary event are used to assess the risk of death in patients with type 2 diabetes, the cardiovascular history needs to be taken into consideration. Trial registration ClinicalTrials.gov number NCT01147250, first posted June 22, 2010.

  View details for DOI 10.1186/s12933-020-01150-0

  View details for PubMedID 33046070

• Associations Between Depressive Symptoms and HFpEF-Related Outcomes. JACC. Heart failure Chandra, A., Alcala, M. A., Claggett, B., Desai, A. S., Fang, J. C., Heitner, J. F., Liu, J., Pitt, B., Solomon, S. D., Pfeffer, M. A., Lewis, E. F. 2020

  Abstract

  OBJECTIVES: This study analyzed changes in depressive symptoms in patients with heart failure and preserved ejection fraction (HFpEF) who were enrolled in the TOPCAT (Aldosterone Antagonist Therapy for Adults With HeartFailure and Preserved Systolic Function) trial.BACKGROUND: There are limited longitudinal data for depressive symptoms in patients with HFpEF.METHODS: In patients enrolled in the United States and Canada (n=1,431), depressive symptoms were measured using Patient Health Questionnaire-9 (PHQ-9). Clinically meaningful changes in PHQ-9 scores were defined as worse (≥3-point increase) or better (≥3-point decrease). Multivariate models were used to identify predictors of change in depressive symptoms. Cox proportional hazard models were used to determine the impact of symptom changes from baseline on subsequent incident cardiovascular events.RESULTS: At 12months, 19% of patients experienced clinically worsening depressive symptoms, 31% better, and 49% unchanged. Independent predictors of clinically meaningful improvement in depressive symptoms included higher baseline PHQ-9 scores, male sex, lack of chronic obstructive pulmonary disease, and randomization to spironolactone. After data were adjusted for cardiovascular comorbidities, higher baseline PHQ-9 was associated with all-cause mortality (hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 1.02 to 1.16; p=0.011), whereas worsening depressive symptoms at 12months were associated with cardiovascular death (HR: 2.47; 95%CI: 1.32 to 4.63; p=0.005) and all-cause mortality (HR: 1.82; 95%CI: 1.13 to 2.93; p=0.014). Randomization to spironolactone was associated with modest but statistically significant reduction in depressive symptoms over the course of the trial (p=0.014).CONCLUSIONS: Higher baseline depressive symptoms and worsening depressive symptoms were associated with all-cause mortality. Randomization to spironolactone was associated with modest reduction in depressive symptoms. (Aldosterone Antagonist Therapy for Adults With HeartFailure and Preserved Systolic Function [TOPCAT]; NCT00094302).

  View details for DOI 10.1016/j.jchf.2020.06.010

  View details for PubMedID 32919912

• IMPROVE-IT A Final Closure to Carcinogenicity of Ezetimibe? JACC: CARDIOONCOLOGY Lewis, E. F., Rhee, J. 2020; 2 (3): 397–99

  View details for DOI 10.1016/j.jaccao.2020.08.003

  View details for Web of Science ID 000613114400004

• IMPROVE-IT: A Final Closure to Carcinogenicity of Ezetimibe? JACC. CardioOncology Lewis, E. F., Rhee, J. W. 2020; 2 (3): 397-399

  View details for DOI 10.1016/j.jaccao.2020.08.003

  View details for PubMedID 34396247

  View details for PubMedCentralID PMC8352260

• Response by Eberly et al to Letter Regarding Article, "Identification of Racial Inequities in Access to Specialized Inpatient Heart Failure Care at an Academic Medical Center". Circulation. Heart failure Eberly, L. A., Wispelwey, B., Richterman, A., Beckett, A. G., Cleveland Manchanda, E. C., Marsh, R. H., Chang, C. Y., Glynn, R. J., Brooks, K. C., Boxer, R., Kakoza, R., Goldsmith, J., Loscalzo, J., Lewis, E. F., Morse, M. 2020: CIRCHEARTFAILURE120007193

  View details for DOI 10.1161/CIRCHEARTFAILURE.120.007193

  View details for PubMedID 32498624

• Standardized Definitions for Evaluation of Heart Failure Therapies: Scientific Expert Panel from the Heart Failure Collaboratory and Academic Research Consortium (HF-ARC). European journal of heart failure Abraham, W. T., Psotka, M. A., Fiuzat, M. n., Filippatos, G. n., Lindenfeld, J. n., Mehran, R. n., Ambardekar, A. V., Carson, P. E., Jacob, R. n., Januzzi, J. L., Konstam, M. A., Krucoff, M. W., Lewis, E. F., Piccini, J. P., Solomon, S. D., Stockbridge, N. n., Teerlink, J. R., Unger, E. F., Zeitler, E. P., Anker, S. D., O'Connor, C. M. 2020

  Abstract

  The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation. CONDENSED ABSTRACT: The Heart Failure Collaboratory and Academic Research Consortium multi-stakeholder partnership convened to establish expert consensus definitions and key concepts for heart failure clinical trials including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. With uniform definitions, heart failure interventions can be better standardized, evaluated, and compared between trials and patient populations, and the quality of generated evidence may be strengthened.

  View details for DOI 10.1002/ejhf.2018

  View details for PubMedID 33017862

• Conduct of Clinical Trials in the Era of COVID-19: JACC Scientific Expert Panel. Journal of the American College of Cardiology Psotka, M. A., Abraham, W. T., Fiuzat, M. n., Filippatos, G. n., Lindenfeld, J. n., Ahmad, T. n., Bhatt, A. S., Carson, P. E., Cleland, J. G., Felker, G. M., Januzzi, J. L., Kitzman, D. W., Leifer, E. S., Lewis, E. F., McMurray, J. J., Mentz, R. J., Solomon, S. D., Stockbridge, N. n., Teerlink, J. R., Vaduganathan, M. n., Vardeny, O. n., Whellan, D. J., Wittes, J. n., Anker, S. D., O'Connor, C. M. 2020; 76 (20): 2368–78

  Abstract

  The coronavirus disease-2019 (COVID-19) pandemic has profoundly changed clinical care and research, including the conduct of clinical trials, and the clinical research ecosystem will need to adapt to this transformed environment. The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory and the Academic Research Consortium, composed of academic investigators from the United States and Europe, patients, the U.S. Food and Drug Administration, the National Institutes of Health, and industry members. A series of meetings were convened to address the challenges caused by the COVID-19 pandemic, review options for maintaining or altering best practices, and establish key recommendations for the conduct and analysis of clinical trials for cardiovascular disease and heart failure. This paper summarizes the discussions and expert consensus recommendations.

  View details for DOI 10.1016/j.jacc.2020.09.544

  View details for PubMedID 33183511

• Standardized Definitions for Evaluation of Heart Failure Therapies: Scientific Expert Panel From the Heart Failure Collaboratory and Academic Research Consortium. JACC. Heart failure Abraham, W. T., Psotka, M. A., Fiuzat, M. n., Filippatos, G. n., Lindenfeld, J. n., Mehran, R. n., Ambardekar, A. V., Carson, P. E., Jacob, R. n., Januzzi, J. L., Konstam, M. A., Krucoff, M. W., Lewis, E. F., Piccini, J. P., Solomon, S. D., Stockbridge, N. n., Teerlink, J. R., Unger, E. F., Zeitler, E. P., Anker, S. D., O'Connor, C. M. 2020

  Abstract

  The Heart Failure Academic Research Consortium is a partnership between the Heart Failure Collaboratory (HFC) and Academic Research Consortium (ARC), comprised of leading heart failure (HF) academic research investigators, patients, United States (US) Food and Drug Administration representatives, and industry members from the US and Europe. A series of meetings were convened to establish definitions and key concepts for the evaluation of HF therapies including optimal medical and device background therapy, clinical trial design elements and statistical concepts, and study endpoints. This manuscript summarizes the expert panel discussions as consensus recommendations focused on populations and endpoint definitions; it is not exhaustive or restrictive, but designed to stimulate HF clinical trial innovation.

  View details for DOI 10.1016/j.jchf.2020.10.002

  View details for PubMedID 33199251

• Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes: Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT) AMERICAN JOURNAL OF KIDNEY DISEASES Mc Causland, F. R., Claggett, B., Burdmann, E. A., Chertow, G. M., Cooper, M. E., Eckardt, K., Ivanovich, P., Levey, A. S., Lewis, E. F., McGill, J. B., McMurray, J. V., Parfrey, P., Parving, H., Remuzzi, G., Singh, A. K., Solomon, S. D., Toto, R. D., Pfeffer, M. A. 2019; 73 (3): 309–15

  View details for DOI 10.1053/j.ajkd.2018.10.006

  View details for Web of Science ID 000459248200005

• Treatment of Anemia With Darbepoetin Prior to Dialysis Initiation and Clinical Outcomes: Analyses From the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT). American journal of kidney diseases : the official journal of the National Kidney Foundation Mc Causland, F. R., Claggett, B., Burdmann, E. A., Chertow, G. M., Cooper, M. E., Eckardt, K., Ivanovich, P., Levey, A. S., Lewis, E. F., McGill, J. B., McMurray, J. J., Parfrey, P., Parving, H., Remuzzi, G., Singh, A. K., Solomon, S. D., Toto, R. D., Pfeffer, M. A. 2018

  Abstract

  RATIONALE & OBJECTIVE: Evidence from clinical trials to guide patient preparation for maintenance dialysis therapy is limited. Although anemia is associated with mortality and cardiovascular (CV) disease in individuals initiating maintenance dialysis therapy, it is not known if treatment of anemia before dialysis therapy initiation with erythropoiesis-stimulating agents alters outcomes.STUDY DESIGN: Post hoc analysis of a randomized controlled trial.SETTING & PARTICIPANTS: Participants with type 2 diabetes and chronic kidney disease who progressed to dialysis therapy (n=590) in the Trial to Reduce Cardiovascular Events With Aranesp Therapy (TREAT).EXPOSURE: Randomized treatment assignment (darbepoetin vs placebo).OUTCOMES: All-cause mortality, CV mortality, nonfatal myocardial infarction, heart failure, and stroke within the first 180 days of dialysis therapy initiation.ANALYTICAL APPROACH: Proportional hazards regression.RESULTS: Overall, 590 of 4,038 (14.6%) participants initiated dialysis therapy during the trial (n=298 and 292 in the darbepoetin and placebo groups, respectively). Corresponding hemoglobin levels were 11.3±1.6 and 9.5±1.5g/dL (P<0.001). Death from any cause occurred in 31 (10.4%) participants assigned to darbepoetin and 28 (9.6%) assigned to placebo (HR, 1.16; 95% CI, 0.69-1.93), while death from CV causes occurred in 15 (5.0%) and 13 (4.5%) participants, respectively (HR, 1.21; 95% CI, 0.58-1.93). There were no differences in risk for nonfatal myocardial infarction or heart failure. Stroke occurred in 8 (2.8%) participants assigned to darbepoetin and 1 (0.3%) assigned to placebo (HR, 8.6; 95% CI, 1.1-68.7).LIMITATIONS: Post hoc analyses of a subgroup of study participants.CONCLUSIONS: Despite initiating dialysis therapy with a higher hemoglobin level, prior treatment with darbepoetin was not associated with a reduction in mortality, myocardial infarction, or heart failure in the first 180 days, but a higher frequency of stroke was observed. In the absence of more definitive data, this may inform decisions regarding the use of erythropoiesis-stimulating agents to treat mild to moderate anemia in patients with type 2 diabetes and chronic kidney disease nearing dialysis therapy initiation.

  View details for PubMedID 30578152

• 2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Hicks, K. A., Mahaffey, K. W., Mehran, R., Nissen, S. E., Wiviott, S. D., Dunn, B., Solomon, S. D., Marler, J. R., Teerlink, J. R., Farb, A., Morrow, D. A., Targum, S. L., Sila, C. A., Hai, M., Jaff, M. R., Joffe, H. V., Cutlip, D. E., Desai, A. S., Lewis, E. F., Gibson, C., Landray, M. J., Lincoff, A., White, C. J., Brooks, S. S., Rosenfield, K., Domanski, M. J., Lansky, A. J., McMurray, J. V., Tcheng, J. E., Steinhubl, S. R., Burton, P., Mauri, L., O'Connor, C. M., Pfeffer, M. A., Hung, H., Stockbridge, N. L., Chaitman, B. R., Temple, R. J., Standardized Data Collection 2018; 71 (9): 1021–34

  Abstract

  This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the U.S. Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials.

  View details for PubMedID 29495982

• 2017 Cardiovascular and Stroke Endpoint Definitions for Clinical Trials CIRCULATION Hicks, K. A., Mahaffey, K. W., Mehran, R., Nissen, S. E., Wiviott, S. D., Dunn, B., Solomon, S. D., Mar-Ler, J. R., Teerlink, J. R., Farb, A., Morrow, D. A., Targum, S. L., Sila, C. A., Hai, M., Jaff, M. R., Joffe, H. V., Cutlip, D. E., Desai, A. S., Lewis, E. F., Gibson, C., Landray, M. J., Lincoff, A., White, C. J., Brooks, S. S., Rosenfield, K., Domanski, M. J., Lansky, A. J., McMurray, J. V., Tcheng, J. E., Steinhubl, S. R., Burton, P., Mauri, L., O'Connor, C. M., Pfeffer, M. A., Hung, H., Stockbridge, N. L., Chaitman, B. R., Temple, R. J., Standardized Data Collection 2018; 137 (9): 961–72

  Abstract

  This publication describes uniform definitions for cardiovascular and stroke outcomes developed by the Standardized Data Collection for Cardiovascular Trials Initiative and the US Food and Drug Administration (FDA). The FDA established the Standardized Data Collection for Cardiovascular Trials Initiative in 2009 to simplify the design and conduct of clinical trials intended to support marketing applications. The writing committee recognizes that these definitions may be used in other types of clinical trials and clinical care processes where appropriate. Use of these definitions at the FDA has enhanced the ability to aggregate data within and across medical product development programs, conduct meta-analyses to evaluate cardiovascular safety, integrate data from multiple trials, and compare effectiveness of drugs and devices. Further study is needed to determine whether prospective data collection using these common definitions improves the design, conduct, and interpretability of the results of clinical trials.

  View details for PubMedID 29483172