المؤلفون: Hagström, Emil, Steg, P Gabriel, Szarek, Michael, Bhatt, Deepak L, Bittner, Vera A, Danchin, Nicolas, Diaz, Rafael, Goodman, Shaun G, Harrington, Robert A, Jukema, J Wouter, Liberopoulos, Evangelos, Marx, Nikolaus, McGinniss, Jennifer, Manvelian, Garen, Pordy, Robert, Scemama, Michel, White, Harvey D, Zeiher, Andreas M, Yang, Eric, Schwartz, Gregory G

المصدر: Circulation. 146(9)

مصطلحات موضوعية: Acute Coronary Syndrome: diagnosis, drug therapy, epidemiology, Antibodies, Monoclonal, Humanized, Anticholesteremic Agents: adverse effects, Apolipoproteins B, Atherosclerosis: drug therapy, Cardiovascular Diseases: diagnosis, epidemiology, prevention & control, Cholesterol, Cholesterol, LDL, Heart Disease Risk Factors, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors: therapeutic use, Risk Factors, Treatment Outcome

الوصف: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain.The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score-matched models.Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9-3.6], 4.0 [95% CI, 3.6-4.5], and 5.5 [95% CI, 5.0-6.1] events per 100 patient-years in strata 35-

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/7z59p110Test

المؤلفون: Bittner, Vera A., Schwartz, Gregory G., Bhatt, Deepak L., Chua, Terrance, De Silva, H. Asita, Diaz, Rafael, Goodman, Shaun G., Harrington, Robert A., Jukema, J. Wouter, McGinniss, Jennifer, Pordy, Robert, Garon, Genevieve, Scemama, Michel, White, Harvey D., Steg, pH. Gabriel, Szarek, Michael

المساهمون: Sanofi US, Regeneron Pharmaceuticals Inc

المصدر: Journal of Clinical Lipidology ; ISSN 1933-2874

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine

الإتاحة: https://doi.org/10.1016/j.jacl.2024.04.122Test
https://api.elsevier.com/content/article/PII:S1933287424001697?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1933287424001697?httpAccept=text/plainTest

المؤلفون: Rosenson, Robert S., Gaudet, Daniel, Ballantyne, Christie M., Baum, Seth J., Bergeron, Jean, Kershaw, Erin E., Moriarty, Patrick M., Rubba, Paolo, Whitcomb, David C., Banerjee, Poulabi, Gewitz, Andrew, Gonzaga-Jauregui, Claudia, McGinniss, Jennifer, Ponda, Manish P., Pordy, Robert, Zhao, Jian, Rader, Daniel J.

المساهمون: Regeneron Pharmaceuticals

المصدر: Nature Medicine ; volume 29, issue 3, page 729-737 ; ISSN 1078-8956 1546-170X

مصطلحات موضوعية: General Biochemistry, Genetics and Molecular Biology, General Medicine

الوصف: Severe hypertriglyceridemia (sHTG) is an established risk factor for acute pancreatitis. Current therapeutic approaches for sHTG are often insufficient to reduce triglycerides and prevent acute pancreatitis. This phase 2 trial ( NCT03452228 ) evaluated evinacumab (angiopoietin-like 3 inhibitor) in three cohorts of patients with sHTG: cohort 1, familial chylomicronemia syndrome with bi-allelic loss-of-function lipoprotein lipase (LPL) pathway mutations ( n = 17); cohort 2, multifactorial chylomicronemia syndrome with heterozygous loss-of-function LPL pathway mutations ( n = 15); and cohort 3, multifactorial chylomicronemia syndrome without LPL pathway mutations ( n = 19). Fifty-one patients (males, n = 27; females, n = 24) with a history of hospitalization for acute pancreatitis were randomized 2:1 to intravenous evinacumab 15 mg kg −1 or placebo every 4 weeks over a 12-week double-blind treatment period, followed by a 12-week single-blind treatment period. The primary end point was the mean percent reduction in triglycerides from baseline after 12 weeks of evinacumab exposure in cohort 3. Evinacumab reduced triglycerides in cohort 3 by a mean (s.e.m.) of −27.1% (37.4) (95% confidence interval −71.2 to 84.6), but the prespecified primary end point was not met. No notable differences in adverse events between evinacumab and placebo treatment groups were seen during the double-blind treatment period. Although the primary end point of a reduction in triglycerides did not meet the prespecified significance level, the observed safety and changes in lipid and lipoprotein levels support the further evaluation of evinacumab in larger trials of patients with sHTG. Trial registration number: ClinicalTrials.gov NCT03452228 .

الإتاحة: https://doi.org/10.1038/s41591-023-02222-wTest
https://www.nature.com/articles/s41591-023-02222-w.pdfTest
https://www.nature.com/articles/s41591-023-02222-wTest

المؤلفون: Raal, Frederick J., Rosenson, Robert S., Reeskamp, Laurens F., Kastelein, John J.P., Rubba, Paolo, Duell, P. Barton, Koseki, Masahiro, Stroes, Erik, Ali, Shazia, Banerjee, Poulabi, Chan, Kuo-Chen, Khilla, Nagwa, McGinniss, Jennifer, Pordy, Robert, Zhang, Yi, Gaudet, Daniel

المصدر: JACC: Advances ; volume 2, issue 9, page 100648 ; ISSN 2772-963X

الإتاحة: https://doi.org/10.1016/j.jacadv.2023.100648Test
https://api.elsevier.com/content/article/PII:S2772963X23006294?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S2772963X23006294?httpAccept=text/plainTest

المؤلفون: Landmesser, Ulf, McGinniss, Jennifer, Steg, Ph Gabriel, Bhatt, Deepak L, Bittner, Vera A, Diaz, Rafael, Dilic, Mirza, Goodman, Shaun G, Jukema, J Wouter, Loy, Megan, Pećin, Ivan, Pordy, Robert, Poulsen, Steen H, Szarek, Michael, White, Harvey D, Schwartz, Gregory G

المساهمون: Sanofi and Regeneron Pharmaceuticals

المصدر: European Journal of Preventive Cardiology ; volume 29, issue 14, page 1842-1851 ; ISSN 2047-4873 2047-4881

الوصف: Aims European guidelines set low-density lipoprotein cholesterol (LDL-C) treatment goals <1.4 mmol/L after acute coronary syndrome (ACS), and <1.0 mmol/L for patients with recurrent cardiovascular events ≤2 years. Many ACS patients do not achieve these goals on statin alone. We examined actual goal achievement with alirocumab and projected achievement with ezetimibe, either added to optimized statin therapy. Methods and results The ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18 924 patients with recent ACS and hyperlipidaemia despite high-intensity or maximum-tolerated statin therapy. This subanalysis comprised 17 589 patients with LDL-C ≥1.4 mmol/L at baseline who did not receive ezetimibe treatment. High-intensity statin treatment was used in 88.8%. Median (interquartile range) baseline LDL-C was 2.3 (1.9−2.7) mmol/L. With alirocumab, 94.6% of patients achieved LDL-C <1.4 mmol/L at ≥1 post-baseline measurement vs. 17.3% with placebo. Among 2236 patients with a previous cardiovascular event within 2 years (before the qualifying ACS), 85.2% vs. 3.5%, respectively, achieved LDL-C <1.0 mmol/L. Among patients not treated with ezetimibe, we projected that its use would have achieved LDL-C <1.4 and <1.0 mmol/L in 10.6 and 0%, respectively, at baseline (assuming 18 ± 3% reduction of LDL-C). Conclusion Among patients with recent ACS and LDL-C ≥1.4 mmol/L despite optimized statin therapy, the addition of alirocumab allowed 94.6% to achieve the 2019 European guideline LDL-C goal <1.4 mmol/L, and 85.2% of those with recurrent cardiovascular events to achieve <1.0 mmol/L. In contrast, the addition of ezetimibe to optimized statin therapy was projected to achieve LDL-C <1.4 mmol/L in only 10.6% of patients at baseline.

الإتاحة: https://doi.org/10.1093/eurjpc/zwac107Test

المؤلفون: Moriarty, Patrick M., Steg, Philippe Gabriel, McGinniss, Jennifer, Zeiher, Andreas M., White, Harvey D., Manvelian, Garen, Pordy, Robert, Loy, Megan, Jukema, J. Wouter, Harrington, Robert A., Gray, Jessica V., Gorby, Lauryn K., Goodman, Shaun G., Diaz, Rafael, Bittner, Vera A., Bhatt, Deepak L., Szarek, Michael, Schwartz, Gregory G.

المصدر: Journal of Clinical Lipidology ; volume 16, issue 5, page 747-756 ; ISSN 1933-2874

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine, Nutrition and Dietetics, Endocrinology, Diabetes and Metabolism, Internal Medicine

الإتاحة: https://doi.org/10.1016/j.jacl.2022.08.004Test
https://api.elsevier.com/content/article/PII:S1933287422002410?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1933287422002410?httpAccept=text/plainTest

المؤلفون: Rosenson, Robert S., Burgess, Lesley J., Ebenbichler, Christoph F., Baum, Seth J., Stroes, Erik S. G., Ali, Shazia, Khilla, Nagwa, McGinniss, Jennifer, Gaudet, Daniel, Pordy, Robert

المصدر: JAMA Cardiology; Nov2023, Vol. 8 Issue 11, p1070-1076, 7p

المؤلفون: Stein, David, Oviedo-Orta, Ernesto, Kampman, Wendy A, McGinniss, Jennifer, Betts, George, McDermott, Margaret, Holly, Beth, Lancaster, Johnathan M, Braunstein, Ned, Yancopoulos, George D, Weinreich, David M

المساهمون: Regeneron Pharmaceuticals, Inc

المصدر: Clinical Infectious Diseases ; volume 75, issue 1, page e509-e515 ; ISSN 1058-4838 1537-6591

مصطلحات موضوعية: Infectious Diseases, Microbiology (medical)

الوصف: Background Patients with immunodeficiency-associated antibody disorders are at a higher risk of prolonged/persistent COVID-19 infection, having no viable treatment options. Methods A retrospective analysis of patients with primary and/or secondary immunodeficiency-associated antibody disorders who received casirivimab and imdevimab (REGEN-COV®) under emergency compassionate use. Objective were to describe safety and response to REGEN-COV, focusing on the subset of patients who had COVID-19 duration ≥21 days before treatment. Results Quantitative (change in oxygenation status and/or viral load) and/or qualitative (physician-reported clinical status) outcomes data are reported from 64 patients. Improvement in ≥1 outcome was observed in 90.6% of the overall patient group. Thirty-seven of these had COVID-19 duration ≥21 days before treatment; median time from diagnosis to REGEN-COV treatment was 60.5 days. Of the 29 patients with COVID-19 duration ≥21 days before treatment and available outcome data, 96.6% showed improvement in ≥1 outcome. In the 14 patients with post-treatment reverse transcription–polymerase chain reaction (RT-PCR) results available, 11 (78.6%) reported a negative RT-PCR following treatment, with 5 (45.5%) and 8 (72.7%) patients reporting a negative RT-PCR within 5 days and 21 days of treatment, respectively. Ten of 85 patients (11.8%) experienced serious adverse events; only one was an infusion-related reaction, possibly related to REGEN-COV. Two deaths were reported; neither were attributed to REGEN-COV. Conclusions In this retrospective analysis of immunodeficient patients granted REGEN-COV under emergency compassionate use, REGEN-COV treatment was associated with rapid viral clearance and clinical improvement in patients with longstanding COVID-19. Adverse events were consistent with COVID-19 and its associated complications, and due to patients’ concurrent medical conditions.

الإتاحة: https://doi.org/10.1093/cid/ciab1059Test
https://academic.oup.com/cid/article-pdf/75/1/e509/45513271/ciab1059.pdfTest

المؤلفون: Hagstrom, Emil, Steg, Philippe Gabriel, Szarek, Michael, Bhatt, Deepak, Bittner, Vera, Danchin, Nicolas, Diaz, Rafael, Goodman, Shaun, Harrington, Robert A., Jukema, Johan Wouter, Kim, Yong-Un, Liberopoulos, Evangelos, Marx, Nikolaus, McGinniss, Jennifer, Roe, Matthew, Louie, Michael, White, Harvey, Zeiher, Andreas, Schwartz, Gregory G.

المصدر: Journal of the American College of Cardiology ; volume 75, issue 11, page 75 ; ISSN 0735-1097

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine

الإتاحة: https://doi.org/10.1016/s0735-1097Test(20)30702-6
https://api.elsevier.com/content/article/PII:S0735109720307026?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S0735109720307026?httpAccept=text/plainTest

المؤلفون: Landmesser, Ulf, McGinniss, Jennifer, Steg, Philippe Gabriel, Bhatt, Deepak, Bittner, Vera, Diaz, Rafael, Goodman, Shaun, Harrington, Robert A., Jukema, Johan Wouter, Laucevicius, Aleksandras, Pecin, Ivan, Pordy, Robert, Poulsen, Steen, Roe, Matthew, Sourdille, Timothee, Szarek, Michael, White, Harvey, Zeiher, Andreas, Schwartz, Gregory G.

المصدر: Journal of the American College of Cardiology ; volume 75, issue 11, page 1978 ; ISSN 0735-1097

مصطلحات موضوعية: Cardiology and Cardiovascular Medicine

الإتاحة: https://doi.org/10.1016/s0735-1097Test(20)32605-x
https://api.elsevier.com/content/article/PII:S073510972032605X?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S073510972032605X?httpAccept=text/plainTest