Search

Your search keyword '"Pordy, Robert"' showing total 19 results
Start Over Author "Pordy, Robert" Publisher lippincott williams & wilkins
19 results on '"Pordy, Robert"'

2. Peripheral Artery Disease and Venous Thromboembolic Events After Acute Coronary Syndrome

Author

Schwartz, Gregory G., Steg, Philippe Gabriel, Szarek, Michael, Bittner, Vera A., Diaz, Rafael, Goodman, Shaun G., Kim, Yong-Un, Jukema, J. Wouter, Pordy, Robert, Roe, Matthew T., White, Harvey D., and Bhatt, Deepak L.

Subjects
proprotein convertase subtilisin/kexin type 9, lipoprotein(a), Original Research Articles, venous thromboembolism, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, low-density lipoproteins, peripheral artery disease, acute coronary syndrome
Abstract

Supplemental Digital Content is available in the text., Background: Patients with acute coronary syndrome are at risk for peripheral artery disease (PAD) events and venous thromboembolism (VTE). PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors reduce lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C) levels. Our objective was to ascertain whether PCSK9 inhibition reduces the risk of PAD events or VTE after acute coronary syndrome, and if such effects are related to levels of lipoprotein(a) or LDL-C. Methods: This was a prespecified analysis of the ODYSSEY OUTCOMES randomized clinical trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome), which was conducted in 18 924 patients with recent acute coronary syndrome on intensive or maximum-tolerated statin treatment who were randomized to the PCSK9 inhibitor alirocumab or placebo. In a prespecified analysis, PAD events (critical limb ischemia, limb revascularization, or amputation for ischemia) and VTE (deep vein thrombosis or pulmonary embolism) were assessed. LDL-C was corrected (LDL-Ccorrected) for cholesterol content in lipoprotein(a). Results: At baseline, median lipoprotein(a) and LDL-Ccorrected were 21 and 75 mg/dL, respectively; with alirocumab, median relative reductions were 23.5% and 70.6%, respectively. PAD events and VTE occurred in 246 and 92 patients, respectively. In the placebo group, risk of PAD events was related to baseline quartile of lipoprotein(a) (Ptrend=0.0021), and tended to associate with baseline quartile of LDL-Ccorrected (Ptrend=0.06); VTE tended to associate with baseline quartile of lipoprotein(a) (Ptrend=0.06), but not LDL-Ccorrected (Ptrend=0.85). Alirocumab reduced risk of PAD events (hazard ratio [HR], 0.69 [95% CI, 0.54–0.89]; P=0.004), with nonsignificantly fewer VTE events (HR, 0.67 [95% CI, 0.44–1.01]; P=0.06). Reduction in PAD events with alirocumab was associated with baseline quartile of lipoprotein(a) (Ptrend=0.03), but not LDL-Ccorrected (Ptrend=0.50). With alirocumab, the change from baseline to Month 4 in lipoprotein(a), but not LDL-Ccorrected, was associated with the risk of VTE and the composite of VTE and PAD events. Conclusions: In statin-treated patients with recent acute coronary syndrome, risk of PAD events is related to lipoprotein(a) level and is reduced by alirocumab, particularly among those with high lipoprotein(a). Further study is required to confirm whether risk of VTE is related to lipoprotein(a) level and its reduction with alirocumab. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.

Published
2020

3. Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

Author

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., Schwartz, Gregory G., and Tricoci, Pierluigi

Published
2022
Full Text
View/download PDF

4. Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants in Patient Lymphocytes to Assess the Effect of Evinacumab in Homozygous Familial Hypercholesterolemia Patients With a Spectrum of LDLR Activity

Author

Bioquímica y biología molecular, Biokimika eta biologia molekularra, Banerjee, Poulabi, Chan, Kuo-Chen, Tarabocchia, Michel, Benito Vicente, Asier, Alves, Ana C., Belloso Uribe, Kepa, Bourbon, Mafalda, Skiba, Paul J., Pordy, Robert, Gipe, Daniel A., Gaudet, Daniel, Martín Plágaro, César Augusto, Bioquímica y biología molecular, Biokimika eta biologia molekularra, Banerjee, Poulabi, Chan, Kuo-Chen, Tarabocchia, Michel, Benito Vicente, Asier, Alves, Ana C., Belloso Uribe, Kepa, Bourbon, Mafalda, Skiba, Paul J., Pordy, Robert, Gipe, Daniel A., Gaudet, Daniel, and Martín Plágaro, César Augusto

Abstract

Objective: Homozygous familial hypercholesterolemia is a rare disease usually caused by LDLR (low-density lipoprotein receptor) mutations. Homozygous familial hypercholesterolemia is characterized by markedly elevated LDL-C (low-density lipoprotein cholesterol) levels and an extremely high risk of premature atherosclerotic cardiovascular disease. A phase 2, proof-of-concept study (NCT02265952) demonstrated that evinacumab, a fully human monoclonal antibody to ANGPTL3 (angiopoietin-like 3 protein), reduced LDL-C levels in 9 patients with genotypically confirmed homozygous familial hypercholesterolemia and was well tolerated. The aim of this study was to analyze the effects of evinacumab on LDLR activity in lymphocytes purified from patients in the proof-of-concept study. Approach and Results: LDLR activity was assessed in patient lymphocytes before and after treatment with evinacumab and versus lymphocytes carrying wild-type LDLR, and also in an LDLR-defective Chinese hamster ovary cell line (CHO-ldlA7) transfected with plasmids encoding the LDLR variants. Overall mean peak reduction in LDL-C with evinacumab was -58 +/- 18%, occurring between Week 4 and Week 12. Mutations identified in the 9 patients were shown to be pathogenic, with loss of LDLR activity versus wild type. Two of the LDLR variants, p.(Cys681*) and p.(Ala627Profs*38), were class 2 type mutations that are retained in the endoplasmic reticulum. Six variants were class 3 type mutations with impaired LDL-C binding activity: p.(Trp87Gly), occurring in 2 patients, p.(Gln254Pro), p.(Ser177Leu), p.(Gly335Val), and p.(Ser306Leu). Evinacumab had no effect on LDLR activity. Conclusions: These results suggest that evinacumab is effective for lowering LDL-C in patients with homozygous familial hypercholesterolemia, and the inhibition of ANGPTL3 in humans lowers LDL-C in a mechanism independent of the LDLR.

Published
2019

5. Clinical Efficacy and Safety of Alirocumab After Acute Coronary Syndrome According to Achieved Level of Low-Density Lipoprotein Cholesterol: A Propensity Score-Matched Analysis of the ODYSSEY OUTCOMES Trial.

Author

Schwartz, Gregory G., Gabriel Steg, Philippe, Bhatt, Deepak L., Bittner, Vera A., Diaz, Rafael, Goodman, Shaun G., Jukema, J. Wouter, Kim, Yong-Un, Li, Qian H., Manvelian, Garen, Pordy, Robert, Sourdille, Timothée, White, Harvey D., Szarek, Michael, and ODYSSEY OUTCOMES Committees and Investigators

Published
2021
Full Text
View/download PDF

6. Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial.

Author

Damask, Amy, Steg, P. Gabriel, Schwartz, Gregory G., Szarek, Michael, Hagström, Emil, Badimon, Lina, Chapman, M. John, Boileau, Catherine, Tsimikas, Sotirios, Ginsberg, Henry N., Banerjee, Poulabi, Manvelian, Garen, Pordy, Robert, Hess, Sibylle, Overton, John D., Lotta, Luca A., Yancopoulos, George D., Abecasis, Goncalo R., Baras, Aris, and Paulding, Charles

Published
2020
Full Text
View/download PDF

7. Effect of Alirocumab on Stroke in ODYSSEY OUTCOMES.

Author

Jukema, J. Wouter, Zijlstra, Laurien E., Bhatt, Deepak L., Bittner, Vera A., Diaz, Rafael, Drexel, Heinz, Goodman, Shaun G., Kim, Yong-Un, Pordy, Robert, Reiner, Željko, Roe, Matthew T., Tse, Hung-Fat, Montenegro Valdovinos, Pablo Carlos, White, Harvey D., Zeiher, Andreas M., Szarek, Michael, Schwartz, Gregory G., Steg, Philippe Gabriel, Reiner, Zeljko, and Valdovinos, Pablo Carlos Montenegro

Published
2019
Full Text
View/download PDF

10. Effect of Alirocumab on Mortality After Acute Coronary Syndromes.

Author

Steg, Philippe Gabriel, Szarek, Michael, Bhatt, Deepak L., Bittner, Vera A., Brégeault, Marie-France, Dalby, Anthony J., Diaz, Rafael, Edelberg, Jay M., Goodman, Shaun G., Hanotin, Corinne, Harrington, Robert A., Jukema, J. Wouter, Lecorps, Guillaume, Mahaffey, Kenneth W., Moryusef, Angèle, Ostadal, Petr, Parkhomenko, Alexander, Pordy, Robert, Roe, Matthew T., and Tricoci, Pierluigi

Published
2019
Full Text
View/download PDF

12. Alirocumab Reduces Total Hospitalizations and Increases Days Alive and Out of Hospital in the ODYSSEY OUTCOMES Trial.

Author

Szarek, Michael, Steg, Ph. Gabriel, DiCenso, Dina, Bhatt, Deepak L., Bittner, Vera A., Budaj, Andrzej, Diaz, Rafael, Goodman, Shaun G., Gotcheva, Nina, Jukema, J. Wouter, Pordy, Robert, Roe, Matthew T., Sourdille, Timothée, White, Harvey D., Xavier, Denis, Zeiher, Andreas M., and Schwartz, Gregory G.

Abstract

Background: In ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), alirocumab was compared with placebo, added to high-intensity or maximum tolerated statin treatment after acute coronary syndrome in 18 924 patients. Alirocumab reduced first occurrence of the primary composite end point-coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or hospitalization for unstable angina-as well as total nonfatal cardiovascular events and all-cause deaths. The present analysis determined whether alirocumab reduced total (first and subsequent) hospitalizations and death and increased days alive and out of hospital (DAOH) and percent DAOH in ODYSSEY OUTCOMES.Methods and Results: In prespecified analyses, hazard functions for total hospitalizations and death were jointly estimated by a semiparametric model, while in post hoc analyses, DAOH and percent DAOH were compared between treatment groups with Poisson regression and one-inflated beta regression, respectively. With 16 629 total hospitalizations and 726 deaths, 331 fewer hospitalizations, and 58 fewer deaths were observed with alirocumab compared with placebo, translating to 15.6 total hospitalizations or deaths avoided with alirocumab per 1000 patient-years of assigned treatment. Alirocumab reduced total hospitalizations (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P=0.04) and increased DAOH relative to placebo (rate ratio, 1.003 [95% CI, 1.000-1.007]; P=0.05), primarily through a reduction in days dead (rate ratio, 0.847 [95% CI, 0.728-0.986]; P=0.03). Patients randomized to alirocumab were also more likely to survive to the end of the study without hospitalization (odds ratio, 1.06 [95% CI, 1.00-1.13]; P=0.03).Conclusions: Alirocumab reduced total hospitalizations with corresponding small increases in DAOH and percent DAOH. These outcomes provide alternative patient-centered metrics to capture the totality of alirocumab clinical efficacy after acute coronary syndrome.Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01663402. [ABSTRACT FROM AUTHOR]

Published
2019
Full Text
View/download PDF

14. Abstract 13393: Alirocumab Reduces Total Nonfatal Cardiovascular and Fatal Events in the ODYSSEY OUTCOMES Trial.

Author

Szarek, Michael, White, Harvey D, Schwartz, Gregory G, Alings, Marco, Bhatt, Deepak L, Bittner, Vera A, Chiang, Chern-En, Diaz, Rafael, Edelberg, Jay M, Goodman, Shaun G, Hanotin, Corinne, Harrington, Robert A, Jukema, J. Wouter, Kimura, Takeshi, Kiss, Robert Gabor, Lecorps, Guillaume, Mahaffey, Kenneth W, Moryusef, Angèle, Pordy, Robert, and Roe, Matthew T

Published
2018

19. Pharmacogenomic Study of Statin-Associated Muscle Symptoms in the ODYSSEY OUTCOMES Trial.

Author

Murphy WA, Lin N, Damask A, Schwartz GG, Steg PG, Szarek M, Banerjee P, Fazio S, Manvelian G, Pordy R, Shuldiner AR, and Paulding C

Subjects
Antigens, CD, Cholesterol, LDL, Creatine Kinase, Genome-Wide Association Study, Humans, Membrane Proteins, PCSK9 Inhibitors, Pharmacogenomic Testing, Receptors, Immunologic, Acute Coronary Syndrome drug therapy, Atorvastatin adverse effects, Hydroxymethylglutaryl-CoA Reductase Inhibitors adverse effects, Muscles drug effects, Rosuvastatin Calcium adverse effects
Abstract

Background: Statin-associated muscle symptoms (SAMS) are the most frequently reported adverse events for statin therapies. Previous studies have reported an association between the p.Val174Ala missense variant in SLCO1B1 and SAMS in simvastatin-treated subjects; however, evidence for genetic predictors of SAMS in atorvastatin- or rosuvastatin-treated subjects is currently lacking., Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; n=18 924) was a double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of alirocumab (a PCSK9 [proprotein convertase subtilisin/kexin type 9] inhibitor) in acute coronary syndrome patients receiving high-intensity statin therapy. The goal of this pharmacogenomic analysis was to identify genetic variants associated with atorvastatin- and rosuvastatin-mediated SAMS among ODYSSEY OUTCOMES subjects who consented to participate in the genetic study (n=11 880). We performed multi-ancestry exome-wide and genome-wide association studies and gene burden analysis across 2 phenotypes (clinical SAMS [n=10 617] and creatine kinase levels [n=9630])., Results: A novel genome-wide significant association for an intronic variant (rs6667912) located within TMEM9 (odds ratio [95% CI], 1.39 [1.24-1.55]; P =3.71×10 -8 ) for patients with clinical SAMS (cases=894, controls=9723) was identified. This variant is located ≈30 kb upstream of CACNA1S , a locus associated with severe SAMS. We replicated 2 loci, at LINC0093 and LILRB5 , previously associated with creatine kinase levels during statin treatment. No association was observed between p.Val174Ala (rs4149056) in SLCO1B1 and SAMS (odds ratio [95% CI], 1.03 [0.90-1.18]; P =0.69)., Conclusions: This study comprises the largest discovery exome-wide and genome-wide association study for atorvastatin- or rosuvastatin-mediated SAMS to date. These novel genetic findings may provide biological/mechanistic insight into this drug-induced toxicity, and help identify at-risk patients before selection of lipid-lowering therapies.

Published
2022
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results