43 results on '"Ofri, A"'
Search Results
2. Abstract 10006: The Effect of Dapagliflozin on Hospital Admissions in Patients With Type 2 Diabetes: Post Hoc Analysis of the DECLARE-TIMI 58 Trial
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Schechter, Meir, Wiviott, Stephen D, RAZ, Itamar, Goodrich, Erica L, Cahn, Avivit, Langkilde, Anna Maria, Gause-nilsson, Ingrid A, Sabatine, Marc S, and Mosenzon, Ofri
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- 2022
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3. Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients With Cardiometabolic Disease
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Marston, Nicholas A., Patel, Parth N., Kamanu, Frederick K., Nordio, Francesco, Melloni, Giorgio M., Roselli, Carolina, Gurmu, Yared, Weng, Lu-Chen, Bonaca, Marc P., Giugliano, Robert P., Scirica, Benjamin M., O’Donoghue, Michelle L., Cannon, Christopher P., Anderson, Christopher D., Bhatt, Deepak L., Gabriel Steg, Philippe, Cohen, Marc, Storey, Robert F., Sever, Peter, Keech, Anthony C., Raz, Itamar, Mosenzon, Ofri, Antman, Elliott M., Braunwald, Eugene, Ellinor, Patrick T., Lubitz, Steven A., Sabatine, Marc S., and Ruff, Christian T.
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- 2021
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4. Abstract 16139: A Targeted Proteomic Approach to Identify Circulating Biomarkers of Heart Failure Risk in Patients With Type 2 Diabetes Mellitus in DECLARE-TIMI 58
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Berg, David, Wiviott, Stephen D, RAZ, Itamar, Kamanu, Frederick, Im, KyungAh, Cahn, Avivit, Mosenzon, ofri, Bhatt, Deepak L, Jarolim, Petr, Leiter, Lawrence A, McGuire, Darren K, WILDING, JOHN, Huo, Yong, Lopez-sendon, Jose L, Ardissino, Diego, Gause-nilsson, Ingrid A, Sabatine, Marc S, and Morrow, David A
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- 2020
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5. Abstract 15701: Relationship Between Cardiac Biomarkers and Major Adverse Cardiovascular Events in DECLARE-TIMI 58
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Zelniker, Thomas A, Morrow, David A, Mosenzon, ofri, Goodrich, Erica, Jarolim, Petr, Cahn, Avivit, Bhatt, Deepak L, Leiter, Lawrence A, McGuire, Darren K, WILDING, JOHN, Averkov, Oleg V, Budaj, Andrzej, Parkhomenko, Alexander, Ray, Kausik K, Gause-nilsson, Ingrid A, Langkilde, Anna Maria, Fredriksson, Martin, RAZ, Itamar, Sabatine, Marc S, and Wiviott, Stephen D
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- 2020
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6. Abstract 14799: Cardiovascular Risk Stratification and Efficacy of Dapagliflozin on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus in the DECLARE-TIMI 58 Trial
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Oyama, Kazuma, Wiviott, Stephen D, RAZ, Itamar, Cahn, Avivit, Goodrich, Erica, Bhatt, Deepak L, Leiter, Lawrence, McGuire, Darren K, WILDING, JOHN, Gause-nilsson, Ingrid A, Mosenzon, ofri, Sabatine, Marc S, and Bohula, Erin A
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- 2020
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7. Abstract 13702: A Novel Genetic Risk Score Predicts Ischemic Stroke in Patients With Cardiometabolic Disease
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Patel, Parth N, Marston, Nicholas A, Kamanu, Frederick K, Weng, Lu Chen, Bonaca, Marc P, Giugliano, Robert P, Scirica, Benjamin M, OʼDonoghue, Michelle L, Cannon, Christopher P, ANDERSON, Christopher D, Bhatt, Deepak L, Steg, Philippe G, Cohen, Marc, Storey, Robert F, Sever, Peter S, Keech, Anthony C, RAZ, Itamar, Mosenzon, ofri, Braunwald, Eugene, Ellinor, Patrick T, Lubitz, Steven A, Sabatine, Marc S, and Ruff, Christian T
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- 2020
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8. Abstract 12948: Low Use of Statins in People With Type 2 Diabetes With or Without Cardiovascular Disease: A Capture Post Hoc Analysis
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Arenas, Jose Luis, Byram, Fahri, Darmon, Patrice, Davis, Timothy, Dieuzeide, Guillermo, Hong, Tianpei, Kaltoft, Margit S, Lengyel, Csaba, Mosenzon, ofri, Rhee, Nicolai A, Russo, Giuseppina T, Shirabe, Shinichiro, Thamattoor, Usha K, Urbancova, Katerina, Vencio, Sergio, and Alguwaihes, Abdullah
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- 2020
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9. Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58
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Bonaca, Marc P., Wiviott, Stephen D., Zelniker, Thomas A., Mosenzon, Ofri, Bhatt, Deepak L., Leiter, Lawrence A., McGuire, Darren K., Goodrich, Erica L., De Mendonca Furtado, Remo Holanda, Wilding, John P.H., Cahn, Avivit, Gause-Nilsson, Ingrid A.M., Johanson, Per, Fredriksson, Martin, Johansson, Peter A., Langkilde, Anna Maria, Raz, Itamar, and Sabatine, Marc S.
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- 2020
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10. Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial
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Zelniker, Thomas A., Bonaca, Marc P., Furtado, Remo H.M., Mosenzon, Ofri, Kuder, Julia F., Murphy, Sabina A., Bhatt, Deepak L., Leiter, Lawrence A., McGuire, Darren K., Wilding, John P.H., Budaj, Andrzej, Kiss, Robert G., Padilla, Francisco, Gause-Nilsson, Ingrid, Langkilde, Anna Maria, Raz, Itamar, Sabatine, Marc S., and Wiviott, Stephen D.
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- 2020
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11. Heart Failure Risk Stratification and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes Mellitus
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Berg, David D., Wiviott, Stephen D., Scirica, Benjamin M., Gurmu, Yared, Mosenzon, Ofri, Murphy, Sabina A., Bhatt, Deepak L., Leiter, Lawrence A., McGuire, Darren K., Wilding, John P.H., Johanson, Per, Johansson, Peter A., Langkilde, Anna Maria, Raz, Itamar, Braunwald, Eugene, and Sabatine, Marc S.
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- 2019
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12. Metformin Use and Clinical Outcomes Among Patients With Diabetes Mellitus With or Without Heart Failure or Kidney Dysfunction: Observations From the SAVOR-TIMI 53 Trial
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Bergmark, Brian A., Bhatt, Deepak L., McGuire, Darren K., Cahn, Avivit, Mosenzon, Ofri, Steg, Ph. Gabriel, Im, KyungAh, Kanevsky, Estella, Gurmu, Yared, Raz, Itamar, Braunwald, Eugene, and Scirica, Benjamin M.
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- 2019
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13. Response by Mann et al to Letter Regarding Article, “Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease: Results From the LEADER Trial”
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Mann, Johannes F.E., Fonseca, Vivian, Mosenzon, Ofri, Raz, Itamar, Goldman, Bryan, Idorn, Thomas, von Scholten, Bernt Johan, and Poulter, Neil R.
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- 2019
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14. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus
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Kato, Eri T., Silverman, Michael G., Mosenzon, Ofri, Zelniker, Thomas A., Cahn, Avivit, Furtado, Remo H.M., Kuder, Julia, Murphy, Sabina A., Bhatt, Deepak L., Leiter, Lawrence A., McGuire, Darren K., Wilding, John P.H., Bonaca, Marc P., Ruff, Christian T., Desai, Akshay S., Goto, Shinya, Johansson, Peter A., Gause-Nilsson, Ingrid, Johanson, Per, Langkilde, Anna Maria, Raz, Itamar, Sabatine, Marc S., and Wiviott, Stephen D.
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- 2019
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15. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction: Subanalysis From the DECLARE-TIMI 58 Trial
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Furtado, Remo H.M., Bonaca, Marc P., Raz, Itamar, Zelniker, Thomas A., Mosenzon, Ofri, Cahn, Avivit, Kuder, Julia, Murphy, Sabina A., Bhatt, Deepak L., Leiter, Lawrence A., McGuire, Darren K., Wilding, John P.H., Ruff, Christian T., Nicolau, Jose C., Gause-Nilsson, Ingrid A.M., Fredriksson, Martin, Langkilde, Anna Maria, Sabatine, Marc S., and Wiviott, Stephen D.
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- 2019
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16. Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Cardiovascular Outcomes Trials
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Zelniker, Thomas A., Wiviott, Stephen D., Raz, Itamar, Im, KyungAh, Goodrich, Erica L., Furtado, Remo H.M., Bonaca, Marc P., Mosenzon, Ofri, Kato, Eri T., Cahn, Avivit, Bhatt, Deepak L., Leiter, Lawrence A., McGuire, Darren K., Wilding, John P.H., and Sabatine, Marc S.
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- 2019
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17. Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease: Results From the LEADER Trial
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Mann, Johannes F. E., Fonseca, Vivian, Mosenzon, Ofri, Raz, Itamar, Goldman, Bryan, Idorn, Thomas, von Scholten, Bernt Johan, and Poulter, Neil R.
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- 2018
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18. Efficacy and Safety of Dapagliflozin in Type 2 Diabetes According to Baseline Blood Pressure: Observations From DECLARE-TIMI 58 Trial
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Remo H.M. Furtado, Itamar Raz, Erica L. Goodrich, Sabina A. Murphy, Deepak L. Bhatt, Lawrence A. Leiter, Darren K. McGuire, John P.H. Wilding, Philip Aylward, Anthony J Dalby, Mikael Dellborg, Doina Dimulescu, José C. Nicolau, Anthonius J.M. Oude Ophuis, Avivit Cahn, Ofri Mosenzon, Ingrid Gause-Nilsson, Anna Maria Langkilde, Marc S. Sabatine, and Stephen D. Wiviott
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Heart Failure ,Male ,Myocardial Infarction ,Blood Pressure ,Acute Kidney Injury ,Middle Aged ,Diabetes Mellitus, Type 2 ,Glucosides ,Physiology (medical) ,Humans ,Female ,Benzhydryl Compounds ,Cardiology and Cardiovascular Medicine ,Sodium-Glucose Transporter 2 Inhibitors ,Aged - Abstract
Background: Dapagliflozin improved heart failure and kidney outcomes in patients with type 2 diabetes (T2DM) with or at high risk for atherosclerotic cardiovascular disease in the DECLARE-TIMI 58 trial (Dapagliflozin Effect on Cardiovascular Events – Thrombolysis in Myocardial Infarction 58). Here, the aim was to analyze the efficacy and safety of dapagliflozin stratified according to baseline systolic blood pressure (SBP). Methods: The DECLARE-TIMI 58 trial randomly assigned patients with T2DM and either previous atherosclerotic cardiovascular disease or atherosclerotic cardiovascular disease risk factors to dapagliflozin or placebo. Patients were categorized by baseline SBP levels: Results: The trial comprised 17 160 patients; mean age, 64.0±6.8 years; 37.4% women; median duration of T2DM, 11 years; 40.6% with prevalent cardiovascular disease. Overall, dapagliflozin reduced SBP by 2.4 mm Hg (95% CI, 1.9–2.9; P P interactions =0.28 and 0.52, respectively). Among normotensive patients, the hazard ratios were 0.66 (95% CI, 0.42–1.05) and 0.39 (95% CI, 0.19–0.78), respectively, for hospitalization for heart failure and the renal-specific outcome. Events of volume depletion, amputation, and acute kidney injury did not differ with dapagliflozin overall or within any baseline SBP group. Conclusions: In patients with T2DM with or at high atherosclerotic cardiovascular disease risk, dapagliflozin reduced risk for hospitalization for heart failure and renal outcomes regardless of baseline SBP, with no difference in adverse events of interest at any level of baseline SBP. These results indicate that dapagliflozin provides cardiorenal benefits in patients with T2DM at high atherosclerotic cardiovascular disease risk independent of baseline blood pressure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01730534.
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- 2022
19. Efficacy and Safety of Dapagliflozin in Type 2 Diabetes According to Baseline Blood Pressure: Observations From DECLARE-TIMI 58 Trial
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Furtado, Remo H.M., primary, Raz, Itamar, additional, Goodrich, Erica L., additional, Murphy, Sabina A., additional, Bhatt, Deepak L., additional, Leiter, Lawrence A., additional, McGuire, Darren K., additional, Wilding, John P.H., additional, Aylward, Philip, additional, Dalby, Anthony J, additional, Dellborg, Mikael, additional, Dimulescu, Doina, additional, Nicolau, José C., additional, Oude Ophuis, Anthonius J.M., additional, Cahn, Avivit, additional, Mosenzon, Ofri, additional, Gause-Nilsson, Ingrid, additional, Langkilde, Anna Maria, additional, Sabatine, Marc S., additional, and Wiviott, Stephen D., additional
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- 2022
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20. Clinical Application of a Novel Genetic Risk Score for Ischemic Stroke in Patients With Cardiometabolic Disease
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Benjamin M. Scirica, Christian T. Ruff, Robert P. Giugliano, Christopher P. Cannon, Peter S. Sever, Eugene Braunwald, Robert F. Storey, Frederick K. Kamanu, Marc S. Sabatine, Yared Gurmu, Steven A. Lubitz, Christopher D. Anderson, Elliott M. Antman, Parth N Patel, Marc P. Bonaca, Philippe Gabriel Steg, Patrick T. Ellinor, Michelle L. O'Donoghue, Lu-Chen Weng, Anthony C Keech, Itamar Raz, Ofri Mosenzon, Marc Cohen, Deepak L. Bhatt, Francesco Nordio, Nicholas A Marston, Carolina Roselli, and Giorgio M. Melloni
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Male ,medicine.medical_specialty ,Genotyping Techniques ,MEDLINE ,030204 cardiovascular system & hematology ,Risk Assessment ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,In patient ,Genetic risk ,Stroke ,Aged ,Ischemic Stroke ,Genetic association ,Aged, 80 and over ,Metabolic Syndrome ,business.industry ,Atrial fibrillation ,medicine.disease ,Cardiometabolic disease ,Ischemic stroke ,Female ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Background: Genome-wide association studies have identified single-nucleotide polymorphisms that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for ischemic stroke after accounting for traditional clinical risk factors in 5 trials across the spectrum of cardiometabolic disease. Methods: Subjects who had consented for genetic testing and who were of European ancestry from the ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation), SOLID-TIMI 52 (Stabilization of Plaques Using Darapladib), SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus), PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin), and FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Patients With Elevated Risk) trials were included in this analysis. A set of 32 single-nucleotide polymorphisms associated with ischemic stroke was used to calculate a GRS in each patient and identify tertiles of genetic risk. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for clinical risk factors. Results: In 51 288 subjects across the 5 trials, a total of 960 subjects had an ischemic stroke over a median follow-up period of 2.5 years. After adjusting for clinical risk factors, a higher GRS was strongly and independently associated with increased risk for ischemic stroke ( P trend=0.009). In comparison with individuals in the lowest third of the GRS, individuals in the middle and top tertiles of the GRS had adjusted hazard ratios of 1.15 (95% CI, 0.98–1.36) and 1.24 (95% CI 1.05–1.45) for ischemic stroke, respectively. Stratification into subgroups revealed that the performance of the GRS appeared stronger in the primary prevention cohort with an adjusted hazard ratio for the top versus lowest tertile of 1.27 (95% CI, 1.04–1.53), in comparison with an adjusted hazard ratio of 1.06 (95% CI, 0.81–1.41) in subjects with previous stroke. In an exploratory analysis of patients with atrial fibrillation and CHA 2 DS 2 -VASc score of 2, high genetic risk conferred a 4-fold higher risk of stroke and an absolute risk equivalent to those with CHA 2 DS 2 -VASc score of 3. Conclusions: Across a broad spectrum of subjects with cardiometabolic disease, a 32–single-nucleotide polymorphism GRS was a strong, independent predictor of ischemic stroke. In patients with atrial fibrillation but lower CHA 2 DS 2 -VASc scores, the GRS identified patients with risk comparable to those with higher CHA 2 DS 2 -VASc scores.
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- 2021
21. Abstract 15035: Liraglutide Reduces Major Cardiovascular Events in Patients With Chronic Kidney Disease: Results From the Leader Trial
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Poulter, Neil R, Mann, Johannes, Fonseca, Vivian, Mosenzon, Ofri, Raz, Itamar, Frimer-Larsen, Helle, von Scholten, Bernt Johan, and Idorn, Thomas
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- 2017
22. Dapagliflozin and Cardiac, Kidney, and Limb Outcomes in Patients With and Without Peripheral Artery Disease in DECLARE-TIMI 58
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Darren K. McGuire, Erica L. Goodrich, Thomas A Zelniker, Marc S. Sabatine, Martin Fredriksson, Lawrence A. Leiter, Ofri Mosenzon, John P.H. Wilding, Anna Maria Langkilde, Itamar Raz, Marc P. Bonaca, Per Johanson, Deepak L. Bhatt, Avivit Cahn, Stephen D. Wiviott, Ingrid Gause-Nilsson, Peter A. Johansson, and Remo H.M. Furtado
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Male ,medicine.medical_specialty ,medicine.medical_treatment ,Myocardial Infarction ,Disease ,Kidney ,Peripheral Arterial Disease ,chemistry.chemical_compound ,Glucosides ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Benzhydryl Compounds ,Dapagliflozin ,Aged ,business.industry ,Type 2 Diabetes Mellitus ,Extremities ,Middle Aged ,medicine.disease ,Stroke ,medicine.anatomical_structure ,Diabetes Mellitus, Type 2 ,chemistry ,Amputation ,Heart failure ,Cardiology ,Female ,Kidney Diseases ,SGLT2 Inhibitor ,Cardiology and Cardiovascular Medicine ,business ,TIMI - Abstract
Background: Patients with peripheral artery disease (PAD) are at heightened risk of cardiovascular complications. The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduces the risk for hospitalization for heart failure (HHF) and kidney events in patients with type 2 diabetes mellitus. An increased risk of amputation has been observed with canagliflozin in 1 previous trial. We examined cardiovascular and kidney efficacy and the risk of limb-related events in patients with and without PAD in an exploratory analysis. Methods: A total of 17 160 patients with type 2 diabetes mellitus, including 1025 (6%) with PAD, were randomized. Key efficacy outcomes were MACE (cardiovascular [CV] death, myocardial infarction, stroke), CV death/HHF, and progression of kidney disease. Amputations, peripheral revascularization, and limb ischemic adverse events were site-reported and categorized by a blinded reviewer. Results: Patients in the placebo arm with PAD versus those without tended to have higher adjusted risk of CV death, myocardial infarction, or stroke (adjusted hazard ratio [HR], 1.23 [95% CI, 0.97–1.56], P =0.094) and significantly higher adjusted risk of CV death/HHF (adjusted HR, 1.60 [95% CI, 1.21–2.12], P =0.0010) and progression of kidney disease (adjusted HR, 1.51 [95% CI, 1.13 – 2.03], P =0.0058), and limb adverse events (adjusted HR, 8.37, P P -interaction=0.79) and progression of kidney disease (HR, 0.78, PAD; HR, 0.76, no-PAD; P -interaction=0.84) were consistent regardless of PAD. There were 560 patients who had at least 1 limb ischemic event, 454 patients with at least 1 peripheral revascularization, and 236 patients with at least 1 amputation, with a total of 407 amputations reported. Overall, there were no significant differences in any limb outcome with dapagliflozin versus placebo including limb ischemic adverse events (HR, 1.07 [95% CI, 0.90–1.26]) and amputation (HR, 1.09 [95% CI, 0.84–1.40]), with no significant interactions by a history of PAD versus not ( P -interactions=0.30 and 0.093, respectively). Conclusions: Patients with versus without PAD are at a higher risk of CV death of CV death, HHF, and kidney outcomes, and have a consistent benefits for CV death/HHF and progression of kidney disease with dapagliflozin. Patients with PAD had a higher risk of limb events, with no consistent pattern of incremental risk observed with dapagliflozin. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01730534.
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- 2020
23. Abstract 13182: Dapagliflozin and Changes in Metabolic Syndrome in Patients With Type 2 Diabetes: A DECLARE TIMI 58 Sub-Analysis
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Moura, Filipe A, primary, RAZ, Itamar, additional, Cahn, Avivit, additional, Goodrich, Erica, additional, Bhatt, Deepak L, additional, Leiter, Lawrence A, additional, WILDING, JOHN, additional, Gause-nilsson, Ingrid A, additional, Mosenzon, Ofri, additional, Sabatine, Marc S, additional, and Wiviott, Stephen D, additional
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- 2021
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24. Abstract 9393: A Genetic Risk Score to Predict Peripheral Artery Disease and Acute Limb Ischemia in Patients With Cardiometabolic Disease
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Patel, Siddharth M, primary, Marston, Nicholas A, additional, Melloni, Giorgio E, additional, Kamanu, Frederick K, additional, Roselli, Carolina, additional, Antman, Elliott M, additional, Bhatt, Deepak L, additional, Braunwald, Eugene, additional, Cannon, Christopher P, additional, Odonoghue, Michelle L, additional, Giugliano, Robert P, additional, Mosenzon, Ofri, additional, Scirica, Benjamin M, additional, Lubitz, Steven A, additional, Ellinor, Patrick T, additional, Bonaca, Marc P, additional, Sabatine, Marc S, additional, and Ruff, Christian T, additional
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- 2021
- Full Text
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25. Heart Failure Risk Stratification and Efficacy of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes Mellitus
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Ofri Mosenzon, Darren K. McGuire, Lawrence A. Leiter, Itamar Raz, Stephen D. Wiviott, Per Johanson, Yared Gurmu, Peter A. Johansson, Sabina A. Murphy, Marc S. Sabatine, David D. Berg, Anna Maria Langkilde, Benjamin M. Scirica, Deepak L. Bhatt, John P.H. Wilding, and Eugene Braunwald
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Male ,medicine.medical_specialty ,Time Factors ,Diabetic Cardiomyopathies ,Health Status ,Clinical Decision-Making ,Developing heart ,Adamantane ,030204 cardiovascular system & hematology ,Risk Assessment ,Article ,Decision Support Techniques ,03 medical and health sciences ,0302 clinical medicine ,Glucosides ,Predictive Value of Tests ,Risk Factors ,Physiology (medical) ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,In patient ,030212 general & internal medicine ,Benzhydryl Compounds ,Sodium-Glucose Transporter 2 Inhibitors ,Aged ,Randomized Controlled Trials as Topic ,Heart Failure ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Patient Selection ,Reproducibility of Results ,Type 2 Diabetes Mellitus ,Dipeptides ,Middle Aged ,medicine.disease ,Treatment Outcome ,Increased risk ,Diabetes Mellitus, Type 2 ,Heart failure ,Sodium/Glucose Cotransporter 2 ,Risk stratification ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: Patients with type 2 diabetes mellitus (T2DM) are at increased risk of developing heart failure. Sodium-glucose cotransporter-2 inhibitors reduce the risk of hospitalization for heart failure (HHF) in patients with T2DM. We aimed to develop and validate a practical clinical risk score for HHF in patients with T2DM and assess whether this score can identify high-risk patients with T2DM who have the greatest reduction in risk for HHF with a sodium-glucose cotransporter-2 inhibitor. Methods: We developed a clinical risk score for HHF in 8212 patients with T2DM in the placebo arm of SAVOR-TIMI 53 (Saxagliptin Assessment of Vascular Outcomes Recorded in Patients With Diabetes Mellitus–Thrombolysis in Myocardial Infarction 53). Candidate variables were assessed using multivariable Cox regression, and independent clinical risk indicators achieving statistical significance of P Results: Five clinical variables were independent risk predictors of HHF: prior heart failure, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. A simple integer-based score (0–7 points) using these predictors identified a >20-fold gradient of HHF risk ( P for trend P for trend=0.04), with high-risk (2 points) and very-high-risk (≥3 points) patients having 1.5% and 2.7% absolute reductions in Kaplan-Meier estimates of HHF risk at 4 years, respectively. Conclusions: Risk stratification using a novel clinical risk score for HHF in patients with T2DM identifies patients at higher risk for HHF who derive greater absolute benefit from sodium-glucose cotransporter-2 inhibition. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifiers: NCT01107886 and NCT01730534.
- Published
- 2019
26. Metformin Use and Clinical Outcomes Among Patients With Diabetes Mellitus With or Without Heart Failure or Kidney Dysfunction
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Eugene Braunwald, Brian A. Bergmark, Yared Gurmu, Estella Kanevsky, KyungAh Im, Avivit Cahn, Itamar Raz, Benjamin M. Scirica, Deepak L. Bhatt, Ph. Gabriel Steg, Darren K. McGuire, Investigators, and Ofri Mosenzon
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Male ,Risk ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,Post-hoc analysis ,medicine ,Humans ,Hypoglycemic Agents ,030212 general & internal medicine ,Aged ,Heart Failure ,business.industry ,Kidney dysfunction ,Type 2 Diabetes Mellitus ,Middle Aged ,medicine.disease ,Survival Analysis ,Metformin ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Heart failure ,Cardiology ,Female ,Kidney Diseases ,Cardiology and Cardiovascular Medicine ,business ,Biomarkers ,TIMI ,Follow-Up Studies ,medicine.drug - Abstract
Background: Metformin is first-line therapy for type 2 diabetes mellitus, although its effects on the cardiovascular system are unproved. Methods: In this post hoc analysis, patients in SAVOR-TIMI 53 (Saxagliptin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus) with baseline biomarker samples (n=12 156) were classified as ever versus never taking metformin during the trial period. Associations between metformin exposure and outcomes were estimated with inverse probability of treatment weighting Cox modeling for the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke, as well as cardiovascular death and all-cause mortality, with biomarkers included as covariates. Additional sensitivity analyses included propensity score matching and Cox multivariable models. Results: Of the 12 156 patients with baseline biomarker samples, 8971 (74%) had metformin exposure, 1611 (13%) had prior heart failure, and 1332 (11%) had at least moderate chronic kidney disease (estimated glomerular filtration rate ≤45 mL·min −1 ·1.73 m −2 ). Metformin use was associated with no difference in risk for the composite end point (hazard ratio for inverse probability of treatment weighting, 0.92 [95% CI, 0.76–1.11]) but lower risk of all-cause mortality (hazard ratio for inverse probability of treatment weighting, 0.75 [95% CI, 0.59–0.95]). There was no significant relationship between metformin use and these end points in patients with prior heart failure or moderate to severe chronic kidney disease. Conclusions: In a cohort of 12 156 patients with type 2 diabetes mellitus and high cardiovascular risk, metformin use was associated with lower rates of all-cause mortality, including after adjustment for clinical variables and biomarkers, but not lower rates of the composite end point of cardiovascular death, myocardial infarction, or ischemic stroke. This association was most apparent in patients without prior heart failure or moderate to severe chronic kidney disease. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01107886.
- Published
- 2019
27. Effect of Dapagliflozin on Heart Failure and Mortality in Type 2 Diabetes Mellitus
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Remo H.M. Furtado, Eri Toda Kato, Michael G. Silverman, Shinya Goto, Stephen D. Wiviott, Darren K. McGuire, Thomas A Zelniker, Ofri Mosenzon, Christian T. Ruff, Peter A. Johansson, Akshay S. Desai, Ingrid Gause-Nilsson, Itamar Raz, Sabina A. Murphy, Anna Maria Langkilde, Marc P. Bonaca, Per Johanson, Julia F Kuder, John P.H. Wilding, Lawrence A. Leiter, Avivit Cahn, Deepak L. Bhatt, and Marc S. Sabatine
- Subjects
medicine.medical_specialty ,business.industry ,Type 2 Diabetes Mellitus ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Physiology (medical) ,Heart failure ,Internal medicine ,Diabetes mellitus ,Cardiology ,medicine ,Myocardial infarction ,Dapagliflozin ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background: In DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58), the sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the composite end point of cardiovascular death/hospitalization for heart failure (HHF) in a broad population of patients with type 2 diabetes mellitus. However, the impact of baseline left ventricular ejection fraction (EF) on the clinical benefit of sodium-glucose cotransporter 2 inhibition is unknown. Methods: In the DECLARE-TIMI 58 trial, baseline heart failure (HF) status was collected from all patients, and EF was collected when available. HF with reduced EF (HFrEF) was defined as EF Results: Of 17 160 patients, 671 (3.9%) had HFrEF, 1316 (7.7%) had HF without known reduced EF, and 15 173 (88.4%) had no history of HF at baseline. Dapagliflozin reduced cardiovascular death/HHF more in patients with HFrEF (hazard ratio [HR], 0.62 [95% CI, 0.45–0.86]) than in those without HFrEF (HR, 0.88 [95% CI, 0.76–1.02]; P for interaction=0.046), in whom the treatment effect of dapagliflozin was similar in those with HF without known reduced EF (HR, 0.88 [95% CI, 0.66–1.17]) and those without HF (HR, 0.88 [95% CI, 0.74–1.03]). Whereas dapagliflozin reduced HHF both in those with (HR, 0.64 [95% CI, 0.43–0.95]) and in those without HFrEF (HR, 0.76 [95% CI, 0.62–0.92]), it reduced cardiovascular death only in patients with HFrEF (HR, 0.55 [95% CI, 0.34–0.90]) but not in those without HFrEF (HR, 1.08 [95% CI, 0.89–1.31]; P for interaction=0.012). Likewise, dapagliflozin reduced all-cause mortality in patients with HFrEF (HR, 0.59 [95% CI, 0.40–0.88;) but not in those without HFrEF (HR, 0.97 [95% CI, 0.86–1.10]; P for interaction=0.016). Conclusions: In the first sodium-glucose cotransporter 2 inhibitor cardiovascular outcome trial to evaluate patients with type 2 diabetes mellitus stratified by EF, we found that dapagliflozin reduced HHF in patients with and without HFrEF and reduced cardiovascular death and all-cause mortality in patients with HFrEF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.
- Published
- 2019
28. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction
- Author
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Ofri Mosenzon, Lawrence A. Leiter, Stephen D. Wiviott, Christian T. Ruff, Remo H.M. Furtado, Thomas A Zelniker, Martin Fredriksson, Itamar Raz, Marc P. Bonaca, Anna Maria Langkilde, Julia F Kuder, Avivit Cahn, Ingrid Gause-Nilsson, Jose C. Nicolau, John P.H. Wilding, Deepak L. Bhatt, Darren K. McGuire, Sabina A. Murphy, and Marc S. Sabatine
- Subjects
medicine.medical_specialty ,business.industry ,Type 2 Diabetes Mellitus ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,medicine.disease ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,chemistry ,Physiology (medical) ,Internal medicine ,medicine ,Cardiology ,In patient ,Myocardial infarction ,Dapagliflozin ,Cardiology and Cardiovascular Medicine ,business ,Cardiovascular outcomes ,Mace - Abstract
Background: Sodium glucose transporter-2 inhibitors reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus and a history of atherosclerotic cardiovascular disease. Because of their baseline risk, patients with previous myocardial infarction (MI) may derive even greater benefit from sodium glucose transporter-2 inhibitor therapy. Methods: DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58) randomized 17 160 patients with type 2 diabetes mellitus and either established atherosclerotic cardiovascular disease (n=6974) or multiple risk factors (n=10 186) to dapagliflozin versus placebo. The 2 primary end points were composite of MACE (cardiovascular death, MI, or ischemic stroke) and the composite of cardiovascular death or hospitalization for heart failure. Those with previous MI (n=3584) made up a prespecified subgroup of interest. Results: In patients with previous MI (n=3584), dapagliflozin reduced the relative risk of MACE by 16% and the absolute risk by 2.6% (15.2% versus 17.8%; hazard ratio [HR], 0.84; 95% CI, 0.72–0.99; P =0.039), whereas there was no effect in patients without previous MI (7.1% versus 7.1%; HR, 1.00; 95% CI, 0.88–1.13; P =0.97; P for interaction for relative difference=0.11; P for interaction for absolute risk difference=0.048), including in patients with established atherosclerotic cardiovascular disease but no history of MI (12.6% versus 12.8%; HR, 0.98; 95% CI, 0.81–1.19). There seemed to be a greater benefit for MACE within 2 years after the last acute event ( P for interaction trend=0.007). The relative risk reductions in cardiovascular death/hospitalization for heart failure were more similar, but the absolute risk reductions tended to be greater: 1.9% (8.6% versus 10.5%; HR, 0.81; 95% CI, 0.65–1.00; P =0.046) and 0.6% (3.9% versus 4.5%; HR, 0.85; 95% CI, 0.72–1.00; P =0.055) in patients with and without previous MI, respectively ( P interaction for relative difference=0.69; P interaction for absolute risk difference=0.010). Conclusions: Patients with type 2 diabetes mellitus and previous MI are at high risk of MACE and cardiovascular death/hospitalization for heart failure. Dapagliflozin appears to robustly reduce the risk of both composite outcomes in these patients. Future studies should aim to confirm the large clinical benefits with sodium glucose transporter-2 inhibitors we observed in patients with previous MI. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.
- Published
- 2019
29. Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease
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Johannes F.E. Mann, Neil R Poulter, Itamar Raz, Ofri Mosenzon, Vivian Fonseca, Bryan Goldman, Bernt Johan von Scholten, and Thomas Idorn
- Subjects
medicine.medical_specialty ,business.industry ,Liraglutide ,Type 2 Diabetes Mellitus ,030204 cardiovascular system & hematology ,medicine.disease ,Placebo ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,Medicine ,In patient ,030212 general & internal medicine ,Cardiology and Cardiovascular Medicine ,business ,Cardiovascular outcomes ,Kidney disease ,medicine.drug - Abstract
Background: LEADER trial (Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results) results demonstrated cardiovascular benefits for patients with type 2 diabetes mellitus at high cardiovascular risk on standard of care randomized to liraglutide versus placebo. The effect of glucagon-like peptide-1 receptor agonist liraglutide on cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and chronic kidney disease is unknown. Liraglutide’s treatment effects in patients with and without kidney disease were analyzed post hoc. Methods: Patients were randomized (1:1) to liraglutide or placebo, both in addition to standard of care. These analyses assessed outcomes stratified by baseline estimated glomerular filtration rate (eGFR; 2 ) and baseline albuminuria. The primary outcome (composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and secondary outcomes, including all-cause mortality and individual components of the primary composite outcome, were analyzed using Cox regression. Results: Overall, 2158 and 7182 patients had baseline eGFR 2 , respectively. In patients with eGFR 2 , risk reduction for the primary composite cardiovascular outcome with liraglutide was greater (hazard ratio [HR], 0.69; 95% CI, 0.57–0.85) versus those with eGFR ≥60 mL/min/1.73 m 2 (HR, 0.94; 95% CI, 0.83–1.07; interaction P =0.01). There was no consistent effect modification with liraglutide across finer eGFR subgroups (interaction P =0.13) and when analyzing eGFR as a continuous variable (interaction P =0.61). Risk reductions in those with eGFR 2 were as follows: for nonfatal myocardial infarction, HR, 0.74; 95% CI, 0.55–0.99 versus HR, 0.93; 95% CI, 0.77–1.13; for nonfatal stroke, HR, 0.51; 95% CI, 0.33–0.80 versus HR, 1.07; 95% CI, 0.84–1.37; for cardiovascular death, HR, 0.67; 95% CI, 0.50–0.90 versus HR, 0.84; 95% CI, 0.67–1.05; for all-cause mortality, HR, 0.74; 95% CI, 0.60–0.92 versus HR, 0.90; 95% CI, 0.75–1.07. Risk reduction for the primary composite cardiovascular outcome was not different for those with versus without baseline albuminuria (HR, 0.83; 95% CI, 0.71–0.97; and HR, 0.92; 95% CI, 0.79–1.07, respectively; interaction P =0.36). Conclusions: Liraglutide added to standard of care reduced the risk for major cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and chronic kidney disease. These results appear to apply across the chronic kidney disease spectrum enrolled. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT01179048.
- Published
- 2018
30. Abstract 13702: A Novel Genetic Risk Score Predicts Ischemic Stroke in Patients With Cardiometabolic Disease
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Peter S. Sever, Christian T. Ruff, Marc Cohen, Michelle L. O'Donoghue, Robert P. Giugliano, Christopher D. Anderson, Marc P. Bonaca, Deepak L. Bhatt, Eugene Braunwald, Benjamin M. Scirica, Patrick T. Ellinor, Frederick K. Kamanu, Nicholas A Marston, Philippe Gabriel Steg, Robert F. Storey, Marc S. Sabatine, Ofri Mosenzon, Christopher P. Cannon, Parth N Patel, Steven A. Lubitz, Lu-Chen Weng, Anthony C Keech, and Itamar Raz
- Subjects
medicine.medical_specialty ,business.industry ,Single-nucleotide polymorphism ,Cardiometabolic disease ,medicine.disease ,Clinical trial ,Physiology (medical) ,Internal medicine ,Ischemic stroke ,medicine ,In patient ,Genetic risk ,Cardiology and Cardiovascular Medicine ,business ,Stroke ,Genetic association - Abstract
Introduction: Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) that are associated with an increased risk of stroke. We sought to determine whether a genetic risk score (GRS) could identify subjects at higher risk for first ischemic stroke after accounting for traditional risk factors in four clinical trials across the spectrum of cardiometabolic disease. Methods: Subjects who had consented for genetic testing, were of European ancestry, and had no prior history of stroke from the SOLID-TIMI 52, SAVOR-TIMI 53, PEGASUS-TIMI 54, and FOURIER trials were included in this analysis. A recently validated GRS composed of 36 SNPs associated with ischemic stroke was calculated in each patient. A Cox model was used to calculate hazard ratios for ischemic stroke across genetic risk groups, adjusted for age, sex, ancestry, hypertension, hyperlipidemia, smoking, diabetes mellitus, atrial fibrillation, coronary artery disease, and congestive heart failure. Results: In 23,089 subjects across the four trials, a total of 313 ischemic strokes occurred over a median follow-up of 3 years. Those with higher genetic risk were at significantly increased risk for ischemic stroke with an adjusted HR per 1-SD GRS of 1.12 (1.004-1.25; p=0.043). Individuals in the top 10% of genetic risk had a 42% greater hazard for ischemic stroke than those in the lower 90% of genetic risk (adjusted HR 1.42 [1.03-1.97]; p=0.034). The magnitude of risk conferred by high genetic risk was similar or greater than the risk provided by well-established clinical risk factors (Figure). Conclusions: Across four large clinical trials of subjects with cardiometabolic disease, a 36-SNP GRS was a strong, independent predictor of first ischemic stroke. The risk of stroke was particularly high in patients in the top 10% of genetic risk.
- Published
- 2020
31. Abstract 14799: Cardiovascular Risk Stratification and Efficacy of Dapagliflozin on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus in the DECLARE-TIMI 58 Trial
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Erica L. Goodrich, Ofri Mosenzon, Darren K. McGuire, Stephen D. Wiviott, Avivit Cahn, Marc S. Sabatine, Ingrid Gause-Nilsson, Lawrence A. Leiter, John P.H. Wilding, Itamar Raz, Deepak L. Bhatt, Erin A. Bohula, and Kazuma Oyama
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medicine.medical_specialty ,business.industry ,Type 2 Diabetes Mellitus ,medicine.disease ,Cardiovascular death ,chemistry.chemical_compound ,chemistry ,Physiology (medical) ,Internal medicine ,Heart failure ,Risk stratification ,Cardiology ,Medicine ,In patient ,cardiovascular diseases ,Dapagliflozin ,Cardiology and Cardiovascular Medicine ,business ,Cardiovascular outcomes ,TIMI - Abstract
Introduction: In DECLARE-TIMI 58, the SGLT-2 inhibitor, dapagliflozin reduced the risk of the composite of cardiovascular death (CVD) or hospitalization for heart failure (HHF), and renal-specific outcomes in a broad range of patients with type 2 diabetes mellitus (T2DM). The TIMI Risk Score for Secondary Prevention (TRS 2°P) is a clinical risk score developed in patients with atherosclerotic cardiovascular disease (ASCVD) that provides risk stratification. Hypothesis: We hypothesized that the TRS 2°P would provide risk stratification in this population and that dapagliflozin would provide cardiovascular protection regardless of risk. Methods: DECLARE-TIMI 58 included patients with T2DM and either multiple risk factors or established ASCVD. Patients were stratified into 3 risk categories based on the 10-point TRS 2°P (see Figure , low: 1 or 2 points, intermediate: 3 points, or high: ≥4 points). Outcomes were major adverse cardiovascular events (MACE) (CVD, myocardial infarction, or ischemic stroke), CVD/HHF, components for MACE, and renal-specific composite outcomes. Results: Low, intermediate, or high risk, comprised respectively 49.8%, 31.2%, and 19.0% of the total of 17159 patients. In the placebo arm, increasing risk category was associated with a higher risk of all the outcomes of interest across risk categories (P-trendFigure ). The C-statistics were 0.67 for MACE and 0.72 for CVD/HHF in the placebo arm. Relative risk reductions in CVD/HHF and renal-specific composite outcomes with dapagliflozin were consistent for patients across the spectrum of TRS 2°P (P>0.05 for each interaction). Conclusions: Cardiovascular risk stratification using TRS 2°P identifies high-risk patients with T2DM for MACE, CVD/HHF, individual components for MACE, and renal-specific outcomes. Reductions in CVD/HHF and renal-specific outcomes with dapagliflozin versus placebo were consistent across the range of TRS 2°P.
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- 2020
32. Abstract 15701: Relationship Between Cardiac Biomarkers and Major Adverse Cardiovascular Events in DECLARE-TIMI 58
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Martin Fredriksson, Erica L. Goodrich, Andrzej Budaj, Ofri Mosenzon, Lawrence A. Leiter, Marc S. Sabatine, Ingrid Gause-Nilsson, David A. Morrow, John P.H. Wilding, Anna Maria Langkilde, Avivit Cahn, Deepak L. Bhatt, Itamar Raz, Alexander Parkhomenko, Thomas A Zelniker, Stephen D. Wiviott, Oleg Averkov, Petr Jarolim, Kausik K. Ray, and Darren K. McGuire
- Subjects
medicine.medical_specialty ,business.industry ,Cardiac biomarkers ,medicine.disease ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,Heart failure ,Cardiology ,medicine ,In patient ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business ,Hemodynamic stress ,ATHEROSCLEROTIC VASCULAR DISEASE ,TIMI - Abstract
Introduction: Biomarkers of hemodynamic stress and myocardial injury are associated with the risk of CV death & heart failure in patients with atherosclerotic vascular disease (ASCVD). Here we explore the association between cardiac biomarkers and ASCVD outcomes in patients with type 2 diabetes (T2DM). Methods: This was a nested biomarker study in DECLARETIMI 58, a randomized, blinded, placebo-controlled trial of dapagliflozin in T2DM and either multiple risk factors (MRF, ~60%) or established ASCVD (~40%). The relationship between baseline NT-proBNP and hsTnT levels (TIMI Biomarker Laboratory, n=14,565) and the composite of myocardial infarction, ischemic stroke, and CV death (MACE), was modeled within the placebo arm using Cox models adjusted for age, sex, race, smoking, baseline eGFR, BMI, T2DM duration, insulin use, history of CAD, MI, ischemic stroke, PAD, HF, dyslipidemia & hypertension. Interaction testing was applied to assess the effect of dapagliflozin according to baseline biomarker value. Results: NT-proBNP and hsTnT were significantly associated with MACE (Adjusted hazard ratio (aHR) per 1-SD in log-transformed biomarker, NT-proBNP: aHR 1.62; hsTnT aHR 1.59). The magnitude of the relationship was similar in patients with ASCVD (NT-proBNP aHR 1.60; hsTnT aHR 1.62) and MRF (NT-proBNP aHR 1.62; hsTnT: aHR 1.51) [Fig A] . Moreover, both biomarkers remained independently associated with MACE when combined in the multivariable model (NT-proBNP aHR 1.46, hsTnT aHR 1.39). The risk of MACE by baseline biomarker level and stratified by treatment arm is shown in Fig B. Conclusions: In patients with T2DM both with and without ASCVD, higher baseline NT-proBNP or hsTnT levels identified patients at increased risk of MACE. The difference in MACE rates between dapagliflozin and placebo tended to be more pronounced in ASCVD patients with higher baseline or NT-proBNP or hsTnT levels.
- Published
- 2020
33. Abstract 12948: Low Use of Statins in People With Type 2 Diabetes With or Without Cardiovascular Disease: A Capture Post Hoc Analysis
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Nicolai Rhee, Katerina Urbancova, Tianpei Hong, Usha K Thamattoor, Shinichiro Shirabe, Jose Luis Arenas, Abdullah M. Alguwaihes, Patrice Darmon, Margit S Kaltoft, Fahri Byram, Giuseppina T. Russo, Sergio Vencio, Timothy M. E. Davis, Csaba Lengyel, Guillermo Dieuzeide, and Ofri Mosenzon
- Subjects
medicine.medical_specialty ,business.industry ,Disease ,Type 2 diabetes ,Statin treatment ,Diabetes type ii ,medicine.disease ,Physiology (medical) ,Internal medicine ,Post-hoc analysis ,Medicine ,cardiovascular diseases ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background and aim: The association between LDL levels, CVD and the benefits of statin use are well established. The CAPTURE study estimated the contemporary (2019) global prevalence of CVD and medication use in adults with type 2 diabetes across 13 countries. This post hoc analysis assessed serum lipid status and statin use in people with type 2 diabetes without CVD (NoCVD), with established CVD, and atherosclerotic CVD (AsCVD, a subgroup of CVD). Methods: CAPTURE was a multinational, cross-sectional and non-interventional study. Participant information on CVD status, serum lipid profiles, and medication use were ascertained during single routine clinical visit in primary or specialist setting. This analysis included people who had data on serum LDL-C and lipid-lowering therapies. LDL-C targets were set at Results: The CAPTURE study enrolled 9823 people aimed to be representative of the general type 2 diabetes population. Most (>80%) had blood LDL-C information. Mean serum levels of lipids varied across 3 groups. (Table) The overall use of any statin was 38% in the NoCVD, 53% in CVD, and 55% in AsCVD groups. In those with documented serum LDL-C levels, 48% in the NoCVD, 67% in CVD, and 66% in AsCVD groups were above LDL-C targets with statin use of 34%, 57%, and 60%, respectively in these participants. Overall, the use of ezetimibe was 3-8% in all the groups and usually in combination with a statin. PCSK9 inhibitors use was Conclusion: In conclusion, this CAPTURE post hoc analysis found that two-thirds of people with CVD and AsCVD had LDL-C levels above recommendations and only around 60% of them were on statins. Intolerability of statins might partly explain this lower than expected statin use.
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- 2020
34. Abstract 16139: A Targeted Proteomic Approach to Identify Circulating Biomarkers of Heart Failure Risk in Patients With Type 2 Diabetes Mellitus in DECLARE-TIMI 58
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Darren K. McGuire, Itamar Raz, Marc S. Sabatine, Deepak L. Bhatt, John P.H. Wilding, Frederick K. Kamanu, David D. Berg, Ofri Mosenzon, Diego Ardissino, Petr Jarolim, Jose Lopez-Sendon, David A. Morrow, KyungAh Im, Lawrence A. Leiter, Ingrid Gause-Nilsson, Yong Huo, Stephen D. Wiviott, and Avivit Cahn
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medicine.medical_specialty ,business.industry ,Type 2 Diabetes Mellitus ,medicine.disease ,Circulating biomarkers ,Physiology (medical) ,Internal medicine ,Heart failure ,medicine ,Cardiology ,In patient ,Cardiology and Cardiovascular Medicine ,business ,TIMI - Abstract
Background: Patients (pts) with type 2 diabetes mellitus (T2DM) are at increased risk of heart failure (HF); however, the underlying mechanisms by which T2DM contributes to HF are incompletely understood. Hypothesis: We aimed to identify biological pathways associated with risk of hospitalization for HF (HHF) in a well-characterized cohort with T2DM followed for a median of 4.2 yrs. Methods: DECLARE-TIMI 58 was a randomized trial of dapagliflozin in pts with T2DM. We performed a nested case-control study of 184 candidate biomarkers (Olink CV II and CV III) in pts hospitalized for HF (n=432) and controls matched on age, sex, prior HF, prior CV disease, and f/u time (n=432). We evaluated associations between baseline biomarkers and HHF using logistic regression with a stringent threshold for significance (Bonferroni). Biomarkers were ranked according to Wald χ 2 values. ORs for the top 10 biomarkers were further adjusted for the components of the TIMI Risk Score for HF in Diabetes (AF, UACR, eGFR, CAD). ORs are per 1-SD. Results: 45 biomarkers were significantly associated with HHF. The 10 strongest associations were seen with N-terminal pro-B type natriuretic peptide (NT-proBNP), B type natriuretic peptide (BNP), spondin-1 (SPON1), insulin-like growth factor-binding protein 7 (IGFBP7), interleukin-6 (IL-6), fibroblast growth factor-23 (FGF-23), transferrin receptor protein 1 (TR), metalloproteinase inhibitor 4 (TIMP4), matrix metalloproteinase-2 (MMP-2), C-X-C motif chemokine 16 (CXCL16) ( Fig ). All 10 biomarkers were significantly associated with HHF both in pts with and without a history of HF. These proteins represent pathobiological axes implicated in hemodynamic stress, inflammation, myocardial hypertrophy, and cellular senescence, among others. Conclusions: A targeted proteomic approach identified established (NT-proBNP, BNP), investigational (IGFBP7, FGF-23, IL-6, TR, TIMP4, MMP-2, CXCL16), and novel (SPON1) biomarkers of HHF in pts with T2DM.
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- 2020
35. Effect of Dapagliflozin on Atrial Fibrillation in Patients With Type 2 Diabetes Mellitus: Insights From the DECLARE-TIMI 58 Trial
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Remo H.M. Furtado, Róbert Gábor Kiss, Marc P. Bonaca, Stephen D. Wiviott, Itamar Raz, Francisco Padilla, Lawrence A. Leiter, Marc S. Sabatine, Julia F Kuder, Sabina A. Murphy, Darren K. McGuire, Deepak L. Bhatt, Anna Maria Langkilde, Ofri Mosenzon, Thomas A Zelniker, Ingrid Gause-Nilsson, Andrzej Budaj, and John P.H. Wilding
- Subjects
Male ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Glucosides ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,Atrial Fibrillation ,medicine ,Humans ,030212 general & internal medicine ,Dapagliflozin ,Benzhydryl Compounds ,business.industry ,Type 2 Diabetes Mellitus ,Atrial fibrillation ,medicine.disease ,Obesity ,chemistry ,Diabetes Mellitus, Type 2 ,Heart failure ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,TIMI ,Atrial flutter - Abstract
Background: Atrial fibrillation (AF) and atrial flutter (AFL) are associated with both diabetes mellitus and its related comorbidities, including hypertension, obesity, and heart failure (HF). SGLT2 (sodium-glucose cotransporter 2) inhibitors have been shown to lower blood pressure, reduce weight, have salutary effects on left ventricular remodeling, and reduce hospitalization for HF and cardiovascular death in patients with type 2 diabetes mellitus. We therefore investigated whether SGLT2 inhibitors could also reduce the risk of AF/AFL. Methods: DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58) studied the efficacy and safety of the SGLT2 inhibitor dapagliflozin versus placebo in 17 160 patients with type 2 diabetes mellitus and either multiple risk factors for atherosclerotic cardiovascular disease (n=10 186) or known atherosclerotic cardiovascular disease (n=6974). We explored the effect of dapagliflozin on the first and total number of AF/AFL events in patients with (n=1116) and without prevalent AF/AFL using Cox and negative binomial models, respectively. AF/AFL events were identified by search of the safety database using MedDRA preferred terms (“atrial fibrillation,” “atrial flutter”). Results: Dapagliflozin reduced the risk of AF/AFL events by 19% (264 versus 325 events; 7.8 versus 9.6 events per 1000 patient-years; hazard ratio [HR], 0.81 [95% CI, 0.68–0.95]; P =0.009). The reduction in AF/AFL events was consistent regardless of presence or absence of a history of AF/AFL at baseline (previous AF/AFL: HR, 0.79 [95% CI, 0.58–1.09]; no AF/AFL: HR, 0.81 [95% CI, 0.67–0.98]; P for interaction 0.89). Similarly, presence of atherosclerotic cardiovascular disease (HR, 0.83 [95% CI, 0.66–1.04]) versus multiple risk factors (HR, 0.78 [95% CI, 0.62–0.99]; P for interaction 0.72) or a history of HF (HF: HR, 0.78 [95% CI, 0.55–1.11]; No HF: HR, 0.81 [95% CI, 0.68–0.97]; P for interaction 0.88) did not modify the reduction in AF/AFL events observed with dapagliflozin. Moreover, there was no effect modification by sex, history of ischemic stroke, glycated hemoglobin A 1c , body mass index, blood pressure, or estimated glomerular filtration rate (all P for interaction >0.20). Dapagliflozin also reduced the total number (first and recurrent) of AF/AFL events (337 versus 432; incidence rate ratio, 0.77 [95% CI, 0.64–0.92]; P =0.005). Conclusions: Dapagliflozin decreased the incidence of reported episodes of AF/AFL adverse events in high-risk patients with type 2 diabetes mellitus. This effect was consistent regardless of the patient’s previous history of AF, atherosclerotic cardiovascular disease, or HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01730534.
- Published
- 2020
36. Response by Mann et al to Letter Regarding Article, 'Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease: Results From the LEADER Trial'
- Author
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Itamar Raz, Neil R Poulter, Thomas Idorn, Johannes F.E. Mann, Ofri Mosenzon, Bryan Goldman, Vivian Fonseca, and Bernt Johan von Scholten
- Subjects
medicine.medical_specialty ,Liraglutide ,business.industry ,Type 2 Diabetes Mellitus ,1103 Clinical Sciences ,medicine.disease ,Placebo ,1117 Public Health and Health Services ,Cardiovascular System & Hematology ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Hypoglycemic Agents ,In patient ,Renal Insufficiency, Chronic ,Cardiology and Cardiovascular Medicine ,business ,1102 Cardiorespiratory Medicine and Haematology ,Kidney disease ,medicine.drug - Published
- 2019
37. Dapagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus and Previous Myocardial Infarction
- Author
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Remo H M, Furtado, Marc P, Bonaca, Itamar, Raz, Thomas A, Zelniker, Ofri, Mosenzon, Avivit, Cahn, Julia, Kuder, Sabina A, Murphy, Deepak L, Bhatt, Lawrence A, Leiter, Darren K, McGuire, John P H, Wilding, Christian T, Ruff, Jose C, Nicolau, Ingrid A M, Gause-Nilsson, Martin, Fredriksson, Anna Maria, Langkilde, Marc S, Sabatine, and Stephen D, Wiviott
- Subjects
Heart Failure ,Male ,Time Factors ,Myocardial Infarction ,Middle Aged ,Risk Assessment ,Brain Ischemia ,Hospitalization ,Stroke ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Double-Blind Method ,Glucosides ,Recurrence ,Risk Factors ,Cause of Death ,Disease Progression ,Humans ,Female ,Benzhydryl Compounds ,Sodium-Glucose Transporter 2 Inhibitors ,Aged - Abstract
Sodium glucose transporter-2 inhibitors reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus and a history of atherosclerotic cardiovascular disease. Because of their baseline risk, patients with previous myocardial infarction (MI) may derive even greater benefit from sodium glucose transporter-2 inhibitor therapy.DECLARE-TIMI 58 (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58) randomized 17 160 patients with type 2 diabetes mellitus and either established atherosclerotic cardiovascular disease (n=6974) or multiple risk factors (n=10 186) to dapagliflozin versus placebo. The 2 primary end points were composite of MACE (cardiovascular death, MI, or ischemic stroke) and the composite of cardiovascular death or hospitalization for heart failure. Those with previous MI (n=3584) made up a prespecified subgroup of interest.In patients with previous MI (n=3584), dapagliflozin reduced the relative risk of MACE by 16% and the absolute risk by 2.6% (15.2% versus 17.8%; hazard ratio [HR], 0.84; 95% CI, 0.72-0.99; P=0.039), whereas there was no effect in patients without previous MI (7.1% versus 7.1%; HR, 1.00; 95% CI, 0.88-1.13; P=0.97; P for interaction for relative difference=0.11; P for interaction for absolute risk difference=0.048), including in patients with established atherosclerotic cardiovascular disease but no history of MI (12.6% versus 12.8%; HR, 0.98; 95% CI, 0.81-1.19). There seemed to be a greater benefit for MACE within 2 years after the last acute event ( P for interaction trend=0.007). The relative risk reductions in cardiovascular death/hospitalization for heart failure were more similar, but the absolute risk reductions tended to be greater: 1.9% (8.6% versus 10.5%; HR, 0.81; 95% CI, 0.65-1.00; P=0.046) and 0.6% (3.9% versus 4.5%; HR, 0.85; 95% CI, 0.72-1.00; P=0.055) in patients with and without previous MI, respectively ( P interaction for relative difference=0.69; P interaction for absolute risk difference=0.010).Patients with type 2 diabetes mellitus and previous MI are at high risk of MACE and cardiovascular death/hospitalization for heart failure. Dapagliflozin appears to robustly reduce the risk of both composite outcomes in these patients. Future studies should aim to confirm the large clinical benefits with sodium glucose transporter-2 inhibitors we observed in patients with previous MI.URL: https://www.clinicaltrials.gov . Unique identifier: NCT01730534.
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- 2019
38. Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus
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Thomas A, Zelniker, Stephen D, Wiviott, Itamar, Raz, KyungAh, Im, Erica L, Goodrich, Remo H M, Furtado, Marc P, Bonaca, Ofri, Mosenzon, Eri T, Kato, Avivit, Cahn, Deepak L, Bhatt, Lawrence A, Leiter, Darren K, McGuire, John P H, Wilding, and Marc S, Sabatine
- Subjects
Male ,Clinical Trials as Topic ,Glucagon-Like Peptide Receptors ,Diabetic Cardiomyopathies ,Middle Aged ,Atherosclerosis ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Commentaries ,Commentary ,Humans ,Hypoglycemic Agents ,Diabetic Nephropathies ,Female ,Kidney Diseases ,Sodium-Glucose Transporter 2 Inhibitors ,Aged ,Proportional Hazards Models - Abstract
Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) have emerged as 2 new classes of antihyperglycemic agents that also reduce cardiovascular risk. The relative benefits in patients with and without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs remain undefined.We performed a systematic review and trial-level meta-analysis of GLP1-RA and SGLT2i cardiovascular outcomes trials using the PubMed and EMBASE databases (Excerpta Medica Database). The primary outcomes were the composite of myocardial infarction, stroke, and cardiovascular death (MACE); hospitalization for heart failure; and progression of kidney disease.In total, data from 8 trials and 77 242 patients, 42 920 (55.6%) in GLP1-RA trials, and 34 322 (44.4%) in SGLT2i trials, were included. Both drug classes reduced MACE in a similar magnitude with GLP1-RA reducing the risk by 12% (hazard ratio [HR], 0.88; 95% CI, 0.84-0.94; P0.001) and SGLT2i by 11% (HR, 0.89; 95% CI, 0.83-0.96; P=0.001). For both drug classes, this treatment effect was restricted to a 14% reduction in those with established atherosclerotic cardiovascular disease (HR, 0.86; 95% CI, 0.80-0.93; P=0.002), whereas no effect was seen in patients without established atherosclerotic cardiovascular disease (HR, 1.01; 95% CI, 0.87-1.19; P=0.81; P interaction, 0.028). SGLT2i reduced hospitalization for heart failure by 31% (HR, 0.69; 95% CI, 0.61-0.79; P0.001), whereas GLP1-RA did not have a significant effect (HR, 0.93; 95% CI, 0.83-1.04; P=0.20). Both GLP1-RA (HR, 0.82; 95% CI, 0.75-0.89; P0.001) and SGLT2i (HR, 0.62; 95% CI, 0.58-0.67; P0.001) reduced the risk of progression of kidney disease including macroalbuminuria, but only SGLT2i reduced the risk of worsening estimated glomerular filtration rate, end-stage kidney disease, or renal death (HR, 0.55; 95% CI, 0.48-0.64; P0.001).In trials reported to date, GLP1-RA and SGLT2i reduce atherosclerotic MACE to a similar degree in patients with established atherosclerotic cardiovascular disease, whereas SGLT2i have a more marked effect on preventing hospitalization for heart failure and progression of kidney disease. Their distinct clinical benefit profiles should be considered in the decision-making process when treating patients with type 2 diabetes mellitus.
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- 2019
39. Heart Failure, Saxagliptin, and Diabetes Mellitus: Observations from the SAVOR-TIMI 53 Randomized Trial
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Petr Jarolim, Benjamin M. Scirica, Jaime A. Davidson, Jacob A. Udell, Eugene Braunwald, Basil S. Lewis, Matthew A. Cavender, Ph. Gabriel Steg, Darren K. McGuire, KyungAh Im, Robert Frederich, Itamar Raz, Pia S. Pollack, Amarachi A. Umez-Eronini, Deepak L. Bhatt, Ofri Mosenzon, David A. Morrow, and Boaz Hirshberg
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Male ,medicine.medical_specialty ,Adamantane ,Saxagliptin ,Risk Assessment ,chemistry.chemical_compound ,Troponin T ,Physiology (medical) ,Internal medicine ,Diabetes mellitus ,Natriuretic Peptide, Brain ,medicine ,Humans ,Myocardial infarction ,Aged ,Heart Failure ,Dipeptidyl-Peptidase IV Inhibitors ,business.industry ,Hazard ratio ,Type 2 Diabetes Mellitus ,Dipeptides ,Middle Aged ,medicine.disease ,Peptide Fragments ,Confidence interval ,Hospitalization ,C-Reactive Protein ,Endocrinology ,Diabetes Mellitus, Type 2 ,chemistry ,Heart failure ,Multivariate Analysis ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,TIMI ,Follow-Up Studies - Abstract
Background— Diabetes mellitus and heart failure frequently coexist. However, few diabetes mellitus trials have prospectively evaluated and adjudicated heart failure as an end point. Methods and Results— A total of 16 492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events were randomized to saxagliptin or placebo (mean follow-up, 2.1 years). The primary end point was the composite of cardiovascular death, myocardial infarction, or ischemic stroke. Hospitalization for heart failure was a predefined component of the secondary end point. Baseline N-terminal pro B-type natriuretic peptide was measured in 12 301 patients. More patients treated with saxagliptin (289, 3.5%) were hospitalized for heart failure compared with placebo (228, 2.8%; hazard ratio, 1.27; 95% confidence intercal, 1.07–1.51; P =0.007). Corresponding rates at 12 months were 1.9% versus 1.3% (hazard ratio, 1.46; 95% confidence interval, 1.15–1.88; P =0.002), with no significant difference thereafter (time-varying interaction, P =0.017). Subjects at greatest risk of hospitalization for heart failure had previous heart failure, an estimated glomerular filtration rate ≤60 mL/min, or elevated baseline levels of N-terminal pro B-type natriuretic peptide. There was no evidence of heterogeneity between N-terminal pro B-type natriuretic peptide and saxagliptin ( P for interaction=0.46), although the absolute risk excess for heart failure with saxagliptin was greatest in the highest N-terminal pro B-type natriuretic peptide quartile (2.1%). Even in patients at high risk of hospitalization for heart failure, the risk of the primary and secondary end points were similar between treatment groups. Conclusions— In the context of balanced primary and secondary end points, saxagliptin treatment was associated with an increased risk or hospitalization for heart failure. This increase in risk was highest among patients with elevated levels of natriuretic peptides, previous heart failure, or chronic kidney disease. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01107886.
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- 2014
40. Response to Letter Regarding Article, 'Heart Failure, Saxagliptin and Diabetes Mellitus: Observations From the SAVOR-TIMI 53 Randomized Trial'
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Amarachi A. Umez-Eronini, David A. Morrow, Jacob A. Udell, Benjamin M. Scirica, Basil S. Lewis, Boaz Hirshberg, Itamar Raz, Eugene Braunwald, Robert Frederich, KyungAh Im, Jaime A. Davidson, Ofri Mosenzon, Matthew A. Cavender, Petr Jarolim, Deepak L. Bhatt, Gabriel Steg, Darren K. McGuire, and Pia S. Pollack
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Male ,medicine.medical_specialty ,Adamantane ,Pharmacology ,Saxagliptin ,Placebo ,chemistry.chemical_compound ,Physiology (medical) ,Internal medicine ,medicine ,Humans ,Myocardial infarction ,Heart Failure ,Unstable angina ,business.industry ,Dipeptides ,medicine.disease ,Blood pressure ,chemistry ,Diabetes Mellitus, Type 2 ,Heart failure ,ACE inhibitor ,Cardiology ,Female ,Cardiology and Cardiovascular Medicine ,business ,TIMI ,medicine.drug - Abstract
We thank Drs Muskiet, Tonneijck, and van Raalte for calling attention to the potentially detrimental consequences of simultaneous inhibition of dipeptidyl peptidase 4 and angiotensin-converting enzyme (ACE).1,2 They note correctly that in Does Saxagliptin Reduce the Risk of Cardiovascular Events When Used Alone or Added to Other Diabetes Medications (SAVOR-TIMI 53), more patients treated with ACE inhibitors at baseline were subsequently hospitalized for heart failure. However, this observation alone is likely a result of confounding by indication, because patients at highest risk of heart failure are more likely to be treated with this class of drug in the first place. A similar observation was seen with β-blockers.3 Despite elegant physiological studies suggesting a potential hemodynamic interaction between dipeptidyl peptidase 4 inhibitors and ACE inhibitors, there were no differences in heart or blood pressure changes after randomization according to baseline ACE inhibitor use in patients treated with saxagliptin or placebo (all P for interaction >0.10). Nor were there any clinical consequences of baseline ACE inhibitor use on the primary end point of cardiovascular death, myocardial infarction, or ischemic stroke (baseline ACE inhibitor: saxagliptin, 7.3% versus placebo, 7.5%; hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.81–1.09; P =0.41 in comparison with no baseline ACE inhibitor: saxagliptin, 7.3% versus placebo, 6.9%; HR, 1.08; 95% CI, 0.91–1.27; P =0.39; P for interaction=0.23), the secondary end point, which included the primary end point plus hospitalization for unstable angina, heart failure, or coronary revascularization (baseline ACE inhibitor: saxagliptin, 12.9% versus placebo, 13.2%; HR, 0.95; 95% CI, 0.85–1.07; P =0.41 in comparison with no baseline ACE inhibitor: saxagliptin, 12.7% versus placebo, 11.5%; HR, 1.11; 95% CI, 0.98–1.27; P =0.11; P for interaction=0.08), or hospitalization for heart failure alone (baseline ACE inhibitor: saxagliptin, 3.6% versus placebo, …
- Published
- 2015
41. Comparison of the Effects of Glucagon-Like Peptide Receptor Agonists and Sodium-Glucose Co-Transporter 2 Inhibitors for Prevention of Major Adverse Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Cardiovascular Outcomes Trials.
- Author
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Zelniker, Thomas A., Wiviott, Stephen D., Raz, Itamar, Im, KyungAh, Goodrich, Erica L., Furtado, Remo H.M., Bonaca, Marc P., Mosenzon, Ofri, Kato, Eri T., Cahn, Avivit, Bhatt, Deepak L., Leiter, Lawrence A., McGuire, Darren K., Wilding, John P.H., and Sabatine, Marc S.
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- 2019
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- View/download PDF
42. Response to Letter Regarding Article, “Heart Failure, Saxagliptin and Diabetes Mellitus: Observations From the SAVOR-TIMI 53 Randomized Trial”
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Scirica, Benjamin M., primary, Braunwald, Eugene, additional, Raz, Itamar, additional, Cavender, Matthew A., additional, Morrow, David A., additional, Jarolim, Petr, additional, Udell, Jacob A., additional, Mosenzon, Ofri, additional, Im, KyungAh, additional, Umez-Eronini, Amarachi A., additional, Pollack, Pia S., additional, Hirshberg, Boaz, additional, Frederich, Robert, additional, Lewis, Basil S., additional, McGuire, Darren K., additional, Davidson, Jaime, additional, Steg, Gabriel, additional, and Bhatt, Deepak L., additional
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- 2015
- Full Text
- View/download PDF
43. Heart Failure, Saxagliptin, and Diabetes Mellitus: Observations from the SAVOR-TIMI 53 Randomized Trial
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Scirica, Benjamin M., primary, Braunwald, Eugene, additional, Raz, Itamar, additional, Cavender, Matthew A., additional, Morrow, David A., additional, Jarolim, Petr, additional, Udell, Jacob A., additional, Mosenzon, Ofri, additional, Im, KyungAh, additional, Umez-Eronini, Amarachi A., additional, Pollack, Pia S., additional, Hirshberg, Boaz, additional, Frederich, Robert, additional, Lewis, Basil S., additional, McGuire, Darren K., additional, Davidson, Jaime, additional, Steg, Ph. Gabriel, additional, and Bhatt, Deepak L., additional
- Published
- 2014
- Full Text
- View/download PDF
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