Darren K McGuire1, Frans Van de Werf2, Paul W Armstrong3, Eberhard Standl4, Joerg Koglin5, Jennifer B Green6, M Angelyn Bethel7, Jan H Cornel8, Renato D Lopes9, Sigrun Halvorsen10, Giuseppe Ambrosio11, John B Buse12, Robert G Josse13, John M Lachin14, Michael J Pencina15, Jyotsna Garg16, Yuliya Lokhnygina15, Rury R Holman7, Eric D Peterson9. 1. Division of Cardiology, Department of Medicine, University of Texas Southwestern Medical Center, Dallas. 2. Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium. 3. Canadian Virtual Coordinating Centre for Global Collaborative Cardiovascular Research (VIGOUR) Centre, Department of Medicine (Cardiology), University of Alberta, Edmonton. 4. Munich Diabetes Research Group e.V. at Helmholtz Centre, Neuherberg, Germany. 5. Global Clinical Development, Merck Research Laboratories, Merck & Co, Inc, Kenilworth, New Jersey. 6. Division of Endocrinology, Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. 7. Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, England. 8. Department of Cardiology, Medisch Centrum Alkmaar, Alkmaar, the Netherlands. 9. Division of Cardiology, Department of Medicine, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. 10. Department of Cardiology, Oslo University Hospital Ulleval and University of Oslo, Oslo, Norway. 11. Division of Cardiology, University of Perugia School of Medicine, Perugia, Italy. 12. Division of Endocrinology, Department of Medicine, University of North Carolina School of Medicine at Chapel Hill. 13. Division of Endocrinology and Metabolism, St Michael's Hospital, Li Ka Shing Knowledge Institute, University of Toronto, Toronto, Ontario, Canada. 14. The Biostatistics Center, George Washington University Biostatistics Center, Rockville, Maryland. 15. Department of Biostatistics and Bioinformatics, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. 16. Department of Clinical Trials Statistics, Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
Abstract
IMPORTANCE: Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS). OBJECTIVE: To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes. DESIGN, SETTING, AND PARTICIPANTS: TECOS was a randomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015. INTERVENTIONS: Patients were randomized to sitagliptin vs placebo added to standard care. MAIN OUTCOMES AND MEASURES: Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF or all-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHF death. Meta-analyses evaluated DPP4i effects on hHF and on hHF or CV death. RESULTS:Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 toplacebo. Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95% CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHFall-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16). CONCLUSIONS AND RELEVANCE: Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00790205.
RCT Entities:
IMPORTANCE: Previous trial results have suggested that dipeptidyl peptidase 4 inhibitor (DPP4i) use might increase heart failure (HF) risk in type 2 diabetes mellitus (T2DM). The DPP4i sitagliptin has been shown to be noninferior to placebo with regard to primary and secondary composite atherosclerotic cardiovascular (CV) outcomes in the Trial Evaluating Cardiovascular Outcomes With Sitagliptin (TECOS). OBJECTIVE: To assess the association of sitagliptin use with hospitalization for HF (hHF) and related outcomes. DESIGN, SETTING, AND PARTICIPANTS: TECOS was a randomized, double-blind, placebo-controlled study evaluating the CV safety of sitagliptin vs placebo, each added to usual antihyperglycemic therapy and CV care among patients with T2DM and prevalent atherosclerotic vascular disease. The median follow-up was 2.9 years. The setting was 673 sites in 38 countries. Participants included 14 671 patients with T2DM and atherosclerotic vascular disease. The study dates were December 2008 through March 2015. INTERVENTIONS:Patients were randomized to sitagliptin vs placebo added to standard care. MAIN OUTCOMES AND MEASURES: Prespecified secondary analyses compared the effect on hHF, hHF or CV death, and hHF or all-cause death composite outcomes overall and in prespecified subgroups. Supportive analyses included total hHF events (first plus recurrent) and post-hHFdeath. Meta-analyses evaluated DPP4i effects on hHF and on hHF or CV death. RESULTS: Of 14 671 patients, 7332 were randomized to sitagliptin and 7339 to placebo. Hospitalization for HF occurred in 3.1% (n = 228) and 3.1% (n = 229) of the sitagliptin and placebo groups, respectively (unadjusted hazard ratio, 1.00; 95% CI, 0.83-1.19). There was also no difference in total hHF events between the sitagliptin (n = 345) and placebo (n = 347) groups (unadjusted hazard ratio, 1.00; 95% CI, 0.80-1.25). Post-hHF all-cause death was similar in the sitagliptin and placebo groups (29.8% vs 28.8%, respectively), as was CV death (22.4% vs 23.1%, respectively). No heterogeneity for the effect of sitagliptin on hHF was observed in subgroup analyses across 21 factors (P > .10 for all interactions). Meta-analysis of the hHF results from the 3 reported DPP4i CV outcomes trials revealed moderate heterogeneity (I2 = 44.9, P = .16). CONCLUSIONS AND RELEVANCE: Sitagliptin use does not affect the risk for hHF in T2DM, both overall and among high-risk patient subgroups. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00790205.
Authors: Stephen J Greene; Muthiah Vaduganathan; Muhammad Shahzeb Khan; George L Bakris; Matthew R Weir; Jonathan H Seltzer; Naveed Sattar; Darren K McGuire; James L Januzzi; Norman Stockbridge; Javed Butler Journal: J Am Coll Cardiol Date: 2018-03-10 Impact factor: 24.094
Authors: Marat Fudim; Jennifer White; Neha J Pagidipati; Yuliya Lokhnygina; Julio Wainstein; Jan Murin; Nayyar Iqbal; Peter Öhman; Renato D Lopes; Barry Reicher; Rury R Holman; Adrian F Hernandez; Robert J Mentz Journal: Circulation Date: 2019-09-23 Impact factor: 29.690