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Effect of linagliptin vs Placebo on major cardiovascular events in adults with type 2 Diabetes and high cardiovascular and renal risk The CARMELINA Randomized Clinical Trial

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datacite.rightshttp://purl.org/coar/access_right/c_14cb
dc.contributor.authorRosenstock, Julio
dc.contributor.authorPerkovic, Vlado
dc.contributor.authorJohansen, Odd Erik
dc.contributor.authorCooper, Mark E.
dc.contributor.authorKahn, Steven E.
dc.contributor.authorMarx, Nikolaus
dc.contributor.authorAlexander, John H.
dc.contributor.authorPencina, Michael
dc.contributor.authorToto, Robert D.
dc.contributor.authorWanner, Christoph
dc.contributor.authorZinman, Bernard
dc.contributor.authorJuergen Woerle, Hans
dc.contributor.authorBaanstra, David
dc.contributor.authorPfarr, Egon
dc.contributor.authorSchnaidt, Sven
dc.contributor.authorMeinicke, Thomas
dc.contributor.authorGeorge, Jyothis T.
dc.contributor.authorvon Eynatten, Maximilian
dc.contributor.authorMcGuire, Darren K.
dc.contributor.authorAroca-Martínez, Gustavo
dc.date.accessioned2024-09-30T22:25:23Z
dc.date.available2024-09-30T22:25:23Z
dc.date.issued2019
dc.description.abstractImportance Type 2 diabetes is associated with increased cardiovascular (CV) risk. Prior trials have demonstrated CV safety of 3 dipeptidyl peptidase 4 (DPP-4) inhibitors but have included limited numbers of patients with high CV risk and chronic kidney disease. Objective To evaluate the effect of linagliptin, a selective DPP-4 inhibitor, on CV outcomes and kidney outcomes in patients with type 2 diabetes at high risk of CV and kidney events. Design, Setting, and Participants Randomized, placebo-controlled, multicenter noninferiority trial conducted from August 2013 to August 2016 at 605 clinic sites in 27 countries among adults with type 2 diabetes, hemoglobin A1c of 6.5% to 10.0%, high CV risk (history of vascular disease and urine-albumin creatinine ratio [UACR] >200 mg/g), and high renal risk (reduced eGFR and micro- or macroalbuminuria). Participants with end-stage renal disease (ESRD) were excluded. Final follow-up occurred on January 18, 2018. Interventions Patients were randomized to receive linagliptin, 5 mg once daily (n = 3494), or placebo once daily (n = 3485) added to usual care. Other glucose-lowering medications or insulin could be added based on clinical need and local clinical guidelines. Main Outcomes and Measures Primary outcome was time to first occurrence of the composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. Criteria for noninferiority of linagliptin vs placebo was defined by the upper limit of the 2-sided 95% CI for the hazard ratio (HR) of linagliptin relative to placebo being less than 1.3. Secondary outcome was time to first occurrence of adjudicated death due to renal failure, ESRD, or sustained 40% or higher decrease in eGFR from baseline. Results Of 6991 enrollees, 6979 (mean age, 65.9 years; eGFR, 54.6 mL/min/1.73 m2; 80.1% with UACR >30 mg/g) received at least 1 dose of study medication and 98.7% completed the study. During a median follow-up of 2.2 years, the primary outcome occurred in 434 of 3494 (12.4%) and 420 of 3485 (12.1%) in the linagliptin and placebo groups, respectively, (absolute incidence rate difference, 0.13 [95% CI, −0.63 to 0.90] per 100 person-years) (HR, 1.02; 95% CI, 0.89-1.17; P < .001 for noninferiority). The kidney outcome occurred in 327 of 3494 (9.4%) and 306 of 3485 (8.8%), respectively (absolute incidence rate difference, 0.22 [95% CI, −0.52 to 0.97] per 100 person-years) (HR, 1.04; 95% CI, 0.89-1.22; P = .62). Adverse events occurred in 2697 (77.2%) and 2723 (78.1%) patients in the linagliptin and placebo groups; 1036 (29.7%) and 1024 (29.4%) had 1 or more episodes of hypoglycemia; and there were 9 (0.3%) vs 5 (0.1%) events of adjudication-confirmed acute pancreatitis. Conclusions and Relevance Among adults with type 2 diabetes and high CV and renal risk, linagliptin added to usual care compared with placebo added to usual care resulted in a noninferior risk of a composite CV outcome over a median 2.2 years.eng
dc.format.mimetypepdf
dc.identifier.citationCARMELINA Investigators (2019). Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk The CARMELINA Randomized Clinical Trial. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 321(1), 69-79. https://doi.org/10.1001/jama.2018.18269eng
dc.identifier.doidoi:10.1001/jama.2018.18269
dc.identifier.issn00987484 (Impreso)
dc.identifier.issn15383598 (Electrónico)
dc.identifier.urihttps://hdl.handle.net/20.500.12442/15719
dc.identifier.urlhttps://www.webofscience.com/wos/woscc/full-record/WOS:000455606000016
dc.language.isoeng
dc.publisherAmerican Medical Associationeng
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United Stateseng
dc.rights.accessrightsinfo:eu-repo/semantics/closedAccess
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/
dc.sourceJAMAeng
dc.sourceVol. 321 No. 1 Año 2019spa
dc.subject.keywordsHEART-FAILUREeng
dc.subject.keywordsKIDNEY-DISEASEeng
dc.subject.keywordsGFR DECLINEeng
dc.subject.keywordsEND-POINTeng
dc.subject.keywordsOUTCOMESeng
dc.subject.keywordsSITAGLIPTINeng
dc.subject.keywordsDEATHeng
dc.subject.keywordsSAXAGLIPTINeng
dc.subject.keywordsMORTALITYeng
dc.subject.keywordsCKDeng
dc.titleEffect of linagliptin vs Placebo on major cardiovascular events in adults with type 2 Diabetes and high cardiovascular and renal risk The CARMELINA Randomized Clinical Trialeng
dc.type.driverinfo:eu-repo/semantics/article
dc.type.spaArtículo científico
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