Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events.
Cardiovasc Diabetol
; 14: 57, 2015 May 21.
Article
em En
| MEDLINE
| ID: mdl-25990013
ABSTRACT
BACKGROUND:
The cardiovascular (CV) safety of linagliptin was evaluated in subjects with type 2 diabetes (T2DM).METHODS:
Pre-specified patient-level pooled analysis of all available double-blind, randomized, controlled trials, ≥ 12 weeks' duration (19 trials, 9459 subjects) of linagliptin versus placebo/active treatment. Primary end point composite of prospectively adjudicated CV death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for unstable angina (4P-MACE). Hospitalization for congestive heart failure (CHF) was also evaluated; adjudication of CHF was introduced during the phase 3 program (8 trials; 3314 subjects). 4P-MACE was assessed in placebo-controlled trials (subgroup of 18 trials; 7746 subjects). Investigator-reported events suggestive of CHF from 24 placebo-controlled trials (including trials <12 weeks' duration, 8778 subjects) were also analyzed.RESULTS:
5847 patients received linagliptin (5 mg 5687, 10 mg 160) and 3612 comparator (glimepiride 775, voglibose 162, placebo 2675); cumulative exposure, 4421.3 and 3254.7 patient-years, respectively. 4P-MACE incidence rates 13.4 per 1000 patient-years, linagliptin (60 events), 18.9, total comparators (62 events); overall hazard ratio (HR), 0.78 (95% confidence interval [CI], 0.55-1.12). HR for adjudicated hospitalization for CHF (n = 21) 1.04 (0.43-2.47). For placebo-controlled trials, 4P-MACE incidence rates 14.9 per 1000 patient-years, linagliptin (43 events), 16.4, total comparators (29 events); overall HR, 1.09 (95% CI, 0.68-1.75). Occurrence of investigator-reported events suggestive of CHF was low for linagliptin- (26 events, 0.5%; serious 16 events, 0.3%) and placebo-treated (8 events, 0.2%; serious 6 events, 0.2%) patients.CONCLUSIONS:
Linagliptin is not associated with increased CV risk versus pooled active comparators or placebo in patients with T2DM.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Cardiovasculares
/
Acidente Vascular Cerebral
/
Diabetes Mellitus Tipo 2
/
Inibidores da Dipeptidil Peptidase IV
/
Linagliptina
/
Insuficiência Cardíaca
/
Angina Instável
/
Infarto do Miocárdio
Tipo de estudo:
Clinical_trials
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Cardiovasc Diabetol
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
ENDOCRINOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos