Author + information
- Received May 14, 2017
- Revision received August 1, 2017
- Accepted August 3, 2017
- Published online December 25, 2017.
- John J.V. McMurray, MDa,∗ (, )
- Piotr Ponikowski, MDb,
- Geremia B. Bolli, MDc,
- Valentina Lukashevich, MDd,
- Plamen Kozlovski, MDe,
- Wolfgang Kothny, MDe,
- James D. Lewsey, PhDf,
- Henry Krum, MDg,
- for the VIVIDD Trial Committees and Investigators
- aBritish Heart Foundation Cardiovascular Research Centre, University of Glasgow, Glasgow, Scotland, United Kingdom
- bDepartment of Heart Diseases, Wroclaw Medical University, Wroclaw, Poland
- cDepartment of Medicine, Perugia University Medical School, Perugia, Italy
- dNovartis Pharmaceuticals Corp., East Hanover, New Jersey
- eNovartis Pharma AG, Basel, Switzerland
- fInstitute of Health and Wellbeing, University of Glasgow, Glasgow, Scotland, United Kingdom
- gMonash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Victoria, Australia
- ↵∗Address for correspondence:
Prof. John J.V. McMurray, Institute of Cardiovascular and Medical Sciences, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 26 University Place, Glasgow G12 8TA, United Kingdom.
Objectives This study sought to examine the safety of the dipeptidyl peptidase-4 inhibitor, vildagliptin, in patients with heart failure and reduced ejection fraction.
Background Many patients with type 2 diabetes mellitus have heart failure and it is important to know about the safety of new treatments for diabetes in these individuals.
Methods Patients 18 to 85 years of age with type 2 diabetes and heart failure (New York Heart Association functional class I to III and left ventricular ejection fraction [LVEF] <0.40) were randomized to 52 weeks treatment with vildagliptin 50 mg twice daily (50 mg once daily if treated with a sulfonylurea) or matching placebo. The primary endpoint was between-treatment change from baseline in echocardiographic LVEF using a noninferiority margin of −3.5%.
Results A total of 254 patients were randomly assigned to vildagliptin (n = 128) or placebo (n = 126). Baseline LVEF was 30.6 ± 6.8% in the vildagliptin group and 29.6 ± 7.7% in the placebo group. The adjusted mean change in LVEF was 4.95 ± 1.25% in vildagliptin treated patients and 4.33 ± 1.23% in placebo treated patients, a difference of 0.62 (95% confidence interval [CI]: −2.21 to 3.44; p = 0.667). This difference met the predefined noninferiority margin of −3.5%. Left ventricular end-diastolic and end-systolic volumes increased more in the vildagliptin group by 17.1 ml (95% CI: 4.6 to 29.5 ml; p = 0.007) and 9.4 ml (95% CI: −0.49 to 19.4 ml; p = 0.062), respectively. Decrease in hemoglobin A1c from baseline to 16 weeks, the main secondary endpoint, was greater in the vildagliptin group: −0.62% (95% CI: −0.93 to −0.30%; p < 0.001; −6.8 mmol/mol; 95% CI: −10.2 to −3.3 mmol/mol).
Conclusions Compared with placebo, vildagliptin had no major effect on LVEF but did lead to an increase in left ventricular volumes, the cause and clinical significance of which is unknown. More evidence is needed regarding the safety of dipeptidyl peptidase-4 inhibitors in patients with heart failure and left ventricular systolic dysfunction. (Effect of Vildagliptin on Left Ventricular Function in Patients With Type 2 Diabetes and Congestive Heart Failure; NCT00894868)
This trial was funded by Novartis. Dr. Lukashevich holds equity shares in and is an employee of Novartis. Drs. Kozlovski and Kothny are employees of Novartis. Dr. Bolli is a consultant to and has been paid for giving lectures for Sanofi-Aventis and Menarini. Dr. Ponikowski is a consultant for Novartis and Boehringer Ingelheim. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Dr. Krum is deceased.
- Received May 14, 2017.
- Revision received August 1, 2017.
- Accepted August 3, 2017.
- 2018 American College of Cardiology Foundation