Gian Paolo Fadini1, Angelo Avogaro2, Luca Degli Esposti3, Pierluigi Russo4, Stefania Saragoni3, Stefano Buda3, Giuseppe Rosano5, Sergio Pecorelli6, Luca Pani4. 1. Department of Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy. 2. Department of Medicine, University of Padova, Via Giustiniani, 2, 35128 Padova, Italy angelo.avogaro@unipd.it. 3. CliCon S.r.l. Health, Economics and Outcomes Research, 48121 Ravenna, Italy. 4. Italian Medicines Agency, 00187 Rome, Italy. 5. Italian Medicines Agency, 00187 Rome, Italy Centro di Ricerca Clinica e Sperimentale, IRCCS San Raffaele Roma IN, Roma, Italy Cardiovascular and Cell Sciences Research Institute, St. George's, University of London, London, UK. 6. Italian Medicines Agency, 00187 Rome, Italy University of Brescia, 25121 Brescia, Italy.
Abstract
AIMS: Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between HF risk and use of sulphonylureas, DPP-4i, and glitazones. METHODS AND RESULTS: We extracted data on patients with type 2 diabetes who initiated treatment with DPP-4i, thiazolidinediones, or sulphonylureas alone or in combination with metformin during an accrual time of 2 years. The endpoint was hospitalization for HF (HHF) occurring after the first 6 months of therapy, and the observation was extended for up to 4 years. A total of 127 555 patients were included, of whom 14.3% were on DPP-4i, 72.5% on sulphonylurea, 13.2% on thiazolidinediones, with average 70.7% being on metformin as combination therapy. Patients in the three groups differed significantly for baseline characteristics: age, sex, Charlson index, concurrent medications, and previous cardiovascular events. During an average 2.6-year follow-up, after adjusting for measured confounders, use of DPP-4i was associated with a reduced risk of HHF compared with sulphonylureas [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.62-0.97; P = 0.026]. After propensity matching, the analysis was restricted to 39 465 patients, and the use of DPP-4i was still associated with a lower risk of HHF (HR 0.70; 95% CI 0.52-0.94; P = 0.018). CONCLUSION: In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas. Published on behalf of the European Society of Cardiology. All rights reserved.
AIMS: Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between HF risk and use of sulphonylureas, DPP-4i, and glitazones. METHODS AND RESULTS: We extracted data on patients with type 2 diabetes who initiated treatment with DPP-4i, thiazolidinediones, or sulphonylureas alone or in combination with metformin during an accrual time of 2 years. The endpoint was hospitalization for HF (HHF) occurring after the first 6 months of therapy, and the observation was extended for up to 4 years. A total of 127 555 patients were included, of whom 14.3% were on DPP-4i, 72.5% on sulphonylurea, 13.2% on thiazolidinediones, with average 70.7% being on metformin as combination therapy. Patients in the three groups differed significantly for baseline characteristics: age, sex, Charlson index, concurrent medications, and previous cardiovascular events. During an average 2.6-year follow-up, after adjusting for measured confounders, use of DPP-4i was associated with a reduced risk of HHF compared with sulphonylureas [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.62-0.97; P = 0.026]. After propensity matching, the analysis was restricted to 39 465 patients, and the use of DPP-4i was still associated with a lower risk of HHF (HR 0.70; 95% CI 0.52-0.94; P = 0.018). CONCLUSION: In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas. Published on behalf of the European Society of Cardiology. All rights reserved.
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