Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic)

a multinational observational analysis

Kåre I. Birkeland, Marit E. Jørgensen, Bendix Carstensen, Frederik Persson, Hanne L. Gulseth, Marcus Thuresson, Peter Fenici, David Nathanson, Thomas Nyström, Jan W. Eriksson, Johan Bodegård*, Anna Norhammar

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Background In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. Methods CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0·9 (SD 4·1) years (80 669 patient-years) and mean age of 61 (12·0) years; 40% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of cardiovascular mortality (HR 0·53 [95% CI 0·40–0·71]), major adverse cardiovascular events (0·78 [0·69–0·87]), and hospital events for heart failure (0·70 [0·61–0·81]; p<0·0001 for all). We did not identify significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs for non-fatal myocardial infarction, non-fatal stroke, or atrial fibrillation. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with a decreased risk of severe hypoglycaemia (HR 0·76 [0·65–0·90]; p=0·001). For cardiovascular mortality, the differences were similar for the 25% of individuals with cardiovascular disease at baseline and those without (HR 0·60 [0·42–0·85] vs 0·55 [0·34–0·90]), while for major adverse cardiovascular events the HR in the group with cardiovascular disease at baseline was 0·70 (0·59–0·83) versus 0·90 (0·76–1·07) in the group without. Interpretation In a population of patients with type 2 diabetes and a broad cardiovascular risk profile, SGLT2 inhibitor use was associated with reduced cardiovascular disease and cardiovascular mortality compared with use of other glucose-lowering drugs—a finding consistent with the results of clinical trials in patients at high cardiovascular risk. Funding AstraZeneca.

OriginalsprogEngelsk
TidsskriftThe Lancet Diabetes and Endocrinology
Vol/bind5
Udgave nummer9
Sider (fra-til)709-717
ISSN2213-8587
DOI
StatusUdgivet - 2017

Fingeraftryk

Type 2 Diabetes Mellitus
Pharmaceutical Preparations
Hypoglycemia
Propensity Score
Denmark
Norway
Proportional Hazards Models
Population
Prescriptions
Inpatients
Cause of Death
Outpatients
Clinical Trials
Incidence

Citer dette

Birkeland, Kåre I. ; Jørgensen, Marit E. ; Carstensen, Bendix ; Persson, Frederik ; Gulseth, Hanne L. ; Thuresson, Marcus ; Fenici, Peter ; Nathanson, David ; Nyström, Thomas ; Eriksson, Jan W. ; Bodegård, Johan ; Norhammar, Anna. / Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic) : a multinational observational analysis. I: The Lancet Diabetes and Endocrinology. 2017 ; Bind 5, Nr. 9. s. 709-717.
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abstract = "Background In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. Methods CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0·9 (SD 4·1) years (80 669 patient-years) and mean age of 61 (12·0) years; 40{\%} (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25{\%} (22 686 of 91 320). 94{\%} of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5{\%} for empagliflozin, and 1{\%} for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of cardiovascular mortality (HR 0·53 [95{\%} CI 0·40–0·71]), major adverse cardiovascular events (0·78 [0·69–0·87]), and hospital events for heart failure (0·70 [0·61–0·81]; p<0·0001 for all). We did not identify significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs for non-fatal myocardial infarction, non-fatal stroke, or atrial fibrillation. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with a decreased risk of severe hypoglycaemia (HR 0·76 [0·65–0·90]; p=0·001). For cardiovascular mortality, the differences were similar for the 25{\%} of individuals with cardiovascular disease at baseline and those without (HR 0·60 [0·42–0·85] vs 0·55 [0·34–0·90]), while for major adverse cardiovascular events the HR in the group with cardiovascular disease at baseline was 0·70 (0·59–0·83) versus 0·90 (0·76–1·07) in the group without. Interpretation In a population of patients with type 2 diabetes and a broad cardiovascular risk profile, SGLT2 inhibitor use was associated with reduced cardiovascular disease and cardiovascular mortality compared with use of other glucose-lowering drugs—a finding consistent with the results of clinical trials in patients at high cardiovascular risk. Funding AstraZeneca.",
author = "Birkeland, {K{\aa}re I.} and J{\o}rgensen, {Marit E.} and Bendix Carstensen and Frederik Persson and Gulseth, {Hanne L.} and Marcus Thuresson and Peter Fenici and David Nathanson and Thomas Nystr{\"o}m and Eriksson, {Jan W.} and Johan Bodeg{\aa}rd and Anna Norhammar",
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doi = "10.1016/S2213-8587(17)30258-9",
language = "English",
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journal = "The Lancet Diabetes & Endocrinology",
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Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic) : a multinational observational analysis. / Birkeland, Kåre I.; Jørgensen, Marit E.; Carstensen, Bendix; Persson, Frederik; Gulseth, Hanne L.; Thuresson, Marcus; Fenici, Peter; Nathanson, David; Nyström, Thomas; Eriksson, Jan W.; Bodegård, Johan; Norhammar, Anna.

I: The Lancet Diabetes and Endocrinology, Bind 5, Nr. 9, 2017, s. 709-717.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Cardiovascular mortality and morbidity in patients with type 2 diabetes following initiation of sodium-glucose co-transporter-2 inhibitors versus other glucose-lowering drugs (CVD-REAL Nordic)

T2 - a multinational observational analysis

AU - Birkeland, Kåre I.

AU - Jørgensen, Marit E.

AU - Carstensen, Bendix

AU - Persson, Frederik

AU - Gulseth, Hanne L.

AU - Thuresson, Marcus

AU - Fenici, Peter

AU - Nathanson, David

AU - Nyström, Thomas

AU - Eriksson, Jan W.

AU - Bodegård, Johan

AU - Norhammar, Anna

PY - 2017

Y1 - 2017

N2 - Background In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. Methods CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0·9 (SD 4·1) years (80 669 patient-years) and mean age of 61 (12·0) years; 40% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of cardiovascular mortality (HR 0·53 [95% CI 0·40–0·71]), major adverse cardiovascular events (0·78 [0·69–0·87]), and hospital events for heart failure (0·70 [0·61–0·81]; p<0·0001 for all). We did not identify significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs for non-fatal myocardial infarction, non-fatal stroke, or atrial fibrillation. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with a decreased risk of severe hypoglycaemia (HR 0·76 [0·65–0·90]; p=0·001). For cardiovascular mortality, the differences were similar for the 25% of individuals with cardiovascular disease at baseline and those without (HR 0·60 [0·42–0·85] vs 0·55 [0·34–0·90]), while for major adverse cardiovascular events the HR in the group with cardiovascular disease at baseline was 0·70 (0·59–0·83) versus 0·90 (0·76–1·07) in the group without. Interpretation In a population of patients with type 2 diabetes and a broad cardiovascular risk profile, SGLT2 inhibitor use was associated with reduced cardiovascular disease and cardiovascular mortality compared with use of other glucose-lowering drugs—a finding consistent with the results of clinical trials in patients at high cardiovascular risk. Funding AstraZeneca.

AB - Background In patients with type 2 diabetes and a high cardiovascular risk profile, the sodium-glucose co-transporter-2 (SGLT2) inhibitors empagliflozin and canagliflozin have been shown to lower cardiovascular morbidity and mortality. Using real-world data from clinical practice, we aimed to compare cardiovascular mortality and morbidity in new users of SGLT2 inhibitors versus new users of other glucose-lowering drugs, in a population with a broad cardiovascular risk profile. Methods CVD-REAL Nordic was an observational analysis of individual patient-level data from the Prescribed Drug Registers, Cause of Death Registers, and National Patient Registers in Denmark, Norway, and Sweden. All patients who filled a prescription for glucose-lowering drugs between 2012 and 2015 were included and followed up until Dec 31, 2015. Patients were divided into new users of SGLT2 inhibitors and new users of other glucose-lowering drugs. Each SGLT2 inhibitor user was matched with three users of other glucose-lowering drugs by use of propensity scores. Hazard ratios (HRs) were estimated by country (Cox survival model) and weighted averages were calculated. Cardiovascular outcomes investigated were cardiovascular mortality, major adverse cardiovascular events (cardiovascular mortality, myocardial infarction, and ischaemic or haemorrhagic stroke), hospital events for heart failure (inpatient or outpatient visit with a primary diagnosis of heart failure), non-fatal myocardial infarction, non-fatal stroke, and atrial fibrillation. We also assessed incidence of severe hypoglycaemia. Findings Matched SGLT2 inhibitor (n=22 830) and other glucose-lowering drug (n=68 490) groups were well balanced at baseline, with a mean follow-up of 0·9 (SD 4·1) years (80 669 patient-years) and mean age of 61 (12·0) years; 40% (36 362 of 91 320) were women and prevalence of cardiovascular disease was 25% (22 686 of 91 320). 94% of the total SGLT2 inhibitor exposure time was for use of dapagliflozin, with 5% for empagliflozin, and 1% for canagliflozin. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with decreased risk of cardiovascular mortality (HR 0·53 [95% CI 0·40–0·71]), major adverse cardiovascular events (0·78 [0·69–0·87]), and hospital events for heart failure (0·70 [0·61–0·81]; p<0·0001 for all). We did not identify significant differences between use of SGLT2 inhibitors and use of other glucose-lowering drugs for non-fatal myocardial infarction, non-fatal stroke, or atrial fibrillation. Compared with other glucose-lowering drugs, use of SGLT2 inhibitors was associated with a decreased risk of severe hypoglycaemia (HR 0·76 [0·65–0·90]; p=0·001). For cardiovascular mortality, the differences were similar for the 25% of individuals with cardiovascular disease at baseline and those without (HR 0·60 [0·42–0·85] vs 0·55 [0·34–0·90]), while for major adverse cardiovascular events the HR in the group with cardiovascular disease at baseline was 0·70 (0·59–0·83) versus 0·90 (0·76–1·07) in the group without. Interpretation In a population of patients with type 2 diabetes and a broad cardiovascular risk profile, SGLT2 inhibitor use was associated with reduced cardiovascular disease and cardiovascular mortality compared with use of other glucose-lowering drugs—a finding consistent with the results of clinical trials in patients at high cardiovascular risk. Funding AstraZeneca.

U2 - 10.1016/S2213-8587(17)30258-9

DO - 10.1016/S2213-8587(17)30258-9

M3 - Journal article

VL - 5

SP - 709

EP - 717

JO - The Lancet Diabetes & Endocrinology

JF - The Lancet Diabetes & Endocrinology

SN - 2213-8587

IS - 9

ER -