TY - JOUR

T1 - Early glycemic changes after initiation of oral anti-diabetic medication and risk of major adverse cardiovascular events

T2 - results from a large primary care population of patients with type 2 diabetes

AU - Ghouse, Jonas

AU - Blanche, Paul

AU - Skov, Morten W

AU - Lind, Bent

AU - Vaag, Allan

AU - Kanters, Jørgen K

AU - Svendsen, Jesper H

AU - Køber, Lars

AU - Olesen, Morten S

AU - Gerds, Thomas A

AU - Holst, Anders G

AU - Nielsen, Jonas B

N1 - © Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2020. For permissions, please email: journals.permissions@oup.com.

PY - 2021

Y1 - 2021

N2 - AIMS: To determine the risk of major cardiovascular events (MACE) and death, associated with an early large and rapid decline in HbA1C following first time initiation of an oral antidiabetic drug (OAD).METHODS AND RESULTS: We included 10,518 primary care patients with T2D, who initiated an OAD for the first time. For each individual, we measured a decline in HbA1C, as the difference between the pre-treatment HbA1C (within 3 months before OAD initiation) and the post-treatment HbA1C (within 1.5-4.5 months after OAD initiation), divided by the time between the two measurements. The decline was reported in mmol/mol change per 3 months in HbA1C and categorized by the median decline into levels of steep (≥ 9 mmol/mol [≥ 0.8%]) and flat decline (< 9 mmol/mol per 3 mo. [< 0.8%]). Pre-treatment HbA1C was categorized by the median, into levels of low (48-62 mmol/mol) and high (> 62 mmol/mol). Multiple Cox regression was used to study the effect of decline (steep vs. flat) on the outcome hazard rates separately for patients with low and high pre-treatment HbA1C. Analyses were adjusted for age, sex, traditional cardiovascular risk factors, severe comorbidities, and concomitant medication treatment. During a median follow-up time of 7.7 years, 1,625 developed MACE and 2,323 died. We found that a steep decline vs. a flat decline was significantly associated with a decreased hazard for MACE, both in individuals with high (HR 0.81; 95% CI 0.69-0.94; P = 0.005) and low pre-treatment HbA1C (HR 0.79; 95% CI 0.66-0.96; P = 0.015). The hazard of MACE was more pronounced on the short-term vs. long-term in individuals with high pre-treatment HbA1C. We found no significant association between combinations of pre-treatment HbA1C and decline categories and hazard of all-cause mortality. However, a combination of a low pre-treatment HbA1C and steep decline was associated with increased 1-year mortality (HR 1.52; 95% CI 1.00-2.29; P = 0.048) and hypoglycemia (HR 1.82; 95% CI 1.11-2.98; P = 0.017).CONCLUSION: A combination of a high pre-treatment HbA1C and a steep decline in HbA1C was associated with a decreased short-term risk of MACE. A low pre-treatment HbA1C and a steep decline was associated with a long-term reduced risk of MACE, but a short-term increased risk of death and hypoglycaemia.

AB - AIMS: To determine the risk of major cardiovascular events (MACE) and death, associated with an early large and rapid decline in HbA1C following first time initiation of an oral antidiabetic drug (OAD).METHODS AND RESULTS: We included 10,518 primary care patients with T2D, who initiated an OAD for the first time. For each individual, we measured a decline in HbA1C, as the difference between the pre-treatment HbA1C (within 3 months before OAD initiation) and the post-treatment HbA1C (within 1.5-4.5 months after OAD initiation), divided by the time between the two measurements. The decline was reported in mmol/mol change per 3 months in HbA1C and categorized by the median decline into levels of steep (≥ 9 mmol/mol [≥ 0.8%]) and flat decline (< 9 mmol/mol per 3 mo. [< 0.8%]). Pre-treatment HbA1C was categorized by the median, into levels of low (48-62 mmol/mol) and high (> 62 mmol/mol). Multiple Cox regression was used to study the effect of decline (steep vs. flat) on the outcome hazard rates separately for patients with low and high pre-treatment HbA1C. Analyses were adjusted for age, sex, traditional cardiovascular risk factors, severe comorbidities, and concomitant medication treatment. During a median follow-up time of 7.7 years, 1,625 developed MACE and 2,323 died. We found that a steep decline vs. a flat decline was significantly associated with a decreased hazard for MACE, both in individuals with high (HR 0.81; 95% CI 0.69-0.94; P = 0.005) and low pre-treatment HbA1C (HR 0.79; 95% CI 0.66-0.96; P = 0.015). The hazard of MACE was more pronounced on the short-term vs. long-term in individuals with high pre-treatment HbA1C. We found no significant association between combinations of pre-treatment HbA1C and decline categories and hazard of all-cause mortality. However, a combination of a low pre-treatment HbA1C and steep decline was associated with increased 1-year mortality (HR 1.52; 95% CI 1.00-2.29; P = 0.048) and hypoglycemia (HR 1.82; 95% CI 1.11-2.98; P = 0.017).CONCLUSION: A combination of a high pre-treatment HbA1C and a steep decline in HbA1C was associated with a decreased short-term risk of MACE. A low pre-treatment HbA1C and a steep decline was associated with a long-term reduced risk of MACE, but a short-term increased risk of death and hypoglycaemia.

U2 - 10.1093/ehjcvp/pvaa072

DO - 10.1093/ehjcvp/pvaa072

M3 - Journal article

C2 - 32614428

VL - 7

SP - 486

EP - 495

JO - European Heart Journal - Cardiovascular Pharmacotherapy

JF - European Heart Journal - Cardiovascular Pharmacotherapy

SN - 2055-6837

IS - 6

ER -