Thiazide use can lead to stroke in type 2 diabetes patients

Japan: The use of thiazides may increase the risk of major cardiovascular events (MACE), particularly stroke, in type 2 diabetes patients having a well-controlled blood pressure (BP), finds an analysis of data from the ACCORD and ACCORDION studies. This is a startling finding as thiazides have been used for decades as a common treatment for high blood pressure and congestive heart failure.

In the present study, published in the AHA journal Hypertension, thiazide use was associated with an increased risk of stroke in type 2 diabetic patients, specifically those receiving intensive BP control.

Evidence regarding the efficacy and safety of thiazides in patients with well-controlled and relatively low blood pressure (BP) is lacking. The study by Tetsuro Tsujimoto and Hiroshi Kajio, from National Center for Global Health and Medicine, Tokyo, Japan, aimed to assess whether thiazide use is effective and safe in type 2 diabetic patients with well-controlled BP and whether intensive BP control leads to a decreased risk of cardiovascular events depending on thiazide use.

For the purpose, the researchers performed an observational cohort study using data from the ACCORD study (Action to Control Cardiovascular Risk in Diabetes). They identified 10,2551 high-risk type 2 diabetics in the current analysis who were either 40 to 79 years old with cardiovascular disease or 55 to 79 with anatomic evidence of significant atherosclerosis, albuminuria, left ventricular hypertrophy, or at least 2 additional cardiovascular disease risk factors.

Exclusion criteria for the current analysis included frequent or serious hypoglycemia, refusal to receive home glucose monitoring or insulin injections, serum creatinine level less than 1.5 mg/dL, or any other serious illness. BMI for patients included in the study needed to be greater than 45.

The primary outcome was major adverse cardiovascular events (MACE), which was a composite endpoint including cardiovascular death, myocardial infarction, and stroke.

A cohort of 10,011 patients were included in the final analysis, of which 7242 were not taking thiazides and 2769 were taking thiazides. Mean systolic BP in patients not taking thiazides was 135.7 mmHg and 137.2 mmHg among those receiving thiazides.

Key findings of the study include:

• Thiazide use was associated with older age, a higher proportion of women, a lower proportion of white patients, lower current smoking rate, greater BMI, more complications due to hypertension and stroke, and fewer complications due to coronary artery disease and heart failure.


• During the follow-up period, which lasted a mean of 7.7 years, 1776 patients experienced MACE. Of the 1776 patients, 1262 were not taking thiazides and 514 were taking thiazides.


• In the entire study population, the event rate per 1000 person-years for MACE among patients taking thiazides was 24.2 compared to 22.5 in those not receiving thiazides.


• After multivariable adjustments, the risk of MACE was found to be significantly higher in those taking thiazides than in those not taking thiazides.


• Risk of MACE in patients reviving intensive BP control was significantly higher in those taking thiazides than in those not taking thiazides.


• Risk of stroke was also significantly higher in patients taking thiazides than in those not taking thiazides.

"Our findings indicate that thiazide use may increase the risk of stroke in type 2 diabetic patients with relatively low BP," concluded the authors.

More Information: "Thiazide Use and Cardiovascular Events in Type 2 Diabetic Patients With Well-Controlled Blood Pressure" published in the AHA journal Hypertension.

DOI: https://doi.org/10.1161/HYPERTENSIONAHA.119.13886

Journal Information: Hypertension