Treatment of type 2 diabetes with rosiglitazone associated with increased risk of cardiovascular events among older adults

Although several studies have demonstrated a potentially increased risk of cardiovascular (CV) events associated with the use of thiazolidinediones (TZDs), this risk has not been well researched in subpopulations. In this study, which focused on patients aged ≥66 years with type 2 diabetes, the incidence of congestive heart failure (CHF), acute myocardial infarction (AMI), and mortality was increased among patients who were treated with TZDs compared with other antidiabetic agents. These increased risks were limited to rosiglitazone.

This nested case-control analysis of a retrospective cohort study was published in the Journal of the American Medical Association (JAMA). It included 159,026 patients who were registered with the Ontario (Canada) Diabetes Database and had been treated with ≥1 oral hypoglycemic agent from 2002 to 2005. Patients who were treated with insulin in the year before entering the cohort were excluded from the study, but patients who began insulin treatment during the follow-up period were included. The median follow-up was 3.8 years. The primary outcome measure was a first hospital visit for CHF. Secondary outcomes were a hospital visit for AMI and all-cause mortality.

During the follow-up period, 7.9% of patients experienced a first hospital visit for CHF, 7.9% of patients experienced a hospital visit for AMI, and 19% of patients died. Each patient who experienced an event was matched with ≤5 control patients. All RRs were adjusted for past TZD use, exposure to other hypoglycemic drugs, and potential confounders (eg, established risk factors for each outcome, previous use of oral hypoglycemic agents, sociodemographic factors, and concomitant use of CV drugs).

TZD monotherapy was associated with a significantly greater risk of AMI (adjusted RR=1.40; 95% CI, 1.05–1.86; P=.02) compared with other oral hypoglycemic combination therapies. This risk was also associated only with the use of rosiglitazone (adjusted RR=1.76; 95% CI, 1.27–2.44; P<.001).

The risk of death was also higher among patients treated with TZDs compared with patients treated with other oral antidiabetic combination therapies. This increased risk was associated with TZD monotherapy (adjusted RR=1.29; 95% CI, 1.02–1.62; P=.03) and TZD combination therapy (adjusted RR=1.24; 95% CI, 1.11–1.39; P<.001). This risk, like that of CHF and AMI, was also limited to use of rosiglitazone monotherapy (adjusted RR=1.47; 95% CI, 1.12–1.93; P=.005) and combination therapy (adjusted RR=1.26; 95% CI, 1.10–1.44; P<.001).

SOURCE

Lipscombe LL, Gomes T, Lévesque LE, Hux JE, Juurlink DN, Alter DA. Thiazolidinediones and cardiovascular outcomes in older patients with diabetes. JAMA. 2007;298:2634–2643.