Physicians' Academy for Cardiovascular Education

TZD reduces ACS risk in insulin-resistant non-diabetic patients with prior stroke or TIA

Cardiac Outcomes After Ischemic Stroke or TIA: Effects of Pioglitazone in Patients with Insulin Resistance Without Diabetes

Literature - Young LH, Viscoli CM, Curtis JP, et al. - Circulation 2017 Feb 28, Epub ahead of print


Epidemiological research showed that insulin resistance is associated with an increased risk for both myocardial infarction (MI) and stroke [1-3]. Moreover, it has recently been reported that insulin resistance was present in 63% of patients without diabetes after a recent ischemic stroke or transient ischemic attack (TIA) [4]. It seems therefore interesting whether intervention of insulin resistance, eg. with thiazolidinediones (TZDs), reduces cardiovascular (CV) risk in patients without diabetes.

The PROactive trial showed that pioglitazone, a TZD, reduced the risk for a secondary outcome of CV mortality and non-fatal stroke by 28% in diabetes patients with a history of stroke [5]. This research was extended by the insulin resistance intervention in stroke (IRIS) trial, in which effectiveness of pioglitazone was shown in patients with insulin resistance non-diabetic patients that recently experienced a stroke or TIA [4].

As pioglitazone has been shown to harbour coronary artery anti-atherosclerotic and possibly vascular stabilizing potential, the effect of pioglitazone on the incidence of acute coronary syndrome (ACS) was studied in a secondary analysis of the IRIS study with insulin resistant non-diabetic patients (n=3876). For this analysis, insulin resistance was defined by HOMA-IR >3.0.

Main results


In this secondary analysis of the IRIS trial, pioglitazone reduced the risk of ACS, particularly the most serious events, in insulin-resistant patients without diabetes after ischemic stroke or TIA. This was most evident for spontaneous type I MI, suggesting coronary artery plaque stabilization, and pioglitazone was more effective in preventing more clinically significant MIs.


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Find this article online at Circulation