Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Decreasing Risk of MI After Ischemic Stroke

Circulation; ePub 2017 Feb 28; Young, Viscoli, et al

Among patients with insulin resistance without diabetes, pioglitazone reduced the risk for acute coronary syndromes (ACS) after a recent cerebrovascular event, especially in preventing spontaneous type 1 myocardial infarctions (MI), a recent study found. This secondary analysis compared the effects of pioglitazone to placebo, on ACS among 3,876 participants in the Insulin Resistance Intervention after Stroke (IRIS) trial (mean age 63 years, 89% white, and 12% with history of coronary artery disease). Researchers found:

  • 225 ACS events, including 141 MIs (28 with ST-segmented elevation) and 84 episodes of unstable angina occurred over a median follow-up of 4.8 years.
  • Pioglitazone reduced the risk of ACS (HR, 0.71) and type 1 MI (HR, 0.62), but not type 2 MI (HR, 1.05). Type 1 is a spontaneous MI related to ischemia from a primary coronary event such as plaque rupture or thrombotic occlusion. Type 2 is secondary to ischemia from a supply-and-demand mismatch.
  • Similarly, pioglitazone reduced the risk of large MIs with serum troponin >100x ULN (HR, 0.44), but not smaller MIs.


Young LH, Viscoli CM, Curtis JP, et al. Cardiac outcomes after ischemic stroke or TIA: Effects of pioglitazone in patients with insulin resistance without diabetes. [Published online ahead of print February 28, 2017]. Circulation. doi:10.1161/CIRCULATIONAHA.116.024863.


Insulin resistance is present in over half of patients without diabetes who have a transient ischemic attack (TIA).1 Thiazolidinediones (TZDs) improve insulin resistance and vascular stability, and the PROactive trial found that pioglitazone reduced the risk for cardiovascular mortality and nonfatal stroke or MI by 28% (p=0.047) in the subgroup of patients with diabetes who entered with a history of stroke.² The Insulin Resistance Intervention in Stroke (IRIS) trial, which included patients who did not have diabetes, but who had insulin resistance, with a TIA or small stroke, showed a reduced risk for the primary outcome of fatal or nonfatal stroke or MI. Risk decreased by 24% (p=0.007). The current analysis of the IRIS data shows that pioglitazone, in addition to the treatment that the patients were already receiving (statins, antiplatelet agents, and antihypertensive agents), reduced the risk for acute coronary syndromes for patients with insulin resistance after a cerebrovascular event. This study supports the use of pioglitazone to decrease CV risk after a TIA or minor stroke in patients with insulin resistance, prediabetes, and diabetes. —Neil Skolnik, MD

  1. Kernan WN, Viscoli CM, Furie KL, et al, for the IRIS Trial investigators. Pioglitazone after ischemic stroke or transient ischemic attack. N Engl J Med. 2016;374:1321-1331. doi:10.1056/NEJMoa1506930.
  2. Wilcox R, Bousser M-G, Betteridge DJ, Shernthaner, et al, for the PROactive investigators. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke. Results from proactive (prospective pioglitazone clinical trial in macrovascular events 04). Stroke. 2007;38:865-873. doi:10.1161/01.STR.0000257974.06317.49.