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Pioglitazone after Ischemic Stroke or Transient Ischemic Attack
Walter N Kernan1, Catherine M Viscoli1, Karen L Furie1
1From the School of Medicine (W.N.K., C.M.V., L.H.Y., S.E.I., A.M.L., L.M.B., J.R.O.) and the School of Public Health (P.D.G., P.N.P., J.R.O.), Yale University, New Haven, and the Cooperative Studies Program Coordinating Center, Veteran Affairs (VA) Connecticut HealthCare System, West Haven (P.D.G., P.N.P.) - all in Connecticut; Alpert Medical School, Brown University, Providence, RI (K.L.F.); Vermont College of Medicine, Burlington (M.G.); the National Institute of Neurological Disorders and Stroke, Bethesda, MD (R.C.); the VA Medical Center and the University of Colorado School of Medicine, Denver (G.G.S.); the University of Iowa, Iowa City (H.P.A.); Hôpital Charles LeMoyne, Greenfield Park, QC (L.B.), the University of Western Ontario, London (J.D.S.), and the Center for Neurological Research, Lethbridge, AB (T.R.W.) - all in Canada; University of L'Aquila, L'Aquila, Italy (A.C.); Oregon Health Sciences University, Portland (W.C.); the University of Arizona, Tucson (B.C.); the University of Oxford and Oxford University Hospitals NHS Foundation Trust, Oxfordshire, United Kingdom (G.A.F.); the University of Cincinnati, Cincinnati (D.K.); John Hunter Hospital, University of Newcastle, New Lambton Heights, NSW, Australia (M.W.P.); the University of Heidelberg, Heidelberg, Germany (P.R.); the University of South Carolina School of Medicine, Columbia (S.S.); Sheba Medical Center, Tel Aviv University, Tel Aviv, Israel (D.T.); and the Illinois Neurological Institute-OSF Saint Francis Medical Center and the Department of Neurology, University of Illinois College of Medicine at Peoria, Peoria (D.W.).
Pioglitazone reduced the risk of stroke or myocardial infarction in patients with insulin resistance and recent TIA or stroke. This treatment also lowered the incidence of diabetes but increased risks of weight gain, edema, and fractures.
Area of Science:
- Cardiovascular Medicine
- Neurology
- Endocrinology
Background:
- Patients with ischemic stroke or transient ischemic attack (TIA) face elevated risks of subsequent cardiovascular events.
- Insulin resistance is a recognized risk factor for stroke and myocardial infarction.
- Pioglitazone, an insulin-sensitizing agent, was investigated for its potential benefits in cerebrovascular disease.
Purpose of the Study:
- To evaluate the efficacy of pioglitazone in preventing major adverse cardiovascular events in patients with recent ischemic stroke or TIA.
- To assess the impact of pioglitazone on the development of diabetes in this patient population.
Main Methods:
- A multicenter, double-blind trial randomized 3876 patients with recent ischemic stroke or TIA to receive pioglitazone (45 mg daily) or placebo.
- Eligible patients were non-diabetic but exhibited insulin resistance (HOMA-IR > 3.0).
- The primary outcome was the composite of fatal or nonfatal stroke or myocardial infarction.
Main Results:
- Pioglitazone significantly reduced the risk of the primary outcome (stroke or myocardial infarction) by 24% (hazard ratio, 0.76; P=0.007).
- The incidence of new-onset diabetes was halved in the pioglitazone group compared to placebo (3.8% vs. 7.7%; P<0.001).
- Pioglitazone was associated with increased weight gain, edema, and bone fractures, but not all-cause mortality.
Conclusions:
- Pioglitazone demonstrated efficacy in reducing the risk of stroke or myocardial infarction in non-diabetic patients with insulin resistance and a history of TIA or ischemic stroke.
- The drug also conferred a lower risk of developing diabetes.
- However, increased risks of weight gain, edema, and fractures necessitate careful consideration of its use.
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