Cochrane for Clinicians

Putting Evidence into Practice

Effectiveness of PPAR Gamma Agonists in Preventing Recurrent Stroke and Other Vascular Events


Am Fam Physician. 2020 Sep 1;102(5):271-272.

Author disclosure: No relevant financial affiliations.

Clinical Question

Are peroxisome proliferator–activated receptor (PPAR) gamma agonists effective at preventing recurrent stroke and other serious vascular events in people with previous stroke or transient ischemic attack (TIA)?

Evidence-Based Answer

PPAR gamma agonists are probably effective in preventing recurrent stroke in people with previous stroke or TIA (absolute risk reduction [ARR] = 2.9%; 95% CI, 0.1% to 4.8%; number needed to treat [NNT] = 35; 95% CI, 21 to 1,000). (Strength of Recommendation [SOR]: B, based on inconsistent or limited-quality patient-oriented evidence.) PPAR gamma agonists also appear to be effective in preventing other serious vascular events (relative risk = 0.73; 95% CI, 0.54 to 0.99). (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.) It is uncertain whether adverse effects are more common in those treated with PPAR gamma agonists vs. placebo.1

Practice Pointers

Cerebrovascular accidents, or strokes, are classified as ischemic (80%) or hemorrhagic. Stroke recurs in 30% of cases.1 People who have a recurrent stroke have more than double the cumulative mortality rate vs. those with only a single episode of stroke.2 Diabetes mellitus contributes to one in nine cases of stroke and TIA.3 PPAR gamma agonists are insulin-sensitizing drugs used to treat hyperglycemia with insulin resistance and have been widely recommended for the treatment of type 2 diabetes.

This Cochrane review is an update of an initial review performed in January 2014. Five RCTs with 5,039 participants were identified; four evaluated pioglitazone (Actos) and one evaluated rosiglitazone (Avandia).1 Three studies that included participants with recurrent stroke from the United States, Japan, and South Africa were ultimately included. They revealed that PPAR gamma agonists probably reduced the recurrence of stroke compared with placebo (ARR = 2.9%; 95% CI, 0.1% to 4.8%; NNT = 35; 95% CI, 21 to 1,000; 4,979 participants). The risk of bias was unclear because of

Author disclosure: No relevant financial affiliations.


show all references

1. Liu J, Wang L. Peroxisome proliferator–activated receptor gamma agonists for preventing recurrent stroke and other vascular events in people with stroke or transient ischaemic attack. Cochrane Database Syst Rev. 2019;(10):CD010693....

2. Aarnio K, Haapaniemi E, Melkas S, et al. Long-term mortality after first-ever and recurrent stroke in young adults. Stroke. 2014;45(9):2670–2676.

3. Sarwar N, Gao P, Kondapally Seshasai SR, et al.; Emerging Risk Factors Collaboration. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies [published correction appears in Lancet. 2010;376(9745):958]. Lancet. 2010;375(9733):2215–2222.

4. Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, et al. Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA. 2010;304(4):411–418.

5. American Diabetes Association. Addendum. 9. Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2020. Diabetes Care. 2020;43(suppl 1):S98–S110.

These are summaries of reviews from the Cochrane Library.

This series is coordinated by Corey D. Fogleman, MD, assistant medical editor.

A collection of Cochrane for Clinicians published in AFP is available at



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