A recent comparative effectiveness study examined the effects of an insulin-sensitizing drug in patients who have suffered a stroke with a high risk for recurrent stroke or myocardial infarction vs those with a low risk, published in JAMA Neurology (online September 18, 2017; doi: 10.1001/jamaneurol.2017.2136).
Many patients with a prior stroke are at high risk for a recurrent episode. The use of an insulin-sensitizing drug, such as pioglitazone hydrochloride (Actos), in insulin-resistant stroke patients with varying degrees of risk for recurrent stroke or myocardial infarction has yet to be assessed.
To determine the therapeutic value of pioglitazone hydrochloride in patients with varying degrees of risk for recurrent stroke or myocardial infarction, researchers led by Walter N Kernan, MD, Yale School of Medicine, conducted a secondary analysis of the Insulin Resistance Intervention After Stroke (IRIS) trial, a double-blind, placebo-controlled study. A total of 3876 patients were sampled from 2005-2013 who had a qualifying ischemic stroke or transient ischemic attack within 180 days of entry and insulin resistance without type 1 or 2 diabetes. Patients were given either pioglitazone hydrochloride or placebo and followed for a mean of 4.1 years.
After the intervention, the reported 5-year risk for stroke or myocardial infarction was 6.0% in patients receiving pioglitazone hydrochloride with lower baseline risk, compared with 7.9% in the placebo group (absolute risk difference, -1.9%; 95% CI, -4.4% to 0.6%). Among those with higher baseline risk, 5-year risk was 14.7% vs 19.6%, respectively (absolute risk difference, -4.9%; 95% CI, -8.6% to 1.25).
Researchers reported that hazard ratios were similar in either treatment arm for patients below or above the median risk (0.77 vs 0.75, respectively; P = .92).
The safety outcomes measured in the analysis included death, heart failure, weight gain, and bone fracture. After the conclusion of the analysis, researchers acknowledged that pioglitazone hydrochloride contributed less to increased weight among patients at higher risk, but contributed more to risk for bone fracture.
Researchers concluded that “after an ischemic stroke or transient ischemic attack, patients at higher risk for stroke or myocardial infarction derive a greater absolute benefit from pioglitazone hydrochloride compared with patients at lower risk.” However, they noted that relative risk reduction was similar, and neither absolute nor relative risk reduction reached statistical significance..—Zachary Bessette