LOS ANGELES – Nondiabetic, insulin-resistant patients who started pioglitazone within 6 months of an ischemic stroke or transient ischemic attack had almost a 3% absolute risk reduction in secondary strokes and myocardial infarctions after 5 years, in a randomized, clinical trial published online Feb. 17 in the New England Journal of Medicine.
Stroke or MI – the study’s primary combined outcome – occurred in 175 of 1,939 (9.0%) pioglitazone (Actos) patients, but 228 of 1,937 (11.8%) placebo patients (hazard ratio, 0.76; P = 0.007). There was no significant difference in all-cause mortality (HR, 0.93; P = 0.52).
Seventy-three pioglitazone patients (3.8%) developed diabetes, compared with 149 (7.7%) in the placebo group (HR, 0.48; P less than 0.001). That wasn’t a surprise; pioglitazone has been shown to protect insulin resistant patients against diabetes, the study investigators noted (N Engl J Med. 2016 Feb 17; doi: 10.1056/NEJMoa1506930).
Known side effects showed up as well. Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg (52.2% versus 33.7%, P less than 0.001), edema (35.6% versus 24.9%, P less than 0.001), and bone fracture requiring surgery or hospitalization (5.1% versus 3.2%, P = 0.003).
Heart failure – another known risk with the drug – did not show up in the trial; people with heart failure histories or other risk factors were excluded.
The median baseline modified Rankin Scale in both groups was 1, and the median NIH Stroke Scale score was 0. The pioglitazone target dose was 45 mg daily.
Insulin resistance is a risk factor for heart attack and stroke, which may help explain the thiazolidinedione’s apparent protective effects. It was defined in the trial as a score greater than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index.
So, should pioglitazone be a part of routine post-stroke care?
In a video interview at the International Stroke Conference, lead investigator Dr. Walter N. Kernan, a professor of general medicine at Yale University, New Haven, Conn., shared his thoughts.