Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk...

Area of Science:

• Neurology
• Cardiology
• Pharmacology

Background:

• Individual patient responses to therapy vary, meaning average treatment effects may not apply universally.
• Insulin resistance is a significant factor in patients following ischemic stroke or transient ischemic attack (TIA).

Purpose of the Study:

• To assess if patients with ischemic stroke/TIA and insulin resistance at higher risk for subsequent stroke or myocardial infarction (MI) gain more benefit from pioglitazone hydrochloride compared to lower-risk patients.
• Investigate the differential efficacy of pioglitazone based on baseline cardiovascular risk in secondary prevention.

Main Methods:

• Secondary analysis of the Insulin Resistance Intervention After Stroke trial (NCT00091949), a double-blind, placebo-controlled study.
• Patients with ischemic stroke/TIA and insulin resistance (without diabetes) were stratified by 5-year risk for stroke/MI using a Cox regression model.
• Efficacy of pioglitazone vs. placebo in preventing stroke/MI was calculated within risk strata. Safety outcomes included death, heart failure, weight gain, and fracture.

Main Results:

• Among 3876 participants, pioglitazone showed a greater absolute risk reduction for stroke/MI in higher-risk patients (-4.9%) compared to lower-risk patients (-1.9%).
• Hazard ratios for stroke/MI were similar across risk strata (0.77 vs. 0.75), indicating consistent relative risk reduction.
• Pioglitazone was associated with less weight gain but a higher risk of fracture in higher-risk individuals.

Conclusions:

• Patients with ischemic stroke/TIA and insulin resistance at higher risk for future stroke/MI derive greater absolute benefit from pioglitazone.
• The increased benefit must be weighed against a higher risk of bone fracture associated with pioglitazone in these patients.