Download Journal Club - WordPress.com

JOURNAL CLUB
ANGELA AZIZ DONNELLY
APRIL 5, 2016
PIOGLITAZONE AFTER ISCHEMIC STROKE
OR TRANSIENT ISCHEMIC ATTACK
NEJM FEB 17, 2016
IRIS
Insulin Resistance
Intervention after Stroke
Hypothesis:
Pioglitazone would
reduce the rates of
stroke and myocardial
infarction after ischemic
stroke or TIA in select
patients
BACKGROUND
• Patients affected by stroke and TIA are
at risk for another event
• Current treatment for secondary stroke
prevention is fairly limited
• Explores insulin resistance as a possible
new treatment target
BACKGROUND
• Many proposed mechanisms for why the presence
of insulin resistance increases risk for vascular
disease
• There are various strategies to improve insulin
sensitivity – including lifestyle modification, TZDs, and
other medications (eg. metformin)
RESEARCH METHODOLOGY
• International, randomized, double-blind, placebocontrolled clinical trial
• Eligible Patients: Men and Women at least 40 years
of age who had a qualifying ischemic stroke or TIA
during the previous 6 months AND met criteria for
insulin resistance
RESEARCH METHODOLOGY
• Exclusion criteria
• Patients with diabetes
• Patients with class 3 or 4 heart failure, or patients with class 2
heart failure with reduced EF
• Pregnancy
• Moderate/severe pitting edema
• Carotid revascularization within 14 days
• Use of an estrogen-containing contraceptive or oral
glucocorticoid
• Temporary Exclusion
• Abnormal liver function
• Severe anemia
RESEARCH METHODOLOGY
• Patients then randomly assigned in a 1:1 ratio to receive either
pioglitazone or matching placebo
• Pioglitazone was titrated from an initial dose of 15 mg to a final
dose of 45 mg if no side effects encountered
• If patient’s had side effects, they were treated according to
algorithms
• Adherence was monitored by asking about drug use and
performing pill counts
• Patient’s individual primary care doctors had direct responsibility
for providing best current medical care for risk factor modification
TRIAL OUTCOMES
Primary outcome
• First fatal or nonfatal stroke or fatal or nonfatal MI
Secondary outcomes
• Recurrent stroke
• Acute MI or unstable angina
• The composite of stroke, MI, or HF resulting in
hospitalization or death
• All-cause mortality
• Progression to overt diabetes
• Cognitive decline from baseline
STATISTICAL ANALYSIS
• Analyses performed on an intention-to-treat basis
• The primary outcome and all secondary outcomes
(except cognitive function) were analyzed by
means of the time-to-first-event method
FINDINGS
CONCLUSION
 Good study design





Multi-center
Double-blind
Randomized controlled trial
Large sample size
5 years
 Groups similar at baseline with similar control of
comorbidities between groups
 Included the patients that would benefit the most from
additional secondary stroke prevention (Low NIHSS/mRS)
CONCLUSION
• Strict inclusion/exclusion criteria – eg. No diabetes,
no heart failure
• Majority of population was white, male
• Used HOMA-IR for measuring insulin resistance –
how would we do this in clinical practice
• No comparison to lifestyle modifications
DISCUSSION/IMPLICATIONS
• Can we apply this study to our current patient
population?
• Given risks versus benefits, would you use this in
clinical practice?
• Impressive NNT of 35. How does this compare to our
current standard of care, eg. treatment with high
intensity statin