Lee et al Pioglitazone and Recurrent Stroke Prevention 389 Data Sources and Searches

Patients with ischemic stroke or transient ischemic attack (TIA) remain at increased risk for recurrent stroke and future vascular events despite the effectiveness of current preventive therapies and a temporal decline in stroke incidence. New preventive strategies to further improve outcomes after ischemic stroke or TIA are needed. Disorders of glucose metabolism are highly prevalent among patients with stroke and TIA, and diabetes mellitus is associated with increased risk for recurrent ischemic stroke. However, oral antidiabetic drugs have not been associated with reduced stroke events, and intensive glycemic control does not seem to prevent risk of stroke in diabetic patients. Similar to statin drugs, which have potent vascular protective properties that go beyond their primary action of cholesterol lowering, it is conceivable that hypoglycemic agents with pleiotropic properties may better at reducing vascular events than traditional hypoglycemic drugs. Pioglitazone is a peroxisome proliferator–activated receptor γ agonist that, in addition to its primary effect on glycemic control, exerts potential beneficial effects on inflammation, fat distribution, lipid and protein metabolism, and vascular endothelial function. The IRIS trial (Insulin Resistance Intervention After Stroke) found that among patients without diabetes mellitus who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of combined stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo, but differences in recurrent stroke alone did not reach statistical significance. The objective of this study was to use the totality of the published literature to qualitatively and quantitatively evaluate the risk of recurrent stroke in stroke patients with abnormal glucose metabolism receiving pioglitazone therapy, by conducting a systematic review and meta-analysis of randomized controlled trials.

[1]  C. Viscoli,et al.  Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. , 2016, The New England journal of medicine.

[2]  D. Tanné,et al.  Pioglitazone after Ischemic Stroke or Transient Ischemic Attack. , 2016, The New England journal of medicine.

[3]  N. Hattori,et al.  Effects of Pioglitazone for Secondary Stroke Prevention in Patients with Impaired Glucose Tolerance and Newly Diagnosed Diabetes: The J-SPIRIT Study. , 2015, Journal of atherosclerosis and thrombosis.

[4]  M. Pencina,et al.  Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. , 2015, The New England journal of medicine.

[5]  Theresa M Beckie,et al.  American Heart Association Council on Cardiovascular and Stroke Nursing. , 2013, The Journal of cardiovascular nursing.

[6]  Kuo-Hsuan Chang,et al.  Effect of pre-diabetes on future risk of stroke: meta-analysis , 2012, BMJ : British Medical Journal.

[7]  Hao Li,et al.  Abnormal Glucose Regulation in Patients With Acute Stroke Across China: Prevalence and Baseline Patient Characteristics , 2012, Stroke.

[8]  M. Hennerici,et al.  Risk of stroke and cardiovascular events after ischemic stroke or transient ischemic attack in patients with type 2 diabetes or metabolic syndrome: secondary analysis of the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) trial. , 2011, Archives of neurology.

[9]  J. Saver,et al.  Declining Stroke and Vascular Event Recurrence Rates in Secondary Prevention Trials Over the Past 50 Years and Consequences for Current Trial Design , 2011, Circulation.

[10]  Devjit Tripathy,et al.  Pioglitazone for diabetes prevention in impaired glucose tolerance. , 2011, The New England journal of medicine.

[11]  Robert L Wilensky,et al.  Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. , 2011, The New England journal of medicine.

[12]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement , 2009, BMJ.

[13]  N. Sattar,et al.  Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials , 2009, The Lancet.

[14]  Renee F Wilson,et al.  Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. , 2008, Archives of internal medicine.

[15]  E. Tuzcu,et al.  Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. , 2008, JAMA.

[16]  S. Nissen,et al.  Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. , 2007, The New England journal of medicine.

[17]  D. Betteridge,et al.  Effects of Pioglitazone in Patients With Type 2 Diabetes With or Without Previous Stroke: Results From PROactive (PROspective pioglitAzone Clinical Trial In macroVascular Events 04) , 2007, Stroke.

[18]  S. Haffner,et al.  Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial. , 2006, JAMA.

[19]  R. Sacco,et al.  Recurrent stroke and cardiac risks after first ischemic stroke , 2006, Neurology.

[20]  Erland Erdmann,et al.  Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial , 2005, The Lancet.

[21]  C. Peterson,et al.  Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues: association with cytokine expression, insulin resistance, and reduction by pioglitazone. , 2005, Diabetes.

[22]  Nikolaus Marx,et al.  Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control: results from the pioneer study. , 2005, Journal of the American College of Cardiology.

[23]  C. Viscoli,et al.  Prevalence of abnormal glucose tolerance following a transient ischemic attack or ischemic stroke. , 2005, Archives of internal medicine.

[24]  曲东锋.  Stroke Prevention by Aggressive Reduction in Cholesterol Levels , 2004 .

[25]  C. Viscoli,et al.  Pioglitazone Improves Insulin Sensitivity Among Nondiabetic Patients With a Recent Transient Ischemic Attack or Ischemic Stroke , 2003, Stroke.

[26]  J. Hardies,et al.  Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. , 2002, The Journal of clinical endocrinology and metabolism.

[27]  W. O'Fallon,et al.  Survival and recurrence after first cerebral infarction , 1998, Neurology.

[28]  Daniel B Hier,et al.  Stroke recurrence within 2 years after ischemic infarction. , 1991, Stroke.

[29]  M. Pencina,et al.  Effect of Sitagliptin on Cardiovascular Outcomes in Type 2 Diabetes. , 2015, The New England journal of medicine.

[30]  V. Chair,et al.  Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. , 2014, Stroke.

[31]  J. Farmer.  High-dose atorvastatin after stroke or transient ischemic attack. , 2007, Current atherosclerosis reports.

[32]  J. Panza,et al.  Peroxisome proliferator-activated receptor-gamma activation with pioglitazone improves endothelium-dependent dilation in nondiabetic patients with major cardiovascular risk factors. , 2006, Circulation.

[33]  K. Alberti,et al.  Prevalence and prediction of unrecognised diabetes mellitus and impaired glucose tolerance following acute stroke. , 2004, Age and ageing.

[34]  S. Johnston.  Clinical practice. Transient ischemic attack. , 2002, The New England journal of medicine.