Rationale and Design of a Large Study to Evaluate the Renal and Cardiovascular Effects of an ACE Inhibitor and Vitamin E in High-Risk Patients With Diabetes: The MICRO-HOPE Study

doi:10.2337/diacare.19.11.1225

Rationale and Design of a Large Study to Evaluate the Renal and Cardiovascular Effects of an ACE Inhibitor and Vitamin E in High-Risk Patients With Diabetes: The MICRO-HOPE Study

Hertzel C Gerstein, MD, MSC, FRCPC,
Jackie Bosch, BSC,
Janice Pogue, MSC,
D Wayne Taylor, MA,
Bernard Zinman, MD, CM, FRCPC,
Salim Yusuf, MBBS, FRCP, DPHIL and
The HOPE Study investigators

McMaster University Hamilton
University of Toronto Toronto, Ontario, Canada; and the Canadian Cardiovascular Collaboration (HOPE Study investigators [1])

Address correspondence to H.C. Gerstein, MD, MSc, FRCPC, Rm. 3V38, McMaster University Medical Centre, 1200 Main St. West, Hamilton, Ontario, Canada L8N 325. E-mail: gerstein{at}fhs.csu.mcmaster.ca
Address reprint requests to H.C. Gerstein, MD, MSc, FRCPC, HOPE Project Office, HGH-McMaster Clinic, 237 Barton St. East, Hamilton, Ontario, Canada L8L 2X2.

Abstract

OBJECTIVE To describe the rationale and design of a large international study (microalbuminuria, cardiovascular, and renal outcomes [MICRO] in the HOPE [Heart Outcomes Prevention Evaluation] study) of an ACE inhibitor and vitamin E for the prevention of diabetic nephropathy (DN) and cardiovascular disease (CVD) in patients with diabetes and microalbuminuria (MA).

RESEARCH DESIGN AND METHODS A total of 3,657 diabetic subjects, including 1,129 with MA, are randomly allocated to receive the ACE inhibitor ramipril (or placebo) and vitamin E (or placebo) for 4 years in a two-by-two factorial design. Diabetic subjects are a subset of the 9,541 subjects enrolled in the HOPE study.

RESULTS The development of DN in microalbuminuric diabetic subjects and the development of MA in normoalbuminuric subjects, as well as cardiovascular death, myocardial infarction, and storke, are the main outcomes. The correlation of changes in albuminuria with changes in carotid atherosclerosis documented in a subset of subjects will also be analyzed.

CONCLUSIONS The effect of both an ACE inhibitor and vitamin E on the progression of renal and CVD in patients with diabetes is being assessed in the MICRO-HOPE study.