Ramipril Benefit for Diabetics
HOPE sub-study shows it prevents nephropathy, lowers albumin-creatinine ratio
Evidence is strong that ramipril reduces cardiovascular deaths, strokes, myocardial infarction, heart failure, and revascularization among patients at high risk of developing complications and CV events arising from hypertension and concomitant conditions like diabetes.
Dr. John Andrew Kennedy, consultant cardiologist at the Western Infirmary at Glasgow, Scotland, said this evidence can be gleaned from the results of the Heart Outcomes Prevention Evaluation (HOPE) studies and the two substudies that looked into the effect of ramipril therapy on diabetic patients and the development of atherosclerosis.
He told Filipino doctors in a scientific symposium that the results showed diabetic patients experienced cardiovascular benefits beyond blood pressure lowering, representing a vasculoprotective, and renoprotective effect of ACE inhibitor ramipril.
The findings could have tremendous impact on Filipinos in the light of the rising incidence of lifestyle-related diseases in the country. Recent data from the Department of Health rank heart diseases as the leading cause of mortality (15.5 percent), trailed closely by vascular diseases (11.6 percent). Diabetes mellitus ranks eighth (1.6 percent), followed by renal-related diseases (1.8 percent).
Hope for Diabetics
The Microalbuminuria, Cardiovascular, and Renal Outcomes (MICRO) substudy is a part of the HOPE study. It involved 3,578 patients who have had diabetes for an average of 11.4 years. More than half were taking hypoglycemic agents and 26 percent were taking insulin.
Overall, the study yielded a 24-percent reduction in mortality, better than in the main HOPE study. The combined primary outcome risk reduction of heart attack, stroke, and cardiovascular death was 25 percent in the ramipril group while the risk reduction was 37 percent for cardiovascular death, 22 percent for heart attacks, and 33 percent for stroke.
Dr. Kennedy took note of two major outcomes.
First, the development of diabetic nephropathy was reduced by 25 percent (p=0.027), confirming ramipril's ability to protect the kidney. Fewer patients in the ramipril group developed new microalbuminuria. Ramipril treatment led to a lower albumin-creatinine ratio at one year and at end of treatment.
Second, no new diabetes mellitus developed during the period of the study. "This would seem to show that ramipril facilitates the action of insulin," he explained.
Dr. Kennedy also noted that the cardiovascular benefit was greater than that attributable to the decrease in blood pressure. Compared to those of the main HOPE study, the MICRO-HOPE results were as effective or even better among patients with diabetes, particularly in the reduction of cardiovascular death and total mortality.
Putting the Brakes on Atherosclerosis
The Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE) sub-study looked into the antiischemic action of ramipril. Using carotid intimal thickness (determined by a high quality B-mode ultrasound) as a measure of atherosclerosis plaque progression, it found significantly less progression (37 percent relative reduction) over 4.5 years in the high-dose ramipril arm. The study found no positive effects attributable to vitamin E therapy.
Dr. Kennedy said the HOPE studies demonstrated that "ramipril slows down atherosclerosis progression and prevents major vascular events, which may be attributed to its direct vasculoprotective effect."
Dr. Kennedy suggested that it might be helpful (in certain cases) to use ACE inhibitors to reduce risks of potentially costly problems even in the absence of hypertension.
Dr. Kennedy lamented, however, that ACE inhibitors are not as often and widely prescribed as they should be, denying patients of their protective benefits. He also stressed that they are also often used in doses that are inadequate and unable to achieve maximal benefit. He corrected common misconception about drug interaction, noting that the figures from the HOPE study found no significant difference between patients on aspirin and those who are not, indicating that aspirin does not negate the effect of ramipril.
Dr. Kennedy noted that breakthrough findings like those of the HOPE study should immediately be put into use in hospitals and clinics for the benefit of millions of patients. Medical infrastructure and support organizations must be in place to maximize benefits from the study, he said.
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