ACE-I and ARB equivalent in diabetic nephropathy

Several years ago, the NEJM published several articles showing the ARBs delayed the progression of diabetic nephropathy (type II patients). We did not have good data on ACE inhibitors in that group of patients (although we did have good data in type I diabetes).

An editorial at that time lamented the lack of a study comparing ACE inhibitors and ARBs in these patients. This echoes my plea earlier this week for comparative drug studies. Europe has come through in this case and done the right study – Both ACE Inhibitors and ARBs Slow Renal Decline in Type 2 Diabetes

In a head-to-head comparison, the angiotensin-converting enzyme (ACE) inhibitor enalapril and the angiotensin-receptor blocker (ARB) telmisartan were equally effective in slowing kidney damage in people with type 2 diabetes, hypertension, and nephropathy, according to results from the Diabetics Exposed to Telmisartan and Enalapril (DETAILS) study reported here at the European Society of Cardiology Congress 2004.

“The results show that telmisartan is a valid choice in selecting a treatment,” Anthony Barnett, MD, consulting physician and clinical director of diabetes and endocrinology at Birmingham HeartLands Hospital and professor of medicine at the University of Birmingham, U.K., said. Dr. Barnett explained that the study represented the largest long-term look at treatment of diabetic patients with kidney dysfunction.

Speaking at an ESC press conference, Dr. Barnett said the trial was designed to “prove noninferiority of telmisartan to enalapril, and we were able to show that.”

The study randomized 250 patients to enalapril 10 mg for one month, with a forced titration to 20 mg for 59 months or 40 mg of telmisartan for one month and then 80 mg for the rest of the five-year period. “Doctors were permitted to reduce the dosing if there were side effects, but that was rare in the trial,” Dr. Barnett said. Patients were excluded if they had previously shown intolerability toward ACE inhibitors.

The primary outcome was change in glomerular filtration rate after five years. In the telmisartan group, the average decline in the glomerular filtration rate was 17.9 mL per minute, while in the enalapril group it was 14.9 mL per minute. The differences were not significant, Dr. Barnett said.

“There were no surprises with the outcomes in this study,” said Lars Ryden, MD, professor of cardiology at Karolinska Hospital in Stockholm, Sweden. “It shows that doctors are correct in beginning treatment of these diabetic patients with an ACE inhibitor.” Dr. Ryden was not involved in the study.

In addition, a dramatic reduction in predicted mortality was seen with the use of either drug. Dr. Barnett said the death rate over the five-year trial was expected to be 35% to 50%, which was based on established five-year mortality rates in people with newly diagnosed diabetic nephropathy. But only six people in each group died – a 5% mortality rate. Moreover, none of the patients in the study progressed to end-stage renal disease. About half of the patients in the study had documented cardiovascular disease.

Asked if the findings illustrate a class effect for both ACE inhibitors and ARBs, Dr. Barnett said “One assumes it is a class effect, but these are the drugs that were used in the study. That is what the science shows.”

Dr. Ryden agreed that the findings are likely to demonstrate a class effect for the drugs, but he noted that that lipophilic ACE inhibitors such as ramipril and enalapril, which was used in the study, are likely better choices.

The study was funded by Boehringer-Ingelheim.

Why is this so important? ACE inhibitors are becoming generic, while ARBs are still patent protected.