No Kidney Benefit for ACE-Inhibitors
The best way to protect kidneys of diabetic patients is to lower blood pressure. Period.
So says Juan P. Casas M.D. and his colleagues of the British Heart Foundation Laboratory at University College London, who reported that a meta-analysis of 127 randomized trials did not confirm a renoprotective effect for either ACE-inhibitors or angiotensin receptor blockers.
The purported benefit of either ACE inhibitors or ARBs comes from placebo-controlled studies, Dr. Casas and his colleagues reported in the Dec. 10 issue of The Lancet. But when these agents were compared with other antihypertensive drugs that also substantially reduce blood pressure "there was no evidence of a significant salutary effect of ACE inhibitors or ARBs on renal outcomes in patients with diabetes."
The authors wrote that their analysis found that in patients with diabetic nephropathy there was no benefit seen in comparative trials of ACE inhibitors or ARBs on the doubling of creatinine, end-stage renal disease, glomerular filtration rate, or creatinine amounts.
On balance, the authors contended that the reported renoprotective benefit of ACE inhibitors and ARBs comes from a handful of smaller studies while the impact of drugs on end-stage renal disease and doubling of creatinine "showed a reduced benefit in large studies."
They pointed out, for example, that in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), there was no evidence for a greater beneficial effect of ACE inhibitors in people with poor renal function.
"In the ALLHAT trial, participants assigned thiazide diuretics had a roughly 2 mm Hg lower systolic blood pressure than those assigned ACE inhibitors, and this difference in blood pressure might have contributed to the absence of any beneficial effect of ACE inhibitors over thiazides on renal outcomes," said Dr. Casas and his colleagues.
The authors found some evidence of "small benefits of the drugs" in trials of patients with non-diabetic renal disease. But those studies were small, they wrote, so the findings are subject to bias.
The take home, the authors concluded, is that the evidence does not support use of ACE inhibitors or ARBs as "first-line choices for renoprotection on the basis of efficacy, and residual uncertainty still exists about the inherent value of these drugs in other renal disorders."
Drug choice, they wrote, should be made on the basis of "blood-pressure-lowering effect, comparative tolerability, and cost of antihypertensive therapy."
Thomas D. Giles, M.D., president of the American Society of High blood pressure and a professor of medicine at Louisiana State University School, said the authors may be jumping to an unwarranted conclusion. He pointed out that a "meta-analysis is not the world's greatest instrument for evaluating clinical benefit."
That said, he added in an interview, "It's been known for quite some time that the key factor in renal protection is lower blood pressure, so no argument there." But he said the vast majority of both basic science and clinical trials support the position that drugs that disrupt "the renin-angiotensin system have a beneficial effect on glomerular pressure."
He said, for example, that clinical trials have demonstrated that "if you continue to increase the dose of ARBs the blood pressure lowering effect will eventually be limited but there will be continued beneficial effects on proteinuria that go beyond blood pressure."
Moreover, while the authors suggested that price is a significant consideration, Dr. Giles said "there are already several generic ACE inhibitors available and some ARBs will soon be coming off patent, so price is really not a factor."
Dr. Giles concluded. "The real issue here is lowering blood pressure and there is universal agreement that in most patients that means using several drugs. I maintain that an ACE inhibitor or an ARB should be in that mix-particularly if the patient has diabetes,"