SNOWMASS, COLO. — Quick: What's the preferred first-line antihypertensive agent for type 2 diabetic patients with hypertension and macroalbuminuria?
Most nondiabetologists will probably be surprised to learn that it's an angiotensin II receptor blocker (ARB), according to American Diabetes Association's treatment guidelines.
“I suspect most cardiologists would guess it would be an ACE inhibitor,” Dr. John S. Schroeder observed at a conference sponsored by the Society for Cardiovascular Angiography and Interventions.
For hypertensive type 2 diabetic patients with microalbuminuria—as defined by a 24-hour urinary albumin excretion rate of 30–299 mg—the guidelines list both ACE inhibitors and ARBs as the preferred initial treatment choices, based upon level A data showing that they delay progression to macroalbuminuria (Diabetes Care 2003;26:S33–50).
But ARBs were singled out as the first-line antihypertensive drug class in patients with macroalbuminuria. The guidelines urge that an ARB “should be strongly considered” in such patients on the basis of compelling level A evidence that this drug class reduces the rate of progression to diabetic nephropathy.
The supporting data come from several clinical trials, including the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study, as well as the Irbesartan Diabetic Nephropathy Trial (IDNT).
But for Dr. Schroeder, the most impressive evidence of the renoprotective benefits of ARB therapy comes from the Irbesartan Microalbuminuria Type 2 Diabetes Mellitus in Hypertensive Patients (IRMA II) trial.
In IRMA II, 590 microalbuminuric type 2 diabetic patients with hypertension were randomized to 150 or 300 mg/day of irbesartan or placebo in addition to other antihypertensive agents as needed to achieve good blood pressure control. The 5.2% rate of progression to nephropathy at 2 years' follow-up in patients treated with 300 mg/day of irbesartan represented a 70% reduction in the relative risk of the primary study end point, compared with placebo (N. Engl. J. Med. 2001;345:870–8).
Most diabetics who are hypertensive “already have some degree of nephropathy and microalbuminuria, and therefore, I think you should really consider ARBs in all patients who have diabetes and hypertension,” said Dr. Schroeder, professor of cardiovascular medicine at Stanford (Calif.) University.
The notion that combined ARB and ACE inhibitor therapy might have additive cardioprotective effects superior to those of either agent alone is being put to the test in the randomized, double-blind Ongoing Telmisartan Alone or in Combination with Ramipril Global Endpoint Trial (ONTARGET). The study involves roughly 25,000 patients with a history of cardiovascular disease, stroke, or diabetes who have been randomized to the ARB, ACE inhibitor, or both. Results are due to be reported next year.
Dr. Schroeder is on the speakers' bureau for Boehringer Ingelheim Pharmaceuticals Inc., which markets telmisartan (Micardis) and sponsors ONTARGET.
'I think you should really consider ARBs in all patients who have diabetes and hypertension.' DR. SCHROEDER