March 10th, 2011
Olmesartan Helps Prevent Microalbuminuria, But a Troubling Question Persists
Olmesartan can help prevent progression to microalbuminuria in type 2 diabetics, according to results of the ROADMAP (Randomized Olmesartan and Diabetes Microalbuminuria Prevention) trial published in the New England Journal of Medicine. But the positive result was partially offset by the troubling finding of a small but significant increase in fatal cardiovascular events.
Type 2 diabetics (n=4447) were randomized to olmesartan or placebo for 3.2 years. Time to the onset of microalbuminuria — the primary endpoint of the trial — was significantly delayed by olmesartan by 23% (HR 0.77, CI 0.63-0.94, p=0.01). Microalbuminura occurred in 8.2% of olmesartan-treated patients versus 9.8% of placebo-treated patients. Although there were fewer nonfatal cardiovascular events in the olmesartan group (3.6% versus 4.1% in the placebo group, p=0.37), the pattern was reversed for fatal cardiovascular events: 15 patients (0.7%) versus 3 patients (0.1%) (p=0.01).
In an accompanying editorial, Julie Ingelfinger notes that due to ROADMAP and a similar finding in the ORIENT trial, olmesartan is the subject of an ongoing investigation by the FDA. Because of the small number of events it is possible that olmesartan is safe, she acknowledges, but she also speculates that the high 40 mg/day dose of olmesartan used in ROADMAP might have caused an excessive reduction of blood pressure in high-risk patients.
Without taking a firm stance, Ingelfinger writes that “most nephrologists and cardiologists have argued that the benefits of olmesartan outweigh the very small risks,” but that “others would argue that there are many ACE inhibitors and ARBs that have not been associated with a signal of increased cardiovascular death, so why not prescribe one of those agents?”