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?”

7 Responses to “Olmesartan Helps Prevent Microalbuminuria, But a Troubling Question Persists”

  1. Hany Ragy, MBBCh, MSc, MD says:

    Actually the “small signal” of increased MI or increased death has been seen with many ARB’s it has never been reported with ACEI to my knowledge, it could be a statistical issue, but the way the pharma industry panicks and hushes it up every time is annoying, I think this issue should be studied properly and we should try and have a consensus , of course the other side of the coin is pharma industry using it against a specific compound or another, if this finding is a true one it most probably is a class effect, there may be a vulnerable group of patients, or as I previously mentioned it may be a statistical issue.

    Competing interests pertaining specifically to this post, comment, or both:

    • Harvey Lerner, MD says:

      One interesting difference between ACE inhibitors (and aliskiren) and ARBs is that levels of angiotensin 2 rise markedly in patients on ARBs. There are several receptors and variable blocking of some receptor sites. Is it possible that the reported increase in lung cancer on ARBs has something to do with angio 2 as growth factor acting on a rogue cell with a receptor for it? and that some of the other adverse effects are related to the high levels of that same notorious bad actor?

  2. Delay to the time of Microalbuminuria onset in diabtic nephropathy “T2DM” as a cardiovascular dis biomarker is not a powerful evidence based in ROADMAP trial , as if ptns enrolled in the study allready under blood pressure lowering therapy (even not ARBs or ACIs) and thier BP by the start of the trial was 140/90 or less,and as if diabetes has effect on Microalbuminuria change in diabetic nephropathy ptn, aslo we Hypertensive nephropathy with Microalbuminuria?? i think this trial to get more powerful evidence should enroled uncontroled systemic HTN ptn not on antihypertenive therapy & with T2DM , and to be head to head double blinded RCT with another ARBs for more proper assessing of Microalbuminuria change effectiveness with Olmesartan.

  3. Robin Motz, M.D., Ph.D. says:

    I prefer to use Coreg to reduce microalbinuria in cardiac diabetic patients, since there is no ambiguity about its safety.

  4. Isaac Vilayil Mammen, M.D., D.M. says:

    Should we stop using Olmesartan?

  5. Charles Weart, Pharm D says:

    I wish we had better data but until we do lets stick with what we do know that makes a difference in patient outcomes, a full dose ACE inhibitor probably dosed at bedtime (HOPE Trial not originally stated that it was dosed HS in the original publication)is probably the best cost effective agent at this time and that is where I will try to go until we get better data with an ARB which to date has not been demonstrated and with the concerns about cost only losartan is generic in this class at this time and it does not have the same CV event reduction in patients with diabetes. I also would likely add either amlodipine or chlorthalidone or indapamide based upon the current evidence and not HCTZ or and ARB to get to the desir4ed BP goal(based upon ACCOMPLISH, ON-TARGET, ALLHAT, HYVET and PROGRESS).

    Competing interests pertaining specifically to this post, comment, or both:

  6. David Powell , md, facc says:

    What do we know? For diabetics who are really normotensive and have no history of CV disease and no microalbuminuria, evidence of CV benefit of ACEI or ARB is scant and debatable. One would have to invoke microsubgroup analysis of HOPE and ONTARGET. How about if youthrow in a” positive” calcium score or asymptomatic PAD or high IMT? Here is the realm of judgement