Olmesartan delays onset of microalbuminuria in type 2 diabetics but may increase fatal cardiovascular events

Alex Proctor, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0SP

Diabetic nephropathy is an important worldwide cause of end-stage renal disease. Although blood pressure control (recommended <130/80) is the major predictor of renal deterioration in type 2 diabetics, microalbuminuria is associated with diabetic nephropathy and premature cardiovascular disease occurring earlier. (1)

Previous studies have shown that ACE inhibitors can function as pre-emptive reno-protective therapy in diabetics by delaying the onset of microalbuminuria. (1) The ‘ROADMAP’ study set out to determine whether it would be possible to prevent/delay the onset of microalbuminuria using olmesartan (an angiotensin receptor blocker – ARB).

4500 patients with type 2 diabetes and no microalbuminuria were assigned to olmesartan or placebo. Blood pressure was targeted towards being <130/80 using additional antihypertensive medication (that did not affect the renin-angiotensin-aldosterone system) as necessary.

Over the average follow-up time of 3.2 years: 8.2% of the olmesartan patients developed microalbuminuria compared to 9.8% in the placebo group. Olmesartan was also shown increase the time delay before microalbuminuria developed by 23%. (1)

Despite these positive results, another of the ROADMAP study’s findings has raised some controversy. Olmesartan was associated with a greater number of fatal cardiovascular events (0.7%) than the placebo (0.1%), especially amongst those with pre-existing coronary artery disease. This finding along with a similar finding by a different study (ORIENT) has prompted a currently on-going FDA investigation. (1)

Other ARBs have not been associated with increased cardiovascular risk, so this could be an olmesartan-specific problem. (2) Because of the relatively small numbers of participants affected by fatal cardiovascular events, it is also possible that this could be a chance finding. (1) Most nephrologists & cardiologists have argued that benefits of olmesartan outweigh the very small risks. (2) Others argue that other ARBs and ACE inhibitors have not been associated with increased cardiovascular death, so should these should be prescribed instead. (2)

References: 

1. Haller H, Ito S, Izzo JL, Januszewicz A, Katayama S, Menne J, Mimran A, Rabelink TJ, Ritz E, Ruilope LM, Rump LC, Viberti G. Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes. New England Journal of Medicine 2011 Mar;364(10):907-917.
doi: 10.1056/NEJMoa1007994

2. Ingelfinger JR. Preemptive Olmesartan for the Delay or Prevention of Microalbuminuria in Diabetes. New England Journal of Medicine 2011 Mar;364(10):970-971.  
doi: 10.1056/NEJMe1014147