Surprise, surprise! Time to INVEST in the gospel ACCORDing to ACCORD

It's a good thing bookies don't frequent medical trial presentations. If I were a gambler, I might have reluctantly put some money on the simvastatin-fenofibrate–therapy arm to reduce cardiovascular events in type 2 diabetics. I probably would have bet on lowering systolic BP to around 120 mm Hg as an optimal therapy as well. After today's presentations from the ACCORD and INVEST trials, I'll have to think about my treatment targets and modalities a little differently and remember to never, ever gamble on trial outcomes.

I've never liked fibrates. Poor trial designs, inconsistent patient populations, marginal cardiovascular risk reduction, and differences among the fibrates themselves have made me wonder why we are so in love with the idea of a normal lipid profile at all costs. Our obsession in some instances yields little, if any, benefit for our patients. Surely, over the past decade and in the wake of ezetimibe, we've learned one thing if nothing else: Patient outcomes matter more than omitting those little H's for "High" and L's for Low alongside our patients' LDL- and HDL-cholesterol levels.

There is also another reason I don't like fibrates: I never liked to mix lipid therapies (other than niacin and statins) for fear of rhabdo. I have a good friend who was sued because the pharmacist kept filling the fibrate unbeknownst to her, while she kept writing for a statin. She had instructed her patient to stop the fibrate, but apparently the patient did not understand, and weeks later, after a long hospital admission for renal failure and severe myopathy, the patient sued my physician friend, the pharmacist, and the pharmaceutical company. Fortunately, the patient dropped the suit against my friend, thanks to sound documentation, but it cost the patient and my friend a year of their lives and their relationship.

Finally, I don't like fibrates because I don't like polypharmacy. Before the $4.00 Wal-Mart option, very few patients were willing to purchase and swallow not one but two pills that didn't do anything "fun" for you, like make you have better sex, grow hair, or produce a surge of energy. In addition, as practitioners, who wants to follow rising creatinines or increase your patient's risk of developing gallstones? Only a very high triglyceride and a very low HDL patient would make me consider fenofibrate-simvastatin combination therapy, and even then, I would dread it.

Thanks to INVEST and ACCORD BP, I'll have to phone my dad to tell him he's been right all along. I've always nagged him because his BP is NOT what I would call optimal. He still hits 140s-150s occasionally but usually is in the upper-130s range. I've insisted on a target of 120/70 or less, though I never got my way, and it's a good thing or I might have seen more hypokalemia or a higher creatinine. Maybe he ought to thank me, though, for having avoided a major stroke thus far and for helping him to avoid the development of full-blown diabetes (wait, that's another trial, with valsartan--NAVIGATOR). It is reassuring that no increase in ESRD or dialysis needs were noted, despite the renal issues with tight control.

With regard to INVEST and ACCORD BP, there are a few points we need to remember. These were not congestive heart-failure patients, who sometimes run a very low BP and still do well when we need to add lifesaving beta blockers. The ACCORD and INVEST patients were not otherwise-healthy patients with just a little high blood pressure. In INVEST, the presence of cardiovascular disease was a requirement for entry, and in ACCORD, approximately 30% of the population had established cardiovascular disease.

It seemed that just about everyone who was interviewed about these trial results was a bit shocked. After these presentations, let's not be like those who pretend to have no idea what is going on when everyone jumps out from behind the couch wearing party hats and blowing noisemakers. Ignoring this data would be a little like playing along, and playing along is only "fun" when it comes to surprise parties. For tight BP control and fenofibrate-statin-induced lipid treatment in type 2 diabetics; the surprise party is finally over.

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Your comments

	Surprise, surprise! Time to INVEST in the gospel ACCORDing to ACCORD
	# 1 of 1	March 29, 2010 11:23 (EDT)
	W.E. Feeman, Jr, MD	I am afraid I must disagree, at least in part, on your position on fibrates, Melissa.  By fibrates, I mean of course, fenofibrate.  I am an aggressive interventional lipidologist, and my patients treated with various statins combined with gemfibrozil have since 1987 suffered four episodes of rhabdolysis--an experience described in the Readers' Comments section of the American Journal of Cardiology on page 1521 in the 15 May 2008 issue.  I too have had a combination therapy lawsut, which was dropped once the plaintif got his money from AG  Bayer.  Since switching to fenofibrate in 2004,  my patients have had no cawses of rhabdomyolysis.  About 255 of my lipid clinic of about 250 patients are receiving combination therapy with statin (usually rosuvastatin) and fibratae (always fenofibrate). In ACCORD patients were put on fenofibrate without regard to lipid status, so it is not surprising that fibrates were not helpful.  I reserve fenofibrate for people with very high TG to prevent pancreatitis or for those with low-HDL/high-TG, not with the idea of particularly lowering TG, but rather with the idea of raising HDL.  I am sure that you are aware that marvelous benefit accrued in the Helsinki Heart Study on gemfibrozil, but only in patients with CT:HDL >4.9 and TG > 300 mg/dl.  Also VA HITshowed benefit, though LDL was not lowered.  It has been known for years that the maximum angiographic regression of coronary plaque occurs when LDL is lowered simultaneously with raising HDL, as was first noted by Bob Levy, MD, about 25 years ago. If you are going to the NLA meeting in Chicago in May, I will be doing a series of posters on my approach to dysliupidemia.  I would be happy to see you there.

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