Do lipid guidelines need to change just because there is a new, expensive drug on the market? NO!

Shrank and colleagues published a viewpoint online today positing that lipid guidelines should return to LDL based targets. I think they are wrong. The use two studies to support their assertion.

First they use the IMPROVE IT study. In this study patients hospitalized for ACS were randomized to a  combination of simvastatin (40 mg) and ezetimibe (10 mg) or simvastatin (40 mg) and placebo (simvastatin monotherapy). The LDLs were already pretty low in this group: baseline LDL cholesterol levels had to be between 50 to 100 mg per deciliter  if they were receiving lipid-lowering therapy or 50 to 125 mg per deciliter if not on lipid lowering therapy (Average baseline LDL was 93.8 mg/dl). The results show minimal benefits as demonstrated below:

IMPROVE IT resultsCurrent guidelines would recommend high potency statin in this patient population. Adding ezetimibe to moderate dose statin is probably equivalent to a high potency statin (from a LDL lowering  perspective). This study (and all ezetimibe studies) should have tested the difference between simva 40-ezetimbe 10 and simva 80mg or atorvastatin 40 or 80mg. So to me IMPROVE IT doesn’t PROVE anything other than a more potent statin leads to less cardiovascular events…something we already know.

Now on to the 2nd argument. They argue that alirocumab (Praluent), the first in a new class, the proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors should lead to LDL guided therapy again. Why? “Early results suggest these drugs have a powerful effect on levels of low-density lipoprotein cholesterol (LDL-C), likely more potent than statins“. A systematic review of studies of this drug shows a mortality reduction but the comparators in these studies was placebo or ezetimibe 10mg. Why? We have proven therapy for LDL and this drug should have been compared to high potency statins. That study will likely not ever be done (unless the FDA demands it) because the companies making this drug cant risk finding that it works only as good as a high potency statin or possibly worse.  Also does this class of drugs have anti-inflammatory effects like statins? Are they safer? This is an injectable drug that has to be warmed to room temperature prior to use and is very costly compared to generic atorvastatin.

In my opinion, no guideline should be changed without appropriately designed outcomes studies for the drugs being recommended. In this case, the risk-benefit margin needs to be impressive to justify the cost as we have dirt cheap potent statins already.

The authors of this viewpoint make no great rational argument for guidelines change other than that there is a new drug on the market and it might work. Lets see if it does and at what cost (both monetary and physiological).

One thought on “Do lipid guidelines need to change just because there is a new, expensive drug on the market? NO!

  1. Thanks for your comments. I had the same concerns.

    Also the author states ” For patients at high risk of a cardiovascular event, high-dose, high-potency statin medications are recommended, indicating that more aggressive management of cholesterol is appropriate—lower LDL-C is better. ” This is incorrect. The new recommendations were based on the fact that lower was not necessarily better. The high dose statin resulted in the benefit, not necessarily the degree of LDL lowering.

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