PCSK9 inhibitors have a remarkable ability to lower low density lipid cholesterol by binding to proprotein convertase subtilisin–kexin type 9 in the liver. Three antibodies were developed to achieve this: evolocumab, alirocumab, and bococizumab.
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A number of landmark studies such as SPIRE, FOURIER and ODYSSEY proclaimed these drugs as massive breakthroughs, potentially changing the future of cardiology.
Tools for Practice, sponsored by the Alberta College of Family Physicians (ACFP), very nicely summarizes the evidence on these agents in their article
PCSK9 Inhibitors: Cardiovascular prevention panacea or pesky, pricey pokes?
The clinical question in the article:
Do pro-protein convertase subtilisin/kexin type 9 (PCSK9) inhibitors decrease cardiovascular events, and if so, are they cost effective?
The bottom line:
For patients with cardiovascular disease (CVD) already on maximally tolerated statins, adding evolocumab or alirocumab decreases new CVD events for an additional one in 65 patients compared to placebo over ~2.5 years. Routine use of these agents is not cost-effective at current prices.
View the ACFP's article in our Quick Links section to get full details.
Richard Lehman, a self-proclaimed Ancient English GP, who writes a weekly journal review in the BMJ, and is somewhat tongue in cheek but very practical, has been on the story since 2015. Initial studies showed promise in reducing CV events, but there were questions of how big the market might be and with the caveat from Sir William Osler that “The first duty of the physician is to educate the masses not to take medicine.”
More recently in March of 2017, it became apparent that the price tag for these drugs is high, up to $14,000 per year in the US, and a cost of $2 million US, or more, to avoid one event in a high risk population over two years. The effect on all cause mortality would zero.
We might anticipate more hyping of the “statin intolerance” concept too, as this will create another market sector.
In our Quick Links section, you can read Dr. Lehman's reviews in more detail.
So the main use of PCSK9 inhibitors may be to treat the more severe forms of hereditary hypercholesterolaemia, as we are not seeing a cost benefit ratio that would favour routine use of these agents for hyperlipidemia.