A new class of cholesterol drugs - the PCSK9 inhibitors - might reduce the risk of heart attacks and strokes, and some trials were recently presented demonstrating these evidences, but we do not have large populacional studies really showing it? What do you think? Is longer the time for regulatory agencies release this group of medications for regular use of the population?
PCSK9 inhibitors target and inactivate a specific protein in the liver. Knocking out this protein, called proprotein convertase subtilisin kexin 9, dramatically reduces the amount of harmful LDL cholesterol circulating in the bloodstream. The results of three clinical trials involving PCSK9 inhibitors were presented at the annual meeting of the American College of Cardiology, and simultaneously published in the New England Journal of Medicine, suggest that these may be a very useful drug for dyslipidemia. The trials show that PCSK9 inhibitors are extremely powerful cholesterol-lowering agents. In all three trials, all of the participants took a statin. Half got a PCSK9 inhibitor (either evolocumab or alirocumab) every two to four weeks; the other half got a placebo. After a year, LDL levels were 60% lower in the PCSK9 groups.
As with all drugs, there are downsides. At least for now, PCSK9 inhibitors which are basically developed as monoclonal antibodies, must be given by injection every 2 to 4 weeks. Neurocognitive problems, such as mental confusion or trouble paying attention, were seen in some of the study participants. And regarding cost, CVS officials have estimated that a year’s worth of treatment could cost as much as $7,000.
PCSK9 inhibitors are still experimental drugs. The three trials presented at the American College of Cardiology meeting were designed to look at how well the drugs lowered LDL, not how well they prevent heart attack, stroke, and other cardiovascular problems. Other trials now underway aim to do just that. The FDA can’t begin to evaluate whether PCSK9 inhibitors should become part of the cholesterol-lowering armamentarium until after the results of these trials have been presented and published, and better information is available about the drugs’ side effects.
Among the ongoing phase 3 trials, one is Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial which is basically a double-blind, randomized, placebo-controlled, multicenter study assessing the impact of additional LDL-cholesterol reduction on major cardiovascular events when evolocumab (AMG 145) is used in combination with statin therapy In patients with clinically evident cardiovascular disease. Estimated time for this study completion is February 2018. Another one is Trial Assessing Long Term Use of PCSK9 Inhibition in Subjects With Genetic LDL Disorders (TAUSSIG) trial whose estimated time foe completion is January 2020.
If approved, these drugs would probably be used first in people who don’t respond to statins or who develop side effects from them. But because it appears that PCSK9 inhibitors reduce the risk of heart attack and other cardiovascular problems in those taking a statin, combining a statin and a PCSK9 inhibitor may be a good option for people at especially high risk for cardiovascular disease. We’ve never before had medications that can reduce LDL cholesterol levels this much. Time will tell if PCSK9 inhibitors safely prevent heart attack and stroke. Thus, let us hope that the trials will eventually come out with promising results, so that regulatory agencies can grant approval as early as possible to control widespread surge of dyslipidemia and associated cardiovascular and cerebrovascular accidents.
do we have any additional literature on the mechanism of action of these PCSK9 family.l
There is a nice editorial just published in NEJM that discusses this:
http://www.nejm.org/doi/full/10.1056/NEJMe1502192#t=article
thank you this is very helpful, i will search for a chart, diagram to the pathways and the direct location of action within the overall biochemical synthesis. Thanks again,
About this issue ,SPIRE 1 and SPIRE 2 clinical trials are currently performed by Pfizer.
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