MedicalResearch.com Interview with:
Prof. Dr. Ioana Gouni-Berthold MD
Center for Endocrinology, Diabetes and Preventive Medicine (ZEDP)
University of Cologne
MedicalResearch.com: What is the background for this study?
Response: In Europe, up to half of the population aged between 35 and 64 has hypercholesterolemia (high levels of low-density lipoprotein cholesterol [LDL-C]), putting them at risk of heart disease. Despite increased treatment rates in recent years, many patients still do not receive adequate therapy, and heart disease remains the biggest cause of death in the USA and most European countries.
Two drugs, alirocumab and evolocumab, have recently been approved for lowering LDL-C in patients with hypercholesterolaemia as an ‘add-on’ therapy to other lipid-lowering medication, or for use alone in patients unable to tolerate statins. These drugs have a unique mode of action– they inhibit proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that binds to LDL receptors and targets them for degradation. In the absence of PCSK9, the LDL receptor recycling is restored and the receptors are able to remove LDL from the blood.
Both alirocumab and evolocumab have been tested in numerous patient populations in phase 3 trials; albeit evolocumab has an additional indication of homozygous familial hypercholesterolemia. We therefore felt that there was a need to collate the available data to assess the efficacy and safety of each agent. We chose reduction in LDL-C as our outcome of interest, because this was the primary endpoint of the pivotal clinical trials.
MedicalResearch.com: What are the main findings?
Response: Our systematic review identified 12 phase 3 studies of alirocumab and nine phase 3 studies of evolocumab, involving more than 10 000 patients overall, illustrating the large evidence base available for these drugs. Both agents were effective at reducing LDL-C across a broad population of patients and in specific subgroups, such as those with different cardiovascular risk levels and those with type 2 diabetes or chronic kidney disease. In addition, the agents had good tolerability profiles, with rates of adverse events similar to those in the control arms of the studies.
MedicalResearch.com: What should readers take away from your report?
Response: The data are encouraging as they suggest that using alirocumab or evolocumab as an ‘add-on’ therapy to statins or ezetimibe, or as monotherapy for patients unable to tolerate statins, will increase the number of patients who achieve their LDL-C goal levels, with few adverse events or treatment discontinuations. Given that high LDL-C is a major risk factor for heart disease, the use of these agents may lead to lower numbers of cardiovascular events such as heart attacks. Ongoing studies are investigating the effect of alirocumab and evolocumab on cardiovascular events and the results are awaited with interest.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: At the time of the study, only two PCSK9 inhibitors had been approved; however, others (such as bococizumab) are in development. It will be interesting to evaluate new agents against alirocumab and evolocumab, if and when they are approved. In addition, there are numerous ongoing studies of these two agents, and analysis of long term cardiovascular outcomes will add to the evidence base supporting use of these agents in clinical practice
MedicalResearch.com: Is there anything else you would like to add?
Response: PCSK9 was discovered in 2003 and less than 15 years later, we will have cardiovascular endpoint studies with antibodies that inhibit its’ function. Such rapid development is unheard of. If the preliminary safety and efficacy data are reproducible in the long-term studies, I think one could safely speak about anti-PCSK9 antibodies being the most exciting development in the lipid field since statins.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Br J Clin Pharmacol. 2016 Aug 1. doi: 10.1111/bcp.13066. [Epub ahead of print]
Systematic review of published phase 3 data on anti-PCSK9 monoclonal antibodies in patients with hypercholesterolaemia.
Gouni-Berthold I1, Descamps OS2, Fraass U3, Hartfield E4, Allcott K4, Dent R5, März W6,7,8.
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.
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