More evidence needed before PCSK9 inhibitor use widens

Prohibitive costs have not dampened enthusiasm for PCSK9 inhibitors with many cardiologists calling for new lipid management guidance to include the use of the agents – and in wider patient groups.

However Professor Stephen Nicholls, director and clinical council chair of the Australian Atherosclerosis Society, cautioned that more outcomes data was needed to better understand the LDL lowering effects of the costly agents.

“Every man and his dog seemed to want to issue PCSK9  guidelines before we had any outcome data whatsoever partly on the basis of what they thought they were going to see in terms of reduced events on the basis of LDL reduction and partly on the basis of, what I thought were inappropriate, outcome reports in the NEJM in 2015 pooling data from longer term lipid studies which were extraordinarily optimistic suggesting that these agents were going to reduce events by 50%.”

“Now we know, at least in the first instance, FOURIER demonstrated that the benefit in high risk patients was far less than that,” he told a lipid management workshop during the CSANZ 2017.

While PCSK9 inhibitors are currently only available in Australia to patients with familial hypercholesterolemia, countries like the US and Europe have embraced their use early on – recommending the drugs also be considered for patients at very high risk for a cardiovascular event, particularly where atherosclerotic cardiovascular disease [ASCVD] is established.

Professor Nicholls called that approach ‘optimistic’.

“The American Endocrinology guidelines – which I thought, frankly, were the most optimistic for these agents particularly in light of the fact that there is very little evidence to date beyond their role in lipid lowering – have a very strong endorsement in patients with familial hypercholesterolemia and a very strong endorsement in those with ASCVD particularly in patients who are unable to achieve conventional treatment goals on maximally tolerated statins.”

He argued that future outcomes data analyses from FOURIER would be needed before such recommendations could be endorsed in Australia.

“These are expensive agents – we need to find the right patient to use these drugs and I think seeing more information come out of FOURIER will help us try to understand where the greater relevant and absolute reductions were … marrying that with real cost effectiveness data as opposed to what’s in the literature at the moment which is largely speculative will help a lot.”

But workshop participants said there might well be many ‘right’ patients missing out on the therapy.

“The patients I’ve got are really sweating on these agents,” said one delegate.

“They’ve got statin intolerance, they’ve got bad coronary disease often poor LV function and I cant get them this stuff while I can get them to patients with FH with normal coronaries – that just doesn’t seem right. It took about 15 years before we started recommending statins for patients at the highest risk and we’re making the same mistake here.”

Another delegate reminded the audience that similar arguments about cost were used in the case of statins before they became a mainstay of cholesterol lowering therapy.

“We had exactly the same discussion about statins and how expensive they were at the time but prices changed dramatically over time … it’s important that we set the goals for what we’d like to be able to do first then ask what we could afford to do rather than take the health economic consideration at the get go.”

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