Cardiologists have moved to defend the use of the lipid lowering drug ezetimibe in certain patients after a post market review reveals that up to 15% of all patients on the drug could be receiving it outside of PBS restriction criteria.

Regulators are now considering recommendations to remove all PBS restrictions on statins while moving ezetimibe to a Restricted Benefit listing instead of its current Authority Required Streamlined listing – a move which the PBS says will remove existing barriers to prescribing cholesterol lowering medicines but will ‘confine’ the more expensive ezetimibe to second line therapy.

But in submissions to the Department of Health, cardiologists have argued that increased ezetimibe use is ‘inevitable’ as it is difficult to achieve increasingly lower LDL targets in the highest risk patients using statins alone.

For most patients, the PBS restrictions for ezetimibe require up-titration of statins to maximally tolerated doses before starting treatment with the drug.

However in its draft report to the PBAC, the ezetimibe reference group said that about 15% of the 45,465 patients who had been prescribed the drug between April 2014 and May 2016 had no prior exposure to statins or other lipid lowering therapy (LLT) in the two years before their first use of ezetimibe.

What’s more, 68% of that group ‘clearly’ do not meet PBS criteria of being statin intolerant or statin contra-indicated the report says.

And while 85% of patients on ezetimibe did have a prior statin or LLT history – indicating general overall compliance to restriction criteria – only 10% up-titrated their statin dose or switched to a statin of higher potency in the two years before being prescribed ezetimibe.

There may be legitimate clinical reasons to explain the absence of statin titration, the group concedes – for instance, patients may have already been optimally titrated before the study period, it said.

But in a number of submissions to the Department of Health, several cardiologists say that current prescribing practices are in line with recent studies like IMPROVE-IT, which showed significant, albeit modest, gains with achieving an LDL-C of 1.4 mm/mol compared to 1.8 mmol/L – a target that many patients won’t reach on statins alone.

Director at the Geelong Cardiac Research Unit in Victoria, Professor John Amerena said in his submission said that while statins are his first line choice for LLT many patients can’t tolerate the high doses required to achieve current target levels and develop adverse effects that usually reoccur even after transient discontinuation of the statin and reintroduction at a lower dose of another agent.

“This is where ezetimibe is a particularity useful drug as it will lower cholesterol by 20-25% on top of any dose of a statin. This is a clinically meaningful and significant reduction in cholesterol and will often allow target levels to be obtained in the absence of side effects,” he told the review committee.

Consultant cardiologist at Alfred Hospital, Melbourne, Professor Paul Nestel said that it was ‘vital’ to recognise that intolerance to statins occurs more frequently than the literature suggests – he says about 10% of patients on any of the statins would be affected by a genetically based low clearance capacity.

“People with low clearance capacity will have a supra-normal blood concentration at conventional dosage. Several manoeuvres enable a proportion of [statin] intolerant patients to tolerate a lower dosage or less frequently taken dosage. It is this scenario that leads to most ezetimibe prescriptions,” he wrote.

Senior cardiologist at Austin Health in Melbourne, Professor David Hare suggested that statin intolerance rates are closer to 20% when less tight definitions of intolerance are used – which is usually the case in clinical practice versus clinical studies, he says – and arguably more clinically significant “because it is the patient perception that determines the adherence to therapy,” he noted.

Meanwhile drug sponsor MSD has said it does not believe there is an issue with inappropriate prescribing and maintains that any minimal use outside of the restriction could be explained and would be clinically appropriate.

The Department of Health is inviting submissions from interested cardiologists addressing the draft Report to the PBAC for this Review. Submissions must be lodged by 5pm Friday, 10 February 2017.