Many patients may no longer have the option to be reimbursed for taking the lipid lowering drug ezetimibe to achieve lower LDL-C targets if the PBS accepts recommendations to clamp down on costly overprescribing.

The number of patients prescribed ezetimibe outside of PBS restriction criteria could be as high 53% the Pharmaceutical Benefits Advisory Committee has claimed in a revised draft post market review of the lipid-lowering therapy (LLT) released this week.

In an earlier draft that number was just 15%, but following a re-analysis of PBS data undertaken in March this year at the request of the PBAC’s Drug Utilisation Sub Committee (DUSC) the review’s reference group now estimates that number could fall ‘somewhere in the range of 18.4% – 53.2%’

According to PBS data, some 45,645 patients had been prescribed the drug between April 2014 and March 2015.

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

The reference group claim that their March 2017 analysis found that 46.9 % of patients were prescribed ezetimibe in accordance with the restriction while just 18.4% of patients did not meet the criteria.

It was unknown whether a patient had previously been trialled with a statin before their ezetimibe prescription in nearly 35% of patients – but, in a much-maligned move, the group has recommended the PBAC consider including these patients in the overall number receiving the drug that do not comply with PBS restrictions.

Despite acknowledging the wide range as the ‘best estimate due to the limitations of PBS data’ and that some of this use might indeed be clinically appropriate, the group has defended its recommendation to further tighten restrictions on the therapy claiming that the estimated level of non-compliance to PBS restrictions is unlikely to be cost effective.

Arguing in its report that there is not enough evidence to support the widespread use of the drug over more potent or higher doses of statins, the group has recommended relegating use of the lipid lowering therapy to those with high risk of cardiovascular events in a secondary prevention population – a group that it claims derives the most significant benefit from the drug according to recent literature.

It says that during the seven years of IMPROVE-IT, patients with prior CABG received significantly greater benefit from treatment with ezetimibe in addition to simvastatin compared to those without prior CABG (Absolute Risk Reduction of 8.8% versus 1.3%).

It also cites another analysis of the IMPROVE-IT trial, which found that those who showed a significant benefit from ezetimibe plus statin therapy over statin monotherapy had three or more additional risk factors.

Low risk patients (nil to one risk factor) showed no benefit from the addition of ezetimibe.

“This underlines the importance of restricting PBS subsidised use of ezetimibe to the high risk population,” the review group maintained.

Among other measures designed to clamp down on overprescribing the group recommends moving ezetimibe to a Restricted Benefit listing while removing all current PBS restrictions from statins – a move which it says will eliminate existing barriers to prescribing cholesterol lowering medications but one that will confine the more expensive ezetimibe to second line therapy.

In response to previous versions of the draft report, several cardiologists expressed concern that if the PBS accepts the recommendations many patients will miss out on the benefits of achieving lower LDL-C targets than they could with 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

The Department of Health is inviting submissions from interested doctors addressing the draft Report to the PBAC for this review. Submissions must be lodged by June 6 2017.