UK
Clinical Pharmacy
Association
UK
Clinical Pharmacy
Association
As well as achieving a reduction in LDL-C of over 50% in a high intensity regime, it has been suggested that statins can also provide anti-inflammatory and antioxidant effects. The European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) task force supports early and intensive statin therapy post-acute coronary syndrome (ACS).
Although placebo controlled randomised trials have shown that statin induced myopathy and true intolerance is rare, we would consider a person intolerant should they experience an adverse drug reaction representing an unacceptable risk to that person or if it may result in non-adherence4.
In 2017, the Leeds Teaching Hospitals NHS Trust developed a pharmacist-led Cardiology Innovative Medicines Optimisation lipid service in response to the publication of the PCSK9 inhibitor NICE technology appraisals. As well as centralising the prescribing of PCSK9 inhibitors in the area, the service leads took a holistic approach to lipid management, including management of those with a perceived intolerance to statins.
Statin therapy is discussed with each new person referred to the clinic. In those referred with a statin intolerance label, the clinic team explore actual versus potential concerns, experience or issues with statins in the past, which statins they had tried and at what doses, what symptoms they suffered with, and how they felt about re-challenge in the future.
As per the AAC Statin Intolerance Pathway, any patients attending clinic who reported muscle related side effects which developed or worsened after initiation of a statin were offered a creatine kinase test (alongside assessment of severity of symptoms). This can either rule out statin as a cause of symptoms and offer reassurance to the affected person, or to confirm that statins are indeed the cause. In the case of a significantly raised CK and intolerable symptoms, alternative lipid lowering therapies are offered. Any patients reporting atypical symptoms of statin related myopathy, with a normal CK, should be investigated for other causes (for example, vitamin D deficiency).
A statin re-challenge is offered where not contraindicated. If agreed, taking a shared decision-making approach, the clinic team will often initially suggest rosuvastatin 5mg once a week, with a clear self-management plan to up- or down-titrate until they are able to identify a tolerated regime. The team measure LDL-C at baseline, then every 2-3 months after any change.
Over six months, 207 clinic patients were reviewed. Of those, 73% were labelled as statin intolerant at referral. Most of these patients reported musculoskeletal adverse effects. As well as the more expected ADRs (such as GI upsets and deranged LFTs), some of the other reactions reported included angioedema, pins and needle, generally feeling unwell, and vertigo.
Just under half (45%) of patients labelled as intolerant accepted a statin re-challenge and 62% of them were successfully restarted and continued on a statin. The vast majority of patients successfully established on a statin were prescribed rosuvastatin, with once a day being the most common dosing regimen.
Around half (51%) of patients did not accept a statin re-challenge. Of these, a 71% majority experienced musculoskeletal adverse events and 81% were eligible for treatment with PCSK9 inhibitors. It was found that patients who were eligible for PCSK9 inhibitors were less likely to accept a statin re-challenge with a two-sided p-value of 0.012.
In patients established on a statin and not on a PCSK9 inhibitor, LDL-C was reduced by an average of 31%. This increased to 40% if in combination with ezetimibe, or reduced to 20% in statin monotherapy. Although 20% seems low, it reflects lower doses used to successfully initiate statins. In patients who were able to successfully continue statins in addition to PCSK9 inhibitor therapy, this reduction in LDL-C increased to 62%.
Since that data was collected, bempedoic acid and inclisiran have also been licensed as LDL lowering treatments and recommended by NICE TAs (TA694 and TA733 respectively). The ES-BempedACS study concluded that adding a statin to high intensity statins plus ezetimibe was safe but did not increase the percentage of patients reaching LDL-C targets at 8 weeks. The Leeds Teaching Hospitals NHS Trust lipid service would therefore not recommend this in practice. However, in patients on less than a daily dose of statins, where other options have been tried or not appropriate, bempedoic acid could be considered and offered.
A combination of lipid-lowering therapies has been shown to produce better reduction in LDL-C and supports the ESC/EAS “strike early and strong” approach.
By adopting a person-centred approach, statins can be initiated or re-established in people on statins who were previously labelled as intolerant. They can be used in combination with other lipid lowering therapies to help support people to reach their LDL-C lowering targets.
The opinions expressed in this article are those of the author. They do not purport to reflect the opinions or views of the UKCPA or its members. We encourage readers to follow links and references to primary research papers and guidance.
The author declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
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