Heart and blood vessel disease remains a major cause of ill-health and deaths worldwide. Management of cholesterol levels is an important part of preventing such disease and often involves use of cholesterol-lowering drugs. As statins are in general the most effective available lipid-lowering drugs, and relatively low cost, they are usually recommended as first line treatment. However, discontinuation of the first trialled statin option is common and often occurs within 1-2 years of starting treatment. As studies indicate many perceived statin side effects are actually unlikely to be attributable to statins per se, guidelines promote statin re-trial in cases of discontinuation due to potential drug intolerance. Recent studies indicate that re-initiation rates are relatively high. However, it is not clear how frequently and quickly reinstated/alternative trialled statin therapies are discontinued. This is important as the impact cholesterol has on blood vessels appears to accumulate across the lifetime, and the extent of treatment benefit is therefore correlated with duration of use. We therefore aim here to investigate the patterns of statin use post-potential intolerance events in a sample of UK primary care patients. As it is also unclear whether alternative cholesterol-lowering drugs are trialled where reinitiated/alternative statins are not used in cases of potential intolerance, we also aim to investigate this.
Aim: To investigate the nature and duration of lipid-modifying therapy (LMT) prescribed in response to potential intolerance to first statin
Study design: Historical open cohort study
Observational period: 1998-2016
Population: A UK primary care cohort, LMT-naïve at baseline, initiated on first statin between 1998-2014
Analyses and outcomes: Descriptive analyses will be undertaken, exploring:
1. Time-to-statin discontinuation (first break in statin coverage for >90 days)
2. Time-to-potential statin intolerance (= any of treatment discontinuation for >90 days, switching to a lower statin dose or alternative statin type of the same or lower intensity)
3. The short-term responses to potential statin intolerance: extent and nature of re-initiated or alternative LMT commenced within 180 days of expiration of prescription of original statin regime
4. Time-to-discontinuation or reduction of the response treatment (where applicable)
5. For statin and non-statin therapies: means days per year covered by prescription, for each year of follow-up post-initiation of first statin
Subgroup analyses: the above outcomes will be described for the full cohort, with survival on first statin regime additionally described by CVD risk category and nature of statin therapy, and survival on treatment initiated in response to potential statin intolerance described by the nature of LMT trialled.
Time-to-discontinuation or reduction of first trialled statin regimen
- Time-to-discontinuation or reduction of LMT regimen trialled post-discontinuation/reduction of first statin therapy regimen
- Time-to-discontinuation of all statins after commencing first statin regimen
- Days per year of follow-up covered by LMT prescription after commencing first statin regimen
Kausik Ray - Chief Investigator - Imperial College London
Ailsa McKay - Corresponding Applicant - Imperial College London
Azeem Majeed - Collaborator - Imperial College London
Roger Newson - Collaborator - Imperial College London