Observational study of ezetimibe discontinuation in primary care practices in the UK

Abstract

Objective:

We investigated the circumstances of ezetimibe discontinuation as its prescribing had been discouraged in some publications.

Research design and methods:

Adults on stable lipid-modifying therapy (LMT) including ezetimibe, who then had >8 weeks cessation in their prescribed ezetimibe regimen (2010–2011) were identified from THIN UK primary care database. Lipid values and parallel changes to other LMT were described overall and in a sub-group with a history of diabetes, cardiovascular disease or familial hypercholesterolaemia (high-risk group).

Results:

Ezetimibe therapy stopped in 7087 patients after a mean of 38 months; 67.0% were in the high-risk group. No lipid readings were recorded for 16.1% of patients in the year before and 26.2% in the year after ezetimibe stopped; 11.0% and 12.4% in the high-risk group respectively. In the prior year, 60.2% patients with any lipid reading had a total cholesterol (T-cholesterol) <5 mmol/l and 59.2% had a T-cholesterol <5 mmol/l and LDL-cholesterol <3 mmol/l. In the high-risk group, 66.8% had a T-cholesterol <5 mmol/l, 38.9% had either a T-cholesterol <4 or a LDL-cholesterol <2 mmol/l and 29.4% had reached both targets. In both populations, 42% patients had 6 months’ follow-up after ezetimibe stopped with no change to other LMT. An LMT change within 8 weeks (19%) was usually a new statin while 27% overall had a further ezetimibe prescription after 8–26 weeks.

Limitations:

Only absolute lipid values were included, as percentage change from baseline level may not be reliable. The study included a larger proportion of patients in Scotland relative to the UK population.

Conclusions:

Prescribed ezetimibe often stopped without either a recent lipid value or attainment of optimal, or sometimes minimum, lipid targets. Patients did not always receive parallel intensification of other LMT or a further ezetimibe prescription within 6 months.

Keywords::

• Cholesterol
• Ezetimibe
• Lipid mediating drugs
• Lipid regulation
• Primary care
• Targets

Transparency

Declaration of funding

The study was funded by Merck Sharp & Dohme Ltd (MSD), without restriction on publication. Gillian Hall was funded by MSD to develop a design and run the study to answer objectives provided by MSD. No payment was made to Gillian Hall for the preparation of the manuscript.

Author contributions: G.C.H. contributed to the design, analysis, interpretation and reporting of the study and was responsible for the manuscript. K.J. contributed to the conception, design and interpretation of data and commented on the manuscript. V.A. contributed to the study design, familial hypercholesterolaemia codes lists, the report and commented on the manuscript. C.O’R. was involved in developing the initial concept, the familial hypercholesterolaemia codes lists, and commented on the manuscript. All authors approved the final manuscript.

Declaration of financial/other relationships

G.C.H. has received funding for research and consultancy from a number of pharmaceutical companies and charities, including MSD. V.A., C.O’R. and K.J. were employed by MSD at the time of the study, and hold shares in the company.

CMRO peer reviewers may have received honoraria for their review work. The peer reviewers on this manuscript have disclosed that they have no relevant financial relationships.

Acknowledgements

The authors thank Michelle Johnson and others at Cegedim Strategic Data who provided the data cut from THIN, and those at practices which contribute data to the THIN database.

Supplementary material available online Supplementary Tables 1--2