Personalised Hyperlipidaemia Therapies Guided by Pharmacogenomics

Designing Therapy to Suit You - Personalised Hyperlipidaemia Therapies Guided by Pharmacogenomics (DTSY Lipid PGx): A Randomised Controlled Trial

This trial aims to evaluate the impact of clinical pharmacists' pharmacogenomics-guided choice and statin titration for managing hyperlipidaemia.

The central hypotheses of this trial are (1) clinical pharmacists' pharmacogenomics-guided choice and titration of statins will lead to a more significant reduction in LDL-c; (2) lower incidence of myopathies with the use of statins for hyperlipidaemia management over 12 months compared to usual care by doctors alone. Active follow-up and titration should occur over the first six months. However, the participants will be followed up to 12 months to confirm the sustained LDL level attainment.

The primary aims are:

• The changes in Low-Density Lipoprotein cholesterol (LDL-c), total cholesterol, triglycerides (TG), and high-density lipoprotein cholesterol (HDL-c) levels, and
• The incidence of myopathies over 12 months.

The secondary aims include:

• Characterisation of the pharmacogenomic relationship between serum levels of statins (and their metabolites) with the changes in LDL-c levels and incidence of myopathies over six months
• Economic outcomes include but are not limited to the cost-effectiveness of pharmacogenomic testing in attaining LDL-c targets
• Change in health-related quality of life over 12 months is measured using the EuroQoL 5-Dimension 5-Level questionnaire

Inclusion Criteria:

• Participants between 21 and 75 years old
• Participants who are planning to start on statin* medication or whose LDL-c goals have not been met, per Appendix B.
• Participants who are able to communicate in English, Chinese or Malay.

Participants who are planning to start or will be started on the following doses are eligible: atorvastatin 10-80 mg/day, rosuvastatin 10-40 mg/day, or simvastatin 10-40 mg/day within the last two to four weeks before enrolment

Exclusion Criteria:

• Participants who are statin-intolerant or in whom statins are contraindicated
• Participants on a statin dosing schedule of every other day (EOD)
• Participants administered on potent Cytochrome P450 3A4 (CYP3A4) or Cytochrome P450 2C9 (CYP2C9) or OATP inhibitors or inducers.
• Participants on evolocumab and alirocumab prior to enrolment
• Participants with documented diagnosis of psychiatric conditions
• Participants requiring palliative care, end-of-life care, or those with a life expectancy of less than one year
• Pregnant and lactating women
• Participants with complaints of myalgia or muscle weakness at baseline, before the commencement of statin
• Participants who are unable to swallow a whole statin tablet