Evaluation of SLCO1B1, ABCG2, and CYP2C9 Genotyping on Statin-Induced Musculoskeletal Adverse Reactions in Cardiovascular Risk Patients

The primary objective of this pragmatic clinical trial is to evaluate the differences in the outcomes of **musculoskeletal adverse reactions** in patients treated with statins. The study compares a control group, receiving statins according to standard clinical practice, with an intervention group, where statin prescription is guided by prospective genotyping of **SLCO1B1**, **ABCG2**, and **CYP2C9**. This evaluation is conducted over a follow-up period of 6 months in patients receiving care from primary healthcare centers and hospitals. The clinical relevance of this objective lies in its potential to optimize statin therapy by reducing adverse reactions, thereby improving patient safety and treatment efficacy.

Secondary objectives include: - Evaluating differences in the incidence of musculoskeletal adverse reactions between the intervention and control groups over a 6-month follow-up period. - Assessing differences in the efficacy of statins, such as the reduction of LDL levels, between the two groups. - Comparing the incidence of cardiac events, mortality, and other musculoskeletal adverse reactions between the groups. - Evaluating the impact of prescribers' professional training on the incidence of musculoskeletal adverse reactions, statin efficacy, and the incidence of cardiac events and mortality. - Assessing the awareness of primary and hospital care physicians regarding the use of pharmacogenetic biomarkers and the need for training as a prescription tool. - Evaluating the cost-effectiveness of prospective genotyping of **SLCO1B1**, **ABCG2**, and **CYP2C9** in preventing musculoskeletal adverse reactions in patients treated with statins. - Exploring the impact of other genetic, clinical, and demographic variables on the efficacy and safety of statins. - Investigating the relationship between musculoskeletal adverse reactions and pharmacogenetic markers in all study participants. - Exploring other genetic variables in relation to other drugs.

The clinical trial involves a study population comprising **adults** with varying degrees of **cardiovascular risk**, including high, moderate, or low risk, for whom statin treatment is indicated. The trial includes both male and female participants, with an age range that spans from young adults to older adults. Participants are required to be outpatients recruited from healthcare centers or hospitals, and they must have either never taken statins, started statin treatment less than 15 days ago, or had their statin dose increased or changed to a more potent statin due to inadequate control of LDL levels within the last 15 days. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. Participants are expected to provide written informed consent. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the impact of preemptive genotyping of **SLCO1B1**, **ABCG2**, and **CYP2C9** on the incidence of musculoskeletal adverse reactions in patients treated with statins. This is a pragmatic, randomized, double-blind, controlled trial involving patients with cardiovascular risk requiring primary or secondary prevention with statins. The trial will compare outcomes between a control group receiving standard clinical practice and an intervention group receiving statins based on prospective genotyping. The trial is expected to last until January 2026, with recruitment starting in March 2024.

Participants will undergo a series of study visits, beginning with an inclusion visit where eligibility is confirmed based on criteria such as being an adult with cardiovascular risk and having recently started or adjusted statin therapy. Follow-up visits will occur at regular intervals to monitor the incidence of musculoskeletal adverse reactions, with primary endpoints assessed at six months and secondary endpoints at twelve months or longer. The end-of-study visit will conclude the participant's involvement, summarizing their health outcomes and any adverse reactions experienced.

The expected duration of participant involvement is up to 24 months, with conditions for early termination including withdrawal of consent or significant adverse reactions. The trial will utilize oral administration of statins, including **pravastatin sodium**, **atorvastatin**, **pitavastatin calcium**, **fluvastatin sodium**, and **rosuvastatin zinc**, with dosages tailored to individual patient needs. The trial is classified as a low-intervention study, as it involves drugs already on the market and does not include additional procedures beyond standard clinical care.

The clinical trial involves the administration of several **statins** to evaluate their effects on musculoskeletal adverse reactions. **Pravastatin sodium** is one of the experimental medications used in this study. It is administered in an oral pharmaceutical form, with a maximum daily dose of 40 mg. The treatment period for pravastatin sodium is up to 24 weeks. Participants are required to take the medication orally, and compliance is monitored throughout the study duration.

Another experimental medication in the trial is **atorvastatin**, which is also administered orally. The maximum daily dose for atorvastatin is 80 mg, and the treatment period extends to 24 weeks. The pharmaceutical form of atorvastatin is designed for oral administration, and participant adherence to the dosing schedule is closely monitored.

**Pitavastatin calcium** is included in the trial as well, with a maximum daily dose of 4 mg. This medication is administered orally, and the treatment period is set for 24 weeks. The pharmaceutical form of pitavastatin calcium is optimized for oral intake, ensuring consistent dosing and monitoring of participant compliance.

**Fluvastatin sodium** is another statin used in the study, with a maximum daily dose of 80 mg. It is administered orally, and the treatment period is 24 weeks. The pharmaceutical form of fluvastatin sodium is suitable for oral administration, and participant adherence is tracked throughout the trial.

Lastly, **rosuvastatin zinc** is administered with a maximum daily dose of 40 mg. The treatment period for rosuvastatin zinc is 24 weeks, and it is provided in an oral pharmaceutical form. Compliance with the dosing schedule is monitored to ensure accurate assessment of the medication's effects.

All medications are administered as part of a pragmatic clinical trial to assess the utility of preemptive genotyping and pharmacogenetics training on the incidence of musculoskeletal adverse reactions in patients treated with statins. The trial does not include any non-experimental treatments such as placebo or comparator treatments. The focus is on evaluating the outcomes of statin treatment based on prospective genotyping of specific genetic markers.

Efficacy in this clinical trial will be assessed by evaluating the incidence of **musculoskeletal adverse reactions** in patients treated with statins. The primary endpoint is the incidence of these adverse reactions during the first 6 months of treatment, with measurements taken at the 6-month mark. A secondary endpoint includes the incidence of musculoskeletal adverse reactions at 12 months or longer follow-up. The trial involves two groups: a control group receiving statins according to clinical practice and an intervention group receiving statins based on prospective genotyping of SLCO1B1, ABCG2, and CYP2C9. The follow-up period for efficacy assessment is 6 months, with the potential for extended observation at 12 months or beyond. The trial is designed to compare outcomes between these groups to determine the impact of genotyping on the incidence of adverse reactions. The study will be conducted in primary healthcare centers and hospitals, ensuring a comprehensive evaluation of the efficacy of the intervention across different care settings.