Clinical trial NCT01894217: Statin Therapy to Improve Medication Adherence
Official title: Pilot Study: Statin Therapy to Improve Medication Adherence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypercholesterolemia
HMG COA Reductase Inhibitor Adverse Reaction
Keywords: high cholesterol
genetic testing
medication adherence
statins
Adverse Effects
Pharmacogenetic
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2013-07-10
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The purpose of this pilot study is to examine if using genetics can improve statin adherence in patients who should be taking statins but are not because of prior side effects with statins. This study will assist physicians in making a personalized health care plan for prevention of cardiovascular disease.

Detailed description: HMG Co-A reductase inhibitors ("statins") are commonly prescribed to lower low density lipoprotein cholesterol (LDLc) and to prevent cardiovascular disease (CVD), a leading cause of morbidity and mortality. Long-term adherence to statins in the primary care environment is challenging; consequences of statin non-adherence include higher LDLc levels, hospitalizations, costs, and death due to CVD.

Medication non-adherence is complex and multifactorial and can be associated with a number of factors including medication cost, complexity of medication regimen, poor provider-patient relationship / communication, and adverse side effects. For statins, side effects such as muscle aches, cramping, and pain (referred to broadly as statin-related myopathy) are a frequent cause of non-adherence. These symptoms are non-specific and are frequent reasons for stopping statin therapy, due to patient or provider concern about the possibility of statin-related myopathy. Many patients may be needlessly deprived of the cardiovascular benefits of long-term statin use.

A genetic risk factor for statin myopathy and subsequent non-adherence has recently been identified. In a genome-wide association study, a genetic variant (named SLCO1B1\*5) was a main contributor of statin myopathy. It was demonstrated that the SLCO1B1\*5 variant is not only a predictor of myopathy, but also of premature statin discontinuation. The risk with the \*5 allele is statin specific: greatest with simvastatin and atorvastatin use, the least with pravastatin or rosuvastatin. Therefore, the SLCO1B1\*5 variant is common, can predict myopathy, subsequent non-adherence, and due to its statin-specific effects creates a novel research paradigm for personalizing statins to an individual's genetic profile. Carriers of the SLCO1B1\*5 variant may do best on rosuvastatin, pravastatin, or fluvastatin whereas non-carriers may be treated with any statin.

Specific Aims:

Aim 1: To measure the effect of genotype-guided statin prescription on patients' concerns regarding the risks of statin therapy.

Aim 2: To measure and compare the effect of genotype-guided statin prescription to non-guided therapy on statin adherence in patients who are currently not adherent to statins.

The approach for this pilot study is to recruit 100 Duke University Health System (DUHS) patients who receive care at Duke Primary Care at Pickett Road (DPC) or Center for Living (CFL) clinics that have an indication for statin therapy to reduce cardiovascular risk, but are not currently taking a statin. Consented patients will be genotyped for the SLCO1B1\*5 allele at the Duke Molecular Diagnostics Laboratory. Test results will be returned first to the provider along with genotype-specific strategies to revise and/or provide a new prescription for statin therapy and next to the patient along with genotype-specific information about their personal risk of side effects on certain statin therapies. The primary outcome measures will be collected through the use of online surveys administered to patients at two time points: 1) before genetic testing and 2) 4-months after testing. Additional survey elements to address the patient's demographics, beliefs and concerns about medications, history with prescription drugs (e.g., side effects and general compliance) and overall experience with genetic testing during the study will be administered as well. It is possible that subjects will re-experience symptoms of their prior statin-intolerance when re-challenged with statins as part of this study. By avoiding certain types of statins (i.e. simvastatin and atorvastatin) in carriers of the SLCO1B1\*5 genetic variant and using those statins (i.e. pravastatin and rosuvastatin) that in placebo controlled trials have no increased risk of adverse events, this risk may be less likely.

Age-, sex-, diagnosis-, and provider-matched concurrent and historical controls will be created in order to compare genetically-guided with non-genetically guided therapy

Eligibility criteria: Inclusion Criteria:

* Current patient (defined as seen in the last year) of the Duke Primary Care at Pickett Road or Center for Living
* Age greater than or equal to 18 years
* Provider interested in prescribing statins for cardiovascular disease prevention
* Ability to provide informed consent

Exclusion Criteria:

* Prior rhabdomyolysis, defined as CK elevation \> 10 times the upper limit of normal with any statin therapy
* Prior unexplained elevation in hepatic enzymes (AST or ALT \> 3 times upper limit of normal) with any statin therapy
* Use of medications known to interfere with statin metabolism or disposition
* Participation in a drug research study in the past 30 days

Primary outcomes:
measure: Change in Beliefs about Medicines
timeFrame: Baseline and four months post genetic testing
measure: Change in Medication adherence
timeFrame: baseline and four month post genotyping
Secondary outcomes:
measure: Percentage of patients who meets their National Cholesterol Education Program (NCEP) low-density lipoprotein cholesterol (LDLc)goals
timeFrame: Four months
measure: Number of new statin prescriptions written
timeFrame: Four months
measure: Patient reported medication utilization, as a surrogate for medication adherence
timeFrame: Four months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke Center for Living
state: North Carolina
city: Durham
country: United States
facility: Duke Primary Care Clinic at Pickett Road
state: North Carolina
Study officials:
affiliation: Duke University
name: Deepak Voora, MD
role: PRINCIPAL_INVESTIGATOR
References: