Clinical trial NCT01894230: Genetically Guided Statin Therapy
Official title: Genetically Guided Statin Therapy to Improve Medication Adherence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypercholesterolemia
Hydroxy-methylglutaryl-coenzyme A (HMG Co-A) Reductase Inhibitors Adverse Reaction
Keywords: high cholesterol
genetic testing
medication adherence
statins
Adverse Effects
pharmacogenetics
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: David Grant U.S. Air Force Medical Center
First posted: 2013-07-10
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this 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. This study will assist physicians/providers in making a personalized health care plan for prevention of cardiovascular disease.

Detailed description: Hydroxy-methylglutaryl-coenzyme A (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.

The objective of this study is to conduct a randomized trial comparing two strategies:

1. genetically guided statin therapy vs.
2. usual care (i.e., a strategy without genetics) on the effects of statin adherence and LDLc lowering.

The overall hypothesis is that genetically guided statin therapy will lead to greater statin adherence and lower LDLc when compared to a non-guided strategy. The design of this trial will randomize primary care patients within Duke University Health System (DUHS) and travis Air Force Base (TAFB) clinics that are nonadherent to statins due to prior side-effects in an unblinded, 1:1 fashion, stratified by SLCO1B1\*5 genotype.

Eligibility criteria: Inclusion Criteria:

* Current patient (defined as seen in the last year) of the Duke Primary Care at Pickett Road, Pickens Family Medicine Center or Travis Air Force Base
* Age greater than or equal to 18 years
* Current non-utilization of statin therapy for either of the following reasons: (a) Prior side effects thought to be attributed by the patient to statin use AND/OR (b) Physician removal of statin due to presumed associated side effects
* No statin use for the past 6 weeks
* Active email account
* Computer access available in order to complete on-line surveys
* Ability to provide informed consent

Exclusion Criteria:

* Prior rhabdomyolysis, or Creatine Kinase (CK) elevation \> 10 times the upper limit of normal with any statin therapy
* Prior unexplained elevation in hepatic enzymes \[Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) \> 3 times upper limit of normal\] with any statin therapy
* Current daily grapefruit juice usage (on average \>1quart/day)
* Expected long term use (longer than 3 months) of the following medications known to interfere with statin metabolism or disposition at time of enrollment until the randomization is complete. However, short-term (\<14 days) is allowed for the duration of the study
* Participation in a drug research study in the past 30 days
* Previous use of 4 or more statins

Primary outcomes:
measure: Morisky Medication Adherence Scale (MMAS) Score
timeFrame: 3 months and 8 months
Secondary outcomes:
measure: Low Density Lipoprotein Cholesterol (LDLc) at Baseline, Month 3 and Month 8
timeFrame: Baseline, Month 3, Month 8
measure: Medication Possession Ratio (MPR) From Baseline to Last Patient Follow-up
timeFrame: Baseline to Last patient follow-up in study (3 months or 8 months)
measure: Number of Participants Reporting New Statin Prescriptions
timeFrame: Baseline, Month 3, Month 8
measure: Brief Pain Inventory (BPI) Score - Pain Severity at Month 3 and Month 8
timeFrame: Month 3 and Month 8
measure: Brief Pain Inventory (BPI) Score - Pain Interference at Month 3 and Month 8
timeFrame: Month 3 and Month 8
measure: Change in Short Form -12 Item (SF-12) Health Survey - Physical Component (PC)
timeFrame: Baseline, Month 3, Month 8
measure: Change in Short Form -12 Item (SF-12) Health Survey - Mental Component (MC)
timeFrame: Baseline, Month 3, Month 8
measure: Physical Activity Scale Score
timeFrame: Baseline and Month 8
measure: Beliefs About Medications (BMQ) Score at Baseline, Month 3 and Month 8
timeFrame: Baseline, Month 3, Month 8
Other outcomes:
Locations:
city: Travis Air Force Base
country: United States
facility: David Grant US Air Force Medical Center
state: California
city: Durham
country: United States
facility: Duke University
state: North Carolina
Study officials:
affiliation: Duke University
name: Deepak Voora, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: David Grant US Air Force Medical Center
name: Henry Lau, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Peyser B, Perry EP, Singh K, Gill RD, Mehan MR, Haga SB, Musty MD, Milazzo NA, Savard D, Li YJ, Trujilio G, Voora D. Effects of Delivering SLCO1B1 Pharmacogenetic Information in Randomized Trial and Observational Settings. Circ Genom Precis Med. 2018 Sep;11(9):e002228. doi: 10.1161/CIRCGEN.118.002228.
citation: Ramsey LB, Johnson SG, Caudle KE, Haidar CE, Voora D, Wilke RA, Maxwell WD, McLeod HL, Krauss RM, Roden DM, Feng Q, Cooper-DeHoff RM, Gong L, Klein TE, Wadelius M, Niemi M. The clinical pharmacogenetics implementation consortium guideline for SLCO1B1 and simvastatin-induced myopathy: 2014 update. Clin Pharmacol Ther. 2014 Oct;96(4):423-8. doi: 10.1038/clpt.2014.125. Epub 2014 Jun 11.