Statin, Statin Adverse Reaction, Statin Therapy
Conditions
Keywords
Statin Intolerance, lipid-lowering medication, LDL, LDL Cholesterol
Brief summary
The DESIFOR pilot study was conducted to determine the feasibility of utilizing an n-of-1 trial to facilitate tolerance of unblinded rosuvastatin in patients with prior statin intolerance
Detailed description
Recently developed lipid lowering therapies have been shown to significantly reduce LDL cholesterol and subsequent CVD risk (1, 2). However, they are expensive, and the cost-effectiveness of these medications remains controversial, especially in primary prevention. Novel lipid lowering therapies are frequently considered for individuals with statin intolerance, but payers frequently deny prescription for these medications due to lack of adequate proof of true statin intolerance. How to accurately determine statin intolerance remains a clinical conundrum for both patients and providers. A more scientific, definitive method to determine statin intolerance could potentially allow appropriate, cost-effective use of statin therapy in individuals found to not actually be statin intolerant as well as judicious use of novel medications in patients who are found to truly be statin intolerant. The DESIFOR pilot study was conducted to determine the feasibility of utilizing an n-of-1 trial to facilitate tolerance of unblinded rosuvastatin in patients with prior statin intolerance. The DESIFOR pilot study was a single-center, randomized, double-blinded, n-of-1 trial in patients aged 21 to 79 years and eligible for statin therapy by current guidelines but not on therapy due to intolerance of \>2 statins. Using a double-blinded, N-of-1 randomized trial in patients with previous statin intolerance, \<10% of patients had data suggestive of true statin intolerance, and 2/3 of patients were subsequently able to tolerate 3-months of unblinded treatment with rosuvastatin (3). These data raise the hypothesis that an n-of-1 trial can be used to facilitate tolerance of unblinded rosuvastatin in patients with prior statin intolerance.
Interventions
The patient will take 3 28-day packs of placebo and 2 28-day packs of rosuvastatin. The order in which they take the placebo or rosuvastatin will be assigned at random.
DRUGPlacebo
The patient will take 3 28-day packs of placebo and 2 28-day packs of rosuvastatin. The order in which they take the placebo or rosuvastatin will be assigned at random.
Sponsors
Minneapolis Heart Institute Foundation
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
There will be unblinded and blinded research staff. Unblinding for the patient and provider will occur at 6-month follow-up.
Intervention model description
Each kit will include 3 28-day packs of placebo and 2 28-day packs of rosuvastatin, assigned at random. Each kit will have a unique identification number, which the pharmacy will record in a drug tracking log as it is dispensed. Within each kit, a unique identifying number will be present on each blister pack which can be used to determine the order of allocation of placebo and rosuvastatin.
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients (≥ 21 years old) with a prior history of statin intolerance. Statin intolerance is defined by discontinuation of at least 2 different statin medications due to possible side effects. Patients can participate in the trial while on other lipid-lowering agents, such as ezetimibe and PSCK9 inhibitors, as long as the patient has been on the other lipid lowering therapy and tolerating it well for at least 1 month. For individuals with established ASCVD or multiple ASCVD risk factors, initiation of other lipid lowering therapy prior to participation in DESIFOR is encouraged. * 2\. At least 30 days since discontinued use of a statin
Exclusion criteria
* Women who are pregnant, nursing or attempting to become pregnant * Individuals who experienced severe reactions in the past, including rhabdomyolysis, severe myositis, anaphylaxis * Individuals who are not otherwise clinically indicated to take rosuvastatin 20 mg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Musculoskeletal symptom presence/absence | 9 months | To determine the prevalence of true statin intolerance, defined by a statistical difference in the mean musculoskeletal symptom score while on statin therapy compared to placebo, in patients previously identified as statin intolerant. |
| Statin Tolerance | 9 months | To determine the prevalence of statin tolerance, defined as continuous use of 3 months of unblinded rosuvastatin, in individuals with previous statin intolerance but without evidence of true statin intolerance in the DESIFOR protocol. |
| Variables associated with statin intolerance | 9 months | To determine the clinical variables associated with true statin intolerance. |
Countries
United States
Contacts
Primary ContactGretchen Program Director, RDN, CDCES
Outcome results
None listed