The Effect of Statin Medications on Muscle Performance (The STOMP Study)

Statins are the most effective medications for reducing high cholesterol levels. They are
extremely well tolerated by the majority of people but can produce a variety of
muscle-related side effects in some people. Of these side effects, the most serious is
rhabdomyolysis, which involves muscle fiber damage that can begin as muscle pain and progress
to a loss of muscle cells, kidney failure, and death. While rhabdomyolysis is extremely rare,
some people experience the more common muscle-related side effects of statins, such as muscle
pain (known as "myalgia"), cramps, and weakness. These more common side effects warrant
attention because they may limit the use of statins, affect mobility, and increase the risk
of injury in older individuals. Also, the term "muscle weakness," often used by patients and
their doctors, is not well defined and can refer to a wide range of complaints from simple
fatigue to an actual inability to perform activities of daily living. It is important to
describe and quantify in more detail the muscle-related side effects associated with statins.
The purpose of this study is to determine the incidence of statin-induced mild muscle
complaints and to determine the effect of statins on skeletal muscle strength, endurance, and
aerobic exercise performance.

This study will enroll healthy people who have never received statin medications. First,
participants will attend three study visits over a period of 2 weeks. These study visits will
include blood collection, questionnaires on physical activity and pain, vital sign
measurements, and body measurements, including height, weight, and head circumference.
Participants will also complete two cardiopulmonary exercise stress tests on a treadmill and
will undergo arm and leg strength testing. Some participants may undergo a muscle biopsy.
Participants will then be randomly assigned to receive either 80 mg of atorvastatin or
placebo on a daily basis for 6 months. Blood will be collected again at Month 3. At Month 6,
participants will attend two study visits for repeat baseline measurements. All participants
will be contacted by phone every other week during the 6-month treatment period to monitor
adverse events and medication compliance.

Inclusion Criteria:

- Statin-naive (i.e., has never taken statins before)

Exclusion Criteria:

- Previous use of statins

- Current treatment with cholesterol- or triglyceride-lowering drugs

- Impaired liver or kidney function

- Untreated hypothyroidism or hyperthyroidism

- Treatment with other medications known to increase risk of myopathy in
atorvastatin-treated patients (e.g., cyclosporine, azithromycin, erythromycin, azole
antifungals, fusidic acid)

- Existing infection requiring treatment with antibiotic therapy

- Consumption of greater that 1 quart of grapefruit juice per day

- Documented history of neuroleptic malignant syndrome

- Inherited muscle disorders or myopathy

- Known sickle cell trait

- Cancer within the 5 years prior to study entry

- Diabetes

- Currently being treated for high blood pressure

- Coronary artery disease

- Peripheral vascular disease

- Physical disability or previous injury that prevents safe exercise testing

- Pregnant or breastfeeding