Simvastatin vs. Therapeutic Lifestyle Changes and Supplements:  Randomized Primary Prevention Trial

 

Background:  As many as 40% of patients that receive a prescription for a statin discontinue the medication within a year due to various reasons (adverse effects, poor explanation of benefits by provider, cost and noncompliance).  Some patients prefer to treat themselves and are more comfortable buying products that are over the counter.

 

Objective:  To determine the efficacy and safety of red yeast rice, fish oil and therapeutic lifestyle changes (alternative regimen) compared to a standard dose of simvastatin with traditional diet and exercise counseling on LDL-C levels.

 

Methods:  The study was a single site, unblinded, randomized parallel trial conducted between April 1, 2006 and June 30, 2006.  Inclusion criteria included baseline LDL of 130mg/dl or greater and 2 or more cardiovascular risk factors or a baseline LDL between 160 and 210 mg/dl for patients with 1 or no risk factors.  Exclusion criteria included known coronary artery disease or a procedure to treat such disease, triglyceride levels at baseline testing higher than 400 mg/dl, use of warfarin, severe liver or kidney disease, an orthopedic condition that would prevent aerobic exercise or other systemic disease.  The primary outcome endpoint was percentage change of LDL from baseline.  Secondary outcome measures were percentage change from baseline levels of HDL and triglycerides at 12 weeks.  A total of 74 patients received either simvastatin 40 mg along with diet and exercise educational materials or fish oil, red yeast rice and lifestyle modifications.  If the initial LDL measurement was greater than 160 mg/dl a total dose of 3.6 g of red yeast rice was given in 2 divided doses.  If the initial LDL measurements was 160 mg/dl or less than a total dose of 2.4 g of red yeast rice was given in 2 divided doses.  They also were enrolled in a multidisciplinary lifestyle program that involved weekly 3 ½ hour meetings.  They were encouraged to follow a modified Mediterranean diet along with restricting sugars and simple carbohydrates.  Patients were taught how to count calories; however, calorie restrictions were not implemented.  Walking, jogging, and swimming for 30 to 45 minutes at a time was encouraged and patients were also exposed to relaxation methods including yoga and tai chi. Patients in both treatment groups received a 30 day supply of medication at each of the 3 monthly visits.  Investigators calculated that 37 patients in each group is sufficient to provide a power of at least 80% and an alpha level of 0.05 to detect a 20% difference in the percentage change between the 2 groups assuming a SD of 30%.  Between-treatment group comparisons at baseline were performed using a 2-sample t test and within treatment group comparison at baseline and at week 12 was performed using a 1 sample t test.  Multiple linear regressions were used for between treatment group comparisons. 

 

Results:  Data was reported using the intention-to-treat population consisting of 37 patients receiving simvastatin 40 mg and 37 patients receiving the alternative treatment.  The primary endpoint was percentage change in LDL, and secondary endpoints were percentage change in HDL and triglycerides from baseline to 12 weeks.  When comparing the two groups’ lipid panels, there were no significant differences between the groups LDL -3.1 (95% CI -17.6 to 11.4; p=0.59) and HDL -3.3 (95% CI -7.1 to 0.5) p= 0.21.  On the other hand, triglyceride reduction in the alternative treatment group was shown to be significantly different from simvastatin therapy with a reduction of 36.4 (95% CI -61.1 to -11.7, p=0.003).  The author’s concluded that red yeast rice, fish oil and lifestyle changes had LDL lowering effects similar to those of a standard dose of simvastatin.

 

Strengths:  The study separately performed random assignment for each gender making the groups more equivalent.  The study also had no dropouts and statistically significant outcome measures.  A washout period for participants on simvastatin prior to the study was provided before the study began.  Also, inclusion and exclusion criteria were sufficient and appropriate enough to extrapolate the study to the population of interest. 

 

Weaknesses:  The trial was short term, single site and unblinded.  The alternative therapy was dosed much higher than the normal range whereas simvastatin was dosed normally; therefore the treatments are not exactly comparable.  In addition, the study’s design prevented us from seeing what each factor of the alternative treatment (ie. exercise, diet, fish oil) contributed to the results.  The study claimed to have “excellent” adherence; however, there was no data provided for that measure.  Also, other medications that were taken by patients that could potentially interfere with results were not reported.

 

Conclusions:  The study’s statistical analysis showed the alternative treatment therapy was comparable to the simvastatin therapy; however, I would not recommend the alternative treatment therapy over simvastatin therapy.  One main reason for studying alternative therapy was due to compliance; however, patients were taking more capsules more frequently on the alternative treatment regimen.  Another rationale for the study was cost of prescription medications; however, simvastatin is available generically and available on most retail chain’s generic plans therefore it may be more cost effective than over the counter products.  Also, red yeast rice is no longer available in the United States as an over the counter product.  Since therapeutic lifestyle changes were thought to be a reason for the huge reduction of triglycerides in the alternative treatment group, a trial should be done to determine the lipid lowering effects of therapeutic lifestyle changes alone.  Also, a study should be done without all the follow-up, education and support provided in the second group to see if the actual therapies are comparable.

 

Reference:  Becker DJ, Gordon RY, Morris PB, Yorko J, Gordon YJ et al. (2008) Simvastatin vs Therapeutic Lifestyle Changes and Supplements:  Randomized Primary Prevention Trial.  Mayo Clin Proc. 2008 Jul;83(7):758-64.

 

Ashley Corcoran, PharmD candidate