Elsevier

American Heart Journal

Volume 166, Issue 1, July 2013, Pages 187-196.e2
American Heart Journal

Clinical Investigation
Prevention and Rehabilitation
Phytosterols, red yeast rice, and lifestyle changes instead of statins: A randomized, double-blinded, placebo-controlled trial

https://doi.org/10.1016/j.ahj.2013.03.019Get rights and content

Background

Many patients who refuse or cannot tolerate statin drugs choose alternative therapies for lipid lowering.

Objectives

This study aimed to determine the lipid-lowering effects of phytosterol tablets and lifestyle change (LC) on top of red yeast rice (RYR) therapy in patients with a history of statin refusal or statin-associated myalgias.

Design

A total of 187 participants (mean low-density lipoprotein cholesterol [LDL-C], 154 mg/dL) took RYR 1800 mg twice daily and were randomized to phytosterol tablets 900 mg twice daily or placebo. Participants were also randomized to a 12-week LC program or usual care (UC). Primary end point was change in LDL-C at 12, 24, and 52 weeks. Secondary end points were effect on other lipoproteins, high-sensitivity C-reactive protein, weight, and development of myalgia.

Results

Phytosterols did not significantly improve LDL-C at weeks 12 (P = .54), 24 (P = .67), or 52 (P = .76) compared with placebo. Compared with the UC group, the LC group had greater reductions in LDL-C at weeks 12 (−51 vs −42 mg/dL, P = .006) and 24 (−48 vs −40 mg/dL, P = .034) and was 2.3 times more likely to achieve an LDL-C <100 mg/dL (P = .004). The LC group lost more weight for 1 year (−2.3 vs −0.3 kg, P < .001). All participants took RYR and had significant decreases in LDL-C, total cholesterol, triglycerides, high-sensitivity C-reactive protein, and an increase in high-density lipoprotein cholesterol for 1 year when compared with baseline (P < .001). Four participants stopped supplements because of myalgia.

Conclusions

The addition of phytosterol tablets to RYR did not result in further lowering of LDL-C levels. Participants in an LC program lost significantly more weight and were more likely to achieve an LDL-C <100 mg/dL compared with UC.

Section snippets

Design overview

We designed a randomized, double-blinded, placebo-controlled trial to evaluate the combined lipid-lowering effects of RYR, phytosterols, and lifestyle change. We selected a 2 × 2 factorial design to simultaneously evaluate the impact of the 2 interventions (phytosterols vs placebo and lifestyle change vs usual care). All participants took RYR. Participants were recruited from July to October 2009 from 2 study centers: Abington Memorial Hospital, Abington, PA, and Chestnut Hill Hospital,

Results

Two hundred twenty participants were randomized; 33 were subsequently identified as ineligible or withdrew consent (Figure 1). Among the remaining 187 participants, mean age was 62 years, 75% were female, and 28% were African American; 68% were low risk (≤5%), 30% were intermediate risk (>5%-<20%), and 2% were high risk (≥20%) according to the Framingham risk score. Eight subjects with a history of coronary artery disease were enrolled on a compassionate basis having refused recommended

Discussion

Our study compared the lipid-lowering efficacy of phytosterol tablets vs placebo and lifestyle changes vs usual care in patients taking RYR who were statin intolerant or refused statin therapy. Phytosterol tablets did not significantly improve lipoprotein levels at any period compared with placebo. Participants in the LCG were 2.3 times more likely to achieve an LDL-C <100 mg/dL and had significantly more weight loss than the UCG. All participants were treated with RYR and LDL-C, TC, TG, and

Conclusion

Phytosterol tablets did not improve lipoprotein levels when added to RYR in participants who either were intolerant of statins or had refused a physician's recommendation to take statin therapy. Subjects randomized to a lifestyle change program had significantly lower TC and LDL-C through week 24 and lost significantly more weight than participants in the UCG. All regimens were well tolerated and safe throughout the yearlong trial. In conclusion, a combination of RYR and lifestyle change may

Disclosures

Drs Becker and Gordon have served as consultants for Lupin Pharmaceuticals, Baltimore, MD. Dr French, Ms. Morris, and Ms. Silvent have no financial disclosures to report.

References (33)

  • F.H. O'Neill et al.

    Comparison of efficacy of plant stanol ester and sterol ester: short-term and longer-term studies

    Am J Cardiol

    (2005)
  • Becker DJ, Gordon RY, Halbert SC, et al. Red yeast rice for dyslipidemia in statin-intolerant patients: a randomized...
  • M.L. Stefanick et al.

    Effects of diet and exercise in men and postmenopausal women with low levels of HDL cholesterol and high levels of LDL cholesterol

    N Engl J Med

    (1998)
  • G.R. Thompson

    Additive effects of plant sterol and stanol esters to statin therapy

    Am J Cardiol

    (2005)
  • Snow G. Blockrand: randomization for block random clinical trials. In. 1.1 ed. R Package;...
  • A. Kashani et al.

    Risks associated with statin therapy: a systematic overview of randomized clinical trials

    Circulation

    (2006)
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