Phytosterols, Red Yeast Rice, and Lifestyle Change vs Statin
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 prescription lipid-lowering therapy because of recurrent adverse effects. There were no differences in baseline characteristics between groups (Table I).
There were no significant differences in lipoprotein levels between the phytosterol and placebo groups at week 12, 24, or 52. (Table II; Figure 2). Likewise, there was no significant difference between groups in the odds of achieving an LDL-C <100 mg/dL (odds ratio 0.77, 95% CI 0.44–1.3, P = .37) (Figure 3).
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Figure 2.
Lipid measurements over the study period for all groups. Vertical lines represent 95% CIs.
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Figure 3.
Percent of participants who achieved an LDL level <100 mg/dL over the study period for all groups (left panel) and relative odds of achieving an LDL level <100 mg/dL by phytosterols vs placebo and lifestyle change vs usual care (right panel). Vertical lines represent 95% CIs.
The LCG had greater decreases in LDL-C compared with the UCG at weeks 12 (−51 vs −42 mg/dL, P = .006) and 24 (−48 vs −40 mg/dL, P = .033) and greater decreases in TC at weeks 12 (−55 vs −44 mg/dL, P = .003) and 24 (−50 vs −42 mg/dL, P = .034) (Table III; Figure 2). Both LDL-C and TC at week 52 did not differ between groups.
In the LCG, 45% of participants (39/86) reached an LDL-C <100 mg/dL at week 12 and 45% (36/79) at week 52 (Figure 3). In the UCG, 27% of participants (23/84) reached an LDL-C <100 mg/dL at week 12 and 28% (21/76) at week 52. Throughout the trial, participants in the LCG were more likely to achieve an LDL-C <100 mg/dL compared with the UCG (odds ratio 2.3, 95% CI 1.3–4.1, P = .004). There were no significant differences in HDL-C, TG, or hs-CRP between groups.
Mean baseline weight in the LCG and UCG was 82.2 and 81.1 kg, respectively. The LCG had greater decreases in weight compared with UCG at weeks 12 (−1.6 kg vs 1.1 kg), 24 (−2.0 kg vs 0.2 kg) and 52 (−2.3 kg vs −0.3 kg) (all P < .001) (Table III; Figure 4). Results were similar for BMI.
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Figure 4.
Weight and BMI over the study period for LCG and UCG. Vertical lines represent 95% CIs.
Among participants randomized to usual care and placebo, we evaluated differences in lipid levels over time to assess the impact of RYR. Among these participants, mean LDL-C at baseline was 150 mg/dL, which decreased to 111 mg/dL at week 12, 110 mg/dL at week 24, and 113 mg/dL at week 52 (all P < .001 compared with baseline). Similarly, mean TC at baseline was 237 mg/dL, which decreased to 194 mg/dL at week 12, 193 mg/dL at week 24, and 199 mg/dL at week 52 (all P < .001); mean TG at baseline was 137 mg/dL, which decreased to 106 mg/dL at week 12, 108 mg/dL at week 24, and 106 mg/dL at week 52 (all P < .001). Mean HDL-C was 60.0 mg/dL at baseline, which increased to 62.5 mg/dL at week 12 (P = .013), 61.6 mg/dL at week 24 (P = .088), and 64.7 mg/dL at week 52 (P < .001). Median hs-CRP was 2.8 mg/L at baseline, which decreased to 1.7 mg/L at week 12 (P = .032), 1.8 at week 24 (P = .079), and 1.7 at week 52 (P = .045).
Four participants, all randomized to phytosterols, experienced intractable myalgias necessitating cessation of RYR. Three participants were in the UCG group and 1 in the LCG. All had a history of SAM. Another participant's supplements were discontinued at week 12 because of transaminases >3× the upper limit of normal. There were no elevations of CPK in any group. Three participants in the placebo arm stopped supplements, 1 because of a rash attributed to RYR and 2 because of gastrointestinal adverse effects.
There were no significant differences between the LCG and the UCG in compliance with RYR or phytosterol/placebo therapy (online Supplementary Table III, Supplementary Table IV).
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 prescription lipid-lowering therapy because of recurrent adverse effects. There were no differences in baseline characteristics between groups (Table I).
Phytosterol Tablets did not Affect Lipid Levels
There were no significant differences in lipoprotein levels between the phytosterol and placebo groups at week 12, 24, or 52. (Table II; Figure 2). Likewise, there was no significant difference between groups in the odds of achieving an LDL-C <100 mg/dL (odds ratio 0.77, 95% CI 0.44–1.3, P = .37) (Figure 3).
(Enlarge Image)
Figure 2.
Lipid measurements over the study period for all groups. Vertical lines represent 95% CIs.
(Enlarge Image)
Figure 3.
Percent of participants who achieved an LDL level <100 mg/dL over the study period for all groups (left panel) and relative odds of achieving an LDL level <100 mg/dL by phytosterols vs placebo and lifestyle change vs usual care (right panel). Vertical lines represent 95% CIs.
Lifestyle Change Significantly Improved Lipid Levels and Weight
The LCG had greater decreases in LDL-C compared with the UCG at weeks 12 (−51 vs −42 mg/dL, P = .006) and 24 (−48 vs −40 mg/dL, P = .033) and greater decreases in TC at weeks 12 (−55 vs −44 mg/dL, P = .003) and 24 (−50 vs −42 mg/dL, P = .034) (Table III; Figure 2). Both LDL-C and TC at week 52 did not differ between groups.
In the LCG, 45% of participants (39/86) reached an LDL-C <100 mg/dL at week 12 and 45% (36/79) at week 52 (Figure 3). In the UCG, 27% of participants (23/84) reached an LDL-C <100 mg/dL at week 12 and 28% (21/76) at week 52. Throughout the trial, participants in the LCG were more likely to achieve an LDL-C <100 mg/dL compared with the UCG (odds ratio 2.3, 95% CI 1.3–4.1, P = .004). There were no significant differences in HDL-C, TG, or hs-CRP between groups.
Mean baseline weight in the LCG and UCG was 82.2 and 81.1 kg, respectively. The LCG had greater decreases in weight compared with UCG at weeks 12 (−1.6 kg vs 1.1 kg), 24 (−2.0 kg vs 0.2 kg) and 52 (−2.3 kg vs −0.3 kg) (all P < .001) (Table III; Figure 4). Results were similar for BMI.
(Enlarge Image)
Figure 4.
Weight and BMI over the study period for LCG and UCG. Vertical lines represent 95% CIs.
Red Yeast Rice Improved Lipid Levels
Among participants randomized to usual care and placebo, we evaluated differences in lipid levels over time to assess the impact of RYR. Among these participants, mean LDL-C at baseline was 150 mg/dL, which decreased to 111 mg/dL at week 12, 110 mg/dL at week 24, and 113 mg/dL at week 52 (all P < .001 compared with baseline). Similarly, mean TC at baseline was 237 mg/dL, which decreased to 194 mg/dL at week 12, 193 mg/dL at week 24, and 199 mg/dL at week 52 (all P < .001); mean TG at baseline was 137 mg/dL, which decreased to 106 mg/dL at week 12, 108 mg/dL at week 24, and 106 mg/dL at week 52 (all P < .001). Mean HDL-C was 60.0 mg/dL at baseline, which increased to 62.5 mg/dL at week 12 (P = .013), 61.6 mg/dL at week 24 (P = .088), and 64.7 mg/dL at week 52 (P < .001). Median hs-CRP was 2.8 mg/L at baseline, which decreased to 1.7 mg/L at week 12 (P = .032), 1.8 at week 24 (P = .079), and 1.7 at week 52 (P = .045).
Safety
Four participants, all randomized to phytosterols, experienced intractable myalgias necessitating cessation of RYR. Three participants were in the UCG group and 1 in the LCG. All had a history of SAM. Another participant's supplements were discontinued at week 12 because of transaminases >3× the upper limit of normal. There were no elevations of CPK in any group. Three participants in the placebo arm stopped supplements, 1 because of a rash attributed to RYR and 2 because of gastrointestinal adverse effects.
Compliance With RYR and Phytosterols
There were no significant differences between the LCG and the UCG in compliance with RYR or phytosterol/placebo therapy (online Supplementary Table III, Supplementary Table IV).
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