Effect of Xuezhikang, an Extract From Red Yeast Chinese Rice, on Coronary Events in a Chinese Population With Previous Myocardial Infarction - Effect of Xuezhikang, an Extract From Red Yeast Chinese Rice, on Coronary Events in a Chinese Population With Previous MI

Description:

Given that red yeast rice extracts have been used for a long time for therapy of patients with circulatory problems in China, the goal of the current trial was to systematically study the safety and efficacy of xuezhikang (XZK), a partially purified extract of red yeast Chinese rice, in Chinese patients with coronary artery disease.

Hypothesis:

XZK is superior to placebo in reducing the incidence of recurrent cardiovascular events in Chinese patients with coronary artery disease.

Study Design

Study Design:

Patients Enrolled: 4,870
NYHA Class: I or II
Mean Follow Up: 4.5 years
Mean Patient Age: 58.9 years
Female: 18

Patient Populations:

• History of MI within the past 5 years
• Total cholesterol 170-250 mg/dl
• Triglycerides ≤400 mg/dl

Exclusions:

• Clinically uncontrolled arrhythmias
• Valvular heart disease
• Unstable angina
• Congestive heart failure
• Planned percutaneous coronary intervention
• Systolic blood pressure >180 mm Hg
• Diastolic blood pressure >110 mm Hg
• New York Heart Association class III or IV symptoms
• History of completed stroke
• Uncontrolled diabetes mellitus, with fasting plasma glucose >200 mg/dl
• Significant hepatic or renal disease
• Active malignancy
• Other uncontrolled clinical condition that may alter plasma lipids or be considered to pose an undue risk or contraindication to study participation
• Premenopausal women of childbearing potential
• History of alcohol or substance abuse

Primary Endpoints:

Nonfatal MI or death from cardiac cause

Secondary Endpoints:

• Total cardiovascular mortality
• Total mortality
• Need for coronary revascularization
• Change in lipoprotein lipids

Drug/Procedures Used:

Patients with a history of MI were randomized to either two 300 mg capsules of XZK (each containing lovastatin 2.5-3.2 mg/capsule, lovastatin hydroxyl acid, ergosterol, and a few other components), or matching placebo.

Concomitant Medications:

Aspirin (95%), beta-blockers (56%), calcium channel blockers (36.5%), and nitrates (91.5%)

Principal Findings:

A total of 4,870 patients were randomized between 1996 and 2003, 2,429 to XZK and 2,441 to placebo. The mean body mass index was 24.8, about 55.5% had hypertension, and 12.5% had diabetes. The baseline low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides were 129 mg/dl, 46 mg/dl, and 163.9 mg/dl, respectively.

Patients treated with XZK (5.7%) had a significant reduction in major coronary events compared with placebo (10.4%) (p < 0.0001), including a significant reduction in the incidence of nonfatal myocardial infarction (MI) (1.9% vs. 4.9%, p < 0.0001), death due to cardiovascular causes (3.8% vs. 5.5%, p = 0.005), and coronary revascularization (1.4% vs. 4.2%, p = 0.004). Total mortality was also lower in the XZK group (5.2% vs. 7.7%, p = 0.0003). There was no difference in the incidence of fatal MI (p = 0.19) or fatal stroke (p = 0.85).

There was also a 10.9% reduction in total cholesterol (p < 0.001), a 17.6% reduction in LDL cholesterol (p < 0.001), a 4.2% increase in HDL cholesterol (p < 0.001), and a 14.6% reduction in triglycerides (p < 0.001) in the XZK group compared with placebo at the end of follow-up. These differences were noted by 6-8 weeks after randomization, and maintained throughout the duration of follow-up.

No significant treatment-related adverse events or deaths were noted during the study period. Minor occasional and transient increases in serum transaminases and creatine kinase were noted between the two groups.

Interpretation:

The results of this intriguing trial indicate that XZK, an extract from red yeast Chinese rice, is associated with a significant reduction in major coronary events compared with placebo, including a significant reduction in total and cardiovascular mortality and nonfatal MI. No significant side effects were noted in the treated arm. If borne out by other randomized controlled trials, XZK could thus prove to be an exciting alternative in patients who are intolerant to statins.

Before these findings can be widely adopted though, several questions remain. Although XZK contains lovastatin to a significant extent, the authors postulate that other ingredients in the extract may also be responsible for the impressive reduction in cholesterol noted in this trial. However, the other ingredients have not been fully identified and characterized yet; thus, further investigations into this hypothesis are necessary. Moreover, the reductions in outcomes noted in this trial are greater than those reported with the use of statins in mainly Caucasian patients. Whether this is a reflection of a difference in genetic and baseline characteristics between the two patient populations will need to be determined by further head-to-head studies in different populations. Further studies will also need to determine whether there is any interaction (positive or negative) between statins and XZK in terms of both efficacy and safety, since no patients were on statins in this trial.

References:

Lu Z, Kou W, Du B, et al., on behalf of the Chinese Coronary Secondary Prevention Study Group. Effect of Xuezhikang, an Extract From Red Yeast Chinese Rice, on Coronary Events in a Chinese Population With Previous Myocardial Infarction. Am J Cardiol 2008;101:1689-93.

Clinical Topics: Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Statins, Hypertension

Keywords: Stroke, Myocardial Infarction, Coronary Artery Disease, Creatine Kinase, Lovastatin, Oryza sativa, Cholesterol, Body Mass Index, Transaminases, Drugs, Chinese Herbal, Triglycerides, Ergosterol, Hypertension, Diabetes Mellitus


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