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CLINICAL RESEARCH: LIPID REDUCTION THERAPY

Statin Therapy Alters the Relationship Between Apolipoprotein B and Low-Density Lipoprotein Cholesterol and Non–High-Density Lipoprotein Cholesterol Targets in High-Risk Patients

The MERCURY II (Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY II) Trial

Christie M. Ballantyne, MD, FACC^_*,_*, Joel S. Raichlen, MD, FACC and Valerie A. Cain, MS

^_* Baylor College of Medicine and the Methodist DeBakey Heart and Vascular Center, Houston, Texas
Clinical Development, AstraZeneca, Wilmington, Delaware.

Manuscript received December 20, 2007; revised manuscript received April 7, 2008, accepted April 29, 2008.

^_* Reprint requests and correspondence: Dr. Christie M. Ballantyne, 6565 Fannin Street, MS A601, Suite A656, Houston, Texas 77030. (Email: cmb{at}bcm.edu).

Objectives: The purpose of this analysis was to compare concentrations of low-density lipoprotein cholesterol (LDL-C), non–high-density lipoprotein cholesterol (HDL-C), and apolipoprotein B (apoB) before and during statin therapy.

Background: Reducing LDL-C to a pre-determined goal may still leave an excess of atherogenic lipoproteins, as reflected in apoB levels.

Methods: The MERCURY II (Measuring Effective Reductions in Cholesterol Using Rosuvastatin therapY II) trial examined the effects of statin treatment in patients with high coronary heart disease (CHD) risk, LDL-C 130 and <250 mg/dl, and triglycerides <400 mg/dl. Therapy consisted of rosuvastatin (10 or 20 mg), atorvastatin (10 or 20 mg), or simvastatin (20 or 40 mg). The apoB and LDL-C or non–HDL-C at baseline and after 16 weeks of therapy were compared using linear regression.

Results: In untreated patients, the apoB target of <90 mg/dl was roughly equivalent to an LDL-C level <100 mg/dl and a non–HDL-C level <130 mg/dl, which is consistent with existing apoB and lipoprotein guidelines. However, during statin therapy, to reach an apoB target of <90 mg/dl it was necessary to reduce non–HDL-C to <100 mg/dl or to reduce LDL-C to <70 mg/dl (in high-triglyceride patients) or <80 mg/dl (in lower-triglyceride patients). The tight correlation seen for non–HDL-C with apoB while on statin therapy (R² = 0.92) implies that non–HDL-C may be an acceptable surrogate for direct apoB measurement.

Conclusions: These data are consistent with the more aggressive cholesterol goals suggested for CHD patients, because achieving such targets also reduced apoB to the recommended level. (Mercury II–Compare the Efficacy and Safety of Lipid Lowering Agents Atorvastatin and Simvastatin With Rosuvastatin in High Risk Subjects With Type IIa and IIb Hypercholesterolemia; NCT00654407 [ClinicalTrials.gov] )

Key Words: apolipoprotein B • low-density lipoprotein cholesterol • non–high-density lipoprotein cholesterol • statins • high-risk patients

Abbreviations and Acronyms   ACC = American College of Cardiology   ADA = American Diabetes Association   AHA = American Heart Association   apoB = apolipoprotein B   CHD = coronary heart disease   HDL-C = high-density lipoprotein cholesterol   LDL-C = low-density lipoprotein cholesterol   TG = triglyceride

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