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KMID : 0928520110210020037
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Korean Journal of Lipidology
2011 Volume.21 No. 2 p.37 ~ p.45
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Challenge to the Hypothesis of “the Lower the Better”
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Choi Ha-Nul
Koh Kwang-kon
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Abstract
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Recent clinical trials demonstrate that intensive-dose statin therapy to lower low-density lipoprotein cholesterol (LDL-C) significantly reduces cardiovascular risk but it also increases the risks such as cancer, type 2 diabetes, myopathy, liver toxicity, and the rate of discontinuation due to adverse events. Further, residual risk factors such as low high-density lipoprotein cholesterol, high triglycerides, small dense LDL, insulin resistance, or obesity are associated with likelihood of disease progression in patients who achieve very low LDL-C levels. Combining low dose statin treatment with other therapies to achieve the same target LDL-C level may allow for beneficial cardiovascular effects of low LDL-C while minimizing adverse outcomes from high dose statin treatment and resolving residual cardiovascular risk. Thus, it may be prudent to reduce LDL-C levels to ~70 mg/dL with statins alone only in patients with very high cardiovascular risk. In light of pleiotropic effects of statins, combination therapy may be an important consideration for a majority of patients. Overall mortality rates are determined by more than a single biomarker. In addition, the mechanisms by which a biomarker is altered may contribute importantly to the clinical outcome. Thus, combination therapy with statins and ezetimibe, renin-angiotensin-aldosterone system blockers or peroxisome proliferator-activated receptors (PPARs) may be more beneficial than monotherapy. These superior benefits of combination therapy are likely mediated by both distinct and interrelated mechanisms that simultaneously target blood pressure, atherosclerosis, and coronary heart disease.
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KEYWORD
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Statins, Cancer, Diabetes, Residual risk, Combination therapy
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