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April 23/30, 2003

Lipid-Lowering Therapy and Risk of Coronary Events

JAMA. 2003;289(16):2070. doi:10.1001/jama.289.16.2071-b

To the Editor: The authors of ALLHAT-LLT1 explored several possible reasons for the failure of lipid-lowering therapy to translate into any change in the risk of CHD. It is possible, however, that there may be a threshold value of the total cholesterol/HDL-C (high-density lipoprotein cholesterol) ratio, below which further lowering will not produce any significant reduction in CHD.2 The average baseline ratios in several studies were greater than 5, which may be a critical value. Following treatment there was a significant reduction in CHD, especially in those studies that reported a ratio less than 5. Particularly noteworthy were the VA-HIT results, in which gemfibrozil produced a 24% decrease in CHD yet had no effect on LDL-C levels.3 The baseline ratio in ALLHAT-LLT was 4.67, so it is not surprising that further lowering of the ratio offered no CHD benefit. In the BIP study,4 a 41% reduction in CHD occurred in patients with a baseline HDL-C level lower than 35 mg/dL (0.91 mmol/L) and virtually all of the 24% CHD benefit in the PROSPER study occurred in patients in the lowest HDL tertile.5 Patients with the lowest HDL-C levels would undoubtedly have the highest ratio at baseline and could most likely benefit from treatment.