Baseline low-density lipoprotein cholesterol is an important predictor of the benefit of intensive lipid-lowering therapy: a PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) analysis.

Description

In these post-hoc analyses of the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22), Giraldez et al. tested the hypothesis that baseline values of LDL cholesterol affect the response to intensive statin therapy. In this trial, 2,986 statin-naïve patients previously randomized to receive either atorvastatin 80 mg (high dose) or pravastatin 40 mg (low dose) were selected (72% of the total cohort). One of the main findings of the study was that the benefits of intensive statin therapy progressively declined as baseline LDL cholesterol levels decreased. In patients treated with atorvastatin with baseline LDL cholesterol in the top quartile (>132 mg/dl [3.42 mmol/l]), the 2-year risk of composite endpoint of death, myocardial infarction, revascularization, and stroke was significantly reduced (hazard ratio=0.63 [95% CI, 0.47-0.85]). However, a risk reduction was not observed in patients with baseline LDL cholesterol values in the bottom quartile (<92 mg/dl [2.38 mmol/l]). In addition, when baseline LDL cholesterol levels were analysed as a continuous variable, the authors found that under a threshold value of 66 mg/dl (1.71 mmol/l), there was no benefit associated with intensive therapy, which suggests that intensive statin therapy may not be useful for patients with very low LDL cholesterol levels. The authors also concluded that additional studies are needed to determine LDL cholesterol threshold values for which atorvastatin 80 mg dose provides cardiovascular disease risk reduction benefits. In their editorial, Albert V.G. Bruschke and J. Wouter Jukema suggested that the article by Giraldez et al. might challenge the concept of “the lower the better” with respect to LDL cholesterol levels. The observation that intensive therapy may be inappropriate below a threshold value of 66 mg/dl (1.71 mmol/l), as proposed by the investigators of PROVE IT-TIMI 22, was seen as having significant clinical consequences. Bruschke and Jukema suggested, however, that the study does not conclusively answer the issue of if and when intensive statin treatment is warranted. Given that the follow-up period was relatively short and the study was not conducted to answer this specific question, they mentioned that additional trials are needed to determine the optimal conditions under which intensive statin treatment should be used. They concluded their editorial by stating that intensive statin treatment should be used in moderation in clinical practice, especially in patients with low LDL cholesterol levels.