Author + information
- Luca Mascitelli, MD∗ ( and )
- Mark R. Goldstein, MD
- ↵∗Medical Service, Comando Brigata Alpina “Julia”/Multinational Land Force, 8 Via S. Agostino, Udine 33100, Italy
Boekholdt et al. (1), reporting a patient-level meta-analysis of data from large statin trials, mostly in the secondary prevention setting, found a clear inverse relationship between attained low-density lipoprotein cholesterol (LDL-C) level and cardiovascular risk among 38,153 patients allocated to statin therapy. However, translating these findings into real-world clinical practice may not be so straightforward.
The primary prevention cohort study of the J-LIT (Japan Lipid Intervention Trial) (2), a 6-year, nationwide cohort study of 47,294 patients treated with open-labeled low-dose simvastatin, found a J-curve between mean achieved LDL-C level and total mortality; the relative risk of death was significantly higher in patients with an LDL-C level <80 mg/dl or ≥200 mg/dl compared with the other groups.
Furthermore, in the meta-analysis by Boekholdt et al. (1), the mean delay in the manifestation of a clinical cardiovascular event was likely very short in patients who reached a very low LDL-C level with respect to other groups. In a secondary prevention setting, the mean delay of revascularization has been calculated at 0.09 years (33 days) over 5 years with a pravastatin-induced reduction in LDL-C level of 43 mg/dl (from 139 to 97 mg/dl) (3). Although it is difficult to make a similar calculation for the whole meta-analysis by Boekholdt et al. (1), considering that revascularization represents an endpoint notoriously subject to preference that falsely inflates benefits, it seems likely that the delay may be even shorter.
When considering the adverse effects of statin-induced low LDL-C levels, which are easily dismissed in randomized trials but not trivial in real life (4,5), lower LDL-C levels may not be better, especially in the primary prevention setting. Finally, the authors of the meta-analysis (1) should provide all-cause mortality data in relation to achieved LDL-C levels in both primary and secondary prevention trials.
- American College of Cardiology Foundation
- Boekholdt S.M.,
- Hovingh G.K.,
- Mora S.,
- et al.
- Matsuzaki M.,
- Kita T.,
- Mabuchi H.,
- et al.,
- J-LIT Study Group. Japan Lipid Intervention Trial