Very low LDL-C levels are safe and effective in high-risk post-ACS patients
Long-term Safety and Efficacy of Achieving Very Low Levels of Low-Density Lipoprotein Cholesterol: A Prespecified Analysis of the IMPROVE-IT TrialLiterature - Giugliano RP, Wiviott SD, Blazing MA, et al. - JAMA Cardiol. 2017; published online ahead of print
- An LDL-C level <30 mg/dL at 1 month was observed in 6.4% of patients and their time-weighted average LDL-C level after randomisation was 34 mg/dL (IQR 27-44 mg/dL) over a median of 6 years’ follow-up.
- There were several significant differences in baseline characteristics when stratified by either achieved LDL-C level or treatment group.
- The rate of new, worsening or relapsing malignancies reported: 9.0%, 8.6%, 8.7% and 7.5%, (unadjusted P for trend = 0.04) for the 4 groups from lowest to highest achieved LDL-C level. However, this was no longer statistically significant after accounting for baseline characteristics (adjusted P for trend = 0.14).
- There were no differences in the other pre-specified safety endpoints, including serious muscle events, elevation in aminotransferases levels greater than 3 times the normal level (2.2% for LDL-C level <30 mg/dL and 1.8-2.1% in the other 3 groups), gall-bladder adverse events (3.6% for LDL-C <30 mg/dL and 3.2-3.6% in the other 3 groups) or neurocognitive events (2.1% for LDL-C <30mg/dL and 2.3-2.9% in the other 3 groups), haemorrhagic stroke (0.3% for LDL-C <30 mg/dL and 0.4-0.9% in the other 3 groups), HF requiring hospitalisation (4.6% for LDL-C <30 mg/dL and 3.4-4.2% in the other 3 groups) or non-CV death (5.8% for LDL-C <30 mg/dL and 4.9-5.6% in the other 3 groups).
- There were no differences in the adjusted risk for cataract-related adverse events across the groups compared with the reference group with LDL-C level ≥70 mg/dL (OR for <30 mg/dL 1.12, 95% CI 0.78-1.62, OR for 30-49 mg/dL 1.20, 95%CI 0.96-1.50, OR for 50-69 mg/dL 1.08, 95% CI 0.86-1.34).
- In the very low LDL-C level group, the unadjusted Kaplan-Meier rate of the primary efficacy endpoint (CV death, myocardial infarction or stroke) at 7 years was 31.9% compared with 36.0% in patients who achieved an LDL-C level ≥70 mg/dL at 1 month (adjusted HR 0.79, 95% CI 0.69-0.91, P<0.001).
Very low LDL-C levels at 1 month were associated with a similar safety profile compared with higher LDL-C levels. Moreover, LDL-C levels below currently recommended targets were associated with even further numerical reductions in CV events. These results support the use of intensive lipid-lowering therapy in very high-risk post-ACS patients.