Higher LDL-C Levels Derive Most Benefit From More Intensive Therapy

Patients with higher baseline low-density lipoprotein cholesterol (LDL-C) levels exhibited greater decreases in all-cause and cardiovascular mortality with more intensive LDL-C-lowering therapies, according to a recent meta-analysis published in the Journal of American Medical Association.

All-cause mortality and cardiovascular mortality outcomes in patients who received either more or less intensive LDL-C-lowering therapies were extracted from randomized clinical trials of statins, ezetimibe, and PCSK9-inhibiting monoclonal antibodies. The researchers searched the electronic databases of Cochrane, MEDLINE, EMBASE, TCTMD, ClinicalTrials.gov, and major congress proceedings. Outcome measurements were compared between the more and less intensive LDL-C-lowering therapies.

Of the participants in the 34 trials analyzed, 136,299 received more intensive LDL-C-lowering therapies, and 133,989 received less-intensive LDL-C-lowering therapies. There was a reduction in all-cause mortality in patients receiving more intensive therapy compared with those receiving less intensive therapy (7.08% vs 7.70%; rate ratio, 0.92; 95% CI, 0.88-0.06).

However, a meta-analysis by subgroups of baseline LDL-C levels demonstrated that all-cause mortality risk was associated with a reduction only in the trials that used baseline LDL-C levels of ≥100 mg/dL (P <.001 for interaction). Better cardiovascular mortality outcomes were also seen in the ≥100 mg/dL LDL-C subgroup of patients who received more intensive LDL-C-lowering therapies (P <.001 for interaction).

In addition, clinical trials with patients who had baseline LDL-C levels of ≥160 mg/dL showed the greatest reductions in all-cause mortality (rate ratio, 0.72; 95% CI, 0.62-0.84; P <.001) and cardiovascular mortality (rate ratio, 0.65; 95% CI, 0.54-0.77; P <.001).

The study authors wrote, “In these meta-analyses and meta-regressions, more intensive compared with less intensive LDL-C lowering was associated with a greater reduction in risk of total and cardiovascular mortality in trials of patients with higher baseline LDL-C levels.”

They added, “This association was not present when baseline LDL-C level was less than 100 mg/dL, suggesting that the greatest benefit from LDL-C-lowering therapy may occur for patients with higher baseline LDL-C levels.”

Reference

Navarese E, Robinson J, Kowalewski M, et al Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering: a systematic review and meta-analysis . JAMA. 2018;319(15):1566-1579.