LDL-lowering therapy may provide cumulative CV benefit over years of use
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Duration of LDL-lowering therapy had a cumulatively beneficial effect on CV outcomes, according to a meta-analysis of 21 randomized clinical trials published in Circulation: Cardiovascular Quality and Outcomes.
For every 1 mmol/L decrease in LDL, the risk for CV death, MI, stroke and revascularization was reduced by 12% at 1 year, 20% at 3 years, 23% at 5 years and 29% at 7 years, researchers reported.
“The seminal Cholesterol Treatment Trialists Collaboration analyses reported approximately constant relative risk reductions in major vascular events (around 24% per mmol/L) after the first year, with no suggestion from those analyses of increasing benefits with increasing duration,” Nelson Wang, BSc, MD, MPhil, of The George Institute for Global Health at the University of New South Wales in Kensington, Australia, and colleagues wrote. “However, Mendelian randomization studies have reported that each mmol/L lower LDL-C is associated with a 55% lower coronary risk, with the difference hypothesized as because of the duration of exposure, since LDL-C differences were sustained over a lifetime.”
To better understand the relationship between duration of LDL-lowering therapy and CV outcomes, researchers conducted the present meta-analysis of randomized trials of statins, ezetimibe and PCSK9 inhibitors that reported LDL levels and CV benefit effect sizes for each year of follow-up. Researchers included 21 trials, enrolling 184,012 patients with an average follow-up of 4.4 years. The primary endpoint was major CV events, defined as CV death, MI, stroke and revascularization.
The researchers observed greater RR reduction for the primary endpoint with increasing duration of statin treatment (P < .001).
The mean difference across the 21 trials in LDL between the treatment and their respective control arms was of 1.05 mmol/L at 1 year, which decreased to 0.98 mmol/L at 3 years and 0.54 mmol/L at 7 years, according to the study.
For every 1 mmol/L decrease in LDL, the RR for the primary endpoint was reduced by 12% at 1 year (95% CI, 8-16), 20% at 3 years (95% CI, 16-24), 23% at 5 years (95% CI, 18-27) and 29% at 7 years (95% CI, 14-42).
The trend remained consistent even when analyses were limited to only trials studying statins for LDL lowering (P < .001).
Researchers reported no significant heterogeneity for individual meta-analyses (I2 between 6% and 39%).
“The potential implications of these findings relate to whether to include intended treatment duration into decision-making. ... At present, this is not done, with the assumption that all patients receive the same relative risk reduction forever into the future, and hence the only determinant of absolute benefits is absolute cardiovascular risk,” the researchers wrote. “However, these data suggest larger relative risk reductions could be attained if the intention is to treat long term, which is almost always the case.
“The key research implications are around the efficacy, tolerability and acceptability of strategies that focus on LDL-C lowering early in life,” the researchers wrote. “This will be explored in the Eliminate Coronary Artery Disease trial, which will investigate whether LDL-C lowering in healthy young to middle-aged adults with a single risk factor for coronary heart disease can eliminate or markedly reduce the incidence of cardiovascular events.”
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