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LDL variability predicts CV events in patients with CAD
Visit-to-visit LDL variability was independently predictive of CV events in patients with CAD, according to new data from the TNT trial.
Researchers evaluated 9,572 patients with CAD and LDL level less than 130 mg/dL who were randomly assigned atorvastatin at doses of 80 mg/day or 10 mg/day. They evaluated visit-to-visit LDL variability from 3 months after randomization to determine its potential impact on CV outcomes.
LDL variability measurements included standard deviation, average successive variability, coefficient of variation and variation independent of mean. The primary outcome was incidence of any coronary event. Secondary outcomes were any CV event, death, MI and stroke.
Sripal Bangalore
Sripal Bangalore, MD, MHA, and colleagues found that in the population studied, standard deviation and average successive variability were lower among those assigned atorvastatin 80 mg/day than in those assigned atorvastatin 10 mg/day (standard deviation, 12.03 ± 9.7 vs. 12.52 ± 7.43; P = .005; average successive variability, 12.84 ± 10.48 vs. 13.76 ± 8.69; P < .0001).
LDL variability linked to hazard
Bangalore, associate professor of medicine, director of research at the Cardiac Catheterization Laboratory and director of the Cardiovascular Outcomes Group at the Cardiovascular Clinical Research Center at New York University School of Medicine, and colleagues found that each 1-unit standard deviation increase in LDL variability by average successive variability increased the risk of any coronary event by 16% on adjusted analysis (HR = 1.16; 95% CI, 1.1-1.23). They also observed increases in the risk for any CV event (HR = 1.11; 95% CI, 1.07-1.15), death (HR = 1.23; 95% CI, 1.14-1.34), MI (HR = 1.1; 95% CI, 1.02-1.19) and stroke (HR = 1.17; 95% CI, 1.04-1.31).
These results were independent of treatment effect and achieved LDL levels, and were consistent after adjustment for medication adherence, according to the researchers.
“Although yet to be confirmed in future studies, our results are important, given the increased variability in LDL in recent clinical trials that used monoclonal antibodies to PCSK9 with every-4-weeks dosing vs. every-2-weeks dosing and with intermittent statin dosing strategies,” Bangalore and colleagues wrote.
Several explanations
Jonathan L. Halperin
In a related editorial, Usman Baber, MD, MS, and Jonathan L. Halperin, MD, wrote that there are several possible explanations for the association between increased CVD risk and LDL variability, including that LDL variability is a marker for the benefit or lack of benefit derived from the pleiotropic effects of statins; that LDL variability can reflect factors impairing responsiveness to statins, such as poor adherence; and that LDL variability may derive from genetic polymorphisms in alleles that regulate the functions of the LDL receptor, HMG-CoA reductase and apolipoprotein E, among others.
“Even without a clear mechanistic explanation, these new data suggest that variability in LDL levels over time has prognostic importance in statin-treated patients,” wrote Baber and Halperin, both from the Cardiovascular Institute of the Icahn School of Medicine at Mount Sinai. “This information may eventually inform clinical practice, guiding dosing intervals or statin formulations to enhance stability.” – by Erik Swain
Disclosures: The TNT study was sponsored by Pfizer. Bangalore reports having been an ad hoc consultant for Boehringer Ingelheim, Daiichi Sankyo and Pfizer. Baber and Halperin report no relevant financial disclosures.