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Lower limit for LDL Target?

Leibowitz et al report a population based observational cohort study of patients with ischemic heart disease to try to quantify the dose (LDL achieved after 1 year statin therapy)-response(major adverse cardiac events included acute myocardial
infarction, unstable angina, stroke, angioplasty, bypass surgery, or all-cause mortality).

Propensity score matching was used and a sensitivity analysis of patient adherence was performed.



International guidelines recommend treatment with statins for patients with
preexisting ischemic heart disease to prevent additional cardiovascular events but differ
regarding target levels of low-density lipoprotein cholesterol (LDL-C). Trial data on this
question are inconclusive and observational data are lacking.


To assess the relationship between levels of LDL-C achieved with statin treatment
and cardiovascular events in adherent patients with preexisting ischemic heart disease.


Population-based observational cohort study from 2009 to 2013 using data from a health care organization in Israel covering more than 4.3 million members. Included patients had ischemic heart disease, were aged 30 to 84 years, were treated with statins, and were at least 80% adherent to treatment or, in a sensitivity analysis, at least 50% adherent. Patients with active cancer or metabolic abnormalities were excluded.


Index LDL-C was defined as the first achieved serum LDL-C measure after at
least 1 year of statin treatment, grouped as low (70.0mg/dL), moderate (70.1-100.0
mg/dL), or high (100.1-130.0mg/dL).


Major adverse cardiac events included acutemyocardial
infarction, unstable angina, stroke, angioplasty, bypass surgery, or all-cause mortality. The
hazard ratio of adverse outcomes was estimated using 2 Cox proportional hazards models
with low vs moderate and moderate vs high LDL-C, adjusted for confounders and further
tested using propensity score matching analysis.


The cohort with at least 80% adherence included 31 619 patients, for whom the
mean (SD) age was 67.3 (9.8) years. Of this population, 27%were female and 29% had low,
53%moderate, and 18%high LDL-C when taking statin treatment. Overall, there were 9035
patients who had an adverse outcome during a mean 1.6 years of follow-up (6.7 per 1000
persons per year). The adjusted incidence of adverse outcomes was not different between
low and moderate LDL-C (hazard ratio [HR], 1.02; 95%CI, 0.97-1.07; P = .54), but it was lower
with moderate vs high LDL-C (HR, 0.89; 95%CI, 0.84-0.94; P < .001). Among 54 884
patients with at least 50% statin adherence, the adjusted HR was 1.06 (95%CI, 1.02-1.10;
P = .001) in the low vs moderate groups and 0.87 (95%CI, 0.84-0.91; P = .001) in the
moderate vs high groups.


Patients with LDL-C levels of 70 to 100mg/dL taking statins
had lower risk of adverse cardiac outcomes compared with those with LDL-C levels between
100 and 130mg/dL, but no additional benefit was gained by achieving LDL-C of 70mg/dL or
less. These population-based data do not support treatment guidelines recommending very
low target LDL-C levels for all patients with preexisting heart disease.



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