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Original Investigation
August 2016

Association Between Achieved Low-Density Lipoprotein Levels and Major Adverse Cardiac Events in Patients With Stable Ischemic Heart Disease Taking Statin Treatment

Author Affiliations
  • 1Clalit Research Institute, Chief Physician’s Office, Clalit Health Services, Tel Aviv, Israel
  • 2Department of Medicine, New York University School of Medicine, New York, New York
  • 3Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
  • 4Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada
  • 5Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada
  • 6Department of Medicine, McGill University, Montreal, Canada
  • 7Department of Epidemiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Copyright 2016 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.

JAMA Intern Med. 2016;176(8):1105-1113. doi:10.1001/jamainternmed.2016.2751

Importance  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.

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

Design, Setting, and Participants  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.

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

Main Outcomes and Measures  Major adverse cardiac events included acute myocardial 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.

Results  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.

Conclusions and Relevance  Patients with LDL-C levels of 70 to 100 mg/dL taking statins had lower risk of adverse cardiac outcomes compared with those with LDL-C levels between 100 and 130 mg/dL, but no additional benefit was gained by achieving LDL-C of 70 mg/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.