Association Between Achieved Low-Density Lipoprotein Levels and Major Adverse Cardiac Events in Patients With Stable Ischemic Heart Disease Taking Statin Treatment.
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 (≤70.0 mg/dL), moderate (70.1-100.0 mg/dL), or high (100.1-130.0 mg/dL).



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.



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 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.
Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel2Department of Medicine, New York University School of Medicine, New York, New York.
Morton
M
Leibowitz
Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel.
Tomas
T
Karpati
Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel.
Chandra J
CJ
Cohen-Stavi
Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel.
Becca S
BS
Feldman
Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel.
Moshe
M
Hoshen
Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel3Ruth and Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel.
Haim
H
Bitterman
Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada5Department of Epidemiology and Biostatistics, McGill University, Montreal, Canada6Department of Medicine, McGill University, Montreal, Canada.
Samy
S
Suissa
Clalit Research Institute, Chief Physician's Office, Clalit Health Services, Tel Aviv, Israel7Department of Epidemiology, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Ran D
RD
Balicer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D007557:Israel; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000517:prevention & control*; D017202:Myocardial Ischemia / Q000188:drug therapy*; D018570:Risk Assessment; D012307:Risk Factors
D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors