Atorvastatin and low-density lipoprotein cholesterol in type 2 diabetes mellitus patients on hemodialysis

Abstract

Background and objectives: Patients undergoing maintenance hemodialysis are at high cardiovascular risk. Lowering LDL-cholesterol with statins reduces the incidence rate of cardiovascular events in patients with chronic kidney disease. In contrast, two randomized, prospective, placebo-controlled trials have been completed in hemodialysis patients that showed no significant effects of statins on cardiovascular outcomes.

Design, setting, participants, & measurements: A post hoc analysis was conducted of the 4D (Die Deutsche Diabetes Dialyze) study to investigate whether LDL-cholesterol at baseline is predictive of cardiovascular events and whether the effect of atorvastatin on clinical outcomes depends on LDL-cholesterol at baseline.

Results: High concentrations of LDL-cholesterol by tendency increased the risks of cardiac endpoints and all-cause mortality. Concordantly, atorvastatin significantly reduced the rates of adverse outcomes in the highest quartile of LDL-cholesterol (≥145 mg/dl, 3.76 mmol/L). The hazard ratios and 95% confidence intervals were 0.69 (0.48 to 1.00) for the composite primary endpoint, 0.58 (0.34 to 0.99) for cardiac death, 0.48 (0.25 to 0.94) for sudden cardiac death, 0.62 (0.33 to 1.17) for nonfatal myocardial infarction, 0.68 (0.47 to 0.98) for all cardiac events combined, and 0.72 (0.52 to 0.99) for death from all causes, respectively. No such decrease was seen in any of the other quartiles of LDL-cholesterol at baseline.

Conclusions: In patients with type 2 diabetes mellitus undergoing hemodialysis, atorvastatin significantly reduces the risk of fatal and nonfatal cardiac events and death from any cause if pretreatment LDL-cholesterol is >145 mg/dl (3.76 mmol/L).

Figure 1.

Cumulative incidence of cardiovascular events according to medication group in participants of the 4D study with an LDL-C in its fourth quartile at baseline (≥145 mg/dl, 3.76 mmol/L). (a) Cumulative incidence of the combined primary endpoint (cardiac death, nonfatal myocardial infarction, or stroke). The HR for atorvastatin, as compared with placebo, was 0.69 (95% CI 0.48 to 0.69). (b) Cumulative incidence of cardiac deaths, for which the HR in the atorvastatin group was 0.58 (95% CI 0.34 to 0.69). (c) Cumulative incidence of sudden cardiac death, for which the HR in the atorvastatin group was 0.48 (95% CI 0.25 to 0.94). (d) Cumulative incidence of nonfatal myocardial infarction, for which the HR in the atorvastatin group was 0.62 (95% CI 0.33 to 1.17). (e) Cumulative incidence of any cardiac event, for which the HR in the atorvastatin group was 0.68 (95% CI 0.47 to 0.98). (f) Cumulative incidence of death from any cause, for which the HR in the atorvastatin group was 0.72 (95% CI 0.52 to 0.99).