The results of 5-year atorvastatin therapy at the doses of 20–40 mg daily in metabolically compromised patients at very high risk
Authors: Korolyuk O 
Published: November 2020

Abstract

Background
Low-density lipoprotein cholesterol (LDL-C) is the main target for cardiovascular risk reduction. Statins remain the first-line therapy, however whether long-term statin use is safe and sufficient for achieving the new LDL-C goal (&lt;1.4 mmol/l instead of &lt;1.8 mmol/l) among patients at very high risk (VHR), especially those with multiple metabolic risk factors, remain uncertain. The purpose of our research was to estimate LDL-C lowering effect and occurrence of cardiovascular events (CVE) in ambulatory VHR patients who received atorvastatin for 5 years.

Methods
107 patients (57 males and 50 females, mean (SD) age in years 59.8 (11.0) and 65.3 (8.5), respectively) with documented coronary artery disease who used atorvastatin at daily doses of 20 mg (n=40, baseline LDL-C 2.39 (0.53) mmol/l) or 40 mg (n=67, baseline LDL-C 4.05 (0.94) mmol/l) were included. The initial assessment included anthropometry, measuring of HbA1c and lipid profile (standard kits Human, Germany, LDL-C was calculated using the Friedewald's equation), and oral glucose tolerance test. During observation once annually patients were interviewing about prior hospitalizations due acute myocardial infarction, decompensated heart failure or stroke with further screening for type 2 diabetes mellitus (T2DM). Survival was analysed by Kaplan-Meier's method, using Cox's F-test; Fisher's exact test or Mann-Whitney U-test were used to compare independent samples; Wilcoxon matched pairs test was used for comparison of dependent samples.

Results
All participants had elevated baseline LDL-C, arterial hypertension and overweight or obesity (BMI ≥30 kg/m2 in 57%); 63.5% had prediabetes, 22.4% had first-detected T2DM, 54.2% had serum triglycerides &gt;1.7 mmol/l, and 62.6% had low serum HDL-C adjusted to gender. Although in the end of observation, LDL-C levels in both atorvastatin regimens were significantly lower comparing to baseline (1.64 (0.20) and 2.20 (0.50) mmol/l, respectively, both P&lt;0.0001), only 40% of patients who used 20 mg of atorvastatin and 49.3% of those who used 40 mg reached LDL-C target &lt;1.8 mmol/l. Only 1.9% of participants reached LDL-C target &lt;1.4 mmol/l. During observation, CVE were documented in 34 patients (n=9 (23.1%) vs n=25 (36.8%) in those who used 20 mg and 40 mg of atorvastatin, resp., P=0.072). This difference was significant when compared patients who achieved and did not achieved LDL-C target &lt;1.8 mmol/l (14.3% vs 46.6%, resp., cumulative proportions surviving (CPS) 85.7% vs 53.5%, P=0.0001). Besides, during observation 29 new cases of T2DM were detected, (n=7 (22.6%) vs n=22 (42.3%) in those who used 20 mg and 40 mg of atorvastatin, resp., CPS 77.4% vs 57.0%, P=0.036).

Conclusion
After 5-year of atorvastatin use, less than 50% of metabolically compromised VHR patients had achieved LDL-C targets &lt;1.8 mmol/l. Therapy was associated with dose-dependent risk of T2DM. To avoid statin dose escalation, combination therapy might be considered.

Funding Acknowledgement
Type of funding source: None