A randomized, open-label, parallel, multi-center Phase IV study to compare the efficacy and safety of atorvastatin 10 and 20 mg in high-risk Asian patients with hypercholesterolemia

Abstract

Background Although accumulating evidence suggests a more extensive reduction of low-density lipoprotein cholesterol (LDL-C), it is unclear whether a higher statin dose is more effective and cost-effective in the Asian population. This study compared the efficacy, safety, and cost-effectiveness of atorvastatin 20 and 10 mg in high-risk Asian patients with hypercholesterolemia. Methods A 12-week, open-label, parallel, multicenter, Phase IV randomized controlled trial was conducted at ten hospitals in the Republic of Korea between October 2017 and May 2019. High-risk patients with hypercholesterolemia, defined according to 2015 Korean guidelines for dyslipidemia management, were eligible to participate. We randomly assigned 250 patients at risk of atherosclerotic cardiovascular disease to receive 20 mg (n = 124) or 10 mg (n = 126) of atorvastatin. The primary endpoint was the difference in the mean percentage change in LDL-C levels from baseline after 12 weeks. Cost-effectiveness was measured as an exploratory endpoint. Results LDL-C levels were reduced more significantly by atorvastatin 20 mg than by 10 mg after 12 weeks (42.4% vs. 33.5%, p < 0.0001). Significantly more patients achieved target LDL-C levels (<100 mg/dL for high-risk patients, <70 mg/dL for very high-risk patients) with atorvastatin 20 mg than with 10 mg (40.3% vs. 25.6%, p < 0.05). Apolipoprotein B decreased significantly with atorvastatin 20mg versus 10 mg (−36.2% vs. −29.9%, p < 0.05). Lipid ratios also showed greater improvement with atorvastatin 20 mg than with 10 mg (total cholesterol/high-density lipoprotein cholesterol ratio, −33.3% vs. −29.4%, p < 0.05; apolipoprotein B/apolipoprotein A1 ratio, −36.7% vs. −31.4%, p < 0.05). Atorvastatin 20 mg was more cost-effective than atorvastatin 10 mg in terms of both the average and incremental cost-effectiveness ratios. Safety and tolerability of atorvastatin 20 mg were comparable to those of atorvastatin 10 mg. Conclusion In high-risk Asian patients with hypercholesterolemia, atorvastatin 20 mg was both efficacious in reducing LDL-C and cost-effective compared with atorvastatin 10 mg.

Associations between statins and adverse events in secondary prevention of cardiovascular disease: Pairwise, network, and dose-response meta-analyses of 47 randomized controlled trials

“…Our searches identified 11,973 citations (11,869 from database searches and 104 from previous meta-analyses). Finally, after assessing the full text, forty-seven eligible studies ( 25 – 71 ) were included ( Figure 1 ). Supplementary Table 3 presents the list of studies excluded after assessing the full text and reasons for exclusion.…”

Clinical Benefit of Fixed‐Dose Combination of Amlodipine and Potent Atorvastatin in Patients With Concomitant Hypertension and Hypercholesterolemia

“…In a randomized, multicenter phase 4 study to compare the efficacy and safety of atorvastatin 10 and 20 mg in high‐risk Korean patients with hypercholesterolemia, the LDL‐C levels were reduced more significantly by atorvastatin 20 mg than by 10 mg after 12 weeks (42.4% versus 33.5%; P <0.0001). 36 To evaluate the long‐term laboratory efficacy and safety of high‐ and low‐dose FDC of amlodipine and atorvastatin, we previously conducted a retrospective, multi‐institutional, real‐world, electronic medical record–based study that demonstrated that an FDC of 5 mg of amlodipine and 20 mg of atorvastatin daily significantly reduced the LDL‐C level when compared with a similar FDC that only contained 10 mg of atorvastatin (−35.7 versus −23.6 mg/dL; regression coefficient, −2.7 [95% CI, −4.3 to −1.2]; P <0.001), and the medication adherence rate did not differ between these 2 regimens in patients with concurrent hypertension and hypercholesterolemia. 22 However, the incidence of MACEs in that study was not significantly different between high and low doses of the amlodipine/atorvastatin FDC, which may be the result of the short follow‐up period and restricted events only recorded in our multi‐institutional database.…”