Efficacy and Tolerability of a Fixed-Dose Combination of Rosuvastatin and Ezetimibe Compared with a Fixed-Dose Combination of Simvastatin and Ezetimibe in Brazilian Patients with Primary Hypercholesterolemia or Mixed Dyslipidemia: A Multicenter, Randomized Trial

Abstract

Background: The addition of ezetimibe to statin therapy has been reported to result in increased efficacy for reduction of LDL-C levels and achievement of lipid targets, compared with monotherapy. Objective: This study was designed to demonstrate the noninferiority of therapy with fixed-dose rosuvastatin plus ezetimibe formulations versus fixed dose simvastatin and ezetimibe formulations for reduction of LDL-C levels in Brazilian patients with hypercholesterolemia or mixed dyslipidemia. Methods: Phase III, multicenter, randomized, parallel, open-label, noninferiority study that included male and female participants (aged 21–80 years) with hypercholesterolemia or mixed dyslipidemia. After a 1-week screening period with washout of lipid-lowering medications when needed, patients were treated with simvastatin 20 mg/d for 5 weeks. Participants with LDL-C levels ≥100 mg/dL after the initial treatment were submitted to a 1-week washout period, and then randomized 1:1 to receive either combined rosuvastatin 10 mg + ezetimibe 10 mg (R/E) or simvastatin 20 mg + ezetimibe 10 mg (S/E) for 4 weeks and, if they still did not achieve the stipulated target, doses were readjusted to rosuvastatin 20 mg + ezetimibe 10 mg or simvastatin 40 mg + ezetimibe 10 mg, respectively, for 4 weeks. Results: One hundred twenty-nine participants were enrolled, including 66 in R/E and 63 in S/E. At the end of simvastatin 20 mg treatment period, mean LDL-C values were 124.79 mg/dL and 121.27 mg/dL for participants randomized to R/E and S/E arms, respectively. After 4 weeks of R/E 10 mg + 10 mg or S/E 20 mg + 10 mg combined treatments, adjusted mean LDL-C values were 74.21 mg/dL and 85.58 mg/dL, respectively ( P = 0.0005), and after 9 weeks, with dose adjustment to R/E 20 mg + 10 mg in 6 patients and to S/E 40 mg +10 mg in 19 patients, LDL-C adjusted mean values were 75.29 mg/dL and 86.62 mg/dL, respectively ( P = 0.0006). There was a statistically significant difference between the association R/E and S/E ( P = 0.0013) in percentage change of LDL-C after 9 weeks of combined treatments. The adjusted mean difference was estimated at –10.32% (95% CI, –16.94% to –3.70%). The LDL-C <100 mg/dL target was achieved in a significantly greater proportion of participants at week 4 in the R/E compared with the S/E arm (84.8% vs 68.2%; P = .0257), and at week 9, the proportion was 81.2% versus 73.0%, respectively ( P = 0.23). LDL­C <70 mg/dL was achieved at a significantly greater proportion in the R/E arm, both at week 4 (45.4% vs 15.9%; P = 0.003) and week 9 (40.9% vs 15.9%; P = 0.0017). A statistically significant difference at week 9 ( P = 0.0106) was observed in fasting blood glucose in the R/E arm, but the overall incidence of adverse events was not significantly different between groups. Conclusions: Rosuvastatin and ezeti...

Statin associated adverse reactions in Latin America: a scoping review

“…In Brazil, Vattimo et al conducted a trial comparing rosuvastatin/ezetimibe versus simvastatin/ezetimibe with a previous simvastatin run-in. 25 The frequency of ADRs in the rosuvastatin/ezetimibe arm was 12% during the run-in phase and 19.5% while on the intervention. On the other hand, the simvastatin/ezetimibe arm presented ADRs in 15.8% of the participants during the run-in phase and in 23.8% during the treatment phase.…”

“…On the other hand, the simvastatin/ezetimibe arm presented ADRs in 15.8% of the participants during the run-in phase and in 23.8% during the treatment phase. 25 The most common ADRs were increased fasting plasma glucose and myalgia. 25 Rodríguez-Roa et al compared two different presentations of atorvastatin (amorphous highly soluble and crystalline) in Venezuela.…”

“… 25 The most common ADRs were increased fasting plasma glucose and myalgia. 25 Rodríguez-Roa et al compared two different presentations of atorvastatin (amorphous highly soluble and crystalline) in Venezuela. 29 They segregated the ADRs by type of atorvastatin and reported a frequency of 12.5% and 35.1% among the amorphous highly soluble and crystalline atorvastatin participants, respectively.…”

“…The mean age of the participants ranged from 50 to 66 years. [25][26][27][28][29][30] One author reported a median age of 67 years. 31 The proportion of male participants ranged from 16.3% to 53.2% while female participation ranged from 46.8% to 83.7%, except for one study that included only women.…”

“…26 27 29-31 The most common comorbidities reported were hypertension (HTN) (30.6%-78%), [25][26][27][28][29][30][31] DM (9.4%-54%), [25][26][27][28][29][30] obesity (28.6%-41.9%) 25-27 30 and smoking (10.4%-30.5%). 25-27 30 31 Regarding the intervention and comparison, three RCTs were direct statin comparisons 25 29 30 with one of them being statin/ezetimibe comparison, 25 two were statin versus policosanol, 26 27 and two were placebocontrolled. 28 31 These studies evaluated both the efficacy and safety of the interventions.…”