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.

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). LDL-C <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 ezetimibe fixed dose combination in both 10 mg/10 mg and 20 mg/10 mg doses, respectively, provided significantly lower levels of LDL-C compared with simvastatin and ezetimibe in doses of 20 mg/10 mg and 40 mg/10 mg, respectively. The fixed-dose combinations were both effective and well tolerated in this Brazilian study population. ClinicalTrials.gov identifier: NCT01420549. (Curr Ther Res Clin Exp. 2020; 81:XXX-XXX).

Comparison of amlodipine/valsartan/hydrochlorothiazide single pill combination and free combination: adherence, persistence, healthcare utilization and costs.

OBJECTIVES: To determine whether amlodipine/valsartan/hydrochlorothiazide single pill combination (SPC) is associated with improved persistence, adherence and reduced healthcare utilization and costs compared to the corresponding free combination (FC). METHODS: Adult (≥18 years) patients covered by commercial and Medicare Supplemental insurance in the Truven MarketScan database with hypertension (HTN) diagnosis between October 2009 and December 2011 were included. At least two filled prescriptions for the SPC cohort or two periods of minimum 15 days of concurrent use of amlodipine, valsartan and hydrochlorothiazide (HCT) for the FC cohort were required. Cohorts were propensity score matched (PSM) to balance on important confounders. Outcomes included: 1) adherence (proportion of days covered [PDC] and medication possession ratio [MPR]); 2) persistence (treatment gap >30 days); 3) all-cause and HTN-specific healthcare utilization and costs at 12 months. RESULTS: After cohort matching with PSM, patients taking SPC (N = 9221) exhibited better outcomes than FC (N = 1884): higher mean adherence (85.7% vs. 77.0%), mean PDC (73.8% vs. 60.6%) and persistence (46.8% vs. 23.6%) (all p < 0.0001). Patients taking SPC were associated with higher odds of persistence (OR: 3.51; 95% CI: 3.08-4.02), MPR ≥80% (OR: 2.72; 95% CI: 2.40-3.08) and PDC ≥80% (OR: 2.88; 95% CI: 2.55-3.26). After PSM, the SPC cohort exhibited statistically significantly lower mean number of resource utilization events compared to FC. Patients in the SPC cohort also had a statistically significantly (p < 0.05) lower percentage of patients with ≥1 all-cause hospitalization (15.0% vs. 18.2%), ≥1 all-cause emergency room (ER) visits (25.7 vs. 31.4%), and ≥1 ER HTN-specific visits (9.7% vs. 14.1%). The costs incurred by SPC cohort patients were 2.8% to 41.7% numerically lower than the FC cohort, statistically significant for all-cause ER costs ($430.6 vs. $549.5, p < 0.05). CONCLUSIONS: Real-world data indicate an association of the amlodipine/valsartan/HCT SPC with improved adherence and persistence vs. FC with no difference in overall healthcare or hypertension specific costs between the cohorts.