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 (original) (raw)
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Atherosclerosis, 2014
Efficacy, safety and effect on biomarkers related to cholesterol and lipoprotein metabolism of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg vs. simvastatin 40 or 80 mg plus ezetimibe 10 mg in high-risk patients: Results of the GRAVITY randomized study a b s t r a c t Objectives: Combination therapy may help high-risk patients achieve low-density lipoprotein cholesterol (LDL-C) goals. Impact of rosuvastatin 10 or 20 mg plus ezetimibe 10 mg (RSV10/EZE10 and RSV20/EZE10) has not been fully characterized previously. GRAVITY (NCT00525824) compared efficacy, safety and effect on biomarkers of RSV10/EZE10 and RSV20/EZE10 vs. simvastatin 40 mg and 80 mg plus EZE10 (SIM40/ EZE10 and SIM80/EZE10) in patients with coronary heart disease (CHD) or CHD risk equivalent. Methods: Adult patients (n ¼ 833) were randomized to RSV10/EZE10, RSV20/EZE10, SIM40/EZE10 or SIM80/EZE10. Following a 6-week dietary lead-in, patients received 6 weeks' statin monotherapy followed by same statin dose plus ezetimibe for 6 more weeks. Primary endpoint was LDL-C change from baseline to 12 weeks. Results: Significantly greater (p < 0.05) reductions in LDL-C and other atherogenic lipids were observed with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. A significantly greater proportion of patients achieved LDL-C goals of <100 mg/dl and <70 mg/dl with RSV20/EZE10 vs. SIM40/EZE10 and SIM80/EZE10 and with RSV10/EZE10 vs. SIM40/EZE10. LDL-C was reduced w10e14% further with combination therapy vs. monotherapy. Statin monotherapy reduced cholesterol and bile acid synthesis biomarkers, ezetimibe reduced b-sitosterol (sterol absorption marker), and combination therapy achieved additive reductions in lipoprotein-associated phospholipase A 2 mass and activity, free cholesterol and 7-ketocholesterol. Safety profiles of rosuvastatin/ezetimibe and simvastatin/ezetimibe combinations were comparable. Conclusion: Co-administration of rosuvastatin 10 or 20 mg plus ezetimibe achieved significant improvements in lipid profiles in high-risk patients vs. simvastatin 40 or 80 mg plus ezetimibe.
Herz Kardiovaskuläre Erkrankungen, 2008
Hintergrund: Obwohl Leitlinien die LDL-C-("low-density lipoprotein cholesterol"-)Reduktion als wesentliche Strategie für die kardiovaskuläre Risikoreduktion hervorheben, ist es oft schwierig, die Zielwerte zu erreichen. Patienten und Methodik: Die Autoren überprüften in einer prospektiv-offenen, kontrollierten Untersuchung die Effektivität und Sicherheit einer hochdosierten Fluvastatintherapie und einer standarddosierten Simvastatintherapie plus Ezetimib. Beide Therapien erfolgten während eines intensiven leitlinienorientierten kardialen Rehabilitationsprogramms zum Erreichen der neuen ATP-III-LDL-C-Zielwerte bei Patienten mit einer erwiesenen koronaren Herzerkrankung. 305 Patienten wurden konsekutiv in die Studie eingeschlossen. Die Patienten wurden zwei Gruppen zugeteilt: Eine Gruppe erhielt eine Tagesdosis von 40 mg Simvastatin plus 10 mg Ezetimib, die andere Gruppe eine alleinige Tagesdosis von 80 mg Fluvastatin. Alle Patienten wurden über 21 Tage im Rahmen eines leitlinienorientierten, standardisierten und intensivierten kardialen Rehabilitationsprogramms behandelt. Ergebnisse: Nach 21 Tagen zeigte sich im Vergleich zu den Ausgangswerten eine signifikante Reduktion des LDL-C in beiden Gruppen mit jedoch signifikant stärker ausgeprägtem Effekt in der Gruppe mit Simvastatin plus Ezetimib. Die Kombination erniedrigte LDL-C auf im Mittel 57,7 ± 1,7 mg/ml, während
Cureus
Longstanding hyperlipidemia can increase the risk of cardiovascular disease. Statins are currently the mainstay of treatment in hyperlipidemia. Combination therapy of statin with ezetimibe is only indicated for severe hypercholesterolemia and very high-risk atherosclerotic cardiovascular disease (ASCVD) population. There is a paucity of studies comparing statin monotherapy vs combination therapy with ezetimibe. This study aims to perform a meta-analysis of the existing literature and compare the effectiveness of statin monotherapy with statin-ezetimibe combination therapy in the management of hyperlipidemia. A systematic electronic search of the scientific literature was performed in PubMed, EMBASE, and Scopus. Only randomized controlled trials comparing simvastatin monotherapy vs simvastatin-ezetimibe combination therapy between the years 2000 and 2021 and published in English language were included. Fifteen studies were included in the final analysis. The main outcomes that were compared were a reduction in low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Our study showed that combination therapy led to a higher reduction of LDL-C (Mean difference:-20.22(-26.38,-14.07); P<0.0001) compared to monotherapy with a statin alone. There was no significant difference in the reduction of HDL-C values (Mean difference:-0.07(-0.45,0.32); P-0.04) between the two groups. Our study indicates that the combination therapy of simvastatin and ezetimibe is more effective in reduction of LDL-C levels compared to simvastatin monotherapy alone. Currently, guidelines recommend combination therapy only for severe hypercholesterolemia and high-risk ASCVD patients, more studies are needed to study the effectiveness of simvastatin-ezetimibe combination therapy in low-risk ASCVD population.
Ezetimibe/simvastatin vs simvastatin in coronary heart disease patients with or without diabetes
Lipids in Health and Disease, 2010
Background: Treatment guidelines recommend LDL-C as the primary target of therapy in patients with hypercholesterolemia. Moreover, combination therapies with lipid-lowering drugs that have different mechanisms of action are recommended when it is not possible to attain LDL-C targets with statin monotherapy. Understanding which treatment or patient-related factors are associated with attaining a target may be clinically relevant. Methods: Data were pooled from two multicenter, randomized, double-blind studies. After stabilization on simvastatin 20 mg, patients with coronary heart disease (CHD) alone and/or type 2 diabetes mellitus (T2DM) were randomized to ezetimibe 10 mg/simvastatin 20 mg (EZ/Simva) or simvastatin 40 mg. The change from baseline in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC/ HDL-C ratio, triglycerides, and the proportion of patients achieving LDL-C < 2.6 mmol/L (100 mg/dL) after 6 weeks of treatment were assessed, and factors significantly correlated with the probability of achieving LDL-C < 2.6 mmol/L in a population of high cardiovascular risk Italian patients were identified. A stepwise logistic regression model was conducted with LDL-C < 2.6 mmol/L at endpoint as the dependent variable and study, treatment, gender, age (≥65 years or < 65 years), as independent variables and baseline LDL-C (both as continuous and discrete variable).
Vascular health and risk management, 2008
The aim of this multi-center, open-label, randomized, parallel-group trial was to compare the efficacy of rosuvastatin with that of simvastatin in achieving the 1998 European Atherosclerosis Society (EAS) lipid treatment goals. 504 patients (> or =18 years) with primary hypercholesterolemia and a 10-year cardiovascular (CV) risk >20% or history of coronary heart disease (CHD) or other established atherosclerotic disease were randomized in a 2:1 ratio to receive rosuvastatin 10 mg or simvastatin 20 mg once daily for 12 weeks. A significantly higher proportion of patients achieved 1998 EAS low-density lipoprotein cholesterol (LDL-C) goal after 12 weeks of treatment with rosuvastatin 10 mg compared to simvastatin 20 mg (64 vs 51.5%, p < 0.01). Similarly, significantly more patients achieved the 1998 EAS total cholesterol (TC) goal and the 2003 EAS LDL-C and TC goals (p < 0.001) with rosuvastatin 10 mg compared with simvastatin 20 mg. The incidence of adverse events and the ...
The American Journal of Cardiology, 2010
Higher than 80% of coronary heart disease-related mortality occurs in patients >65 years of age. Guidelines recommend low-density lipoprotein (LDL) cholesterol targets for these at-risk patients; however, few clinical studies have evaluated lipid-lowering strategies specifically in older adults. This multicenter, 12-week, randomized, double-blind, parallelgroup trial evaluated the efficacy and safety of the usual starting dose of ezetimibe/ simvastatin (10/20 mg) versus atorvastatin 10 or 20 mg and the next higher dose of ezetimibe/simvastatin (10/40 mg) versus atorvastatin 40 mg in 1,289 hypercholesterolemic patients >65 years of age with or without cardiovascular disease. Patients randomized to ezetimibe/simvastatin had greater percent decreases in LDL cholesterol (؊54.2% for 10/20 mg vs ؊39.5% and ؊46.6% for atorvastatin 10 and 20 mg, respectively; ؊59.1% for 10/40 mg vs ؊50.8% for atorvastatin 40 mg; p <0.001 for all comparisons) and the number attaining LDL cholesterol <70 mg/dl (51.3% for 10/20 mg, 68.2% for 10/40 mg) and <100 mg/dl (83.6% for 10/20 mg; 90.3% for 10/40 mg) was significantly larger compared to those receiving atorvastatin for all prespecified dose comparisons (p <0.05 to <0.001). A significantly larger percentage of high-risk patients achieved LDL cholesterol <70 mg/dl on ezetimibe/simvastatin 10/20 mg (54.3%) versus atorvastatin 10 mg (10.9%, p <0.001) or 20 mg (28.9%, p <0.001) and ezetimibe/simvastatin 10/40 mg (69.2%) versus atorvastatin 40 mg (38.2%, p <0.001), and a significantly larger percentage of intermediate-risk patients achieved LDL cholesterol <100 mg/dl on ezetimibe/simvastatin 10/20 mg (82.1%) versus atorvastatin 10 mg (59.3%, p <0.05). Improvements in non-high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and lipoprotein ratios were significantly greater with ezetimibe/simvastatin than atorvastatin for all comparisons (p <0.01 to <0.001).