Efficacy and Safety of Ezetimibe Added to Atorvastatin Versus Atorvastatin Uptitration or Switching to Rosuvastatin in Patients With Primary Hypercholesterolemia

Hypercholesterolemic patients (n = 1,547) at high atherosclerotic cardiovascular disease risk with low-density lipoprotein cholesterol (LDL-C) levels 65100 and 64160 mg/dl while treated with atorvastatin 10 mg/day entered a multicenter, randomized, double-blind, active-controlled, clinical trial using two 6-week study periods. Period I compared the efficacy/safety of (1) adding ezetimibe 10 mg (ezetimibe) to stable atorvastatin 10 mg, (2) doubling atorvastatin to 20 mg, or (3) switching to rosuvastatin 10 mg. Subjects in the latter 2 groups who persisted with elevated LDL-C levels ( 65100 and 64160 mg/dl) after period I, entered period II; subjects on atorvastatin 20 mg had ezetimibe added to their atorvastatin 20 mg, or uptitrated their atorvastatin to 40 mg; subjects on rosuvastatin 10 mg switched to atorvastatin 20 mg plus ezetimibe or uptitrated their rosuvastatin to 20 mg. Some subjects on atorvastatin 10 mg plus ezetimibe continued the same treatment into period II. At the end of period I, ezetimibe plus atorvastatin 10 mg reduced LDL-C significantly more than atorvastatin 20 mg or rosuvastatin 10 mg (22.2% vs 9.5% or 13.0%, respectively, p <0.001). At the end of period II, ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than atorvastatin 40 mg (17.4% vs 6.9%, p <0.001); switching from rosuvastatin 10 mg to ezetimibe plus atorvastatin 20 mg reduced LDL-C significantly more than uptitrating to rosuvastatin 20 mg (17.1% vs 7.5%, p <0.001). Relative to comparative treatments, ezetimibe added to atorvastatin 10 mg (period I) or atorvastatin 20 mg (period II) produced significantly greater percent attainment of LDL-C targets <100 or <70 mg/dl, and significantly greater percent reductions in total cholesterol, non-high-density lipoprotein cholesterol, most lipid and lipoprotein ratios, and apolipoprotein B (except ezetimibe plus atorvastatin 20 vs atorvastatin 40 mg). Reports of adverse experiences were generally similar among groups. In conclusion, treatment of hypercholesterolemic subjects at high cardiovascular risk with ezetimibe added to atorvastatin 10 or 20 mg produced significantly greater improvements in key lipid parameters and significantly greater attainment of LDL-C treatment targets than doubling atorvastatin or switching to (or doubling) rosuvastatin at the compared doses

Prevalence Of Potential Familial Hypercholesteremia (Fh) In 54,811 Statin-Treated Patients In Clinical Practice

Background and aims: Familial hypercholesterolemia (FH) is a life-threatening disease, characterized by elevated LDL-C levels and a premature, increased risk of coronary heart disease (CHD) that is globally underdiagnosed. The percentage of patients with possible or probable FH in various countries was examined in the Dyslipidemia International Study (DYSIS). Methods: DYSIS is a multinational, cross-sectional observational study of 54,811 adult outpatients treated with statin therapy. The percentages of patients with high levels of LDL-C, and with possible or probable FH, were assessed using the Dutch scoring method for FH across 29 countries, in age subgroups for the analysis population and among diabetes patients. Results: Despite statin therapy, 16.1% (range 4.4-27.6%) of patients had LDL-C > 3.6 mmol/L (140 mg/dL) across countries and the prevalence of possible FH was 15.0% (range 5.5-27.8%) and 1.1% (range 0.0-5.4%) for probable FH. The highest percentages of probable FH occurred in Egypt (5.4%), the Baltic states (4.2%), Russia (3.2%), and Slovenia (3.1%), with the lowest rates in Israel (0.0%), Canada (0.2%), and Sweden (0.3%). Rates of FH were the highest in younger patients (45-54 years) for secondary prevention, regardless of the presence/absence of diabetes. Conclusions: Despite statin therapy, high LDL-C levels and rates of possible and probable FH were observed in some countries. The prevalence of FH was the highest in younger age patients, and > 60% of patients with probable FH displayed CHD. Earlier diagnosis and treatment of patients with FH are needed to reduce CHD risk in these patients. (C) 2016 The Authors. Published by Elsevier Ireland Ltd

Contemporary data on treatment practices for low-density lipoprotein cholesterol in 3867 patients who had suffered an acute coronary syndrome across the world

DYSIS II ACS was a longitudinal, observational study in 3867 patients from 18 countries. They were being hospitalized after suffering an acute coronary syndrome. Evaluations were performed at the time of admission and again 120±15 days following the date of admission (the follow-up time point). 2521 patients were on active lipid lowering treatment (LLT) at admission. Mean atorvastatin dose was 22 mg per day and 2.7% received ezetimibe in combination with a statin. At discharge from hospital, 3767 patients received LLT expressed as a mean atorvastatin dose of 36 mg per day with 4.8% receiving ezetimibe on top of a statin. After 120 days, intensity in lipid lowering treatment was reduced to 32 mg per day with 4.9% of the patients receiving ezetimibe and a statin. Of note, during this 4-month follow up period, only 32% of all patients received laboratory lipid testing. 37% attained the low density lipoprotein cholesterol (LDL-C) target value of <70 mg/dl after 120 days. There are differences in the therapy administered as well as in the switch strategies when comparing the data from the respective countries studied. Conclusions: Only one in three patients achieved the LDL-C target value following only marginal improvements in atorvastatin dose or combination therapy after an ACS event. Keywords: Low-density lipoprotein cholesterol, Treatment target, Global, Region, Statin

Skuteczność połączenia ezetymibu/simwastatyny w dawkach 10/40 mg w porównaniu z podwójną dawką statyny u pacjentów hospitalizowanych z powodu ostrego incydentu wieńcowego: badanie INFORCE

Wstęp: Celem pracy było zbadanie skuteczności i bezpiecze&#241;stwa stosowania skojarzonego preparatu ezetymibu/simwastatyny (Eze/Simva) w dawce 10/40 mg w porównaniu z podwójną dawką statyny, które włączano przy wypisie ze szpitala u pacjentów przyjmujących dotychczas statyny, a u których powodem hospitalizacji była diagnostyka epizodu wieńcowego. Metody: Było to otwarte wieloośrodkowe badanie IV fazy, z randomizacją, prowadzone w układzie równoległym z grupą kontrolną, do którego zakwalifikowano 424 pacjentów (w wieku &#8805; 18 lat) hospitalizowanych z powodu ostrego epizodu wieńcowego. Pacjenci przyjmowali wcześniej statyny (przez &#8805; 6 tygodni) w stałej dawce, której wartość można było podwoić zgodnie z zaleceniami producenta preparatu. W momencie wypisu ze szpitala pacjent ów dzielono na grupy pod wzgl&#234;dem dawki/siły działania statyny (duża, średnia, mała) i przydzielano losowo w stosunku 1:1 do grupy, która przyjmowała następnie podwojoną dawkę tego preparatu (n = 211) lub preparat Eze/Simva w dawce 10/40 mg (n = 213) przez 12 tygodni. Pierwszorzędową zmienną określającą skuteczność zastosowanego leczenia było stężenie frakcji cholesterolu o małej gęstości (LDL-C) wyrażone w wartościach bezwzględnych [mmol/l] w momencie zakończenia badania. Wyniki: Średnie wartości stężenia cholesterolu frakcji LDL w punkcie wyjściowym wynosiły 2,48 mmol/l w grupie Eze/Simva i 2,31 mmol/l w grupie leczonej tylko statyną. W momencie zako&#241;czenia badania wartości najmniejszych kwadratów stężenie LDL-C wyniosły odpowiednio 1,74 mmol/l w grupie Eze/Simva i 2,22 mmol/l w grupie leczonej statyną; różnica pomiędzy grupami osiągnęła wartość znamienną statystycznie, rzędu -0,49 mmol/l (p &#8804; 0,001). Przyjmowanie skojarzonego preparatu Eze/Simva powodowało także znamienne zmniejszenie stężenia cholesterolu całkowitego (&#8211;0,49 mmol/l), cholesterolu frakcji lipoprotein innych ni&#191; te o dużej gęstości [(nie-HDL); &#8211;0,53 mmol/l] oraz apolipoproteiny B (&#8211;0,14 mmol/l) w porównaniu z przyjmowaniem podwójnej dawki statyny (p &#163; 0,001 dla wszystkich porównywanych warto&#339;ci). Oba protokoły leczenia miały zbliżony wpływ na stężenia triglicerydów, białka C-reaktywnego i cholesterolu frakcji lipoprotein o dużej gęstości (HDL, high-density protein); porównania pomiędzy grupami przyniosły wartości nieznamienne (p &#8805; 0,160). U istotnie większej liczby pacjentów przyjmujących Eze/Simva stężenie cholesterolu frakcji LDL spadło do poniżej 2,5 mmol/l (< 100 mg/dl; 86% pacjentów leczonych Eze/Simva vs. 72% osób leczonych podwójną dawką statyny), do poniżej 2,0 mmol/l (< 77 mg/dl; 70% vs. 42%) oraz do poniżej 1,8 mmol/l mmol/l (< 70 mg/dl; 60% vs. 13%) w porównaniu z grupą otrzymującą samą statynę (p &#8804; 0,001 dla wszystkich porównywanych wartości). Połączenie preparatów Eze/Simva było ogólnie dobrze tolerowane, a jego profil bezpieczeństwa był zbliżony do profilu samej statyny. Nie stwierdzono różnic pomiędzy grupami pod względem częstości występowania zwyżki aktywności aminotransferaz wątrobowych do wartości równej przynajmniej 3-krotności górnej granicy przedziału warto&#339;ci prawidłowych (ULN) ani zwyżki aktywności kinazy kreatynowej do wartości równej przynajmniej 10-krotności ULN. Wnioski: W populacji pacjentów leczonych wcześniej statyną, których hospitalizowano w celu diagnostyki incydentu wie&#241;cowego, leczenie skojarzonym preparatem Eze/Simva w dawce 10/40 mg przez 12 tygodni powoduje większą normalizację lipemii niż podwojenie dawki przyjmowanej wcze&#339;niej statyny, z zachowaniem zbliżonego profilu bezpieczeństwa

Combination therapy in dyslipidemia : where are we now?

Lowering low-density lipoprotein cholesterol (LDL-C) reduces the risk of cardiovascular disease: each 1.0mmol/L (38.7mg/dL) reduction in LDL-C reduces the incidence of major coronary events, coronary revascularizations, and ischemic stroke by approximately 20%. Statins are a well-established treatment option for dyslipidemia, with LDL-C reduction in the range of 27-55%.Several lipid goal-driven guidelines recommend reducing LDL-C to <2.59mmol/L (100mg/dL) or <1.81mmol/L (70mg/dL) in very high-risk patients. Many patients treated with statins do not reach these goals, and remain at risk of future cardiovascular events. The 2013 American College of Cardiology/American Heart Association guidelines move away from advocating LDL-C treatment targets with focus placed on identifying patients most likely to benefit from high-intensity or moderate-intensity statin therapy.While increasing the statin dose can prove efficacious in some patients, this approach typically offers limited additional LDL-C lowering, and is associated with increased incidence of adverse side effects. Indeed, this has led to the investigation of statins in combination with other lipid-modifying agents for the treatment of dyslipidemia.This review of the evidence for statin use in combination with fibrates, niacin, bile acid sequestrants, and the cholesterol absorption inhibitor, ezetimibe, in dyslipidemic patients at increased risk of cardiovascular disease, explores the impact of such combination therapies on lipids, attainment of lipid targets, inflammatory markers, and on cardiovascular outcomes and pathology. Additionally, new and emerging dyslipidemia treatments are summarized

Lipid-Altering Efficacy of Ezetimibe/Simvastatin 10/20 mg Compared to Rosuvastatin 10 mg in High-Risk Patients with and without Type 2 Diabetes Mellitus Inadequately Controlled Despite Prior Statin Monotherapy.

AIMS: This post hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg (EZE/SIMVA) or rosuvastatin 10 mg (ROSUVA) in uncontrolled high-risk hypercholesterolemic patients with/without type 2 diabetes mellitus (T2DM) despite statin monotherapy. METHODS: Patients (n = 618) at high risk for coronary vascular disease with elevated LDL-C ≥100 and ≤190 mg/dL despite use of statins were randomized 1:1 to double-blind EZE/SIMVA 10/20 mg or ROSUVA 10 mg for 6 weeks. Patients were classified as having T2DM based on ≥1 of the following: diagnosis of T2DM, antidiabetic medication, or FPG ≥126 mg/dL. This analysis evaluated percent changes from baseline in lipids among patients with (n = 182) and without T2DM (n = 434). RESULTS: EZE/SIMVA was more effective than ROSUVA at lowering LDL-C, TC, non-HDL-C, and apo B in the overall study population and within both subgroups. Numerically, greater between-treatment reductions in LDL-C, TC, non-HDL-C, and apo B were seen in patients with T2DM versus those without T2DM. A significant interaction (P= 0.015) was seen for LDL-C indicating that patients with T2DM achieved larger between-group reductions versus those without T2DM. CONCLUSIONS: Switching to EZE/SIMVA 10/20 mg versus ROSUVA 10 mg provided superior lipid reductions in patients with/without T2DM

Lipid-altering efficacy of switching to ezetimibe/simvastatin 10/20 mg versus rosuvastatin 10 mg in high-risk patients with and without metabolic syndrome

Metabolic syndrome (MetS) is a clustering of atherosclerotic coronary heart disease risk factors. This post-hoc analysis compared the effects of switching to ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg in a cohort of 618 high-risk hypercholesterolaemic patients with (n=368) and without (n=217) MetS who had previously been on statin monotherapy. Patients were randomised 1:1 to double-blind ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg for 6 weeks. Least squares mean percent change from baseline and 95% confidence intervals in lipid efficacy parameters were calculated for the population and within subgroups. Treatment with ezetimibe/simvastatin was significantly more effective than rosuvastatin at lowering low-density lipoprotein cholesterol, total cholesterol, non- high-density lipoprotein cholesterol, and apolipoprotein B (all p<0.001). No significant differences in treatment effects were seen between the presence and absence of MetS. In this post-hoc analysis of high-risk hypercholesterolaemic patients the lipid-reducing effects of ezetimibe/simvastatin or rosuvastatin were not altered significantly by the presence of MetS

Lipid-altering efficacy of ezetimibe/simvastatin 10/20 mg compared with rosuvastatin 10 mg in high-risk hypercholesterolaemic patients inadequately controlled with prior statin monotherapy - The IN-CROSS study.

AIMS: To evaluate the efficacy of switching from a previous statin monotherapy to ezetimibe/simvastatin (EZE/SIMVA) 10/20 mg vs. rosuvastatin (ROSUVA) 10 mg. METHODS: In this randomised, double-blind study, 618 patients with documented hypercholesterolaemia [low-density lipoprotein cholesterol (LDL-C) > or = 2.59 and or = 6 weeks prior to the study randomisation visit entered a 6-week open-label stabilisation/screening period during which they continued to receive their prestudy statin dose. Following stratification by study site and statin dose/potency, patients were randomised to EZE/SIMVA 10/20 mg (n = 314) or ROSUVA 10 mg (n = 304) for 6 weeks. RESULTS: EZE/SIMVA produced greater reductions in LDL-C (-27.7% vs. -16.9%; p < or = 0.001), total cholesterol (-17.5% vs. -10.3%; p < or = 0.001), non-high-density lipoprotein cholesterol (HDL-C) (-23.4% vs. -14.0%; p < or = 0.001) and apolipoprotein B (-17.9% vs. -9.8%; p < or = 0.001) compared with ROSUVA, while both treatments were equally effective at increasing HDL-C (2.1% vs. 3.0%; p = 0.433). More patients achieved LDL-C levels < 2.59 mmol/l (73% vs. 56%), < 2.00 mmol/l (38% vs. 19%) and < 1.81 mmol/l (25% vs. 11%) with EZE/SIMVA than ROSUVA (p < or = 0.001). A borderline significantly greater reduction in triglycerides (p = 0.056) was observed for EZE/SIMVA (-11.0%) vs. ROSUVA (-5.3%). There were no between-group differences in the incidences of adverse events or liver transaminase and creatine kinase elevations. CONCLUSION: EZE/SIMVA 10/20 mg produced greater improvements in LDL-C, total cholesterol, non-HDL-C and apoB with a similar safety profile as for ROSUVA 10 mg