A Paradigm Shift in Dyslipidemia Management in Primary Care: A 12-Month Cohort Study

PurposeLDL-lowering therapy is beneficial to reduce the risk of cardiovascular disease (CVD). Higher statin doses lower LDL-C levels and prevent CVD; however, they increase adverse events, such as muscle-related adverse events and new-onset diabetes mellitus (DM). Ezetimibe combined with statin therapy improves LDL-C–lowering levels and tolerability in patients with established CVD. We aimed to analyze the efficacy and safety of a fixed-dose rosuvastatin and ezetimibe (R+E) combination therapy in intermediate-risk patients with hypercholesterolemia and no DM after 12 months of visiting a primary physician.MethodsThis multicenter, open-label, single-arm, prospective observational study involved 5717 patients from 258 primary health care centers in Korea enrolled between 2016 and 2018. Patients had no DM or previous CVD but had cardiovascular risk factors and were taking a statin or a fixed-dose combination of E (10 mg) + R (5, 10, or 20 mg). We analyzed 700 patients using propensity score matching.FindingsA fixed-dose R+E combination therapy significantly reduced LDL-C in 5/10 mg R+E (29.35%), 10/10 mg R+E (36.19%), and 20/10 mg R+E (41.83%) compared with statin monotherapy (19.09%) at 12-month follow-up (P = 0.017). Compared with statin monotherapy, HDL-C levels increased in 5/10 mg R+E (mean change at 12 months; P = 0.004), and triglyceride levels decreased in 10/10 mg R+E (mean change at 12 months; P = 0.033). The fixed-dose R+E combination therapy was associated with fewer adverse events and a neutral effect on glucose deterioration compared with statin monotherapy at 12 months of follow-up.ImplicationsIn a possible paradigm shift, a fixed-dose R+E combination therapy may be beneficial for primary cardiovascular prevention with potent LDL-lowering efficacy and tolerability; however, further large prospective studies are needed.     

A Phase III,Multicenter, Randomized,Double-blind,Active Comparator Clinical Trial to Compare the Efficacy and Safety of Combination Therapy With Ezetimibe and Rosuvastatin Versus Rosuvastatin Monotherapy in Patients With Hypercholesterolemia: I-ROSETTE (Ildong Rosuvastatin & Ezetimibe for Hypercholesterolemia) Randomized Controlled Trial

Purpose

Combination therapy with ezetimibe and statins is recommended in cases of statin intolerance or insufficiency. The objective of this study was to compare the efficacy and safety of combination therapy with ezetimibe and rosuvastatin versus those of rosuvastatin monotherapy in patients with hypercholesterolemia.

Efficacy and Tolerability of Ezetimibe/Atorvastatin Fixed-dose Combination Versus Atorvastatin Monotherapy in Hypercholesterolemia: A Phase III,Randomized, Active-controlled Study in Chinese Patients

PurposeThe 3-hydroxy-3-methylglutaryl–coenzyme A reductase inhibitors (“statins”) and the cholesterol-lowering medication ezetimibe are widely used in the treatment of patients with high- and very high–risk atherosclerotic cardiovascular disease. This study compared the efficacy and tolerability of a fixed-dose combination (FDC) of ezetimibe/atorvastatin (EZ/AS) with those of escalating doses of atorvastatin monotherapy in Chinese patients with hypercholesterolemia uncontrolled with statin monotherapy.MethodsThis Phase III, 12-week, randomized, double-blind study included patients aged 18 to 80 years with hypercholesterolemia uncontrolled on atorvastatin 10 or 20 mg/d monotherapy. After a 5-week run-in period of treatment with atorvastatin 10 or 20 mg/d (cohorts A and B, respectively), or a bioequivalent dosage of another statin, patients were randomized in a 1:1 ratio within each cohort to receive EZ/AS 10/10 mg FDC (EZ10/AS10) or atorvastatin 20 mg (AS20), once daily (cohort A); or EZ/AS 10/20 mg FDC (EZ10/AS20) or atorvastatin 40 mg (AS40), once daily (cohort B). The primary end point was the percentage change from baseline in low-density lipoprotein cholesterol (LDL-C). Tolerability was also evaluated.FindingsOf the 454 patients enrolled, 412 (90.7%) completed the study. The percentage change from baseline in LDL-C was statistically greater with EZ10/AS10 treatment (n = 88) compared with AS20 monotherapy (n = 89) (treatment difference, ?19.5%; 95% CI, ?26.7% to ?12.3%; P < 0.001). The percentage change from baseline in LDL-C was statistically greater with EZ10/AS20 treatment (n = 137) compared with AS40 monotherapy (n = 140) (treatment difference, ?15.9%; 95% CI, ?21.0% to ?10.7%; P < 0.001). The safety profile was comparable between the EZ/AS and atorvastatin groups in the two cohorts.ImplicationsThe LDL-C level at week 12 was significantly improved with both FDCs compared with escalated doses of atorvastatin (20 or 40 mg/d) in these Chinese patients with hypercholesterolemia uncontrolled on atorvastatin 10 or 20 mg/d. Both FDCs were well tolerated, with no new tolerability-related findings. Chinadrugtrials.org.cn identifier: CTR20190172; ClinicalTrials.gov identifier: NCT03768427     

Combination Therapy of Rosuvastatin and Ezetimibe in Patients with High Cardiovascular Risk

Purpose

The aim of this study was to evaluate the efficacy and tolerability of rosuvastatin/ezetimibe combination therapy in Korean patients with high cardiovascular risk.

Effects of Fixed-dose Combination of Low-intensity Rosuvastatin and Ezetimibe Versus Moderate-intensity Rosuvastatin Monotherapy on Lipid Profiles in Patients With Hypercholesterolemia: A Randomized,Double-blind,Multicenter, Phase III Study

PurposeWe investigated whether the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy in patients requiring cholesterol-lowering therapy.MethodsThis was a multicenter randomized, double‐blind study to investigate the safety and efficacy of a fixed-dose combination of rosuvastatin 2.5 mg and ezetimibe 10 mg (R2.5+E10) compared to those of ezetimibe 10 mg monotherapy (E10), rosuvastatin 2.5 mg (R2.5), and rosuvastatin 5 mg monotherapy (R5) in patients with hypercholesterolemia. A total of 348 patients at 15 centers in Korea were screened, and 279 patients were randomized to different groups in the study. Clinical and laboratory examinations were performed at baseline and 4 and 8 weeks after intervention. The primary endpoint was the percentage change of low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up.FindingsBaseline characteristics were similar among the four groups. There were significant changes in lipid profiles at the 8-week follow-up. A greater decrease in the LDL cholesterol levels (primary endpoint) were found in the R2.5+E10 group (−45.7±18.6%) than in the E10 group (−16.7±14.7%, p<0.0001), R2.5 group (−32.6±15.1%, p<0.0001), and R5 group (−38.9±13.9%, p=0.0003). Similar outcomes were observed regarding the decrease in total cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B protein. In addition, changes in the triglyceride and HDL levels in the R2.5+E10 group were significantly different compared with those in the E10 group; however, the changes were similar to those in the other treatment groups. In patients with low and moderate risk, all patients achieved the target LDL cholesterol levels in the R2.5+E10 group (100%) compared to 13.0% in the E10 group, 47.6% in the R2.5 group, and 65.2% in the R5 group. Adverse effects were rare and similar in the four groups.ImplicationsFixed-dose combination of low-intensity rosuvastatin and ezetimibe was more effective in lowering LDL cholesterol and achieving LDL cholesterol goals than moderate-intensity rosuvastatin monotherapy. These findings suggest that the combination therapy of low-intensity rosuvastatin and ezetimibe is an useful alternative to moderate-intensity rosuvastatin monotherapy for cholesterol management, particularly in patients with low and moderate risk. ClinicalTrials.gov identifier: NCT04652349.     

Effect of 1PC111, a Fixed-dose Combination of Pitavastatin and Ezetimibe,Versus Pitavastatin or Ezetimibe Monotherapy on Lipid Profiles in Patients With Hypercholesterolemia or Mixed Dyslipidemia: A Randomized,Double-blind,Multicenter, Phase III Study

PurposeThis study aimed to show that the efficacy of 1PC111 is superior to that of either ezetimibe or pitavastatin alone (monotherapy) for the treatment of hypercholesterolemia.MethodsThis was a multicenter, randomized, double-blind, Phase III study. Patients with hypercholesterolemia or mixed dyslipidemia were randomized to receive 1PC111 (which was a fixed-dose combination of pitavastatin 2 mg and ezetimibe 10 mg), pitavastatin 2 mg, or ezetimibe 10 mg daily for 12 weeks. The primary end point was the difference in the percent change in LDL-C from baseline to week 12 between the 1PC111 and each monotherapy group. The secondary end points were the percent change in other lipid profiles from baseline to each visit. All patients were assessed for adverse events until end of study.FindingsA total of 388 patients were randomly assigned to the 1PC111 (n = 128), pitavastatin (n = 132), or ezetimibe (n = 128) group. Generally, baseline characteristics were similar among the 3 groups. A statistically significant decrease in the LDL-C level at week 12 was observed in the 1PC111 group (–50.50% [14.9%]) compared with either the pitavastatin (–36.11% [11.4%]; P < 0.001) or ezetimibe (–19.85% [12.4%]; P < 0.001) group. Also, there was a statistically significant difference between 1PC111 and each monotherapy group in the reduction in total cholesterol, non–HDL-C, and apolipoprotein B levels. Moreover, there was a trend toward more efficient lowering of LDL-C levels in elderly patients (age ≥65 years) than in younger patients (age <65 years) by 1PC111 treatment. In patients given a class I recommendation for atherosclerotic cardiovascular disease prevention, the percentage of patients achieving the LDL-C target of <100 mg/dL at week 12 was significantly higher in the 1PC111 group than in both monotherapy groups (P < 0.001). Overall, the incidence of adverse events was similar among 3 groups.Implications1PC111 was more effective in improving lipid profiles and achieving the LDL-C goal than pitavastatin or ezetimibe alone for hypercholesterolemia treatment. Furthermore, 1PC111 may provide more benefit in treating elderly patients. ClinicalTrials.gov identifier: NCT04643093.     

Effectiveness of Fimasartan and Rosuvastatin Combination Treatment in Hypertensive Patients With Dyslipidemia

PurposeThe goal of this study was to evaluate the concurrent control rate of hypertension and dyslipidemia by fimasartan and rosuvastatin in patients who were concomitantly prescribed both drugs.Methods: This single-center, cross-sectional study was conducted in 536 patients with hypertension and dyslipidemia who were taking fimasartan and rosuvastatin together for at least 12 weeks. Patients were enrolled from October 2016 to March 2018 at a tertiary hospital in the Republic of Korea. The primary end point was the concurrent control rate of blood pressure (<140/90 mm Hg) and LDL-C. As a secondary end point, the target blood pressure <130/80 mm Hg was adopted in all patients or in high-risk patients with atherosclerotic cardiovascular diseases. Target LDL-C and non–HDL-C levels followed the domestic guidelines. Correlation between blood pressure control and lipid profile was also evaluated. All parameters were assessed in a clinic by board-certified physicians.FindingsOf the total 536 patients, 69% (n = 368) had very high (n = 308) or high (n = 60) cardiovascular risk, with an average age of 65 years; 57% were male. When the target blood pressure was set at 140/90 mm Hg, the proportion of patients meeting the targeting LDL-C level was 40.3% (95% CI, 36.2–44.5; P < 0.001). When applied to the revised blood pressure criteria targeting 130/80 mm Hg, the concurrent control rate dropped by one half to 20.3% (95% CI, 17.2–24.0; P < 0.001). To apply the new blood pressure criteria, more intensive management is mandatory in patients with high or very high cardiovascular risk. There was no positive correlation between the controlled rate of hypertension and dyslipidemia.ImplicationsFimasartan and rosuvastatin were shown to have effects on target diseases, but there was no synergistic effect when administered in combination. The higher the cardiovascular risk of the patients, the lower the rate of concurrent control when fimasartan and rosuvastatin were administered simultaneously. More active treatment is therefore required in high-risk patients.     

Clinical Efficacy and Tolerability of Ezetimibe in Combination With Atorvastatin in Japanese Patients With Hypercholesterolemia—Ezetimibe Phase IV Randomized Controlled Trial in Patients With Hypercholesterolemia

ObjectiveThe purpose of this study was to compare the efficacy and tolerability of combination therapy of ezetimibe and atorvastatin in patients with high LDL cholesterol that had not reached the lipid management target value with 10 mg atorvastatin monotherapy, against increasing the dose to 20 mg atorvastatin or switching to 2.5 mg rosuvastatin.Design, setting, and participantsThis was an open-label, randomized, multicenter, 3-parallel-group comparison trial at 23 community hospitals and clinics in Japan (enrollment period March 2009 to May 2010) in 125 patients with high LDL cholesterol.InterventionsA total of 125 Japanese patients with high LDL cholesterol level were randomized to 1 of the following 3 treatment groups: the ezetimibe (10 mg/d) and atorvastatin (10 mg/d) group, the atorvastatin (20 mg/d) group, or the rosuvastatin (2.5 mg/d) group for 12 weeks after treatment with 10 mg atorvastatin alone for 4 weeks.Main outcome measurePercent change in LDL cholesterol level from baseline (4 weeks after treatment with 10 mg atorvastatin alone) until study completion.ResultsThe percent change in LDL cholesterol level from baseline until study completion was statistically greater for the combination of 10 mg ezetimibe + 10 mg atorvastatin compared with increasing atorvastatin to 20 mg (?25.8% vs ?15.1%; P < 0.0001). A similar result was observed for ezetimibe + atorvastatin compared with switching to 2.5 mgt rosuvastatin (?25.8% vs 0.8%; P < 0.0001). The proportion of patients who reached the target LDL cholesterol value with the combination of ezetimibe + atorvastatin was significantly higher than increasing atorvastatin and switching to rosuvastatin (78.7%, 41.3%, and 3.1%, respectively). Although 5 serious adverse experiences bearing no relation to the study medications were reported, there were no adverse reactions.ConclusionsThe combination of 10 mg ezetimibe +10 mg atorvastatin was more effective than increasing atorvastatin to 20 mg or switching to 2.5 mg rosuvastatin in patients with hypercholesterolemia whose LDL cholesterol levels had not reached the recommended target value with 10 mg atorvastatin monotherapy for 4 weeks. Ezetimibe coadministration with atorvastatin was well tolerated. ClinicalTrials.gov identifier: NCT00871351.     

Efficacy and Safety of Ezetimibe and Rosuvastatin Combination Therapy Versus Those of Rosuvastatin Monotherapy in Patients With Primary Hypercholesterolemia

Purpose

The aim of this study was to evaluate the safety and efficacy of combination treatment of rosuvastatin with ezetimibe in patients with primary hypercholesterolemia.

Rosuvastatin 5 and 10 mg/d: a pilot study of the effects in hypercholesterolemic adults unable to tolerate other statins and reach LDL cholesterol goals with nonstatin lipid-lowering therapies

BACKGROUND: Patients with high levels of low-density lipoprotein cholesterol (LDL-C) might not tolerate 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors ("statins") because of adverse effects (AEs) and might not respond well enough to nonstatin lipid-lowering therapies (LLTs) to meet LDL-C goals. OBJECTIVE: The purpose of this study was to assess the acceptability, effectiveness, and safety profile of rosuvastatin 5 and 10 mg/d in consecutively referred patients with primary high LDL-C who were unable to tolerate other statins because of myalgia and, subsequently in some cases, unable to reach LDL-C goals with nonstatin LLT. METHODS: This prospective, open-label pilot study was conducted in consecutively referred male and female patients aged 38 to 80 years with primary high LDL-C (mean, 177 mg/dL) at The Cholesterol Center, Jewish Hospital, Cincinnati, Ohio. Patients were instructed in the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) therapeutic lifestyle changes diet. Rosuvastatin 5 mg/d was administered to patients categorized by NCEP ATP III risk stratification as moderately high risk, and rosuvastatin 10 mg/d was administered to patients categorized as high or very high risk. End points included acceptability (assessed using patient-initiated discontinuation of rosuvastatin), effectiveness (absolute and percentage reductions in LDL-C and triglycerides), and safety profile (aspartate and alanine aminotransferases [AST and ALT, respectively] >3 times the laboratory upper limit of normal [xULN] or elevations in creatine kinase [CK]>10xULN). RESULTS: A total of 61 patients were enrolled (41 women, 20 men; mean [SD] age, 60 [10] years; 5-mg/d dose, 25 patients; 10-mg/d dose, 36 patients). Myalgia, a predominant AE, had caused 50 patients to previously discontinue treatment with atorvastatin; 30, simvastatin; 19, pravastatin; 5, fluvastatin; 2, ezetimibe/simvastatin; and 1, lovastatin. Eighteen patients subsequently failed to reach LDL-C goals with nonstatin LLT(s) alone (colesevelam, 10 patients; ezetimibe, 8; niacin extended release, 2; and fenofibrate, 1). After a median treatment duration of 16 weeks, rosuvastatin 5 mg/d+diet was associated with a mean (SD) decrease from baseline in LDL-C of 75 (34) mg/dL (mean [SD] %Delta, -42% [18%]) (P<0.001 vs baseline). After a median treatment duration of 44 weeks, rosuvastatin 10 mg/d+diet was associated with a mean (SD) decrease from baseline in LDL-C of 79 (49) mg/dL (mean [SD] %Delta, -42% [24%]) (P<0.001 vs baseline). Of the 61 patients, 1 receiving the 10-mg/d dose discontinued rosuvastatin treatment because of unilateral muscular pain after 4 weeks; no AST or ALT levels were >3xULN, and no CK levels were >10xULN. CONCLUSION: In these 61 hypercholesterolemic patients unable to tolerate other statins and, subsequently in some cases, unable to meet LDL-C goals while receiving nonstatin LIT monotherapy, these preliminary observations suggest that rosuvastatin at doses of 5 and 10 mg/d+diet was well tolerated, effective, and had a good safety profile.     

A Randomized,Double-Blind Study of Fenofibric Acid Plus Rosuvastatin Compared With Rosuvastatin Alone in Stage 3 Chronic Kidney Disease

Background

Patients with chronic kidney disease (CKD) often have mixed dyslipidemia and high cardiovascular disease risk. Although statins reduce LDL-C, adding a fibrate may further improve lipid parameters.

Objective

This multicenter, randomized study evaluated the short-term efficacy and safety profile of fenofibric acid (FA) + rosuvastatin (R) combination therapy for improving lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. The study also assessed estimated glomerular filtration rate after study drug washout.

Methods

Patients received FA 45 mg + R (5 mg for 8 weeks, then 10 mg for 8 additional weeks) or R monotherapy (5 mg for 8 weeks, then 10 mg for 8 additional weeks), followed by an 8-week washout period. Primary and secondary end points were percent changes in triglycerides and HDL-C, respectively, from baseline to week 8.

Results

FA 45 mg + R 5 mg, compared with R 5 mg, resulted in significant improvements in triglycerides (median % changes: week 8, −38.0% vs −22.4%, P < 0.001; week 16, −42.6% vs −29.7%, P < 0.001) and HDL-C (mean % changes: week 8, 16.9% vs 7.8%, P < 0.001; week 16, 17.3% vs 8.9%, P < 0.001). Adverse event rates were similar between groups (70.7% with FA + R vs 68.6% with R). Mean serum creatinine level at baseline was 1.36 mg/dL in the FA + R group and 1.38 mg/dL in the R group. The final treatment serum creatinine value, defined as the last nonmissing postbaseline value collected within 30 days after the last dose of study drug, was 1.52 mg/dL with FA + R (vs 1.41 mg/dL with R; P < 0.001), which then decreased to 1.39 mg/dL after the 8-week washout (vs 1.42 mg/dL with R).

Conclusions

The data suggest that, after 16 weeks of therapy, FA + R has an acceptable safety profile and improved TG and HDL-C efficacy versus R. FA + R combination therapy may thus further improve lipid parameters in patients with stage 3 CKD and mixed dyslipidemia. ClinicalTrials.gov identifier: NCT00680017.     

Rosuvastatin versus atorvastatin in achieving lipid goals in patients at high risk for cardiovascular disease in clinical practice: A randomized, open-label, parallel-group, multicenter study (DISCOVERY Alpha study)

Background:

The majority of clinical trials investigating the clinical benefits of lipid-lowering therapies (LLTs) have focused on North American or western and nothern European populations. Therefore, it is timely to confirm the efficacy of these agents in other patient populations in routine clinical practice.

Objective:

The aim of the Direct Statin COmparison of low-density lipoprotein cholesterol (LDL-C) Values: an Evaluation of Rosuvastatin therapY (DISCOVERY) Alpha study was to compare the effects of rosuvastatin 10 mg with those of atorvastatin 10 mg in achieving LDL-C goals in the Third Joint Task Force of European and Other Societies on Cardiovascular Disease Prevention in Clinical Practice guidelines.

Methods:

This randomized, open-label, parallel-group study was conducted at 93 centers in eastern Europe (Estonia, Latvia, Romania, Russia, Slovenia), Central and South America (Chile, Dominican Republic, El Salvador, Guatemala, Honduras, Nicaragua, Panama), and the Middle East (Israel, Kuwait, Saudi Arabia, United Arab Emirates). Male and female patients aged ≥18 years with primary hypercholesterolemia (LDL-C level, >135 mg/dL if LLT-naive or ≥120 mg/dL if switching statins; triglyceride [TG] level, <400 mg/dL) and a 10-year coronary heart disease (CHD) risk >20% or a history of CHD or other established atherosclerotic disease were eligible for inclusion in the study. Patients were randomly assigned to receive rosuvastatin 10-mg or atorvastatin 10-mg tablets QD for 12 weeks. No formal statistical analyses or comparisons were performed on lipid changes between switched and LLT-naive patients because of the different lipid inclusion criteria for these patients. The primary end point was the proportion of patients achieving 1998 European LDL-C goals after 12 weeks of treatment. A subanalysis was performed to assess the effects of statins in patients who had received previous statin treatment versus those who were LLT-naive. Tolerability was assessed using laboratory analysis and direct questioning of the patients.

Results:

A total of 1506 patients (52.1% women, 47.9% men; mean [SD] age, 58.2 [10.8] years) participated in the study (rosuvastatin, 1002 patients; atorvastatin, 504 patients; previous LLT, 567 patients). A significantly higher proportion of patients achieved 1998 European LDL-C goals after 12 weeks with rosuvastatin 10 mg than with atorvastatin 10 mg (72.5% vs 56.6%; P < 0.001). Similarly, more patients achieved the 2003 European LDL-C goals with rosuvastatin 10 mg compared with atorvastatin 10 mg (57.5% vs 39.2%). Rosuvastatin 10 mg was associated with a significantly greater change in LDL-C levels compared with atorvastatin 10 mg, in patients who were LLT-naive (LDL-C: −44.7% vs −33.9%; P < 0.001) and in patients who had received previous LLT (LDL-C: −32.0% vs −26.5%; P = 0.006). TG levels were also decreased with rosuvastatin 10 mg and atorvastatin 10 mg, although there was no significant difference between treatments. Similarly, there was no significant difference in the increase in high-density lipoprotein cholesterol levels between treatments. The most common adverse events overall were headache 16/1497 (1.1%), myalgia 10/1497 (0.7%), and nausea 10/1497 (0.7%).

Conclusions:

In this study in patients with primary hypercholesterolemia in clinical practice, greater reductions in LDL-C levels were achieved with a starting dose (10 mg) of rosuvastatin compared with atorvastatin 10 mg, with more patients achieving European LDL-C goals. Both treatments were well tolerated     

Switching from statin monotherapy to ezetimibe/simvastatin or rosuvastatin modifies the relationships between apolipoprotein B, LDL cholesterol, and non-HDL cholesterol in patients at high risk of coronary disease

ObjectiveTo evaluate relationships between apolipoprotein B (Apo B), LDL cholesterol (LDL-C), and non-HDL-C in high-risk patients treated with lipid-lowering therapy.Design and methodsThis post-hoc analysis calculated LDL-C and non-HDL-C levels corresponding to an Apo B of 0.9 g/L following treatment with 1) statin monotherapy (baseline) and 2) ezetimibe/simvastatin 10/20 mg or rosuvastatin 10 mg (study end). The percentages of patients reaching LDL-C, non-HDL-C, and Apo B targets were calculated at study end.ResultsAfter switching to ezetimibe/simvastatin or rosuvastatin, the LDL-C and non-HDL-C corresponding to Apo B = 0.9 g/L were closer to the more aggressive LDL-C and non-HDL-C goals (1.81 and 2.59 mmol/L, respectively). Only slightly > 50% of the patients who reached minimum recommended LDL-C or non-HDL-C at study end also had an Apo B level < 0.9 g/L with both treatments.ConclusionThe use of Apo B for monitoring the efficacy of lipid-altering therapy would likely lead to more stringent criteria for lipid lowering.     

Efficacy and Safety of Fixed-dose Combination Therapy With Telmisartan and Rosuvastatin in Korean Patients With Hypertension and Dyslipidemia: TELSTA-YU (TELmisartan-rosuvaSTAtin from YUhan), a Multicenter,Randomized, 4-arm,Double-blind,Placebo-controlled,Phase III Study

Purpose

Hypertension and dyslipidemia are 2 risk factors of cardiovascular disease that often present simultaneously. Traditionally, treatment of these multiple conditions required separate medications for each disease, which may result in poor compliance and thus lead to possible treatment failure. Fixed-dose combination (FDC) therapy with a single pill may be a solution in these situations.

The Effect of a Moderately Restricted Carbohydrate Diet on Cardiometabolic Risk Factors in Overweight and Obese Women With Metabolic Syndrome: A Randomized Controlled Trial

PurposeMetabolic syndrome (MetS) is a major public health concern that increases the risk of cardiovascular disease and mortality. In previous studies of MetS management, low-carbohydrate diets have been strongly emphasized, despite the fact that many apparently healthy individuals have difficulties adhering to these diets on a long-term basis. The purpose of the present study was to elucidate the effects of a moderately restricted carbohydrate diet (MRCD) on cardiometabolic risk factors in women with MetS.MethodsThis parallel 3-month, single-blind randomized controlled trial was conducted in Tehran, Iran, among 70 women with overweight or obesity aged 20 to 50 years with MetS. Patients were randomly allocated to receive either MRCD (42%–45% carbohydrates and 35%–40% fats) (n = 35) or a normal weight loss diet (NWLD) (52%–55% carbohydrates and 25%–30% fats) (n = 35). Both diets contained the same quantity of protein, which accounted for 15% to 17% of total energy. Anthropometric measurements, blood pressure, lipid profile, and glycemic indices were all assessed before and after the intervention.FindingsCompared with the NWLD group, following an MRCD significantly decreased weight (−4.82 vs −2.40 kg; P = 0.01), body mass index (−1.88 vs −0.94 kg/m²; P = 0.01), waist circumference (−5.34 vs −2.75 cm; P = 0.01), hip circumference (−2.58 vs −1.11 cm; P = 0.01), serum triglyceride (−26.8 vs −7.19 mg/dL; P = 0.01), and increased serum HDL-C levels (1.89 vs. 0.24 mg/dL; P = 0.01). There was no significant difference between the 2 diets in waist-to-hip ratio, serum total cholesterol, serum LDL-C, systolic and diastolic blood pressure, fasting blood glucose, insulin levels, or the homeostasis model assessment for insulin resistance.ImplicationsModerate carbohydrate replacement with dietary fats significantly improved weight, body mass index, waist circumference, hip circumference, serum triglyceride, and HDL-C levels among women with MetS. Iranian Registry of Clinical Trials identifier: IRCT20210307050621N1.     

A Multicenter,Randomized, Double-blind,Active-controlled,Factorial Design,Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of Pitavastatin and Ezetimibe Versus Monotherapy of Pitavastatin in Patients With Primary Hypercholesterolemia

PurposePitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia.MethodsKorean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4–8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients.FindingsThe percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (–52.8% [11.2%]) and pooled pitavastatin (–37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C–lowering effect than that with pitavastatin (difference, –15.8 mg/dL; 95% CI, –18.7 to –12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups.ImplicationsPitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy. ClinicalTrials.gov identifier: NCT04584736.     

Efficacy and Safety of Triple Therapy With Telmisartan,Amlodipine, and Rosuvastatin in Patients With Dyslipidemia and Hypertension: The Jeil Telmisartan,Amlodipine, and Rosuvastatin Randomized Clinical Trial

Purpose

Fixed-dose combination therapy with telmisartan, amlodipine, and rosuvastatin is needed in patients with hypertension and dyslipidemia for better adherence and cost-effectiveness than free–equivalent combination therapies. This study aimed to compare the efficacy and safety of combination therapy with telmisartan, amlodipine, and rosuvastatin versus telmisartan plus amlodipine or telmisartan plus rosuvastatin in patients with hypertension and dyslipidemia.

Effect of More Intensive LDL-C–Lowering Therapy on Long-term Cardiovascular Outcomes in Early-Phase Acute Coronary Syndrome: A Systematic Review and Meta-analysis

PurposeThe effect of more intensive LDL-C–lowering therapy (ILLT) on long-term cardiovascular outcomes during the early phase of acute coronary syndromes (ACSs) remains uncertain. We aimed to explore the influence of more intensive LDL-C–lowering therapyduring the early disease phase on long-term cardiovascular events among patients with ACSs.MethodsRandomized controlled trials that focused on the effect of more ILLT during early-phase ACSs on long-term major adverse cardiac events (MACEs) were searched in electronic databases (MEDLINE, Embase, and Cochrane Central Register of Controlled Trials databases) from database inception until November 23, 2019. The end points included the incidence of MACEs, myocardial infarction, stroke, revascularization, heart failure, and death events. Study risk of bias was assessed using the Cochrane Collaboration tools. Fixed- or random-effects models and meta-regression were performed to evaluate the association between baseline/proportional reduction of LDL-C levels during early-phase disease and the risk of end points using risk ratios with 95% CIs.FindingsA total of 53,199 participants were involved from 19 studies. The risk of MACEs decreased by 17% (95% CI, 0.76–0.90; P = 0.0012) for more intensive versus control therapy but varied by baseline and proportional reduction of LDL-C levels during early disease phase. The risk reduction of MACEs for more intensive versus control therapy among different subgroups was 26% (95% CI, 0.57–0.95; P = 0.06) with a baseline level >130 mg/dL, 23% (95% CI, 0.63–0.94; P = 0.02) with a baseline level of 100 to 130 mg/dL, and 10% (95% CI, 0.83–0.99; P = 0.07) with a baseline level <100 mg/dL. A significant difference of risk reduction for MACEs existed between patients treated with statin plus ezetimibe versus statin alone in the subgroup with a baseline level >130 mg/dL and proportional reduction >50%. Patients treated with more intensive therapy benefited from reduced risk of myocardial infarction, stroke, revascularization, and heart failure compared with control therapy.ImplicationsMore ILLT during early disease phase could significantly reduce the risk of long-term cardiovascular outcome in patients with ACSs. This benefit was most pronounced in patients with higher baseline and larger reduction of LDL-C levels in MACEs.     

超声造影评价瑞舒伐他汀与阿托伐他汀对颈动脉斑块新生血管作用的比较

目的：使用超声造影比较瑞舒伐他汀与阿托伐他汀对颈动脉软斑块新生血管的治疗效果。方法：对颈动脉软斑块患者,分别服用瑞舒伐他汀10mg/d或阿托伐他汀20mg/d,治疗6个月,利用血脂检查、常规超声及超声造影进行治疗前后相关指标的评估。结果：入选斑块数共80例,瑞舒伐他汀组与阿托伐他汀组血清总胆固醇（TC）、甘油三酯（TG）和低密度脂蛋白胆固醇（LDL-C）水平均显著低于治疗前（P<0.05）,瑞舒伐他汀组TC和LDL-C水平显著低于阿托伐他汀组（P<0.05）,但两组间TG水平无显著差别（P>0.05）。瑞舒伐他汀组与阿托伐他汀组斑块积分、增强强度（EI）及时间-强度曲线下面积（AUC）均显著低于治疗前（P<0.05）,瑞舒伐他汀组斑块积分、EI及AUC均显著低于阿托伐他汀组（P<0.05）。结论：瑞舒伐他汀及阿托伐他汀有确切降脂作用,均可有效减少颈动脉软斑块内的新生血管,且瑞舒伐他汀作用强于阿托伐他汀。