ezetimibe--simvastatin-drug-combination and Acute-Coronary-Syndrome

The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) demonstrated the clinical benefit of the combination of ezetimibe-simvastatin compared to placebo-simvastatin following acute coronary syndrome (ACS). This review highlights key findings from this study with particular attention to the practice-changing impact on guidelines for low-density lipoprotein cholesterol (LDL-C) reduction after ACS, especially among high-risk populations.. Consistent reductions in LDL-C have been reported with newer lipid-lowering therapies (proprotein convertase subtilisin/kexin type 9 inhibitors, cholesterol ester transfer proteins, bempedoic acid) in combination with statin in high-risk subgroups. Since high-risk subgroups remain a focus of guidelines, exploration of high-risk subgroups can help define the optimal use of new therapies. Ezetimibe reduced the LDL-C by 16.7 mg/dL compared to placebo at 1 year, resulting in a significant reduction in the primary composite endpoint (absolute risk difference 2.0%; relative risk difference 6.4%, hazard ratio, 0.936; 95% confidence interval, 0.89 to 0.99; P = 0.016). The benefits achieved with ezetimibe in both LDL-C reduction and the primary clinical composite across 10 pre-specified high-risk subgroups, including the elderly; women; patients with diabetes, prior coronary artery bypass graft, history of stroke, polyvascular disease, low baseline LDL-C, renal dysfunction, prior heart failure, and an elevated TIMI risk score for secondary prevention, were similar or greater than in the corresponding non-high-risk subgroups. Safety events were similar between ezetimibe and placebo across the high-risk subgroups. These data support the addition of ezetimibe to statin therapy in high-risk patients who require additional therapy to lower the LDL-C post-ACS.

Topics: Acute Coronary Syndrome; Aged; Anticholesteremic Agents; Cholesterol, LDL; Drug Therapy, Combination; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Treatment Outcome

IMPROVE-IT study demonstrated that the addition 10 mg of ezetimibe to 40 mg of simvastatin in patients after acute coronary syndrome reduces significantly not only their LDL-cholesterol, but also the number of cardiovascular events. Recently published subanalysis of this study was focused on whether these combinations of drugs is more preferable for patients with diabetes mellitus or for patients without diabetes. The addition of ezetimibe to a simvastatin resulted in a greater decline of LDL-cholesterol level in diabetic group than in patients without diabetes. In patients with diabetes mellitus their cardiovascular morbidity and mortality were decreased significantly; reduction of these clinical end-points in the group of patients without diabetes were not statistically significant.

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Cholesterol, LDL; Diabetes Mellitus; Europe; Ezetimibe, Simvastatin Drug Combination; Humans; Incidence

Background Unlike patients with low ejection fraction after an acute coronary syndrome (ACS), little is known about the long-term incidence and influence of cardiovascular events before sudden death among stabilized patients after ACS. Methods and Results A total of 18 144 patients stabilized within 10 days after ACS in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) were studied. Cumulative incidence rates (IRs) and IRs per 100 patient-years of sudden death were calculated. Using Cox proportional hazards, the association of ≥1 additional postrandomization cardiovascular events (myocardial infarction, stroke, and hospitalization for unstable angina or heart failure) with sudden death was examined. Early (≤1 year after ACS) and late sudden deaths (>1 year) were compared. Of 2446 total deaths, 402 (16%) were sudden. The median time to sudden death was 2.7 years, with 109 early and 293 late sudden deaths. The cumulative IR was 2.47% (95% CI, 2.23%-2.73%) at 7 years of follow-up. The risk of sudden death following a postrandomization cardiovascular event (150/402 [37%] sudden deaths; median 1.4 years) was greater (IR/100 patient-years, 1.45 [95% CI, 1.23-1.69]) than the risk with no postrandomization cardiovascular event (IR/100 patient-years, 0.27 [95% CI, 0.24-0.30]). Postrandomization myocardial infarction (hazard ratio [HR], 3.64 [95% CI, 2.85-4.66]) and heart failure (HR, 4.55 [95% CI, 3.33-6.22]) significantly increased future risk of sudden death. Conclusions Patients stabilized within 10 days of an ACS remain at long-term risk of sudden death with the greatest risk in those with an additional cardiovascular event. These results refine the long-term risk and risk effectors of sudden death, which may help clinicians identify opportunities to improve care. Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.

Topics: Acute Coronary Syndrome; Death, Sudden, Cardiac; Ezetimibe, Simvastatin Drug Combination; Heart Failure; Humans; Myocardial Infarction; Risk Factors; Treatment Outcome

Studies have demonstrated an association between single measures of high-sensitivity troponin (hsTn) and future cardiovascular events in patients with chronic coronary syndromes. However, limited data exist regarding the association between changes in serial values of hsTn and subsequent cardiovascular events in this patient population.. To evaluate the association between changes in high-sensitivity troponin T (hsTnT) and subsequent cardiovascular events in patients stabilized after acute coronary syndrome (ACS).. This is a secondary analysis from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), a randomized clinical trial of ezetimibe vs placebo on a background of simvastatin in 18 144 patients hospitalized for an ACS across 1147 sites in 39 countries. The current biomarker substudy includes the 6035 participants consenting to the biomarker substudy with available hsTnT at months 1 and 4. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed from February 28, 2021, through August 14, 2022.. The outcomes of interest were cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HHF). Associations of absolute and relative changes in hsTnT between month 1 and month 4 as a function of the starting month 1 hsTnT and the composite outcome were examined using landmark analyses.. Of 6035 patients in this analysis (median [IQR] age, 64 [57-71]), 1486 (24.6%) were female; 361 (6.0%) were Asian; 121 were (2.0%) Black; 252 (4.2%) were Spanish descent; 4959 were (82.2%) White; and 342 (5.7%) reported another race (consolidated owing to small numbers), declined to respond, or were not asked to report race owing to regulatory prohibitions. Most patients (4114 [68.2%]) had stable hsTnT values (change <3 ng/L), with 1158 (19.2%) and 763 (12.6%) having changes of 3 to less than 7 ng/L and 7 ng/L or more, respectively. After adjustment for clinical risk factors and stratification by the starting month 1 hsTnT level, an absolute increase in hsTnT of 7 ng/L or more was associated with a more than 3-fold greater risk of the composite outcome (adjusted hazard ratio [aHR], 3.33; 95% CI, 1.99-5.57; P < .001), whereas decreases of 7 ng/L or more were associated with similar to lower risk (aHR, 0.51; 95% CI, 0.26-1.03; P = .06) compared with stable values. There was a stepwise association moving from larger absolute decreases (aHR, 0.51; 95% CI, 0.26-1.03) to larger absolute increases (aHR, 3.33; 95% CI, 1.99-5.57) in hsTnT with future risk of the composite outcome (P trend <.001). A similar association was observed when analyzed on the basis of relative percent and continuous change.. Among stable patients post-ACS, changes in hsTnT were associated with a gradient of risk of subsequent cardiovascular events across the range of starting hsTnT values. Serial assessment of hsTnT may refine risk stratification with the potential to guide therapy decisions in this patient population.. ClinicalTrials.gov Identifier: NCT00202878.

Topics: Acute Coronary Syndrome; Biomarkers; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Male; Middle Aged; Troponin T

Although cholesterol-lowering medications can reduce the risk of recurrent cardiovascular events, premature discontinuation limits effectiveness. Discontinuation rates have not been systematically reported for lipid-lowering trials.. We evaluated medication discontinuation in IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial), which evaluated placebo+simvastatin versus ezetimibe+simvastatin in patients hospitalized with the acute coronary syndrome and followed longitudinally postdischarge. Reasons for discontinuation were evaluated from randomization through study end (median 71.9 [interquartile range 51.8-85.8] months). Kaplan-Meier (KM) discontinuation rates were evaluated at 30 days, 1 year, and through year 7, and compared by treatment arm and region, with Cox proportional hazards modeling used to evaluate predictors of discontinuation. Overall, 46.7% of subjects discontinued study medication (KM rate by study end 50.9% [95% CI, 50.1%-51.7%]). The risk of discontinuation was highest early in the trial but decreased with increasing time, with a terminal KM rate per 100 person-years of 8.4 (8.2-8.6) from years 1 to 7. Discontinuation was higher in the placebo+simvastatin versus ezetimibe+simvastatin arm (KM rate 52.0% versus 49.8%, P=0.049) and was highest in the United States (7-year KM rate 57.4%). In multivariable modeling, smoking, prior revascularization, hypertension, unstable angina, female sex, nonwhite race, and US location were associated with higher discontinuation rates.. Although discontinuation was highest early and stabilized to 8% per year, because of prolonged follow-up, most discontinuation occurred after year 1. Adding ezetimibe to statin therapy did not increase discontinuation risk. Geographic differences and patient-level factors should be considered in trial design and analysis.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT00202878.

Topics: Acute Coronary Syndrome; Aged; Asia; Australia; Biomarkers; Double-Blind Method; Drug Administration Schedule; Drug Utilization; Dyslipidemias; Europe; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipids; Male; Middle Aged; New Zealand; North America; Practice Patterns, Physicians'; Risk Factors; South America; Time Factors; Treatment Outcome

Risk prediction following acute coronary syndrome (ACS) remains challenging. Data-driven machine-learning algorithms can potentially identify patients at high risk of clinical events. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial randomized 18,144 post-ACS patients to ezetimibe + simvastatin or placebo + simvastatin. We performed hierarchical cluster analysis to identify patients at high risk of adverse events. Associations between clusters and outcomes were assessed using Cox proportional hazards models. The primary outcome was cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, unstable angina hospitalization, or coronary revascularization ≥30 days after randomization. We evaluated ezetimibe's impact on outcomes across clusters and the ability of the cluster analysis to discriminate for outcomes compared with the Global Registry of Acute Coronary Events (GRACE) score. Five clusters were identified. In cluster 1 (n = 13,252), most patients experienced a non-STEMI (54.8%). Cluster 2 patients (n = 2,719) had the highest incidence of unstable angina (n = 83.3%). Cluster 3 patients (n = 782) all identified as Spanish descent, whereas cluster 4 patients (n = 803) were primarily from South America (56.2%). In cluster 5 (n = 587), all patients had ST elevation. Cluster analysis identified patients at high risk of adverse outcomes (log-rank p <0.0001); Cluster 2 (vs 1) patients had the highest risk of outcomes (hazards ratio 1.33, 95% confidence interval 1.24 to 1.43). Compared with GRACE risk, cluster analysis did not provide superior outcome discrimination. A consistent ezetimibe treatment effect was identified across clusters (interaction p = 0.882). In conclusion, cluster analysis identified significant difference in risk of outcomes across cluster groups. Data-driven strategies to identify patients who may differentially benefit from therapies and for risk stratification require further evaluation.

Topics: Acute Coronary Syndrome; Aged; Anticholesteremic Agents; Cause of Death; Coronary Artery Bypass; Double-Blind Method; Drug Therapy, Combination; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Middle Aged; North America; Phenotype; Risk Assessment; Risk Factors; Simvastatin; Survival Rate; Treatment Outcome

Limited evidence is available regarding the benefit and hazard of higher-intensity treatment to lower lipid levels among patients 75 years or older. As a result, guideline recommendations differ for this age group compared with younger patients.. To determine the effect on outcomes and risks of combination ezetimibe and simvastatin compared with simvastatin monotherapy to lower lipid levels among patients 75 years or older with stabilized acute coronary syndrome (ACS).. In this prespecified secondary analysis of the global, multicenter, prospective clinical randomized Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), outcomes and risks were compared by age among patients 50 years or older after a hospitalization for ACS. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed May 29, 2015, through March 13, 2018, using Kaplan-Meier curves and Cox proportional hazards models.. Double-blind randomized assignment to combined simvastatin and ezetimibe or simvastatin and placebo with follow-up for a median of 6 years (interquartile range, 4.3-7.1 years).. The primary composite end point consisted of death due to cardiovascular disease, myocardial infarction (MI), stroke, unstable angina requiring hospitalization, and coronary revascularization after 30 days. Individual adverse ischemic and safety end points and lipid variables were also analyzed.. Of 18 144 patients enrolled (13 728 men [75.7%]; mean [SD] age, 64.1 [9.8] years), 5173 (28.5%) were 65 to 74 years old, and 2798 (15.4%) were 75 years or older at randomization. Treatment with simvastatin-ezetimibe resulted in lower rates of the primary end point than simvastatin-placebo, including 0.9% for patients younger than 65 years (HR, 0.97; 95% CI, 0.90-1.05) and 0.8% for patients 65 to 74 years of age (hazard ratio [HR], 0.96; 95% CI, 0.87-1.06), with the greatest absolute risk reduction of 8.7% for patients 75 years or older (HR, 0.80; 95% CI, 0.70-0.90) (P = .02 for interaction). The rate of adverse events did not increase with simvastatin-ezetimibe vs simvastatin-placebo among younger or older patients.. In IMPROVE-IT, patients hospitalized for ACS derived benefit from higher-intensity therapy to lower lipid levels with simvastatin-ezetimibe compared with simvastatin monotherapy, with the greatest absolute risk reduction among patients 75 years or older. Addition of ezetimibe to simvastatin was not associated with any significant increase in safety issues among older patients. These results may have implications for guideline recommendations regarding lowering of lipid levels in the elderly.. ClinicalTrials.gov identifier: NCT00202878.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Double-Blind Method; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Hypolipidemic Agents; Lipids; Male; Middle Aged; Prospective Studies; Simvastatin

Ezetimibe, when added to simvastatin therapy, reduces cardiovascular events after recent acute coronary syndrome. However, the impact of ezetimibe on cardiovascular-related hospitalizations and associated costs is unknown.. We used patient-level data from the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) to examine the impact of simvastatin-ezetimibe versus simvastatin-placebo on cardiovascular-related hospitalizations and related costs (excluding drug costs) over 7 years follow-up. Medicare Severity-Diagnosis Related Groups were assigned to all cardiovascular hospitalizations. Hospital costs were estimated using Medicare reimbursement rates for 2013. Associated physician costs were estimated as a percentage of hospital costs. The impact of treatment assignment on hospitalization rates and costs was estimated using Poisson and linear regression, respectively. There was a significantly lower cardiovascular hospitalization rate with ezetimibe compared with placebo (risk ratio, 0.95; 95% confidence interval, 0.90-0.99;. Addition of ezetimibe to statin therapy in patients with a recent acute coronary syndrome leads to reductions in cardiovascular-related hospitalizations and associated costs, with the greatest cost offsets in high-risk patients. These cost reductions may completely offset the cost of the drug once ezetimibe becomes generic, and may lead to cost savings from the perspective of the healthcare system, if treatment with ezetimibe is targeted to high-risk patients.. URL: https://www.clinicaltrials.gov. Unique Identifier: NCT00202878.

Topics: Acute Coronary Syndrome; Aged; Anticholesteremic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Female; Follow-Up Studies; Forecasting; Hospital Costs; Hospitalization; Humans; Male; Middle Aged; Treatment Outcome

Evaluating the short-term influence of Ezetimibe and Simvastatin Combination Therapy on LDL-C, TG and hs-CRP expression level in patients with percutaneous coronary intervention.. 57 cases of percutaneous coronary intervention patients were selected, and randomly divided into two groups: Simvastatin (40mg/day) and Ezetimibe (10mg/day) combination therapy group (observation group) with 28 patients, Simvastatin (40mg/day) group (control group) with 29 patients. Each group was treated for 10days. After treatment, compare blood lipid LDL-C, TG, hs-CRP levels with each other and the results before treatment.. Comparison of the results of the 10th day with the baseline: LDL-C, TG decreased significantly (P<0.01) in the observation group, while the control group did not have a significantly change (P>0.05). Comparison of observation group and control group: after treatment, LDL-C and TG decreased more significantly in the observation group than the control group (-27.2% vs -14.6%, P<0.05). Whether according to LDL-C <2.07mmol/L standard or LDL-C <1.8mmol/L standard, the compliance rate of the observation group was significantly better than the control group, the results were (69% vs 28.9%, P<0.05) and (47.6% vs 13.2% P<0.05), respectively. After 10days treatment, comparing to baseline, hs-CRP was significantly lowered in these two groups (P<0.01). And there is no liver and kidney toxicity, myopathy and other adverse reactions during treatment.. Combination therapy of Ezetimibe (10mg/day) and Simvastatin (40mg/day) was more effective than mono-therapy with Simvastatin (40mg/day) on reducing LDL-C, TG and hs-CRP level in percutaneous coronary intervention patients, leading to more significant anti-inflammatory effect.

Topics: Acute Coronary Syndrome; Adolescent; Adult; Aged; Angina, Unstable; Anticholesteremic Agents; Coronary Angiography; Coronary Vessels; Dose-Response Relationship, Drug; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Lipids; Male; Middle Aged; Percutaneous Coronary Intervention; Postoperative Complications; Stents; Treatment Outcome; Young Adult

IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) showed that adding the nonstatin ezetimibe to statin therapy further reduced cardiovascular events in patients after an acute coronary syndrome. In a prespecified analysis, we explore results stratified by sex.. In IMPROVE-IT, patients with acute coronary syndrome and low-density lipoprotein cholesterol of 50 to 125 mg/dL were randomized to placebo/simvastatin 40 mg or ezetimibe/simvastatin 10/40 mg. They were followed up for a median of 6 years for the primary composite of cardiovascular death, myocardial infarction, hospitalization for unstable angina, coronary revascularization ≥30 days, and stroke. Among 18 144 patients in IMPROVE-IT, 4416 (24%) were women. At 12 months, the addition of ezetimibe to simvastatin significantly reduced low-density lipoprotein cholesterol from baseline compared with simvastatin monotherapy in men and women equally (absolute reduction, 16.7 mg/dL in men and 16.4 mg/dL in women). Women receiving ezetimibe/simvastatin had a 12% risk reduction over those receiving placebo/simvastatin for the primary composite end point (hazard ratio, 0.88; 95% confidence interval, 0.79-0.99) compared with a 5% reduction for men (hazard ratio, 0.95; 95% confidence interval, 0.90-1.01;. IMPROVE-IT demonstrated that the benefit of adding ezetimibe to statin is present in both women and men, with a good safety profile supporting the use of intensive, combination, lipid-lowering therapy to optimize cardiovascular outcomes.. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00202878.

Topics: Acute Coronary Syndrome; Aged; Anticholesteremic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Ezetimibe, Simvastatin Drug Combination; Female; Global Health; Humans; Incidence; Male; Middle Aged; Myocardial Infarction; Secondary Prevention; Sex Factors; Survival Rate; Treatment Outcome

In the Improved Reduction of Outcomes: Vytorin Efficacy International Trial, intensive low-density lipoprotein cholesterol (LDL-C)-reducing therapy with ezetimibe/simvastatin compared with simvastatin alone was associated with a significant reduction in cardiovascular events in 18 144 patients after acute coronary syndrome. The safety of very low LDL-C levels over the long-term is unknown.. To assess the safety and clinical efficacy of achieving a very low (<30 mg/dL) level of LDL-C at 1 month using data from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial.. This prespecified analysis compared outcomes in patients stratified by achieved LDL-C level at 1 month in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial and adjusted for baseline characteristics during 6 years' median follow-up. Patients were enrolled from October 26, 2005, to July 8, 2010, and the data analysis was conducted from December 2014 to February 2017.. Safety end points included adverse events leading to drug discontinuation; adverse muscle, hepatobiliary, and neurocognitive events; and hemorrhagic stroke, heart failure, cancer, and noncardiovascular death. Efficacy events were as specified in the overall trial.. Among the 15 281 patients included in the study, 11 645 (76.2%) were men and the median age was 63 years (interquartile range, 56.6-70.7 years). In these patients without an event in the first month, the achieved LDL-C values at 1 month were less than 30 mg/dL, 30 to 49 mg/dL, 50 to 69 mg/dL, and 70 mg/dL or greater in 6.4%, 31%, 36%, and 26% of patients, respectively. Patients with LDL-C values less than 30 mg/dL (median, 25 mg/dL; interquartile range, 21-27 mg/dL) at 1 month were more likely randomized to ezetimibe/simvastatin (85%), had lower baseline LDL-C values, and were more likely older, male, nonwhite, diabetic, overweight, statin naive, and presenting with a first myocardial infarction. After multivariate adjustment, there was no significant association between the achieved LDL-C level and any of the 9 prespecified safety events. The adjusted risk of the primary efficacy composite of cardiovascular death, major coronary events, or stroke was significantly lower in patients achieving an LDL-C level less than 30 mg/dL at 1 month (adjusted hazard ratio, 0.79; 95% CI, 0.69-0.91; P = .001) compared with 70 mg/dL or greater.. Patients achieving an LDL-C level less than 30 mg/dL at 1 month had a similar safety profile (and numerically the lowest rate of cardiovascular events) over a 6-year period compared with patients achieving higher LDL-C concentrations. These data provide reassurance regarding the longer-term safety and efficacy of the continuation of intensive lipid-lowering therapy in very higher-risk patients resulting in very low LDL-C levels.. clinicaltrials.gov Identifier: NCT00202878.

Topics: Acute Coronary Syndrome; Aged; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, LDL; Double-Blind Method; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Liver Diseases; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Muscular Diseases; Myocardial Infarction; Neoplasms; Patient Care Planning; Practice Guidelines as Topic; Proportional Hazards Models; Rhabdomyolysis; Stroke; Treatment Outcome

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Diabetes Mellitus, Type 1; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Humans; Hypercholesterolemia; Survival Rate

The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is evaluating the potential benefit for reduction in major cardiovascular (CV) events from the addition of ezetimibe versus placebo to 40 mg/d of simvastatin therapy in patients who present with acute coronary syndromes and have low-density lipoprotein cholesterol (LDL-C) 125 mg/dl.. Randomized double blind clinical trial in patients with acute coronary syndrome and low cholesterol level. The simvastatin monotherapy arms LDL-C target was < 70 mg/dl, the comparison arm was simvastatin + ezetimibe. Ezetimibe was assumed to further lower LDL-C by 15 mg/dl and produce an estimated ~ 8 % to 9 % treatment effect. The primary composite end point was CV death, nonfatal myocardial infarction (MI), nonfatal stroke, rehospitalization for unstable angina (UA), and coronary revascularization ( 30 days postrandomization). The targeted number of events was 5,250.. 18,144 patients were enroled with either ST segment elevation MI (STEMI, n = 5,192) or UA/non-ST segment elevation MI (UA/NSTEMI, n = 12,952) from October 2005 to July 2010. Primary endpoint occured in 2 742 patients (34.7 %) treated with simvastatin in monotherapy and in 2 572 patients (32.7 %) (p = 0.016) treated with combination. Compared to patients with coronary heart disease given the drug simvastatin plus a placebo, those given both simvastatin and the non-statin drug, ezetimibe, had a 6.4 % lower combined risk of subsequent heart attack, stroke, cardiovascular death, rehospitalization for unstable angina and procedures to restore blood flow to the heart. Heart attacks alone were reduced by 13 %, and non-fatal stroke by 20 %. Deaths from cardiovascular disease were statistically the same in both groups. Patients were followed an average of approximately six years, and some as long as 8.5 years. Approximately 2 patients out of every 100 patients treated for 7 years avoided a heart attack or stroke [Number Needed to Treat (NNT) = 50/7 years].. The study has shown a claer benefit from combination treatment with simvastatin and ezetimibe in patients with acute coronary syndrome and low LDL-C.

Topics: Acute Coronary Syndrome; Aged; Anticholesteremic Agents; Azetidines; Cholesterol, LDL; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Female; Humans; Male; Middle Aged; Myocardial Infarction; Simvastatin

Reduction in low-density lipoprotein cholesterol (LDL-C) improves clinical outcomes in patients with chronic coronary artery disease and acute coronary syndromes (ACSs). The combination of ezetimibe/simvastatin produces greater reductions in LDL-C compared to simvastatin monotherapy. The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is a multicenter, randomized, double-blind, active-control trial designed to test the hypothesis that the addition of ezetimibe to statin therapy, using ezetimibe/simvastatin, will translate into increased clinical benefit on cardiovascular outcomes relative to simvastatin monotherapy in patients with ACS.. The study will recruit up to 18,000 moderate- to high-risk patients stabilized after ACS. Patients are randomized in a 1:1 ratio to once-daily doses of either ezetimibe/simvastatin 10/40 mg or simvastatin monotherapy 40 mg. Follow-up visits are at 1 and 4 months, and every 4 months thereafter. If consecutive measures of LDL-C are >79 mg/dL at follow-up visits, the simvastatin dose will be increased to 80 mg in a double-blind manner. The primary end point is the first occurrence of cardiovascular death, nonfatal myocardial infarction, rehospitalization for unstable angina, coronary revascularization (occurring at least 30 days after randomization), or stroke. Patients will be followed for a minimum of 2.5 years and until at least 5,250 patients experience a primary end point.. IMPROVE-IT will determine whether the addition of ezetimibe to statin therapy, using ezetimibe/simvastatin, improves cardiovascular outcomes compared with simvastatin monotherapy in patients after ACS. In addition, the difference in achieved LDL-C levels between the groups will provide data on whether the target for LDL-C lowering should be reduced further.

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Azetidines; Double-Blind Method; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Humans; Multicenter Studies as Topic; Simvastatin; Treatment Outcome

It remains uncertain whether statin/ezetimibe combination therapy serves as a useful and equivalent alternative to statin monotherapy for reducing atherosclerotic plaque inflammation. The aim of the present study was to compare the effects of statin/ezetimibe combination therapy and statin monotherapy on carotid atherosclerotic plaque inflammation using 18F-fluorodeoxyglucose (18FDG) positron emission tomography (PET)/computed tomography (CT) imaging. Data were pooled from 2 clinical trials that used serial 18FDG PET/CT examination to investigate the effects of cholesterol-lowering therapy on carotid atherosclerotic plaque inflammation. The primary outcome was the percent change in the target-to-background ratio (TBR) of the index vessel in the most diseased segment (MDS) at 6-month follow-up. Baseline characteristics were largely similar between the 2 groups. At the 6-month follow-up, the MDS TBR of the index vessel significantly decreased in both groups. The percent change in the MDS TBR of the index vessel (primary outcome) did not differ significantly between the 2 groups (-8.41 ± 15.9% vs -8.08 ± 17.0%, respectively, P = .936). Likewise, the percent change in the whole vessel TBR of the index vessel did not differ significantly between the 2 groups. There were significant decreases in total and LDL cholesterol levels in both groups at follow-up (P < .001). There were no significant correlations between the percent changes in MDS TBR of the index vessel, changes in the lipid, and high-sensitive C-reactive protein levels. The reduction in carotid atherosclerotic plaque inflammation by statin/ezetimibe combination therapy was equivalent to that by the statin monotherapy.

Topics: Acute Coronary Syndrome; Aged; C-Reactive Protein; Carotid Arteries; Carotid Artery Diseases; Cholesterol, LDL; Clinical Trials as Topic; Datasets as Topic; Ezetimibe, Simvastatin Drug Combination; Female; Follow-Up Studies; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inflammation; Male; Middle Aged; Plaque, Atherosclerotic; Rosuvastatin Calcium; Simvastatin

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Simvastatin

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Simvastatin

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Simvastatin

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Stroke

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Stroke

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Stroke

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Stroke

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Stroke

After an acute coronary syndrome, the 6-year results of the "IMPROVE-IT" randomized trial showed a 1.6% reduction in the number of nonfatal myocardial infarctions with the ezetimibe + simvastatin combination compared with simvastatin alone, but no reduction in mortality.

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Biomarkers; Cholesterol, LDL; Dyslipidemias; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome

Topics: Acute Coronary Syndrome; Anticholesteremic Agents; Brazil; Cholesterol; Dose-Response Relationship, Drug; Ezetimibe; Ezetimibe, Simvastatin Drug Combination; Humans; Incidence; Randomized Controlled Trials as Topic; Treatment Outcome

The recent IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is the first study to demonstrate a significant benefit of another medication (ezetimibe) on top of statin therapy in patients who have recently experienced an acute coronary syndrome. Despite the fact that ezetimibe led to positive results on the primary endpoint, the clinical benefit translated to real-life practice is only modest at best. However, this is the first major trial to demonstrate a significant benefit of a lipid medication in addition to statins. We explore the strengths and weaknesses of IMPROVE-IT in the context of current-day acute coronary syndrome practice, where high-dose statins now are prescribed widely.

Topics: Acute Coronary Syndrome; Azetidines; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Humans; Randomized Controlled Trials as Topic; Research Design; Simvastatin; Treatment Outcome

Topics: Acute Coronary Syndrome; Azetidines; Cholesterol, LDL; Drug Combinations; Ezetimibe, Simvastatin Drug Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Models, Statistical; Patient Compliance; Research Design; Simvastatin; Treatment Outcome