AUCTORES
Globalize your Research
Research Article | DOI: https://doi.org/10.31579/2641-0419/422
University hospital MOHAMED VI, Department of cardiology, Intensive care unit, Marrakesh, Morocco.
*Corresponding Author: Noussaiba Malhabi, University hospital MOHAMED VI, Department of Cardiology, Intensive care unit, Marrakesh, Morocco.
Citation: Ait Yahya AE, Ztati Mohamed, Noussaiba Malhabi, Imane Katif, Mohammed EL Jamili, et al, (2024), Comparison of different intensive lipid-lowering therapies for patients with acute coronary syndrome: Ezetimibe and rosuvastatin versus high-dose rosuvastatin, J Clinical Cardiology and Cardiovascular Interventions, 7(13); DOI: 10.31579/2641-0419/422
Copyright: © 2024, Noussaiba Malhabi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 02 October 2024 | Accepted: 28 October 2024 | Published: 26 November 2024
Keywords: Coronary Syndrome; LDL; cardiovascular disease: open heart surgery
Introduction: Dyslipidaemias is a risk factor for atherosclerosis that leads to unstable atherosclerotic plaque rupture and acute coronary syndrome. Therefore, it is crucial to find a better control of risk factors to prevent the occurrence of a new acute cardiovascular event.
Study aims: We aim to determine whether combining ezetimibe with a high-intensity statin would be a more effective and safer alternative therapy compared to high-intensity statin monotherapy for patients with coronary atherosclerotic heart disease.
Materiel and methods: 65 patients were randomly assigned to high-intensity rosuvastatin (group 1) (rosuvastatin 20 mg/d, n = 33), or a combination therapy (group 2) (ezetimibe 10 mg/d and rosuvastatin 10 mg/d, n = 32) with a 3 month of follow-up. A lipid and general blood test to assess effectiveness and safety is done in 3 weeks and 3 months. Informed consent from patients is obtained before they participate in the study.
Results: The primary endpoint was the proportion of patients who achieved the LDL-C goal of 55mg/dL in the third month: 60% in the second group vs. 33% in the first group, with a statistically significant difference (p=0.001). It was noted that there was a decrease in high-sensitivity C-reactive protein (Crp) without an increase in blood transaminases.
Discussion and conclusion: Statin combined with ezetimibe demonstrates significant benefits in lowering LDL-C and preventing cardiovascular as statin high dose in acute coronary syndromes. Our results are consistent with the literature.
In the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) study, ezetimibe treatment was administered early after an acute coronary syndrome (ACS) event (within 10 days) either in addition to existing statin therapy or started simultaneously in statin-naïve patients and was compared to statin monotherapy. The results demonstrated that ezetimibe was safe and provided long-term cardiovascular benefits. Therefore, for patients on the highest tolerated dose of statins, or those with no prior statin treatment, and whose LDL-C levels suggest that target levels are unlikely to be achieved with statin therapy alone, the initiation of ezetimibe alongside a statin (or as part of a statin and ezetimibe combination therapy) may be considered during their hospitalization for ACS.(1) (2)
Another study published in the NEJM demonstrated that when added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit.(3)
Furthermore, the addition of ezetimibe to rosuvastatin was demonstrated to further reduce LDL-C, Crp and Lp-PLA2 compared with rosuvastatin monotherapy in patients with acute coronary syndrome(4)
Dyslipidaemias is a risk factor for atherosclerosis that leads to unstable atherosclerotic plaque rupture and acute coronary syndrome. Therefore, it is crucial to find a better control of risk factors to prevent the occurrence of a new acute cardiovascular event. (1)
Statins, or 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, effectively lower low-density lipoprotein (LDL) cholesterol and reduce the risk of cardiovascular events in patients with and without existing cardiovascular disease. Intensive statin therapy, compared to moderate doses, further reduces LDL cholesterol levels and decreases the incidence of nonfatal cardiovascular events. However, due to the remaining risk of recurrent cardiovascular events and safety concerns with high-dose statins, alternative lipid-modifying therapies are explored. (4)
Ezetimibe works by targeting the Niemann–Pick C1–like 1 (NPC1L1) protein, which reduces cholesterol absorption from the intestine. When used in combination with statins, ezetimibe lowers LDL cholesterol levels by an additional 23 to 24% on average. Genetic polymorphisms affecting NPC1L1 are linked to both lower LDL cholesterol levels and a reduced risk of cardiovascular events. However, it is unclear whether the further reduction in LDL cholesterol levels from adding ezetimibe to statin therapy results in improved clinical outcomes. The Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) studied the impact of combining ezetimibe with simvastatin versus using simvastatin alone in stable patients who had experienced an acute coronary syndrome, with LDL cholesterol levels within recommended guidelines. (4)
Study aims:
We aim to determine whether combining ezetimibe with a high-intensity statin would be a more effective and safer alternative therapy compared to high-intensity statin monotherapy for patients with coronary atherosclerotic heart disease.
This study was a prospective, randomized trial, from December 2023 to February 2024 including patients with acute coronary syndrome managed and receiving care in Mohamed VI University Hospital of Marrakech
Study population:
We selected 65 patients hospitalized for the management of acute coronary syndrome in the cardiac intensive care unit of Mohamed VI University Hospital of Morocco; the diagnosis of acute coronary syndrome, which is the principal selection criteria, is based on the European Society of Cardiology last guidelines: acute coronary syndrome can be presented as severe acute angina with ST-segment changes and a positive enzymatic response in its STEMI and NSTEMI forms, or without enzymatic changes in unstable angina. (1)
We excluded from the study population: Received lipid-lowering therapy within the past six months; severe congestive heart failure (New York Heart Association class IIIb or IV with left ventricular ejection fraction below 30%); alanine transaminase (ALT) and aspartate aminotransferase (AST) levels at or above three times the upper limit of normal (ULN); renal insufficiency; unexplained elevated creatine kinase (CK) levels at or above one time the ULN; current use of medications that may interact with statins and/or ezetimibe; history of statin-induced myopathy or significant hypersensitivity to statins or ezetimibe. Informed consent from all our patients is obtained before their participation.
Trial design:
The included patients received the standard treatment of acute coronary syndrome including; aspirin, clopidogrel, and low molecular weight heparin with a loading dose, beta-blockers and angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists
65 patients were randomly assigned to high-intensity Rosuvastatin (group 1) (Rosuvastatin 20 mg/d, n = 33), or a combination therapy (group 2) (ezetimibe 10 mg/d and Rosuvastatin 10 mg/d, n = 32), lipid lowring therapy is started within 24 hours after the performance lipid levels, C-reactive protein (CRP), liver and renal function tests, and creatine kinase (CK).
Within 3 months of follow-up, a lipid and general blood test is done to assess effectiveness and safety in 3 weeks and 3 months.
Endpoints:
The primary endpoint was: the proportion of patients who achieved the LDL-C goal of 55mg/dL after four weeks and three months. The safety is also assessed through systematic measurement of hepatic enzymes and muscular enzymes if symptoms are present, and monitoring of CRP kinetics is required.
Statistical analysis:
Quantitative data are expressed as a mean plus or minus standard deviation and compared by the student test. While the qualitative data are expressed in number and percentage and compared by the chi 2 test. A value of p<0>
Baseline characteristics :
This study included 65 patients, including 33 males and 32 females. The average age was 53.5 ± 8.4 years old. There were no significant differences at baseline among the two groups in lipid, ALT, AST, CK, myocardial enzymes, or CRP. Groups also had similar rates of smoking, hypertension, cerebral infarction, and diabetes histories, as well as other cardiovascular disease risk factors and the use of drug combinations (aspirin, clopidogrel, β-blocker, and ACEI/ARB)
| Variable | Groupe 1 | Groupe 2 | p between groups |
| Demographic characteristics | |||
| Patients, n | 33 | 32 | .345 |
| Sex, % men | 16 | 15 | .678 |
| Diabetes, n | 23 | 25 | .378 |
| Dyslipidemia, % | 33 | 32 | .456 |
| Cigarette smoking, % | 30 | 29 | .340 |
| Obesity, % | 5 | 7 | .737 |
| Hypertension, % | 20 | 25 | .015 |
| Clinical presentation | |||
| STEMI, n | 20 | 15 | .010 |
| NSTEMI, n | 10 | 12 | .213 |
| Unstable angina, n | 3 | 5 | .045 |
| Drugs and stents locations n (%) | |||
| Aspirin | 33 | 32 | .123 |
| Clopidogrel | 33 | 32 | .123 |
| ACI and ARB | 30 | 28 | .234 |
| B-blockers | 28 | 32 | .345 |
| LAD | 25 | 22 | .234 |
| LCX | 21 | 20 | .123 |
| MB | 5 | 6 | .455 |
| RCA | 15 | 14 | .234 |
Table 1: Baseline characteristics of patients investigated according to high-intensity Rosuvastatin (group 1) (Rosuvastatin 20 mg/d), or a combination therapy (group 2) (ezetimibe 10 mg/d and Rosuvastatin 10 mg/d)
2 Efficacy:
| Variable | Group 1 | Group 2 | p between groups |
| TG (mg/dl) | |||
| Week 0 | 148±41 | 145±33 | .997 |
| Week 4 | 120±34 | 122±38 | .735 |
| Week 12 | 110±30 | 112±27 | .876 |
| TC (mg/dl) | |||
| Week 0 | 250±43 | 242±48 | .987 |
| Week 4 | 160±30 | 120±15 | <0> |
| Week 12 | 124±20 | 103±12 | <0> |
| HDL-C | |||
| Week 0 | 39±6 | 37±5 | .876 |
| Week 4 | 42±8 | 45±6 | .674 |
| Week 12 | 45±9 | 45±9 | .334 |
| LDL-C (mg/dl) | |||
| Week 0 | 160±5 | 159±6 | .655 |
| Week 4 | 83±3 | 60±6 | <0> |
| Week 12 | 64±15 | 45±5 | <0> |
| Non-HDL C (mg/dl) | |||
| Week 0 | 165±44 | 165±32 | 0.765 |
| Week 4 | 109±25 | 92±30 | <0> |
| Week 12 | 86±15 | 67±35 | <0> |
| CRP (mg/dl) | |||
| Week 0 | 40±16 | 50±20 | 0.345 |
| Week 4 | 1±0.5 | 3±0.2 | 0.456 |
Table 2: Lipid levels at week0 and week4 by group follow-up in 12 week.
In our studied population, we did not observe a statistically significant difference between the two groups regarding reduction in triglycerides, HDL cholesterol, and inflammatory markers, specifically CRP.
However, there is a statistically significant difference between the two groups regarding reduction in LDL cholesterol, total cholesterol, and non-HDL cholesterol, starting from the 4th week, with a greater decrease observed at the 3-month follow-up. The most significant reduction is noted in the group receiving the combination of Ezetimibe 10 mg and Rosuvastatin 10 mg.
3-Safety:
A total of 4 patients experienced adverse drug events during the12-week follow-up period in the group 1, versus no adverse effects in the group 2.
Statin combined with ezetimibe demonstrates significant benefits in lowering LDL-C and preventing cardiovascular as statin high dose in acute coronary syndromes. Our results are consistent with the literature.
In the IMPROVE-IT (Improved Reduction of Outcomes: Vytorin Efficacy International Trial) study, ezetimibe treatment was administered early after an acute coronary syndrome (ACS) event (within 10 days) either in addition to existing statin therapy or started simultaneously in statin-naïve patients and was compared to statin monotherapy. The study aims to enroll up to 18,000 moderate- to high-risk patients who are stabilized after an acute coronary syndrome (ACS). Participants will be randomly assigned in a 1:1 ratio to receive either a daily dose of ezetimibe/simvastatin 10/40 mg or simvastatin monotherapy 40 mg. Follow-up visits will occur at 1 month, 4 months, and every 4 months thereafter. If two consecutive LDL-C measurements exceed 79 mg/dL during follow-up, the simvastatin dose will be increased to 80 mg in a double-blind manner. The primary endpoint is the first occurrence of cardiovascular death, nonfatal myocardial infarction, rehospitalization for unstable angina, coronary revascularization (occurring at least 30 days post-randomization), or stroke. Patients will be monitored for at least 2.5 years, with the study continuing until at least 5,250 participants experience a primary endpoint event. (2)
The results demonstrated that ezetimibe was safe and provided long-term cardiovascular benefits. Therefore, for patients on the highest tolerated dose of statins, or those with no prior statin treatment, and whose LDL-C levels suggest that target levels are unlikely to be achieved with statin therapy alone, the initiation of ezetimibe alongside a statin (or as part of
a statin and ezetimibe combination therapy) may be considered during their hospitalization for ACS.(1) (2)
Another study published in the NEJM in 2015, Is a double blind, randomized trial with 18,144 patients hospitalized for acute coronary syndrome within the past 10 days. These patients had LDL cholesterol levels of 50 to 100 mg/dL (1.3 to 2.6 mmol/L) if they were already on lipid-lowering therapy or 50 to 125 mg/dL (1.3 to 3.2 mmol/L) if they were not. The trial compared a combination of simvastatin (40 mg) and ezetimibe (10 mg) (simvastatin–ezetimibe) with simvastatin (40 mg) and placebo (simvastatin monotherapy). The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, unstable angina requiring rehospitalisation, coronary revascularization (occurring 30 days or more after randomization), or nonfatal stroke. The median follow-up period was 6 years. (3)
They demonstrated that when added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefits. (3)
Furthermore, the addition of ezetimibe to rosuvastatin was demonstrated to further reduce LDL-C, Crp and Lp-PLA2 compared with rosuvastatin monotherapy in patients with acute coronary syndrome, we talk here about a Chinese study; where a total of 125 patients were randomly assigned to one of three groups: an intermediate-intensity rosuvastatin group (rosuvastatin 10 mg/day, n = 42), a high-dose rosuvastatin group (rosuvastatin 20 mg/day, n = 41), or a combination therapy group (ezetimibe 10 mg/day and rosuvastatin 10 mg/day, n = 42), with a 12-week follow-up period. The primary endpoint was the proportion of patients who achieved the 2011 ESC/EAS LDL-C goal of less than 70 mg/dL (1.8 mmol/L) by week 12. Secondary endpoints included changes from baseline in lipid levels, the occurrence of any cardiovascular events, levels of high-sensitivity C-reactive protein, and safety markers. (4)
In the primary endpoint, the combination therapy group showed a significantly higher success rate compared to the rosuvastatin 20 mg and rosuvastatin 10 mg groups at week 12 (81.0% vs. 68.3% vs. 33.3%, P < 0>
A meta-analysis published in 2024, aimed to evaluate the efficacy of rosuvastatin monotherapy versus combination therapy with ezetimibe in patients with type 2 diabetes. A systematic literature search was conducted across multiple databases until April 2024, identifying six randomized controlled trials meeting the inclusion criteria. The meta-analysis revealed that the rosuvastatin plus ezetimibe combination resulted in significantly greater reductions in total cholesterol (mean difference, or MD: 19.49; 95% CI: 13.99 to 24.99), triglycerides (MD: 13.44; 95% CI: 2.04 to 24.85), and low-density lipoprotein cholesterol (MD: -17.68; 95% CI: 12.85 to 22.51) compared to rosuvastatin monotherapy. (5)
The findings suggest that the combination of rosuvastatin and ezetimibe may be a more effective lipid-lowering strategy for patients with type 2 diabetes, although larger studies are needed to evaluate long-term safety and determine the optimal dosing. Additionally, while rosuvastatin monotherapy resulted in modest reductions in HbA1c, the clinical significance of this effect remains unclear, and the potential risks associated with high-dose statins should be taken into account. (5)
The present findings suggest that compared with rosuvastatin20mg and the combination of ezetimibe 10 mg/rosuvastatin 10 mg is much more effective in lowering lipid levels and caused lower incidences of drug-related adverse events in our study population.
This study is a single-center study, the sample size is small, and the follow-up time is short. Maybe there is a certain bias, and if we extended their follow-up and expanded the sample size, the benefit of cardiovascular events would be more obvious, and the long-term adverse side effects would be more persuasive
No funding
Data is collected with respect of anonymity and confidentiality of the information provided after patient consent.
Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.
