Combination Lipid-lowering Therapy Research Articles

Lipid-lowering therapy with Inclisiran in the real-world setting: Initial data from a national health care service

BackgroundInclisiran, a small-interfering RNA enabling long-term inhibition of PCSK9 synthesis, demonstrates good safety and efficacy profile in clinical trials. Real-world data on the potential to attain lipid-goals and reduce treatment gaps is lacking. ObjectivesTo investigate the implementation of inclisiran in real-world clinical setting. MethodsData from a nationwide healthcare organization on patients initiating inclisiran between 3/2022-11/2023. Patients’ characteristics, lipid-lowering therapies, post-treatment reduction in low-density lipoprotein cholesterol (LDL-C), and attainment of treatment goals, were evaluated. ResultsInclisiran was initiated by 503 patients (57% women; mean age 66±11 years). Cardiovascular disease was present in 54%, and peak LDL-C levels >190 mg/dL documented in 64%. Prior exposure to PCSK9 monoclonal antibodies was evident in 28%. Lipid profile >2 months after filling first prescription, was available in 397 patients (347 with ≥2 injections). In patients treated by inclisiran only (n=254), median LDL-C reduction from peak levels was 57% (IQR, 48%-67%), and from pre-injection levels 40% (19%-54%). In those with concomitant lipid-lowering therapies (n=143), median LDL-C reduction from peak levels was 66% (IQR, 55%-73%), and from pre-injection levels 46% (23%-59%). LDL-C <70 mg/dL was attained by 39% and LDL-C <55 mg/dL by 21.9%. Of those treated with concomitant statin therapy, 38% attained LDL-C <55 mg/dL. Overall, 6.5% discontinued inclisiran therapy after initial injection. ConclusionsIn real-world practice, inclisiran showed good efficacy in reducing LDL-C with high interindividual variability. However, attainment rates of lipid-goals were suboptimal due to limited use of combination lipid-lowering therapy and high-rates of severe hypercholesterolemia in our patient population cohort.

Combined lipid lowering therapy, including ezetimibe, in the post-infarction period

Aim. To study the effect of 48-week therapy with atorvastatin and ezetimibe on laboratory parameters, structural and functional arterial characteristics and heart failure markers in the post-infarction period.Material and methods. A total of 87 patients with acute myocardial infarction were included. In the first 24 hours, atorvastatin 80 mg/day was prescribed. During hospitalization, after 5-6, 24, 48 weeks, clinical and paraclinical examinations were performed. In the level of low-density lipoprotein cholesterol (LDL-C) &gt;1,4 mmol/l and the decrease &lt;50% at one of the follow-up visits, ezetimibe 10 mg/day was additionally prescribed.Results. Eighty participants (93%) completed the study. Patients were divided into following groups: group 1 (n=32) — atorvastatin monotherapy; group 2 (n=49) — ezetimibe and atorvastatin therapy. In group 1, LDL-C decreased after 48 weeks by 53% (p&lt;0,001), while in group 2 by 63,2% (p&lt;0,001). According to carotid ultrasound in group 2, a decrease in the intima media thickness after 24 and 48 weeks was revealed by 9,1% (p&lt;0,001) and 10,5% (p&lt;0,001) compared to the baseline value, while in group 1 — by 4,5% only on the 24th week (p=0,012). When analyzing endothelial function, there was an increase in flow-dependent vasodilation only in group 2 from 9,1 (5,6; 11,8)% to 14,3±6,8% after 48 weeks (p&lt;0,001). With the addition of ezetimibe, there was a regression of the N-terminal pro-brain natriuretic peptide after 24 weeks by 69,6% (p=0,005), after 48 weeks — by 72,4% (p=0,009). In group 2, it decreased by 75,5% by the end of follow-up (p=0,010).Conclusion. The results rationale adding ezetimibe to statins in very high-risk patients due to the most pronounced lipid lowering effect, improvement of the structural and functional properties of the common carotid arteries, endothelial function and clinical and laboratory heart failure markers.

Left Main Coronary Artery Calcium and Diabetes Confer Very-High-Risk Equivalence in Coronary Artery Calcium>1,000.

Although a coronary artery calcium (CAC) of≥1,000 is a subclinical atherosclerosis threshold to consider combination lipid-lowering therapy, differentiating very high from high atherosclerotic cardiovascular disease (ASCVD) risk in this patient population is not well-defined. Among persons with a CAC of≥1,000, the authors sought to identify risk factors equating with very high-risk ASCVD mortality rates. The authors studied 2,246 asymptomatic patients with a CAC of≥1,000 from the CAC Consortium without a prior ASCVD event. Cox proportional hazards regression modelling was performed for ASCVD mortality during a median follow-up of 11.3 years. Crude ASCVD mortality rates were compared with those reported for secondary prevention trial patients classified as very high risk, defined by≥2 major ASCVD events or 1 major event and≥2 high-risk conditions (1.4 per 100 person-years). The mean age was 66.6 years, 14% were female, and 10% were non-White. The median CAC score was 1,592 and 6% had severe left main (LM) CAC (vessel-specific CAC≥300). Diabetes (HR: 2.04 [95%CI: 1.47-2.83]) and severe LM CAC (HR: 2.32 [95%CI: 1.51-3.55]) were associated with ASCVD mortality. The ASCVD mortality per 100 person-years for all patients was 0.8 (95%CI: 0.7-0.9), although higher rates were observed for diabetes (1.4 [95%CI: 0.8-1.9]), severe LM CAC (1.3 [95%CI: 0.6-2.0]), and both diabetes and severe LM CAC (7.1 [95%CI: 3.4-10.8]). Among asymptomatic patients with a CAC of≥1,000 without a prior index event, diabetes, and severe LM CAC define very high risk ASCVD, identifying individuals who may benefit from more intensive prevention therapies across several domains, including low-density lipoprotein-cholesterol lowering.

New possibilities for lipid level control using inclisiran — prospects for interaction between a cardiologist and a neurologist

Dyslipidemia is one of the most significant modifiable cardiovascular risk factors. The change in the modern paradigm for dyslipidemia treatment from high-intensity statin therapy to high-intensity lipid-lowering therapy makes it possible to more often use new drug classes to achieve the target level of low-density lipoprotein cholesterol. The article presents two case reports on the use of inclisiran as part of combination lipid-lowering therapy for secondary prevention in patients at very high cardiovascular risk. Based on the presented cases, following clinical aspects of the management of cardiovascular patients are discussed: the safety of achieving low-density lipoprotein cholesterol levels below 1 mmol/l in a patient with asymptomatic cerebral infarction, the need for adequate dyslipidemia treatment after revascularization, the strategic importance of prescribing lipid-lowering therapy in patients with cerebrovascular disease to reduce the cardiovascular risk, adherence to therapy as a significant aspect of effective dyslipidemia control.

Premature coronary artery disease and severe hypertriglyceridemia in a patient with monogenic diabetes: a case report

Aim. Maturity- onset diabetes of the young (MODY) is a group of monogenic diseases with an autosomal dominant inheritance. This is a rarely diagnosed disease, occurring in 1 of 10 thousand adults and in 1 of 23 thousand children. Brief description. We present a case report of a patient with a monogenic diabetes HNF4A-MODY, severe hypertriglyceridemia, progressive premature coronary artery disease and a HNF4A gene pathogenic variant (ENST00000316099.8:c.1145dup).Discussion. This case demonstrates the effectiveness of triple hypoglycemic therapy, including empagliflozin for the treatment of monogenic diabetes. Despite the fact that the patient with diabetes reached the target glycated hemoglobin level, the combination of the disease with other cardiovascular risk factors (hypertension, hypertriglyceridemia, obesity, smoking, male sex) led to the progression of coronary and peripheral atherosclerosis. Considering the data of genetic testing, returning to sulfonylurea therapy should be considered. It is important for patient to follow a strict lipid-lowering diet and taking combination lipid-lowering therapy (rosuvastatin, fenofibrate and omega-3 polyunsaturated fatty acids) in order to achieve the target level of low-density lipoprotein cholesterol &lt;1,4 mmol/l and triglycerides &lt;1,7 mmol/l.

Combination therapy with moderate-intensity atorvastatin and ezetimibe vs. high-intensity atorvastatin monotherapy in patients treated with percutaneous coronary intervention in practice: assessing RACING generalizability

Abstract Aims Using rosuvastatin, the RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial showed the beneficial effects of combining moderate-intensity statin with ezetimibe compared with high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease. This study investigated whether the beneficial effects of combination lipid-lowering therapy extend to patients treated with atorvastatin, not rosuvastatin, in daily clinical practice. Methods and results Using stabilized inverse probability of treatment weighting, a total of 31 993 patients who were prescribed atorvastatin after drug-eluting stent (DES) implantation were identified from a nationwide cohort database: 6215 patients with atorvastatin 20 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 25 778 patients with atorvastatin 40–80 mg monotherapy. The primary endpoint was the 3-year composite of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or non-fatal stroke in accordance with the RACING trial design. Combination lipid-lowering therapy was associated with a lower incidence of the primary endpoint (12.9% vs. 15.1% in high-intensity atorvastatin monotherapy; hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.74–0.88, P &amp;lt; 0.001). Compared with high-intensity atorvastatin monotherapy, combination lipid-lowering therapy was also significantly associated with lower rates of statin discontinuation (10.0% vs. 8.4%, HR 0.81, 95% CI 0.73–0.90, P &amp;lt; 0.001) and new-onset diabetes requiring medication (8.8% vs. 7.0%, HR 0.80, 95% CI 0.70–0.92, P = 0.002). Conclusion In clinical practice, a combined lipid-lowering approach utilizing ezetimibe and moderate-intensity atorvastatin was correlated with favourable clinical outcomes, drug compliance, and a reduced incidence of new-onset diabetes requiring medications in patients treated with DES implantation. Trial registration: ClinicalTrial.gov (NCT04715594).

Guideline-directed low-density lipoprotein cholesterol management following acute ischemic stroke: findings from Clalit health services

Abstract Background Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated (2019) guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets after ischemic stroke are limited. Methods Data from a single national health care service on patients hospitalized with acute ischemic stroke between Jan. 2020 and Feb. 2022. Included were 3027 patients surviving ≥1-year post-stroke, with documented LDL-C levels and lipid-lowering medications at 2 timepoints (&amp;lt;3 months and during 6-12 months post-discharge). Participants were classified according to preexisting stroke and/or coronary artery disease (CAD). Results LDL-C levels &amp;lt;70 mg/dL and &amp;lt;55 mg/dL were attained by 42.3% and 22.9% of patients early post-hospitalization, and in 49.5% and 27.1% during 6-12 months post-hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in those with preexisting cardiovascular disease. The use of combination lipid-lowering therapy (ezetimibe and/or PCSK9 inhibitor plus statin) increased between the 2 timepoints: from 2% to 3.2% in those without prior stroke and/or CAD, and from 5.4% to 7% in those with prior stroke and/or CAD. Conclusions Despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies 6-12 months following hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Therapeutic gaps in low-density lipoprotein cholesterol management have narrowed over time but remain wide: a wide study of 40,141 acute coronary syndrome patients from 2016 to 2021

Abstract Background There are significant therapeutic gaps in ‘real-word’ low-density lipoprotein cholesterol (LDL-C) management in very-high risk patients. Understanding these gaps is important for developing strategies to bridge these gaps. Purpose We aimed to evaluate trends and identify therapeutic gaps in LDL-C management in very-high risk patients. Methods We retrospectively analyzed consecutive patients admitted with a diagnosis of acute coronary syndrome (ACS) to 16 public hospitals in between 2016 and 2021. Baseline and 12-month lipid-lowering therapy (LLT) including statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and LDL-C levels were recorded. We evaluated trends-over-time in percentage achievement of guideline Class I recommendations including (i) in-hospital initiation of high-intensity LLT; (ii) lipid-profile at follow-up post discharge; (iii) achieve at least 50% reduction in LDL-C from baseline with a goal of (iv) LDL-C &amp;lt;1.4 mmol/L. Results Of 40,141 ACS patients (mean age 71, male 66.5%), 61.2% were statin-naïve on admission. Baseline average LDL-C was 2.35 mmol/L (IQR 1.74 to 3.13 mmol/L). LLT prescription on discharge increased over time from 63.8% in 2016 to 96.2% in 2021. The use of high-intensity statins on discharge also increased over time from 24.7% to 53.7% but still suboptimal. The use of high-intensity statins increased significantly at 12-months (29.4% in 2016 and 59% in 2021) compared to on discharge (44.1% vs. 40.9% overall, p&amp;lt;0.001). The use of combination LLT was very low (1.3%-3.8%). Up to 22% of patients did not have repeated lipid profile after discharge. Of patients who had follow-up lipid profile, the median LDL-C was 1.74 mmol/L with a median LDL-C reduction of 29%. Only 27.5% reached the LDL-C goal of &amp;lt;1.4 mmol/L and 22.5% achieved at least 50% of LDL-C reduction. LDL-C reduction improved over time from 25.8% in 2016 to 31% in 2021, proportion of patients who reached LDL-C goal of &amp;lt;1.4 mmol/L improved over time from 20.8% in 2016 to 28.7% in 2021, and proportion of patients who achieved at least 50% of LDL-C reduction improved over time from 18.5% in 2016 to 24.6% in 2021, respectively. Conclusion Despite an increasing trend in the use of high-intensity statins and combination LLT over time, most patients did not reach guideline-recommended LDL-C target. Early up-titration of statin and addition of non-statin LLT may be required in the majority of patients.

Inclisiran in patients with acute ischemic stroke: first data

To evaluate the effect of inclisiran therapy on parameters of lipid metabolism in hospitalized patients with acute ischemic stroke. A prospective, observational, non-randomized study was performed. The study included 12 patients with acute ischemic stroke prescribed with a combination lipid-lowering therapy with inclisiran (284 mg as a single dose). At 15 days after the start of therapy, changes in blood lipid composition were assessed. For quantitative variables, median, maximum and minimum values were determined. The significance of differences between related samples in quantitative variables was assessed using the Mann-Whitney test. Before the start of combination lipid-lowering therapy, total cholesterol (TC) was 7.33 mmol/l and low-density lipoprotein C (LDL-C) was 5.23 mmol/l. At 15 days after the start of inclisiran therapy, TC significantly decreased by 52.1 % and LDL-C decreased by 71.1 %. The proportion of patients who reached the LDL-C goal was 66.7 %. There were no adverse events considered by the investigators to be related with the therapy. The strategy of early administration of inclisiran (or its combination with a statin) in patients with ischemic stroke allows safe achievement of a significant reduction in LDL-C already in 15 days after the start of therapy.

Hypercholesterolemia and cardiovascular risk

Pharmacological reduction of LDL-cholesterol (LDL-C) is a major treatment strategy in limiting atherosclerotic cardiovascular (ASCVD) risk. Statins remain the primary therapeutic cornerstone in ASCVD prevention. Furthermore, ezetimibe, bempedoic acid, and PCSK9 inhibition have recently also shown to reduce cardiovascular risk. Unfortunately, a treatment gap remains between guideline-recommended LDL-C goals and what is achieved in real-world practice. An important reason for this is the limited use of novel and effective non-statin lipid-lowering therapies. In order to achieve LDL-C treatment goals and, ultimately, reduction of cardiovascular events, a combination lipid-lowering therapy needs to be considered as the standard of care for patients at very high cardiovascular risk.

Guideline-Directed Low-Density Lipoprotein Cholesterol Management After Acute Ischemic Stroke: Findings from a National Health Care Service

Patients with ischemic stroke are at high risk for future cardiovascular events and should be treated intensively with lipid-modifying agents. Combination lipid-lowering therapies are often needed to achieve updated guideline-directed treatment goals. However, real-world data on intensification of lipid-lowering therapies and attainment of low-density lipoprotein cholesterol (LDL-C) targets early after ischemic stroke are limited. We extracted data from the largest healthcare provider in Israel on patients hospitalized with acute ischemic stroke between January 2020 and February 2022. Included were 3,027 patients surviving ≥1 year after stroke, with documented LDL-C levels and lipid-lowering medications at 2 time periods (0 to 3months and 6 to 12months after discharge). Participants were classified according to preexisting stroke and/or coronary artery disease. The use of combination lipid-lowering therapy (ezetimibe and/or proprotein convertase subtilisin/kexin type 9 [monoclonal antibodies] inhibitor plus statin) in the study population increased between the 2 timepoints from 3.6% to 5.1%, reaching 10.5% in those with previous coronary artery disease and stroke. LDL-C levels <70 and <55mg/100ml were attained by 42.3% and 22.9% of patients early after hospitalization, and in 49.5% and 27.1% during 6 to 12months after hospitalization, respectively. Attainment of guideline-recommended LDL-C goals was higher in patients treated with combination lipid-lowering therapies and in those with preexisting cardiovascular disease. In conclusion, despite the advances in drug development and the availability of several mechanisms to lower cholesterol levels, the attainment of guideline-recommended LDL-C targets after acute ischemic stroke is suboptimal. Intensification of treatment with combination lipid-lowering therapies after hospitalization is uncommonly performed in clinical practice, even in those with preexisting cardiovascular disease.

Combination Lipid-Lowering Therapy in Patients Undergoing Percutaneous Coronary Intervention

BackgroundThe RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial examined the effects of combination therapy with moderate-intensity statin and ezetimibe in patients with atherosclerotic cardiovascular disease compared with high-intensity statin monotherapy. ObjectivesThis observational study was conducted to evaluate the impact of 2 treatment strategies used in the RACING trial in clinical practice. MethodsAfter stabilized inverse probability of treatment weighting, a total of 72,050 patients who were prescribed rosuvastatin after drug-eluting stent implantation were identified from a nationwide cohort database: 10,794 patients with rosuvastatin 10 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 61,256 patients with rosuvastatin 20 mg monotherapy. The primary endpoint was the 3-year composite event of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or nonfatal stroke in accordance with the RACING trial. ResultsCombination lipid-lowering therapy was associated with a lower occurrence of the primary endpoint (11.6% vs 15.2% for those with high-intensity statin monotherapy; HR: 0.75; 95% CI: 0.70-0.79; P < 0.001). Compared with high-intensity statin monotherapy, combination lipid-lowering therapy was associated with fewer discontinuations of statin (6.5% vs 7.6%; HR: 0.85; 95% CI: 0.78-0.94: P < 0.001) and a lower occurrence of new-onset diabetes requiring medication (7.7% vs 9.6%; HR: 0.80; 95% CI: 0.72-0.88; P < 0.001). ConclusionsIn clinical practice, combination lipid-lowering therapy with ezetimibe and moderate-intensity statin was associated with favorable clinical outcomes and drug compliance in patients treated with drug-eluting stent implantation. (CONNECT DES Registry; NCT04715594)

Lipid-lowering therapy and LDL-cholesterol in patients after acute coronary syndromes

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): Medical University of Vienna. Background Intensive lipid lowering after acute coronary syndromes (ACS) reduces recurrent cardiovascular events, however recent studies have shown that LDL-cholesterol goal achievement is low in patients after myocardial infarction. We compared LDL-C goal achievement in patients after ACS that were discharged with statin monotherapy or with a combination lipid lowering therapy (LLT). Methods and Results We included 227 consecutive patients with a median age of 62 (IQR 52-72) years of which 67.8% of patients were male. 59.5% of patients underwent PCI because of ST-elevation myocardial infarction (STEMI) and 40.5% because of NSTEMI. 30.4% were on LLT at time of the ACS. Median LDL-C decreased from 104.8 (IQR 75.3-139.2) mg/dL before the acute event to 52.2 (IQR 37.8-74.6) mg/dL three to six months after the myocardial infarction, resulting in 55.1% of patients on LDL-C goal of 55 mg/dL. Only 5 (2.2 %) patients were discharged without LLT and 5 (2.2 %) patients were treated with PCSK9-inhibitors. 89.4% of patients were treated with high dose and 7.5% of patients with moderate or low dose statins. Patients that were discharged on statin monotherapy (n=160, 70.5%) reached a median LDL-C of 55.0 (IQR 41.0 to 78.8) mg/dL that was significantly higher as compared to patients on combination therapy with ezetimibe (n=62, 27.3%) that was 43.0 (IQR 32.3 to 62.5) mg/dL (p&amp;lt;0.002). The proportion of patients with statin monotherapy that reached the LDL-C goal was only 50.6% as compared to 71.0% of patients with combination therapy (p&amp;lt;0.001). Logistic regression analysis revealed that out of age, gender, type of myocardial infarction and statin-pretreatment only baseline LDL-C (p&amp;lt;0.005) and combination therapy (HR 4.6; p&amp;lt;0.001) were predictors for LDL-C goal achievement. Conclusions After acute myocardial infarction, only 50.6% of patients on statin monotherapy reach the recommended LDL-C goal of 55mg/dL. LLT combination therapy with ezetimibe significantly increased the proportion of patients reaching the treatment target and should be mandatory in most of the patients after acute myocardial infarction.

P361 SMALL INTERFERING RNA: REAL–LIFE DATA WITH A NEW FRONTIER IN HYPOLIPIDEMIC THERAPY

Abstract Inclisiran (Leqvio® 284 mg) is a new small interfering RNA that acts on the mRNA coding for the gene PCSK9. Inclisiran is indicated in adults with primary hypercholesterolemia (heterozygous familial and non–familial) or mixed dyslipidemia as an adjunct to diet alone or in combination with a statin or other lipid–lowering therapies in patients unable to reach LDL–cholesterol goals with the maximum tolerated dose of a statin, or alone or in combination with other lipid–lowering therapies in patients who are statin–intolerant/contraindicated. The drug is administered subcutaneously and should be performed by a healthcare professional. After the initial dose, a second dose is given at 3 months followed by every 6 months. Real–life data with inclisiran is very limited. Herein, we present real–life data on 6 patients with a mean age of 71 years who started therapy with inclisiran in September 2022 (Fig. 1). Three patients were receiving combined lipid–lowering therapy with a statin and exetimibe, 2 were on ezetimibe alone because they were statin–intolerant, 1 patient was not receiving any therapy because intolerant. All patients had high to very high cardiovascular risk according to current ESC guidelines, and the lipid target was not met on optimized oral lipid–lowering therapy. Following initiation of inclisiran, lipids were assessed at 1 week, and at 1, 2, and 3 months. Changes in serum levels of LDL–cholesterol are shown in Figure 2. Reduction in LDL–cholesterol was seen as early as week 1. The mean percentage reduction in LDL–cholesterol at 1 month was 50% in patients not receiving statin therapy and 40% in those receiving a statin. The greatest reduction in LDL–cholesterol was seen in patients receiving combined therapy with a statin and ezetimibe. There was a clear reduction in LDL–cholesterol regardless of the type of statin and dosage. All patients receiving combined therapy with a statin reached their lipid target within 1 week after the start of treatment. No adverse effects were observed in any patient. From these preliminary observations, in a real–life setting therapy with inclisiran therapy appears to be safe and effective in lowering LDL–cholesterol in patients with high cardiovascular risk, especially when given in combination with a statin.

Grado de consecución de los objetivos lipídicos a largo plazo en una cohorte de pacientes con síndrome coronario agudo en práctica clínica real

Introduction and objectivesAccording to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. MethodsThis work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. ResultsA total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70mg/dl and 9.3% had LDL levels <55mg/dl. At the end of the follow-up (101 [88-111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved a LDL level <55mg/dl. ConclusionsAchievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7-10 years), especially in patients with recurrent ACS.

Achievement of long-term lipid targets in a cohort of patients with acute coronary syndrome in real-world clinical practice

Introduction and objectivesAccording to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. MethodsThis work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. ResultsA total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70 mg/dl and 9.3% had LDL levels <55 mg/dl. At the end of the follow-up (101 [88–111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved an LDL level <55 mg/dl. ConclusionsAchievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7–10 years), especially in patients with recurrent ACS.

Intensive lipid-lowering therapy for early achievement of guideline-recommended LDL-cholesterol levels in patients with ST-elevation myocardial infarction (“Jena auf Ziel”)

Background and aimsCurrently, less than 20% of patients at very high-risk achieve ESC/EAS dyslipidemia guideline-recommended LDL-C target levels in Europe. “Jena auf Ziel—JaZ” is a prospective cohort study in which early combination therapy with atorvastatin 80 mg and ezetimibe 10 mg was initiated on admission in patients with ST-elevation myocardial infarction (STEMI) and lipid-lowering therapy was escalated during follow-up with bempedoic acid and PCSK9 inhibitors to achieve recommended LDL-C targets in all patients. Moreover, we evaluated side-effects of lipid-lowering therapy.MethodsPatients admitted with STEMI at Jena University Hospital were started on atorvastatin 80 mg and ezetimibe 10 mg on admission. Patients were followed for EAS/ESC LDL-C target achievement during follow-up.ResultsA total of 85 consecutive patients were enrolled in the study. On discharge, 32.9% achieved LDL-C targets on atorvastatin 80 mg and ezetimibe 10 mg. After 4–6 weeks, 80% of all patients on atorvastatin 80 mg and ezetimibe started at the index event were on ESC/EAS LDL-C targets. In 20%, combined lipid-lowering therapy was escalated with either bempedoic acid or PCSK9 inhibitors. All patients achieved LDL-C levels of or below 55 mg/dL during follow-up on triple lipid-lowering therapy. Combined lipid-lowering therapy was well-tolerated with rare side effects.ConclusionsEarly combination therapy with a high-intensity statin and ezetimibe and escalation of lipid-lowering therapy with either bempedoic acid or PCSK9 inhibitors gets potentially all patients with STEMI on recommended ESC/EAS LDL-C targets without significant side effects.Graphical abstract

Сравнительная оценка комбинированной гиполипидемической терапии у пациентов с очень высоким сердечно-сосудистым риском

Aim: to assess the efficacy and safety of combined lipid-lowering therapy including statin and ezetimibe in patients with acute coronary syndrome (ACS) who are followed up in a short-term study. Patients and Methods: a prospective cohort study involved 50 patients who were divided into 2 groups (25 patients in each group) by sequential inclusion. In group 1, atorvastatin (80 mg) plus ezetimibe (10 mg) were prescribed. In group 2, pitavastatin (4 mg) plus ezetimibe (10 mg) were prescribed. Over a 6-month follow-up period, changes in the clinical signs and parameters of carbohydrate and lipid metabolism were evaluated. Results: at baseline, total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and glucose levels were similar in the groups. After 1 month, LDL-C &lt;1.4 mmol/L were reported in less than 50%. Meanwhile, a decrease in LDL-C &lt;1.4 mmol/L or a decrease in LDL-C by ≥50% occurred in 17 (68%) patients in each group. After 6 months, glucose levels in group 1 were significantly higher than those in group 2 (p=0.034). Intragroup analysis of blood glucose changes over time revealed a significant increase after 6 months in group 1 (p=0.005) but no significant changes in group 2. Over a 6-month follow-up period, diabetes was newly diagnosed in four patients, with no significant differences between the groups. Conclusion: a comparable clinical lipid-lowering efficacy of both treatment regimens was demonstrated. Significantly higher blood glucose levels were reported in the atorvastatin group than in the pitavastatin group, with no significant differences between the groups in newly diagnosed carbohydrate metabolism disorders. The most significant limitation of this study was the small sample size and relatively short follow-up period. KEYWORDS: diabetes, acute coronary syndrome, atorvastatin, pitavastatin, ezetimibe, lipid metabolism, carbohydrate metabolism. FOR CITATION: Druk I.V., Korennova O.Yu., Yukhina Yu.E., Savchenko M.V., Podol'naya S.P., Shukil L.V. Comparative assessment of combined lipid-lowering therapy in patients with very high cardiovascular risk. Russian Medical Inquiry. 2023;7(9):572–579 (in Russ.). DOI: 10.32364/2587-6821-2023-7-9-3.

Effect of combined lipid-lowering therapy on atherosclerotic plaque vulnerability in patients with acute coronary syndrome (Combi-LLT ACS): randomized trial protocol

Aim. To study the effect of high-dose combined lipid-lowering therapy (statins + ezetimibe vs statins + PCSK9 inhibitors) on plaque vulnerability assessed using multimodal imaging (coronary computed tomography angiography (CCTA) and optical coherence tomography, as well as biomarkers in patients with acute coronary syndrome (ACS).Material and methods. This open, prospective, randomized, single-center study will include 120 patients admitted urgently with an ACS. All patients will undergo percutaneous coronary intervention of the infarct-related artery, as well as intracoronary imaging using optical coherence tomography of one or two noninfarct-related arteries. During hospitalization, patients will receive standard therapy for ACS according to clinical guidelines, while statins will initially be prescribed at a maximum dosage of atorvastatin 80 mg/rosuvastatin 40 mg.Patients who showed high compliance and did not reach the target low-density lipoprotein cholesterol (LDL-C) values (≤1,4 mmol/l) 1 month after myocardial infarction/unstable angina at the second visit will be randomized into two groups. Patients of group 1 will receive PCSK9 inhibitors (alirocumab 150 mg by subcutaneous injection once every 2 weeks or evolocumab 140 mg by subcutaneous injection once every 2 weeks) in addition to maximum statin therapy (atorvastatin 80 mg/rosuvastatin 40 mg), while group 2 participants will take ezetimibe at a dose of 10 mg in combination with the maximum dose of statins. In addition, at the second visit, patients will undergo CCTA, assess the cardio-ankle vascular index (CAVI) index and laboratory tests (complete blood count (neutrophil-to-lymphocyte ratio NLR), lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Troponin I, Galectin-3, high-sensitivity C-reactive protein (hs-CRP), metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL). Total follow-up will last 52 weeks. At the final visit, patients will undergo CCTA, assessment of the CAVI index and laboratory status (NLR, lipid profile, ALT, AST), Troponin I, Galectin-3, hs-CRP, MMP-9, TIMP-1, NGAL).Primary endpoint: reduction in plaque vulnerability according CCTA in non-infarct-related coronary arteries Secondary endpoints: death, stent thrombosis/restenosis, non-fatal myocardial infarction, readmissions with progressive angina, repeat revascularization; changes of the lipid profile (total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides) against the background of maximum combination therapy with statin + PCSK9 inhibitors or statin + ezetimibe; changes of the biomarkers of cardiac injury (Troponin I), inflammation (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).Conclusion. Our study will allow for the first time to compare and evaluate the effect of both PCSK9 inhibitors and ezetimibe in combination with high-dose statin therapy on reducing the plaque vulnerability according to CCTA in non-infarction-related coronary arteries in patients with ACS undergoing percutaneous coronary intervention, as well as to evaluate the diagnostic value of inflammatory biomarkers (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).

Diagnostic Features and Selection of Hypolipidemic Therapy in Patients with Coronary Artery Disease with “Possible” Familial Hypercholesterolemia

The aim. To optimize the diagnostic algorithm for patients with true “possible” familial hypercholesterolemia (FH) and differential diagnosis with hypercholesterolemia on the background of comorbid endocrinopathies for selection of optimal hypolipidemic therapy.&#x0D; Materials and methods. We examined 130 patients with hypercholesterolemia and comorbid pathology (type 2 diabetes mellitus, hypothyroidism, obesity grade II-III). In each group, subgroups with low-density lipoproteins (LDL) ≥5 mmol/l were selected and followed up on the background of maximum tolerated doses of statins in combination with therapy aimed to compensate comorbid pathology. The control group consisted of 20 patients with verified FH.&#x0D; Results and discussion. Combined dyslipidemia was detected in groups 1 and 3, pure hypercholesterolemia in group 2. Direct correlations between lipid profile and comorbid pathology characteristics were revealed. Patients of the subgroups with “possible” FH had higher atherogenicity of the lipid profile associated with comorbid pathology destabilization and high percentage of atherosclerosis of carotid and coronary arteries. According to the results of the follow-up, it was established that statin therapy and comorbid pathology compensation led to the achievement of target levels of LDL (group 3) or a reduction of LDL by 50% (group 1, 2). In patients of the control group, statin therapy with maximally tolerated doses did not show such results.&#x0D; Conclusions. The cohort of patients defined as having “possible” FH is heterogeneous and may include patients with secondary dyslipidemia on the background of comorbid pathology destabilization, timely verification and treatment of which contributes to achieving the goals of lipid-lowering therapy. Taking into account that only obese patients reached the target level of LDL &lt;1.8 mmol/l, combined lipid-lowering therapy is recommended for patients with hypothyroidism and diabetes. Refractoriness to statin therapy in patients with verified “possible” FH emphasizes the need for combined lipid-lowering therapy (ezetimibe, PCSK9 inhibitors).