UNASSIGNED: Bempedoic Acid (BA) is a novel drug that has a potential to serve as an alternative to statins to decrease lipid levels and improve cardiovascular disease (CVD) outcomes, particularly for statin-intolerant individuals. However, insufficient statistical power has limited our understanding of the efficacy and safety of BA. This meta-analysis utilizes the latest data to improve our knowledge of BA\'s effects on lipids and CVD with increased statistical power.
UNASSIGNED: MEDLINE, Embase, Cochrane Central, Clinicaltrials.gov, abstracts of national and international conferences, and reference lists of studies were searched for relevant studies. Rayyan was used to screen the search results, and Revman 5.3 was used for the meta-analysis and sensitivity analysis.
UNASSIGNED: Our final analysis included seven randomized control trials (RCTs) with 17,782 participants, 53.6 % in the BA group (n = 9535) and 46.4 % in the placebo group (n = 8247). BA significantly decreased major adverse cardiovascular events (MACE) (OR: 0.86; 95 % CI 0.78-0.95; p = 0.03), non-fatal myocardial infarction (OR 0.72; 95 % CI 0.61-0.85; p = 0.0001), and new onset/worsening diabetes (OR:0.55; 95 % CI 0.30-0.98, p = 0.04), while reducing low-density lipoprotein cholesterol (LDL-C) levels by 22.5 % (MD: -22.53 %; 95 % CI -25.54 to -19.52, p < 0.00001).
UNASSIGNED: The findings of this meta-analysis suggest that BA is a promising and effective alternative to statin therapy, particularly for statin-intolerant and high CVD-risk patients. However, further studies with diverse populations are needed to quantify the long-term efficacy and safety endpoints.

The ideal approach to the secondary dyslipidemia goal of lowering triglycerides (TG) is not well established. The available ω-3 fatty acid products differ from each other in composition and content. The purpose of the present study was to investigate the effect of a highly purified eicosapentaenoic acid (EPA) formulation on cardiometabolic biomarkers in high cardiovascular (CV) risk patients. The study included 226 subjects with high TG and ≥1 of the following CV risk factors: arterial hypertension, diabetes mellitus, ultrasound-documented atheromatosis, peripheral artery disease, previous myocardial infarction, or ischemic stroke. Participants received 2 g EPA twice daily for 3 months, along with typical nutritional counseling. Cardiometabolic hematological parameters (TG, low-density lipoprotein [LDL], high-density lipoprotein [HDL], non-HDL, total cholesterol [TChol], apolipoprotein A1 [Apo A1], apolipoprotein B [Apo B], glucose, glycated hemoglobin [HbA1c], and C-reactive protein [CRP]) were measured at baseline and at 3 months. The mean patients\' age was 61.1 ± 1.4 years and the mean baseline TG was 2.97 ± 0.15 mmol/L. Apart from Apo A1, all other biomarkers significantly (p < 0.05) improved at 3 months, regardless of sex (except Apo B) and age: TG 1.75 ± 0.09 versus 2.97 ± 0.15 mmol/L, LDL 2.46 ± 0.08 versus 3.05 ± 0.13 mmol/L, HDL 1.22 ± 0.03 versus 1.11 ± 0.03 mmol/L, non-HDL 3.29 ± 0.10 versus 4.14 ± 0.16 mmol/L, TChol 4.55 ± 0.10 versus 5.15 ± 0.13 mmol/L, Apo A1 26.8 ± 9.3 versus 22.5 ± 8.6 μmol/L, Apo B 1.25 ± 0.23 versus 1.29 ± 0.23 μmol/L, glucose 5.66 ± 0.11 versus 5.99 ± 0.17 mmol/L, HbA1c 5.83 ± 0.1 versus 5.97 ± 0.1% and CRP 1.92 ± 0.2 versus 5.26 ± 2.8 mg/L. In conclusion, adding highly purified EPA product (4 g daily) on nutritional counseling leads to a significant TG reduction. In addition, this treatment appears to have pleiotropic beneficial cardiometabolic actions.

Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outcomes trial.
Tirzepatide is being studied in a randomized, double-blind, active-controlled CV outcomes trial. People with type 2 diabetes aged ≥40 years, with established atherosclerotic CV disease, HbA1c ≥7% to ≤10.5%, and body mass index ≥25 kg/m2 were randomized 1:1 to once weekly subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1.5 mg. The primary outcome is time to first occurrence of any major adverse cardiovascular event (MACE), defined as CV death, myocardial infarction, or stroke. The trial is event-driven and planned to continue until ≥1,615 participants experience an adjudication-confirmed component of MACE. The primary analysis is noninferiority for time to first MACE of tirzepatide vs dulaglutide by demonstrating an upper confidence limit <1.05, which will also confirm superiority vs a putative placebo, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis).
Over 2 years, 13,299 people at 640 sites in 30 countries across all world regions were randomized. The mean age of randomized participants at baseline was 64.1 years, diabetes duration 14.7 years, HbA1c 8.4%, and BMI 32.6 kg/m2. Overall, 65.0% had coronary disease, of whom 47.3% reported prior myocardial infarction and 57.4% had prior coronary revascularization. 19.1% of participants had a prior stroke and 25.3% had peripheral artery disease. The trial is fully recruited and ongoing.
SURPASS-CVOT will provide definitive evidence as to the CV safety and efficacy of tirzepatide as compared with dulaglutide, a GLP-1 receptor agonist with established CV benefit.

Although the benefits of moderate exercise in patients at high cardiovascular risk are well established, the effects of strenuous exercise remain unknown. We aimed to study the impact of strenuous exercise in a very high cardiovascular risk model. Nephrectomized aged Zucker obese rats were trained at a moderate (MOD) or high (INT) intensity or were kept sedentary (SED) for 10 weeks. Subsequently, echocardiography and ex vivo vascular reactivity assays were performed, and blood, aortas, perivascular adipose tissue (PVAT), and left ventricles (LVs) were harvested. An improved risk profile consisting of decreased body weight and improved response to a glucose tolerance test was noted in the trained groups. Vascular reactivity experiments in the descending thoracic aorta demonstrated increased endothelial NO release in the MOD group but not in the INT group, compared with SED; the free radical scavenger TEMPOL improved endothelial function in INT rats to a similar level as MOD. An imbalance in the expression of oxidative stress-related genes toward a pro-oxidant environment was observed in the PVAT of INT rats. In the heart, INT training promoted eccentric hypertrophy and a mild reduction in ejection fraction. Obesity was associated with LV fibrosis and a transition toward β-myosin heavy chain and the N2Ba titin isoform. Exercise reverted the myosin imbalance, but only MOD reduced the predominance of the N2Ba titin isoform. In conclusion, moderate exercise yields the most intense cardiovascular benefits in a high-cardiovascular-risk animal model, while intense training partially reverts them.

OBJECTIVE: To evaluate the results of two-year use of alirokumab in Karelia Republic.
METHODS: The observation group consisted of 27 patients (17 patients with familial hypercholesterolemia, 10 patients with the history of myocardial infarction), mean age 53.4±4.3 years, 70.3% men, follow-up duration from one year to 2.5 years, 18 (66.6%) patients received therapy for more than 2 years. 19 patients received alirocumab at a dose of 75 mg/ml once every 2 weeks, eight - at a dose of 150 mg/ml once every 2 weeks. Before the start of therapy, the majority received maximally tolerated statin therapy, 10 patients received statin therapy in combination with ezetemibe, 3 patients received ezetemibe monotherapy due to statin intolerance. The target levels of LDL cholesterol were considered for very high risk patients less than 1.4 mmol/L, high risk - less than 1.8 mmol/L, extreme risk - less than 1 mmol/L.
RESULTS: The reduction of LDL on therapy with alirocumab was 58%; target levels of LDL were achieved in 77.8%. The level of decrease in LDL cholesterol less than 50% was noted only in 7.4% of cases. Patients requiring a large dose of the drug were classified as very high risk, had higher cholesterol and LDL-C levels. The level of Lp(a) decrease on 29.7% by 6-12 months. No destabilization of coronary heart disease, new cases of stroke were registered.
CONCLUSIONS: The inclusion of alirocumab in the treatment regimen contributed to the stable course of atherosclerosis-associated diseases, the achievement of LDL cholesterol targets in 77.8% of patients, was not accompanied by side effects during 2.5 years therapy.
Цель. Оценить результаты двухлетнего применения ингибитора PCSK9 алирокумаба. Материалы и методы. Группу наблюдения составили 27 пациентов (17 человек с семейной гиперхолестеринемией и 10 пациентов, перенесших инфаркт миокарда), средний возраст – 53,4±4,3 года, мужчин – 70,3%, длительность наблюдения – от 1 до 2,5 года, 18 (66,6%) пациентов получали терапию более 2 лет. Так, 19 пациентов получали алирокумаб в дозе 75 мг/мл 1 раз в 2 нед, 8 – в дозе 150 мг/мл 1 раз в 2 нед. До начала терапии большинство получали максимально переносимую терапию статинами, 10 человек – терапию статинами в сочетании с эзетимибом, 3 пациента – монотерапию эзетимибом из-за непереносимости статинов. Целевыми уровнями холестерина (ХС) липопротеидов низкой плотности (ЛНП) считали для пациентов очень высокого риска менее 1,4 ммоль/л, высокого риска – менее 1,8 ммоль/л, экстремального риска – менее 1 ммоль/л. Результаты. Снижение ХС ЛНП на терапии алирокумабом 58%; целевые уровни ХС ЛНП достигнуты у 77,8%. Уровень снижения ХС ЛНП менее 50%, несмотря на увеличение дозы алирокумаба до 150 мг, отмечен только в 7,4% случаев. Пациенты, потребовавшие перевода на большую дозу препарата, относились к категории очень высокого риска и характеризовались более высоким уровнем ХС и ХС ЛНП, большей частотой встречаемости ишемической болезни сердца, преобладанием мультифокального атеросклеротического поражения. Уровень снижения липопротеидов (а) составил 24,3% к 3-му месяцу терапии, 29,7% – к 6–12-му месяцу. Дестабилизации течения ишемической болезни сердца, новых случаев острого нарушения мозгового кровообращения и транзиторных ишемических атак не зарегистрировано. Для терапии алирокумабом характерны высокая приверженность и хорошая переносимость с отсутствием побочных реакций, в том числе и местного характера. Заключение. Включение в схему лечения алирокумаба способствовало стабильному течению ИБС, достижению ассоциированных с атеросклерозом целевых показателей ХС ЛНП у 77,8% пациентов, не сопровождалось побочными эффектами в течение двухлетней терапии.

UNASSIGNED: European data pre-2019 suggest statin monotherapy is the most common approach to lipid management for preventing cardiovascular (CV) events, resulting in only one-fifth of high- and very high-risk patients achieving the 2019 ESC/EAS recommended low-density lipoprotein cholesterol (LDL-C) goals. Whether the treatment landscape has evolved, or gaps persist remains of interest.
UNASSIGNED: Baseline data are presented from SANTORINI, an observational, prospective study that documents the use of lipid-lowering therapies (LLTs) in patients ≥18 years at high or very high CV risk between 2020 and 2021 across primary and secondary care settings in 14 European countries.
UNASSIGNED: Of 9602 enrolled patients, 9044 with complete data were included (mean age: 65.3 ± 10.9 years; 72.6% male). Physicians reported using 2019 ESC/EAS guidelines as a basis for CV risk classification in 52.0% (4706/9044) of patients (overall: high risk 29.2%; very high risk 70.8%). However, centrally re-assessed CV risk based on 2019 ESC/EAS guidelines suggested 6.5% (308/4706) and 91.0% (4284/4706) were high- and very high-risk patients, respectively. Overall, 21.8% of patients had no documented LLTs, 54.2% were receiving monotherapy and 24.0% combination LLT. Median (interquartile range [IQR]) LDL-C was 2.1 (1.6, 3.0) mmol/L (82 [60, 117] mg/dL), with 20.1% of patients achieving risk-based LDL-C goals as per the 2019 ESC/EAS guidelines.
UNASSIGNED: At the time of study enrolment, 80% of high- and very high-risk patients failed to achieve 2019 ESC/EAS guidelines LDL-C goals. Contributory factors may include CV risk underestimation and underutilization of combination therapies. Further efforts are needed to achieve current guideline-recommended LDL-C goals.
UNASSIGNED: ClinicalTrials.gov Identifier: NCT04271280.
UNASSIGNED: This study is funded by Daiichi Sankyo Europe GmbH, Munich, Germany.

This study aimed to investigate the association between the plant-based diet index (PDI) score and T2D risk among residents of Shanxi Province, China, and explore whether the association was influenced by different levels of cardiovascular risk. A total of 50,694 participants aged 35-75 years were recruited between 2017 and 2019, and they were further divided into the high cardiovascular risk population (HCRP; n = 17,255) and the non-high cardiovascular risk population (non-HCRP; n = 33,439). The PDI was calculated based on food frequency from a food frequency questionnaire (FFQ). Incident T2D was defined based on elevated plasma glucose (≥7 mmol/L) or hypoglycemic medicine use. We investigated the association of the PDI andT2D risk using a two-level generalized estimating equation and restricted cubic splines model. The results showed that quartile 4 of the PDI indicated significantly reduced T2D risk in the total population (OR: 0.83; 95% CI: 0.75-0.92), HCRP (OR: 0.80; 95% CI: 0.71-0.91), and non-HCRP (OR: 0.80; 95% CI: 0.74-0.87) compared with corresponding quartile 1 (OR = 1). In stratified analysis, the negative associations between PDI and T2D risk were stronger in the total population with the elderly (age > 60 years), BMI < 24, and men, and in the non-HCRP with men and BMI 24-28, and in the HCRP with the elderly and BMI < 24 than those with corresponding subgroups (pinteraction < 0.05). Linear curves were observed for the total population and non-HCRP, but an L-shaped association was observed for the HCRP. Therefore, our results suggest that higher PDI scores may effectively attenuate the T2D risk in the Chinese population and non-HCRP, and a beneficial association of PDI with T2D risk was observed in the HCRP at a certain threshold level. Longitudinal studies and intervention trials are required to validate our study findings.

UNASSIGNED: Clinical practice before 2019 suggests a substantial proportion of high and very high CV risk patients taking lipid-lowering therapy (LLT) would not achieve the new LDL-C goals recommended in the 2019 ESC/EAS guidelines (<70 and < 55 mg/dL, respectively). To what extent practice has changed since the last ESC/EAS guideline update is uncertain, and quantification of remaining implementation gaps may inform health policy.
UNASSIGNED: The SANTORINI study is a multinational, multicentre, prospective, observational, non-interventional study documenting patient data at baseline (enrolment) and at 12-month follow-up. The study recruited 9606 patients ≥18 years of age with high and very high CV risk (as assigned by the investigators) requiring LLT, with no formal patient or comparator groups. The primary objective is to document, in the real-world setting, the effectiveness of current treatment modalities in managing plasma levels of LDL-C in high- and very high-risk patients requiring LLT. Key secondary effectiveness objectives include documenting the relationship between LLT and levels of other plasma lipids, high-sensitivity C-reactive protein (hsCRP) and overall predicted CV risk over one year. Health economics and patient-relevant parameters will also be assessed.
UNASSIGNED: The SANTORINI study, which commenced after the 2019 ESC/EAS guidelines were published, is ideally placed to provide important contemporary insights into the evolving management of LLT in Europe and highlight factors contributing to the low levels of LDL-C goal achievement among high and very high CV risk patients. It is hoped the findings will help enhance patient management and reduce the burden of ASCVD in Europe.

To describe treatment patterns, low-density lipoprotein cholesterol (LDL-C) levels and healthcare resource utilization (HCRU) in the Netherlands in 2018 of patients with hypercholesterolaemia or mixed dyslipidaemia at high or very high cardiovascular (CV) risk.
From the PHARMO Database Network adult patients with a diagnosis or receiving lipid lowering therapy (LLT) between 2009 and 2018 were selected. Patients at high or very high CV risk according to 2016 ESC/EAS guidelines with recorded LDL-C levels who were treated with LLT or were characterized as statin intolerant in 2018 were included. LLT treatment patterns, LDL-C levels and HCRU (General Practitioner [GP] consultations and hospitalizations) were assessed.
The study population included 54,346 patients, of which 70% were at very high CV risk and 30% at high CV risk. The majority (93%) received statin monotherapy, mostly of moderate (73%) or high (15%) intensity. Only 3% received a combination of statin and ezetimibe. Statin intolerance, based on a treatment algorithm, was estimated at 3%. Average LDL-C decreased with LLT intensity. Overall, 74% reached LDL-C < 2.5 mmol/l and 34% <1.8 mmol/l with their current treatment, and 46% reached their LDL-C goal according to 2016 ESC/EAS guidelines. The highest rates of hospitalizations and GP consultations, including home visits, were recorded in patients with peripheral artery disease or polyvascular disease.
The treatment of hypercholesterolaemia and mixed dyslipidaemia in patients at high or very high CV risk in the Netherlands was suboptimal in 2018. To further lower CV risk alternative treatment strategies using add-on therapies are needed.

OBJECTIVE: ODYSSEY APPRISE trial evaluated efficacy and safety of alirocumab in 994 patients with hypercholesterolemia and high CV risk in a real-life setting. The aim of the present report is to detail on the Italian cohort enrolled and treated in the trial.
RESULTS: The methodology of the of the multinational, single-arm, Phase 3b open-label ODYSSEY APPRISE (Clinicaltrials.gov: NCT02476006) has been previously reported. 255 Italian patients were enrolled and treated according to the trial protocol. Overall mean exposure to alirocumab was 83.3 ± 27.7 weeks. At week 12, LDL-C decreased by 51.3 ± 23.1% and this reduction was overall maintained for the duration of the study. A similar reduction was observed in patients with and without heterozygous familial hypercholesterolemia (HeFH 50.7% ± 23.9 vs. non-FH, 53.6% ± 19.6). LDL-C was reduced below 1.8 mmol/L and/or by ≥ 50% reduction from baseline in 62% of patients overall (61% in HeFH and 67% in non-FH). Alirocumab was similarly well tolerated in the Italian cohort as in the entire study population and the more common treatment emergent adverse events (TEAEs) were influenza, myalgia and nasopharyngitis. The incidence LDL-C levels <25 mg/dl and <15 mg/dl, was 8.2% and 2.9% respectively.
CONCLUSIONS: The efficacy and safety of alirocumab in a real-life setting, in the Italian subgroup of patients are consistent with findings in the entire study population and confirm that alirocumab is a beneficial approach to further reduce LDL-C levels in patients at high CV risk on maximally tolerated conventional lipid lowering treatment.
RESULTS:
UNASSIGNED: NCT02476006.