High-intensity Lipid-lowering Therapy Research Articles

Lipid-lowering therapy in patients with coronary artery disease in primary care practices: what has changed over 7 years?

Aim. To analyze changes in the pattern of lipid-lowering therapy (LLT) in outpatients with stable coronary artery disease (SCAD) over the 7-year period.Material and methods. This pharmacoepidemiological, retrospective, cross-sectional, two-stage study was conducted on the basis of primary care facility of Moscow. We analyzed 1,834 and 805 medical records of patients with SCAD at the first (2011) and second (2018) stages, respectively. Data on demography, medical history, lipid profile, and administrated LLT were collected. Statistical analysis was performed using SPSS Statistics V16.0 and MS Excel. Differences were considered significant at p<0,05.Results. Overall LLT prescription rate in outpatients with SCAD increased from 48,5 up to 86,4% (p<0,05) over the 7-year period. Statin monotherapy continued to prevail in the structure of LLT: its prescription rate increased from 48,2 up to 82,3% (p<0,05) in total sample. Use of statin/ezetimibe combination was registered only in 2018 (2,4% in LLT structure). Atorvastatin was the most frequently recommended medication at both study stages (51,5 vs 66,3%; p<0,05); prescription rate of simvastatin decreased from 44,5 to 3,9% (p<0,05), rosuvastatin — increased from 1,7 to 29,5% (p<0,05). Over the study period, the proportion of patients receiving high-intensity LLT increased (2,0 vs 41,8%; p<0,05). We also revealed a significant increase of patients who reached target levels of low-density lipoprotein cholesterol (11,1 vs 23,3%; p<0,05) and total cholesterol (17,0 vs 33,0%; p<0,05).Conclusion. The results demonstrated significant improvements in the LLT pattern over the 7-year period in outpatients with SCAD. Number of patients receiving statins doubled, and the cases of prescribing lowintensity LLT have become very rare. However, control of blood lipids in the target group remained inadequate.

Inhibitors in the Management of Patients with Atherosclerotic Cardiovascular Diseases: Guidelines and Reimbursement Issues

Current guidelines for the management of patients with dyslipidemia define low-density lipoprotein cholesterol (LDL-C) as the primary target in addressing lipid-lowering therapy. The target level of LDL-C in real clinical practice is achieved in no more than a third of patients who have undergone a coronary event and receive high-intensity lipid-lowering therapy. Achieving the goals of lipid-lowering therapy in a significant proportion of patients with atherosclerotic cardiovascular diseases (ACVD) is impossible with the use of even high doses of statins, which requires its enhancement by other drugs. The article considers the place of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors in the prevention of cardiovascular diseases in patients with ACVD in accordance with the latest Russian and international guidelines. A modern decision-making algorithm for the initiation of PCSK9 inhibitors therapy in patients with ACVD is presented. The authors provide a clear understanding about the patient populations that will benefit most from the taking of PCSK9 inhibitors. Particular attention is paid to Guidelines for the management of dyslipidemias developed by European Society of Cardiology and European Atherosclerosis Society in 2019. The issues of patients provision with PCSK9 inhibitors with reference to Russian conditions are described in details in accordance with the requirements for territorial programs of state guarantees. Further improvement in the provision of PCSK9 inhibitors to patients with indications for this therapy is necessary, considering the potential of these drugs in reducing cardiovascular morbidity and mortality in patients with ACVD.

Long-term outcomes after acute myocardial infarction in patients with familial hypercholesterolemia: The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction program

Patients with familial hypercholesterolemia (FH) are prone to develop acute myocardial infarction (AMI) at a younger age. The aim of the present study was to assess 5-year outcomes after AMI according to the presence of FH in a large multicenter cohort of patients. The French registry of Acute ST-elevation and non-ST-elevation Myocardial Infarction consists of nationwide surveys recruiting patients over a 1- to 2-month period every 5 years. Patients recruited in 2005 and 2010 were followed up to 5years. Of 5147 patients discharged alive and in whom FH status could be assessed, 2.8% had probable/definite FH, using an adapted Dutch Lipid Clinic score. They were 12years younger, on average, than non-FH patients. Before adjustment, their 5-year survival and event-free survival did not differ from non-FH patients. After adjustment, however, both mortality (hazard ratio [HR] 1.82, 95% confidence interval [CI] 1.15-2.89; P=.011) and the combined endpoint of death, AMI, or stroke (HR 2.22, 95% CI: 1.51-3.26; P<.001) were higher in FH patients. The higher risk in FH patients was also present in patients receiving high-intensity lipid-lowering therapy at discharge: adjusted HR for mortality 2.29, 95% CI: 1.18 to 4.47, P=.015; HR for cardiovascular events 2.57, 95% CI: 1.48 to 4.48, P=.001. Concordant results were observed in propensity score-marched cohorts. The risk of long-term mortality and cardiovascular events is twice as high in FH than in non-FH patients, when adjusted on baseline characteristics, even for those receiving high-intensity lipid-lowering therapy. Additional therapeutic measures are needed in these patients.

Вплив ранньої ліпідознижувальної терапії різної інтенсивності на функцію ендотелію у хворих з гострим інфарктом міокарда з елевацією сегмента ST

Мета роботи – оцінити вплив різних режимів ліпідознижувальної терапії на зміни функції ендотелію в пацієнтів з гострим інфарктом міокарда (ГІМ) з елевацією сегмента ST.Матеріали і методи. У дослідження залучили 135 пацієнтів, госпіталізованих до відділення реанімації та інтенсивної терапії ННЦ «Інститут кардіології ім. акад. М.Д. Стражеска» НАМН України з діагнозом ГІМ з елевацією сегмента ST у перші 12 год (у середньому (4,7±1,0) год) від появи симптомів захворювання. Методом конвертів пацієнтів розділили на 4 групи, яким відразу при госпіталізації і до проведення реваскуляризації – черезшкірного коронарного втручання – призначали ліпідознижувальну терапію. До 1-ї групи увійшло 26 осіб, яким призначали комбінацію аторвастатину в дозі 10 мг та езетимібу – 10 мг, до 2-ї – 24 пацієнти, що приймали аторвастатин у дозі 40 мг, до 3-ї – 43 хворих, які отримували аторвастатин у дозі 80 мг, до 4-ї – 42 пацієнти, яким призначили комбінацію аторвастатину в дозі 40 мг і езетимібу – 10 мг. Базисну терапію формували відповідно до чинних рекомендацій Європейського товариства кардіологів і національних протоколів діагностики. Групи не відрізнялися за основними клініко-анамнестичними характеристиками і методами лікування. Визначення реактивної гіперемії за допомогою проби з потокозалежною вазодилатацією (ПЗВД) проводили в 1-шу, на 10-ту та 90-ту добу від початку захворювання. Результати та обговорення. Застосування високоінтенсивної ліпідознижувальної терапії з використанням аторвастатину в дозі 80 мг (3-тя група) і аторвастатину в дозі 40 мг та езетимібу в дозі 10 мг (4-та група) мало більший ліпідознижувальний ефект порівняно із середньоінтенсивною терапією (1-ша та 2-га групи) у динаміці спостереження. У пацієнтів 3-ї групи реєстрували зменшення середнього рівня холестерину ліпопротеїнів низької щільності (ХСЛПНЩ) на 10-ту та 90-ту добу, а його зниження досягало значень, нижчих за рекомендовані, – (1,75±0,11) ммоль/л. У 4-й групі на 10-ту добу також реєстрували статистично значуще зниження ХСЛПНЩ, а до 90-ї доби він становив 1,55 ммоль/л. Середнього рівня ХСЛПНЩ, нижчого за цільовий, було досягнуто тільки в 3-й і 4-й групах. Нормалізацію функції ендотелію (приріст діаметра плечової артерії за результатами проби з ПЗВД понад 10 %) статистично значуще частіше реєстрували в пацієнтів, які досягли на 90-ту добу цільового рівня ХСЛПНЩ менше 1,8 ммоль/л.Висновки. Для нормалізації функції ендотелію (приросту діаметра плечової артерії за результатами проби з ПЗВД) при проведенні ліпідознижувальної терапії у хворих, які перенесли ГІМ, необхідно досягнення цільових значень ХСЛПНЩ до 90-ї доби захворювання, що можливо лише при проведенні високоінтенсивної ліпідознижувальної терапії. Відсутність поліпшення функції ендотелію під час спостереження у сталої кількості хворих дозволяє припустити наявність додаткових, можливо генетичних, факторів, на які не впливають застосовані методи лікування.

Role Of Innate And Adaptive Immunity On Atherosclerosis In Subjects With Familial Hypercholesterolemia

Background and Aims: Familial hypercholesterolemia (FH) is characterized by exposure to high LDL-c (LDL-cholesterol) and premature atherosclerotic cardiovascular disease (ASCVD). However, ASCVD severity can be heterogeneous among FH subjects with similar LDL-c levels. Objectives: To evaluate the role of immune-inflammatory system on atherosclerosis development in FH individuals under high-intensity lipid-lowering therapy (HI-LLT).

Effect of lipid-lowering treatment in cardiovascular disease prevalence in familial hypercholesterolemia

Background and aimsThe impact on heterozygous familial hypercholesterolemia (HeFH) health led by high-intensity lipid-lowering therapy (HILLT) is unknown, and the question remains if there is still an unacceptably high residual risk to justify treatment with new lipid-lowering drugs. MethodsThis observational, retrospective, multicenter, national study in Spain, whose information was obtained from a national dyslipemia registry, was designed to establish the current prevalence of cardiovascular disease (CVD) in HeFH and to define the impact of HILLT on CVD in this population. Odds were estimated using several logistic regression models with progressive adjustment. Results1958 HeFH, mean age 49.3 ± 14.3 years, were included in the analysis. At inclusion in the registry, 295 patients (15.1%) had suffered CVD and 164 (55.6%) had suffered the first event before the onset lipid-lowering treatment. Exposition to treatment associated more than ten times lower odds for CVD than in subjects naïve to treatment (OR 0.085, 95% CI 0.063–0.114, p < 0.001). A first CVD event after a mean treatment period of 9.1 ± 7.2 years occurred in 131 out of 1615 (8.1%) HeFH subjects, and 115 (87.8%) of them were on HILLT. ConclusionsCurrent prevalence of CVD among HeFH is one third of that reported before the statins era. Early initiation and prolonged lipid-lowering treatment was associated with a reduction in CVD. New cases of CVD, in spite of HILLT, appeared mostly among patients accumulating risk factors and probably they may be considered for further lipid-lowering drugs.

Familial hypercholesterolemia in a European Mediterranean population—Prevalence and clinical data from 2.5 million primary care patients

Familial hypercholesterolemia (FH), the most frequent hereditary cause of premature coronary heart disease (CHD), is underdiagnosed and insufficiently treated. The objectives of the study were to estimate the prevalence of the FH phenotype (FH-P) and to describe its clinical characteristics in a Mediterranean population. Data were obtained from the Catalan primary care system's clinical records database (Catalan acronym: SIDIAP). Patients aged >7years with at least 1 low-density lipoprotein cholesterol measurement recorded between 2006 and 2014 (n=2,554,644) were included. Heterozygous FH-P and homozygous FH-P were defined by untreated low-density lipoprotein cholesterol plasma concentrations. The presence of cardiovascular diseases and risk factors was defined by coded medical records from primary care and hospital discharge databases. The age- and sex-standardized prevalence of heterozygous FH-P and homozygous FH-P were 1/192 individuals and 1/425,774 individuals, respectively. In the group aged 8 to 18years, 0.46% (95% confidence interval: 0.41-0.52) had FH-P; overall prevalence was 0.58% (95% confidence interval: 0.58-0.60). Among patients with FH-P aged >18years, cardiovascular disease prevalence was 3.5 times higher than in general population, and CHD prevalence in those aged 35 to 59years was 4.5 times higher than in those without FH-P. Lipid-lowering therapy was lacking in 13.5% of patients with FH-P, and only 31.6% of men and 22.7 of women were receiving high or very high-intensity lipid-lowering therapy. Prevalence of FH-P was higher than expected, but underdiagnosed and suboptimally treated, especially in women. Moreover, treatment started late considering the high CHD incidence associated with this condition.

How many familial hypercholesterolemia patients are eligible for PCSK9 inhibition?

Background and aimsFamilial hypercholesterolemia (FH) is a high cardiovascular risk condition. Less than 20% of patients achieve the LDL targets. Although PCSK9 inhibitors improve control and reduce cardiovascular events, official recommendations for their use are restrictive. We aim to assess the number of FH patients suitable for PCSK9 inhibition according to the European guidelines. MethodsA total of 2685 FH patients, with a minimum follow-up of 6 months, included in the Dyslipidemia Registry of the Spanish Arteriosclerosis Society, were sorted according to the intensity of their lipid-lowering therapy (LLT) and LDL cholesterol levels achieved. The number of patients who met the recommendations for PCSK9 inhibition treatment according to the European Atherosclerosis Society (ESC/EAS), Spanish Arteriosclerosis Society and the European Medicines Agency was calculated. ResultsIn total, 1573 patients were on high-intensity LLT; 607 were on moderate-intensity statins; 82 were on low-intensity LLT, and 423 were neither on statins nor on ezetimibe in the last visit registered. The mean LDL reduction among those on high-intensity LLT was 54%. Ninety-one percent of patients on high-intensity LLT had an LDL below 5.2 mmol/L, 53% below 3.4 mmol/L, and 23% below 2.6 mmol/L. Only 12% of FH patients with cardiovascular disease achieved 1.8 mmol/L. Despite this, only 17% of patients qualified for PCSK9 inhibition according to ESC/EAS guidelines. ConclusionsFor patients with a condition that exposes them to high cardiovascular risk and who have extreme difficulties in achieving LDL targets, wider access to PCSK9 inhibitor therapy is warranted.