PCSK9 Inhibitors in Clinical Practice: Experience of a Specialized Lipid Center

Aim. To characterize patients receiving PCSK9 inhibitors, and assess the efficiency of their treatment in a specialized lipid center.Material and methods. A retrospective analysis of the medical records of patients who visited the Lipid clinic of the National Medical Research Center for Therapy and Preventive Medicine (Moscow, Russia), receiving PCSK9 inhibitor and having lipid profile in dynamics, was carried out (n=77). Cardiovascular risk (CVR) and low-density lipoprotein cholesterol (LDL-C) target levels were evaluated in accordance with the Russian guidelines for the diagnostics and correction of dyslipidemias 2020.Results. Of 77 patients taking PCSK9 inhibitors (44.2% males, the median of age 56 [47; 66] years), the majority (64.0%) had a probable or definite familial hypercholesterolemia (FH). The proportion of other lipid metabolism disorders, pure hypercholesterolemia and combined hyperlipidemia was 21% and 15%. More than half of the patients (68.8%) had a very high CVR, mainly due to the presence of coronary heart disease (84.9%). The proportion of patients receiving PCSK9 inhibitors as monotherapy was 7.8%, in combination with high-intensity statin therapy – 33.8%, as part of triple lipid-lowering therapy (high-intensity statin, ezetimibe, PCSK9 inhibitors) – 50.6%. Addition of PCSK9 inhibitors to combined lipid-lowering therapy enabled to reduce the LDL-C level to 1.02 [0.62; 1.39] mmol/l with its total decrease from the baseline by 87.3%. While taking PCSK9 inhibitors, LDL-C <1.8 mmol/l and <1.4 mmol/l achieved at 78.3% and 57.7% FH patients with high and very high CVR, respectively. Among patients with other hyperlipidemias, 74.1% of patients with very high CVR was achieved the target LDL-C level <1.4 mmol/l.Conclusion: In a specialized lipid center, PCSK9 inhibitors are prescribed to patients with high or very high CVR, most of whom are FH patients. The effectiveness of the use of PCSK9 inhibitors in real-world practice is comparable to the results of clinical trials.

Unsolved Issues of Atherosclerosis Prevention and of Adequate Lipid-lowering Therapy in Patients with Acute Ischemic Cerebrovascular Accident

The existing system of medical care for patients with acute cerebrovascular accident of atherothrombotic genesis, namely lipid metabolism disorders, the modern evidence base for lipid-lowering therapy in this category of patients and the feasibility of interdisciplinary interaction of cardiologists and neurologists were discussed at a meeting of the expert council of cardiologists and neurologists in Moscow on 2021 July 7.

Effectiveness of lipid-lowering therapy in outpatients with coronary artery disease living in a large industrial center of Eastern Siberia

Aim. To study the prescription rate of lipid-lowering therapy and achieving the target low-density lipoprotein cholesterol (LDL-C) values in outpatients with coronary artery disease (CAD) living in Krasnoyarsk.Material and methods. The study included all patients with CAD hospitalized in the cardiology department of the clinic of the Research Institute of Medical Problems of the North (Krasnoyarsk) in 2018-2019. The analysis included data from 1671 patients (men, 770; women, 901). During hospitalization, an in-depth survey of patients was carried out on the subject of prescribing and taking lipid-lowering drugs. On admission, lipid profile was assessed in all patients.Results. At the time of admission, only 51,4% of patients received lipidlowering therapy. The majority received statin monotherapy (99,2%). Only 0,8% of patients received combination therapy (statin+ezetimibe). The most frequently prescribed statin in the study was atorvastatin — 74,6%. Rosuvastatin was received by 17,1% of patients. In most cases, the doses of atorvastatin and rosuvastatin corresponded to the moderate-intensity statin therapy regimen. The frequently prescribed dose of atorvastatin was 20 mg/day — 54,4%, rosuvastatin — 10 mg/day — 68,7%. The target level of LDL-C <1,8 mmol/L was reached by 16,3%, <1,5 mmol/L — by 9,0%, <1,4 mmol/L — only 6,5% of patients. Most often, the target LDL-C levels were achieved by patients receiving high-intensity statin (HIS) therapy. The target level of LDL-C <1,8 mmol/L was reached by 37,5%, <1,5 mmol/L — 23,9%, LDL cholesterol <1,4 mmol/L — 20,7% of patients, receiving HIS.Conclusion. In patients with CAD living in Krasnoyarsk, the most commonly prescribed statins were atorvastatin and rosuvastatin, but only 32% of patients received HIS. Combination lipid-lowering therapy has been used extremely rarely. Among the surveyed patients, the current target level of LDL-C for patients with CAD (<1,4 mmol/L) was achieved only in 6,5% of patients. In the group of patients receiving high-intensity statin therapy, this target level was achieved in 20,7% of patients, which indicates the need for strict adherence to current clinical guidelines.

Ranolazine Improves Glycemic Variability and Endothelial Function in Patients with Diabetes and Chronic Coronary Syndromes: Results from an Experimental Study

Background. Ranolazine is a second-line drug for the management of chronic coronary syndromes (CCS). Glucose-lowering and endothelial effects have also been reported with this agent. However, whether ranolazine may improve short-term glycemic variability (GV), strictly related to the prognosis of patients with type 2 diabetes (T2D), is unknown. Thus, we aimed to explore the effects of adding ranolazine to standard anti-ischemic and glucose-lowering therapy on long- and short-term GV as well as on endothelial function and oxidative stress in patients with T2D and CCS. Methods. Patients starting ranolazine ( n = 16 ) were evaluated for short-term GV, haemoglobin 1Ac (Hb1Ac) levels, endothelial-dependent flow-mediated vasodilation (FMD), and oxidative stress levels at enrolment and after 3-month follow-up. The same measurements were collected from 16 patients with CCS and T2D that did not receive ranolazine, matched for age, gender, and body mass index. Results. A significant decline in Hb1Ac levels was reported after 3-month ranolazine treatment (mean change -0.60%; 2-way ANOVA p = 0.025 ). Moreover, among patients receiving ranolazine, short-term GV indexes were significantly improved over time compared with baseline ( p = 0.001 for time in range; 2-way ANOVA p = 0.010 ). Conversely, no significant changes were reported in patients without ranolazine. Finally, greater FMD and lower oxidative stress levels were observed in patients on ranolazine at 3 months. Conclusions. Ranolazine added to standard anti-ischemic and glucose-lowering therapy demonstrated benefit in improving the glycemic status of patients with T2D and CCS. How this improvement contributes to the overall myocardial benefit of ranolazine requires further studies.

Inclisirán as an alternative treatment for Hypercholesterolemia

Hypercholesterolemia (CH) is defined as the elevation of serum cholesterol levels, especially low-density lipoprotein (LDL) cholesterol, which is considered to be one of the most relevant risk factors for triggering cardiovascular disease, for This is vitally important to start treatment, there are several highly useful pharmacological groups for lipid-lowering therapy, among them we highlight the PCSK9 inhibitors, among the molecules that are part of this group we find inclisirán, this being a structure that promises a lot in regarding the management of hypercholesterolemia.

Control of Low-Density Lipoprotein Cholesterol in Secondary Prevention of Coronary Artery Disease in Real-Life Practice: The DAUSSET Study in French Cardiologists

Introduction: Patients with established coronary artery disease (CAD) are at very high risk for cardiovascular events. Methods: The DAUSSET study is a national, multicenter, non-interventional study that included very high-risk CAD patients followed by French cardiologists. It aimed to describe real-life clinical practices for low-density lipoprotein (LDL) cholesterol control in the secondary prevention of CAD. Results: A total of 912 patients (mean age, 65.4 years; men, 76.1%; myocardial infarction, 69.4%; first episode, 80.1%) were analyzed. The LDL cholesterol goal was 70 mg/dL in most cases (84.9%). The LDL cholesterol goal <70 mg/dL was achieved in 41.7% of patients. Of the 894 (98.0%) patients who received lipid-lowering therapy, 81.2% had been treated more intensively after the cardiac event, 27.0% had been treated less intensively and 13.1% had been maintained. Participating cardiologists were very satisfied or satisfied with treatment response in 72.6% of patients. Moderate satisfaction or dissatisfaction with lipid-lowering therapy was related to not achieving objectives (100%), treatment inefficacy (53.7%), treatment intolerance (23.4%) and poor adherence (12.3%). Conclusion: These real-world results show that lipid control in very high-risk patients remains insufficient. More than half of the patients did not achieve the LDL cholesterol goal. Prevention of cardiovascular events in these very high-risk patients could be further improved by better education and more intensive lipid-lowering therapy.

Association of the Q141K polymorphism of the ABCG2 gene with the effectiveness of urate-lowering therapy in patients with gout (a pilot study)

Achieving the target serum uric acid (UA) level is a priority in the treatment of gout.Objective: to study the relationship of the ABCG2 gene polymorphism (rs2231142) with the efficacy of allopurinol and febuxostat in patients with gout.Patients and methods. The study included 82 patients with gout over 18 years of age with serum UA level >360 μmol/L who did not take uratelowering therapy.All patients were prescribed allopurinol 100 mg daily, followed by its titration until the target UA level was reached (<360 μmol/L or <300 μmol/L in patients with chronic tofus gout), up to a maximum of 900 mg/day, in patients with glomerular filtration rate <60 ml/min/1.73 m2 – up to 300 mg/day. Patients who did not reach the target UA level when using allopurinol were prescribed febuxostat 80 mg/day, which, if necessary, was increased to 120 mg/day. Monitoring of each patient was continued until the target serum UA level was reached.All patients underwent genotyping of the C>A polymorphism (rs2231142) of the ABCG2 gene. We compared the probability of achieving the target UA level, the mean values of a decrease in the serum UA level, and the mean doses of urate-lowering drugs in patients with different genotypes (CC, CA, AA) of the ABCG2 gene.Results and discussion. The target UA level in 45 (55%) of 82 patients was defined as <300 μmol/L, in the remaining 37 – as <360 μmol/L.In 26 patients, the dose of allopurinol did not exceed 300 mg/day. In 28 (34%) patients treated with allopurinol, the target UA level was achieved, in the remaining 54 (66%) patients, allopurinol was substituted by febuxostat, and in 22 (41%) of them the UA level decreased and was below the target.The CC genotype of the ABCG2 gene was detected in 51 (62%) patients, the CA genotype in 30 (37%) and the minor genotype AA in 1 (1%).The probability of achieving the target UA level during therapy with allopurinol in carriers of homozygous CC genotype and genotypes CA or AA did not differ: 17 (33%) and 11 (35%) cases, respectively, but patients with CA and AA genotypes required a significantly higher dose of allopurinol (365±102 mg/day) than patients with the CC genotype (290±85 mg/day), p=0.002. Of the 54 patients who took febuxostat and did not reach the target UA level, 30 (56%) had the CC genotype and 24 (44%) had the CA genotype, the probability of reaching the target UA level was also comparable (p=0.22).Conclusion. The probability of reaching the target serum UA level in patients with gout taking allopurinol is not associated with the C>A polymorphism of the ABCG2 gene, but the presence of CA and AA genotypes is identified with a higher dose of the drug. The C>A (rs2231142) polymorphism of the ABCG2 gene does not affect the ability to achieve the goal of therapy when using febuxostat in patients with allopurinol ineffectiveness.

The Effect of Plasma Triglyceride-Lowering Therapy on the Evolution of Organ Function in Early Hypertriglyceridemia-Induced Acute Pancreatitis Patients With Worrisome Features (PERFORM Study): Rationale and Design of a Multicenter, Prospective, Observational, Cohort Study

Background: Acute pancreatitis (AP) is a potentially life-threatening inflammatory disease with multiple etiologies. The prevalence of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) has been increasing in recent years. It is reported that early triglyceride (TG) levels were associated with the severity of the disease, and TG- lowering therapies, including medical treatment and blood purification, may impact the clinical outcomes. However, there is no consensus regarding the optimal TG-lowering therapy, and clinical practice varies greatly among different centers. Our objective is to evaluate the TG-lowering effects of different therapies and their impact on clinical outcomes in HTG-AP patients with worrisome features.Methods: This is a multicenter, observational, prospective cohort study. A total of approximately 300 patients with HTG-AP with worrisome features are planned to be enrolled. The primary objective of the study is to evaluate the relationship between TG decline and the evolution of organ failure, and patients will be dichotomized depending on the rate of TG decline. The primary outcome is organ failure (OF) free days to 14 days after enrollment. Secondary outcomes include new-onset organ failure, new-onset multiple-organ failure (MOF), new-onset persistent organ failure (POF), new receipt of organ support, requirement of ICU admission, ICU free days to day 14, hospital free days to day 14, 60-day mortality, AP severity grade (Based on the Revised Atlanta Classification), and incidence of systemic and local complications. Generalized linear model (GLM), Fine and Gray competing risk regression, and propensity score matching will be used for statistical analysis.Discussion: Results of this study will reveal the current practice of TG-lowering therapy in HTG-AP and provide necessary data for future trials.

Lipid lowering therapy in primary and secondary prevention in Austria: are LDL-C goals achieved?

Summary Background Cardiovascular disease (CVD) is the most frequent cause of death in Austria. The European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines recommend intensive lipid lowering therapy (LLT) in patients at high or very high CV risk. Lipid management and achievement of low-density lipoprotein cholesterol (LDL-C) goals in Austria have not recently been assessed. Methods Subgroup analysis for Austria of a European 18 country, cross-sectional, observational study. Patients received LLT for primary (PP) or secondary prevention (SP). Data including LLT in the preceding 12 months and most recent LDL‑C were collected during a single visit between June 2017 and November 2018. Achievement of the risk-based 2016 and 2019 ESC/EAS LDL‑C goal while receiving stabilized LLT was assessed. Results A total of 293 patients were enrolled from 8 Austrian sites, of which 200 (PP = 104, SP = 96) received stabilized LLT at the LDL‑C measurement date. Overall, 58% (71% PP, 43% SP) and 38% (52% PP, 23% SP) achieved the risk-based 2016 and 2019 goals, respectively. Most patients received moderate-intensity statin monotherapy (46%), while 34% used high-intensity statin monotherapy. Combination therapy of moderate/high-intensity statin with ezetimibe (12%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors with statin ± ezetimibe (1%), was used infrequently. Conclusion The current Austrian routine lipid management using mainly moderate-intensity or high-intensity statin monotherapy is insufficient to attain ESC/EAS guideline goals, in particular the more stringent 2019 recommendations, a situation comparable to other participating European countries. In addition to switching to and optimizing doses of high-intensity statins, a combination with ezetimibe or PCSK9 inhibitors will be needed in many cases.