LDL-C Target Research Articles

Real-World Attainment of Low-Density Lipoprotein Cholesterol Goals in Patients at High Risk of Cardiovascular Disease Treated with High-Intensity Statins: The TERESA Study.

Despite steady improvements in cardiovascular disease (CVD) prevention, a scarce proportion of patients achieve the recommended LDL-C goals, even under high-intensity lipid-lowering therapy (LLT). Our study aimed to evaluate the attainment rate of LDL-C targets recommended by the 2019 European guidelines, and to characterize potential factors associated with LDL-C goal achievement and change patterns in LLT. We conducted a retrospective, observational study on patients treated with high-intensity atorvastatin or rosuvastatin ± ezetimibe at cardiology and internal medicine clinics across Spain. It included 1570 evaluable patients (median age: 62 years; established CVD: 77.5% [myocardial infarction: 34.3%]; and 85.8% at very high cardiovascular risk). Rosuvastatin ± ezetimibe was the LLT in 52.2% of patients, and atorvastatin ± ezetimibe in 47.8%. LLT had been modified in 36.8% of patients (side effects: 10%), being the most common switch from atorvastatin- to rosuvastatin-based treatment (77.2%). The risk-based LDL-C goal attainment rate was 31.1%, with 78.2% high-risk and 71.7% very high-risk patients not achieving the recommended LDL-C targets. Established CVD and familial hypercholesterolemia were significantly associated with the non-achievement of LDL-C goals. Although having limitations, this study shows that the guideline-recommended LDL-C goal attainment rate is still suboptimal despite using high-intensity statin therapy in a real-world setting in Spain.

Dyslipidemia treatment and attainment of LDL-cholesterol treatment goals in patients participating in the Managed Care for Acute Myocardial Infarction Survivors program.

Patients after acute myocardial infarction (AMI) are at very high cardiovascular (CV) risk. Therefore, appropriate management of dyslipidemia with adequate lipid-lowering therapy is crucial for preventing subsequent CV events in these patients. Our analysis aimed to assess the treatment of dyslipidemia and attainment of low-density lipoprotein cholesterol (LDL-C) treatment goals in patients after AMI who participated in the Managed Care for Acute Myocardial Infarction Survivors (MACAMIS) program. This study is a retrospective analysis of consecutive patients with AMI who agreed to participate and completed the 12-month MACAMIS program at one of three tertiary referral cardiovascular centers in Poland between October 2017 and January 2021. 1499 patients after AMI were enrolled in the study. High-intensity statin therapy was prescribed for 85.5% of analyzed patients on hospital discharge. Combined therapy with high-intensity statin and ezetimibe increased from 2.1% on hospital discharge to 18.2% after 12 months. In the whole study cohort, 20.4% of patients achieved the LDL-C target of < 55 mg/dl ( < 1.4 mmol/l), and 26.9% of patients achieved at least a 50% reduction in LDL-C level one year after AMI. Our analysis suggests that participation in the managed care program might be associated with improved quality of dyslipidemia management in AMI patients. Nonetheless, only one-fifth of patients who completed the program achieved the treatment goal for LDL-C. This highlights the constant need for optimizing lipid-lowering therapy to meet treatment targets and reduce CV risk in patients after AMI.

Control de la hipercolesterolemia en España: una misma situación con diferentes realidades autonómicas

Introduction and objectiveThe cardiovascular prevention strategy by autonomous communities can be variable since the competences in health are transferred. The objective of the study was to determine the degree of dyslipidaemia control and the lipid-lowering pharmacological therapy used in patients at high/very high cardiovascular risk (CVR) by autonomous communities. MethodsObservational, cross-sectional, descriptive study based on a consensus methodology. Information on the clinical practice of 145 health areas belonging to 17 Spanish autonomous communities was collected through face-to-face meetings and questionnaires administered to the 435 participating physicians. Furthermore, aggregate non-identifiable data were compiled from 10 consecutive dyslipidaemic patients that each participant had recently visited. ResultsOf the 4010 patients collected, 649 (16%) had high and 2458 (61%) very high CVR. The distribution of the 3107 high/very high CVR patients was balanced across regions, but there were inter-regional differences (P<.0001) in the achievement of target LDL-C <70 and <55mg/dL, respectively. High-intensity statins in monotherapy or in combination with ezetimibe and/or PCSK9 inhibitors were used in 44, 21 and 4% of high CVR patients, while in those at very high CVR it rose to 38, 45 and 6%, respectively. The use of these lipid-lowering therapies at national level was significantly different between regions (P=.0079). ConclusionsEven though the distribution of patients at high/very high CVR was similar between autonomous communities, inter-territorial differences were identified in the degree of achievement of LDL cholesterol therapeutic goal and use of lipid-lowering therapy.

LDL cholesterol targets rarely achieved in familial hypercholesterolemia patients: A sex and gender-specific analysis

Background and aimsDespite lipid lowering therapy (LLT), reaching LDL-C targets in patients with familial hypercholesterolemia (FH) remains challenging. Our aim was to determine attainment of LDL-C target levels and reasons for not reaching these in female and male FH patients. MethodsWe performed a cross-sectional study of heterozygous FH patients in five hospitals in the Netherlands and Norway. Clinical characteristics and information about LLT, lipid levels and reasons for not being on LDL-C treatment target were retrospectively collected from electronic medical records. ResultsWe studied 3178 FH patients (53.9% women), median age 48.0 (IQR 34.0–59.9) years. Median LDL-C before treatment and on-treatment was higher in women compared to men (6.2 (IQR 5.1–7.3) and 6.0 (IQR 4.9–7.2) mmol/l (p=0.005) and 3.0 (IQR 2.4–3.8) and 2.8 (IQR 2.3–3.5) mmol/L (p<0.001)), respectively. A minority of women (26.9%) and men (28.9%) reached LDL-C target. In patients with CVD, 17.2% of women and 25.8% of men reached LDL-C target. Women received less often high-intensity statins and ezetimibe. Most common reported reasons for not achieving the LDL-C target were insufficient effect of maximum LLT (women 17.3%, men 24.3%) and side effects (women 15.2%, men 8.6%). ConclusionsIn routine practice, only a minority of women and men with FH achieved their LDL-C treatment target. Extra efforts have to be made to provide FH patients with reliable information on the safety of statins and their long-term effects on CVD risk reduction. If statin treatment is insufficient, alternative lipid lowering therapies such as ezetimibe or PCSK9-inhibitors should be considered.

Sex differences in efficacy and safety of PCSK9 monoclonal antibodies: A real-world registry

Background and aimsProprotein convertase subtilisin/kexin 9 monoclonal antibodies (PCSK9 mAbs) reduce low-density lipoprotein (LDL-c) with a favourable safety profile. Available data from PCSK9 antibody trials suggest LDL-c reduction is lower in women compared to men. Data in real-world setting is scarce. The aim of this study was to assess sex differences in efficacy and safety of PCSK9 antibodies in clinical care. MethodsAll patients starting with evolocumab or alirocumab in our lipid clinic were included in a prospective registry. We collected clinical information, including baseline and follow-up mean LDL-C levels after initiation of PCSK9 mAbs treatment. In addition, side effects and PCSK9 mAbs discontinuation were recorded. ResultsWe analysed 436 patients (209 women), mean age 58 ± 11 years. Women had higher baseline LDL-c levels compared to men (4.7 ± 1.6 mmol/L vs 4.1 ± 1.4 mmol/L, p < 0.01). PCSK9 mAbs resulted in less relative LDL-c reduction in women compared to men (50% vs 61% p<0.01), but equal absolute LDL-c reduction (respectively 2.3 ± 1.3 mmol/L vs 2.5 ± 1.1 mmol/L, p = 0.087). Women less often reached LDL-c target levels than men (50% vs 72%). No sex differences were observed in reporting of side effects (women 32% vs men 27% p = 0.26) or PCSK9 mAbs discontinuation (women 13% vs men 10%, p = 0.46). ConclusionsIn clinical practice, PCSK9 mAbs are less effective in reducing LDL-c levels in women compared to men and equally safe, implying the importance of sex differences in PCSK9 metabolism.

Management of Statin Intolerant Patients in the Era of Novel Lipid Lowering Therapies: A Critical Approach in Clinical Practice

Statins are the cornerstone of lipid-lowering therapies effective for cardiovascular risk reduction. Although they are generally well tolerated, statin intolerance (SI) is frequent in clinical practice, and it is usually related to the onset of muscle symptoms, which are defined under the acronym SAMS (Statin-Associated Muscle Side Effects). These side effects are responsible for statin treatment discontinuation that results in increased cardiovascular risk. The National Lipid Association (NLA) has recently provided an updated definition of statin intolerance, and a distinction between complete and partial statin intolerance has been reported. The evaluation of symptom severity and the presence of muscle damage biomarker alterations make it essential to adopt a patient-centered approach aimed at obtaining a personalized therapeutic strategy. Firstly, it could be useful to administer a different statin, reduce the dosage or adopt an alternate dosage regimen. However, some patients are unable to tolerate any statin at every dosage, or despite taking statins at the maximum tolerated dose, they fail to achieve the recommended LDL-C target, and thus it is necessary to introduce a non-statin hypolipidemic treatment. Ezetimibe, proprotein-convertase subtilisin/kexin type 9 (PCSK9) inhibitors such as monoclonal antibodies (alirocumab and evolocumab) or RNA messenger silencing (inclisiran), bempedoic acid or nutraceuticals are non-statin lipid-lowering therapies that could be used as an alternative or in addition to statins to achieve an early and sustained LDL-C reduction in clinical practice. In this review, we evaluated SI management focusing on non-statin lipid lowering therapies and their implications in lipid lowering approaches in clinical practice.

Atorvastatin

Atorvastatin

Implementation of risk enhancers in ASCVD risk estimation and hypolipidemic treatment eligibility: A sex-specific analysis

ObjectiveSex-specific data are limited regarding eligibility for hypolipidemic treatment. We aim to explore the sex-specific clinical utility of high-sensitivity C-reactive protein (hsCRP) and carotid ultrasound as risk modifiers for hypolipidemic treatment in primary prevention of atherosclerotic cardiovascular disease (ASCVD). MethodsWe aimed to explore these sex-specific trends in two pooled contemporary independent Greek cohorts (Athens Vascular Registry n = 698, 50.9% women and Menopause Clinic n = 373, 100% women) of individuals without overt ASCVD. Baseline ASCVD risk was estimated using the Systematic COronary Risk Evaluation-2 (SCORE2) tools. The presence of carotid plaque and hsCRP ≥2 mg/L were integrated as risk modifiers. ResultsMen had increased odds to achieve target LDL-C levels based on ASCVD risk (23.8% vs. 17.7%, OR: 1.45 95% CI: 1.05–2.00, p = 0.023, for men vs. women). Additionally, considering carotid plaque or high hsCRP levels did not change this association but reduced on-target LDL-C rate in both sexes. Women had decreased odds of being eligible for hypolipidemic treatment by ASCVD risk estimation (11.5% vs. 26.4%, p < 0.001) compared with men. The addition of carotid plaque presence or high hsCRP levels and their combination resulted in a higher relative increase in hypolipidemic treatment eligibility in women (from 11.5% to 70.9% vs. 26.4% to 61.4% for carotid plaque, from 11.5% to 38.5% vs. 26.4% to 50.8% for hsCRP and from 11.5% to 79.1% vs. 26.4% to 75% for their combination, all for women vs. men, pforinteraction < 0.001 for all) than men. ConclusionsImplementation of carotid plaque and hsCRP levels increases hypolipidemic treatment eligibility more prominently in women than in men. The impact on clinical outcomes in these untreated patients merits further investigation.

Abstract TP196: Real Life Utility Of PCSK9 Inhibitors Following Ischemic Stroke

Introduction: Hyperlipidemia is a modifiable risk factor for stroke, with the magnitude of LDL-C reduction correlating to risk of recurrent ischemic stroke. A high-intensity statin is considered standard of care in addition to dietary modification. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are used if the LDL-C target is not achieved despite maximally tolerated statins with ezetimibe. We investigated the role for PCSK9 inhibitors in our ischemic stroke population. Methods: An IRB approved retrospective review of patients admitted for acute ischemic stroke between 2019 – 2020 was performed. We estimated the probability of benefit from PCSK9 treatment with the following criteria: LDL &gt; 190 regardless of treatment, LDL 161-190 on any dose statin therapy, and LDL 131-160 on high intensity statin therapy. Results: 774 patients with ischemic stroke were admitted during this time frame. Mean age 62.8 +/- 13.2 with 57% male (52% Black, 42% White). 584 (75%) of these patients had LDL above goal. One patient was on PCSK9 therapy on admission. Although the majority of our patients had uncontrolled cholesterol, only one additional patient would meet the strict prescription criteria for PCSK9 therapy of being adherent to maximal tolerated statin dose and ezetimibe with LDL above goal. Other potential patients with estimated benefit include LDL &gt;190 (20 patients), LDL 161-190 (16 patients), LDL 131-160 (13 patients). In total this amounts to 6.7% of stroke patients who we would expect to need PCSK9 inhibitors in the future. Conclusion: Using conservative projections, we estimate that about 1 in 14 patients with ischemic stroke could benefit from PCSK9 therapy. Achieving LDL targets more consistently is a promising approach to decreasing the recurrent stroke rate. Further prospective data evaluating outcomes after initiating PCSK9 inhibitor treatment are needed to validate these findings.

Prevalencia de dislipemia aterogénica, factores relacionados y grado de control lipídico en la población general de Galicia. Estudio GALIPEMIAS

ObjectivesGALIPEMIAS is a study designed to establish the prevalence of familial dyslipidemia in the general population of Galicia. The objective of the present study was to assess the prevalence of atherogenic dyslipidemia (AD), its relationship with other cardiovascular risk (CVR) factors, and the degree of lipid control. MethodsCross-sectional study carried out in the general population over 18 years of age residing in Galicia and with a health card from the Galician Health Service (N=1,000). Selection of the sample by means of random sampling by conglomerates. The AD prevalence adjusted for age and sex and the related variables were analyzed. ResultsThe prevalence of AD adjusted for age and sex was 6.6% (95% CI: 5.0-8.3%). Arterial hypertension, altered basal glycemia, type 2 diabetes mellitus and cardiovascular disease were more frequent in subjects with AD than in the rest of the population. 47.5% of the subjects with AD had a high or very high CVR. Lipid-lowering drugs were received by 38.9% (30.5% statins) of the participants with AD (46.1% of those with high and 71.4% of those with very high CVR). 25.4% of the subjects with AD had target LDL-c levels, all of them with low or moderate CVR. ConclusionsThe prevalence of AD in the general adult population of Galicia is not negligible, and it was related to several CVR factors and cardiovascular disease. Despite this, this lipid alteration was underdiagnosed and undertreated.

Heart failure (MYHF) registry: shedding light on lipid profiles and in-hospital outcome of heart failure patients

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Novartis Corporation Sdn Bhd Background Heart failure is a debilitating disease associated with multiple comorbidities and poor prognosis. Dyslipidemia, is the top 5 most common comorbidities, including HF patients. Nonetheless, the lipid profiles in HF population is scarcely available and poorly understood. Purpose This report aimed to describe the lipid profiles and in-hospital outcome of hospitalized HF patients. Methods MYHF registry is a prospective, observational study of symptomatic HF patients (NYHA II-IV) hospitalized in 18 tertiary care centers in Malaysia over a period of 3 years starting in 2019. Lipid profiles will be described, and in-hospital outcome will be analyzed using univariate and multivariate models. Results In MYHF registry, 1 out of 2 hospitalized HF patients (55.7%) had ischemic heart disease, significantly higher in patients with HFrEF and HFmrEF, as compared to HFpEF (p&amp;lt;0.001). Similarly, 1 in 2 (46.6%) patients had dyslipidemia as comorbidity but was comparable across EF subgroups (p=0.365). Statin utilization at discharge increased by 20% from admission (from 62.2% to 74.6%), indicating that hospitalization provides good opportunity for statin initiation in indicated HF patients. At admission, the mean total cholesterol, LDL-C, HDL, and TG levels were 4.30 mmol/L (SD 1.66), 2.62 mmol/L (SD 1.34), 1.05 (SD 0.46), and 1.37 (SD 1.08), respectively. Of those with measured LDL-C level, only 31.4% achieved LDL-C goal of &amp;lt;1.8 mmol/L and 39.8% of patients had LDL-C ≥2.6 mmol/L. With univariate analysis, patients with LDL-C goal of ≥ 1.8 mmol/L had lesser risk of in-hospital mortality [OR 0.42 (0.21,0.86), p-value = 0.018], indicating LDL-C paradox. Further analysis with multivariate model revealed that patients with LDL-C goal of ≥ or &amp;lt; 1.8 mmol/L did not differ in in-hospital mortality outcome (p-value = NS). Conclusion Dyslipidemia is highly common in general population and in HF patients. With statin therapy, only 31.4% achieved LDL-C &amp;lt; 1.8 mmol/L at admission. The finding highlights the unmet need for combination lipid lowering therapies to get patient to LDL-C target goal. Hospitalization also provided good opportunity of statin therapy initiation. The knowledge gained will be crucial for guiding management of HF patients with common comorbidity like dyslipidemia.

Inclisiran-Safety and Effectiveness of Small Interfering RNA in Inhibition of PCSK-9.

Dyslipidemia is listed among important cardiovascular disease risk factors. Treating lipid disorders is difficult, and achieving desirable levels of LDL-cholesterol (LDL-C) is essential in both the secondary and primary prevention of cardiovascular disease. For many years, statins became the basis of lipid-lowering therapy. Nevertheless, these drugs are often insufficient due to their side effects and restrictive criteria for achieving the recommended LDL-C values. Even the addition of other drugs, i.e., ezetimibe, does not help one achieve the target LDL-C. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9) discovery has triggered intensive research on a new class of protein-based drugs. The protein PCSK9 is located mainly in hepatocytes and is involved in the metabolism of LDL-C. In the beginning, antibodies against the PCSK9 protein, such as evolocumab, were invented. The next step was inclisiran. Inclisiran is a small interfering RNA (siRNA) that inhibits the expression of PCSK9 by binding specifically to the mRNA precursor of PCSK9 protein and causing its degradation. It has been noticed in recent years that siRNA is a powerful tool for biomedical research and drug discovery. The purpose of this work is to summarize the molecular mechanisms, pharmacokinetics, pharmacodynamics of inclisiran and to review the latest research.

Efficacy, safety, adherence and persistence of PCSK9 inhibitors in clinical practice: A single country, multicenter, observational study (AT-TARGET-IT)

Background and aimsProprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients at high and very-high cardiovascular (CV) risk, with documented atherosclerotic CV disease (ASCVD), and for very-high risk patients with familial hypercholesterolaemia not achieving LDL-cholesterol (LDL-C) goal while receiving maximally tolerated dose of lipid-lowering therapy (LLT). However, single country real-life data, reporting the use of PCSK9i in clinical practice, are limited. Therefore, we designed AT-TARGET-IT, an Italian, multicenter, observational registry on the use of PCSK9i in clinical practice. MethodsAll data were recorded at the time of the first prescription and at the latest observation preceding inclusion in the study. Results798 patients were enrolled. The median reduction in LDL-C levels was 64.9%. After stratification for CV risk, 63.8% achieved LDL-C target; of them, 83.3% took LLTs at PCSK9i initiation and 16.7% did not. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) poor adherence. At 6 months, 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow-up of at least 12 and 18 months, respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 3.5% of patients discontinued therapy. No differences in efficacy, adherence, and persistence were found between alirocumab and evolocumab. ConclusionsPCSK9i are safe and effective in clinical practice, leading to very high adherence and persistence to therapy, and achievement of recommended LDL-C target in most patients, especially when used as combination therapy.

Achievement of treatment targets among patients with type 2 diabetes in 2015 and 2020 in Canadian primary care.

An update on the degree to which patients with type 2 diabetes in Canada achieve treatment targets is needed to document progress and identify subgroups that need attention. We sought to estimate the frequency with which patients managed in primary care met treatment targets (i.e., HbA1c ≤ 7.0%, blood pressure < 130/80 mm Hg and low-density lipoprotein cholesterol [LDL-C] < 2.00 mmol/L), guideline-based use of statins and of angiotensin-convertingenzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and the effects of patient age and sex. We conducted a cross-sectional study of 32 503 and 44 930 adults with diabetes in Canada on June 30, 2015, and 2020, respectively, using electronic medical record data from primary care practices across 5 provinces. We grouped achievement of diabetes targets by age and sex, and compared between groups using logistic regression with adjustment for cardiovascular comorbidities. In 2020, target HbA1c levels were achieved for 63.8% of women and 58.9% of men. Blood pressure and LDL-C targets were achieved for 45.6% and 45.8% of women, and for 43.1% and 59.4% of men, respectively. All 3 treatment targets were achieved for 13.3% of women and 16.5% of men. Overall, 45.3% and 54.0% of women and men, respectively, used statins; 46.5% of women used ACE inhibitors or ARBs, compared with 51.9% of men. With the exception of blood pressure and HbA1c levels among women, target achievement was lower among younger patients. Achievement of the LDL-C target, statin use and ACE inhibitor or ARB use were lower among women at any age. From 2015 to 2020, target achievement increased for HbA1c, remained consistent for LDL-C and declined for blood pressure; use of statins and of ACE inhibitors or ARBs also declined. Target achievement for blood pressure and use of statins and of ACE inhibitors and ARBs declined between 2015 and 2020, and was suboptimal in all patient groups. Widespread quality improvement is needed to increase evidence-based therapy for people with diabetes.

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

555 ADHERENCE AND PERSISTENCE OF PCSK9 INHIBITORS IN CLINICAL PRACTICE: THE REAL-WORLD ITALIAN EXPERIENCE (AT-TARGET-IT STUDY)

Abstract Introduction Hypercholesterolemia is a major risk factor for the development of atherosclerotic cardiovascular disease (ASCVD). Proprotein Convertase Subtilisin/Kexin type 9 inhibitors (PCSK9i) are recommended in patients with documented ASCVD or Familial Hypercholesterolaemia (FH), not achieving LDL-C target while treated with maximally tolerated dose of lipid-lowering therapy (LLTs). In this conext, single country real-life data, reporting use of PCSK9i in clinical practice are needed. Purpose AT-TARGET-IT is an observational, retrospective, IV phase registry, involving 10 Italian sites, designed to study adherence and persistence of PCSK9i (either Evolocumab or Alirocumab) in patients with ASCVD or FH. Methods All clinical and demographic characteristics were recorded at the time of first prescription and at the latest observation preceding inclusion in the study. Adherence was calculated as Medical Possession Ratio (MPR), defined as the ratio between the drug units dispensed during the treatment period and the duration of the treatment period itself. Persistence was defined as therapeutic continuity from the start of treatment upon enrollment and was assessed at the time points of 6, 12 and 18 months from prescription. Results 798 patients were enrolled. In the overall population, mean age was 62 years (±7.8) and the majority were male (66%). Patients were followed for a median time of 19.33 months. 760 patients (95.2%) showed high adherence to therapy, 13 (1.6%) partial adherence, and 25 (3.1%) no adherence. At 6 month 99.7% of patients enrolled in the study remained on therapy; there were 519 and 423 patients in the study with a follow up of at least 12 and 18 months respectively. Persistence in these groups was 98.1% and 97.5%, respectively. Overall, 28 patients (3.5%) discontinued therapy. No differences in adherence and persistence were found between patients on Alirocumab or Evolocumab. Conclusion The AT-TARGET-IT registry study demonstrated that, in a large single-country real-world population, PCSK9i therapy is extremely successful in routine clinical practice, very high adherence and persistence.

Pharmacist intervention in cardiovascular disease prevention: lipid modifying treatment optimisation in type 2 diabetes within hastings primary care network

Abstract Introduction Cardiovascular disease (CVD) leads to 1 in 4 premature deaths with higher likelihood in the most deprived population1. Consistent data demonstrated efficacy of statins in CVD prevention and mortality reduction through modifying lipid profile1,2. NICE:CG181 recommends high-intensity statin, namely atorvastatin 20mg daily in type 2 diabetes (T2DM) with high risk of developing CVD1, whilst the European Society of Cardiology suggests LDL-C target below 1.4mmol/L, the lower the better 2. In contrast, 30% of patients in Hastings Primary Care Network (PCN) are prescribed sub-optimal statin therapy3 with scope to promote medicine optimisation through modification of CVD risk factor in one of the England’s most deprived areas. Aim Lowering patient’s CVD risk through optimising statin therapy and improving practice’s compliance with NICE:CG181. Methods NHS Health Research Authority Decision tool was followed, ethics approval was not required. Statin prescribing data were obtained through OpenPrescribing database. This pilot study focused on the prescribing of simvastatin at one surgery within the PCN where patients were identified using the surgery medical information system with the inclusion clinical codes of: “T2DM”, “QRISK2&amp;gt;10%”, “latest LDL-C&amp;gt;1.4mmol/L” and “current simvastatin 10/20/40mg prescription”. Systematic review of patient medical records was followed, including medical history, latest lipid profile and liver function, allergies, history of statin intolerance, previous lipid therapy and frailty status determined using the electronic frailty index, Rockwood score and medical notes. Patients with heterozygous familial hypercholesterolaemia diagnosis, confirmed statin intolerance and moderately-to-severely frail were excluded. Patients were contacted to exercise shared decision-making. Once intervention agreed, prescription was initiated for prescriber authorisation. Blood test 3 months post-intervention monitored for liver function and lipid profile. Results Search in February 2022 identified 44 patients with 39 suitable for intervention after exclusion. Thirty-six contactable patients were all switched to high-intensity statin. Thirty-four were switched to atorvastatin 20 mg whilst two with prior atorvastatin intolerance were switched to rosuvastatin 10 mg. At baseline, 32 patients (88%) had cholesterol profile done within a year as per NICE:CG181. Three-month post-intervention blood tests were completed for 21, with 15 pending; 33% (7/21) had a reduction of LDL-C. In February 2022, 28.9% of the practice’s statin prescriptions were of low and medium intensity and was reduced to 25.6% post intervention. Discussion/Conclusion All contactable patients had statin therapy optimised after exercising shared decision-making with improvement of prescribing compliance to NICE:CG181 demonstrated in this practice. Findings were inconclusive whether the intensification of statin therapy demonstrated cholesterol lowering effect in this cohort. Study limitations due to small sample size, currency of baseline profile at time of intervention and patient compliance not measured. Raised LDL-C observed could have been influenced by lifestyle changes such as poor diet and lack of exercise1. The limitations of this study will be reviewed for future roll out across Hastings PCN. Further exploration of therapy compliance, lifestyle education and the barriers to regular blood test would facilitate such medicine optimisation intervention. In conclusion, patients prescribed with sub-optimal lipid therapy should be reviewed and managed through healthy lifestyle recommendations and aggressive pharmacological intervention.

Cardiovascular risk management: the success of target level achievement in high- and very high-risk patients in Hungary

BackgroundThe management of risk factors in patients with high cardiovascular risk and its effectiveness is of paramount importance. Over the last decade, several studies have examined the achievement of cardiovascular risk factors’ target levels in Europe. In the present Hungarian study, we assessed the cardiovascular risk level of participants aged 40–65 years and the success of achieving risk factors’ target levels in high- and very high-risk patients. We compared these results with the results of two similar European studies.MethodsWe conducted a cross-sectional study involving 37,778 patients aged 40–65 years from Hungary between 2019 and 2020. Cardiovascular risk levels and target values were set according to the 2016 European Guideline. Target achievement was evaluated for body mass index, waist circumference, blood pressure, total, LDL, and HDL cholesterol, triglyceride, and HbA1c (in diabetics).ResultsFor 37,298 patients, all the data were available to determine their cardiovascular risk category. Of these, 23.1% had high and 31.4% had very high cardiovascular risk (men: 27.1 and 39.6%, women: 20.5 and 26.1%, respectively). Achievement of the LDL-C target of 1.8 mmol/l was only 8.0% among very high-risk patients, which was significantly lower than the European average (29%). Achievement of target blood pressure among high-risk patients was better than the European average (63.4% vs. 44.7%, respectively); however, achievement was slightly lower among very high-risk patients compared with the European average (49.4% vs. 58%, respectively). The proportion of patients with type 2 diabetes who achieved a HbA1c below 7% was 57.3% in the high-risk population and 53% in the very high-risk population, which was in line with the European average success rates (58.5 and 54%, respectively). Waist circumference (< 88 cm for women and < 102 cm for men) was achieved by 29.4% of patients in the very high-risk group in our survey, which was lower than the European average of 41%.ConclusionsThe success rate of cardiovascular risk management in Hungary is lower than the European average in several parameters. Furthermore, our data highlight the poor effectiveness of obesity management in Hungary. General practice partnerships may be important sites for positive change.

Cardiovascular Risk Profile and Lipid Management in the Population-Based Cohort Study LATINO: 20 Years of Real-World Data.

The rising prevalence of cardiovascular (CV) risk factors in Portugal has translated into more than 35,000 annual deaths due to CV diseases. We performed a multicenter observational cohort study encompassing clinical activities performed between 2000 and 2019 to characterize the CV risk profile and LDL-C management of patients in every CV risk category using electronic health records of a regional population in Portugal. We analyzed data from 14 health centers and 1 central hospital in the north of Portugal of patients between 40 and 80 years that had at least 1 family medicine appointment at these institutions. Living patients were characterized on 31 December 2019. CV risk assessment was computed according to the 2019 ESC/EAS Guidelines. Lipid-lowering therapy (LLT) and achievement of LDL-C targets were assessed. In total, the analysis included 78,459 patients. Patient proportions were 33%, 29%, 22%, and 17% for low, intermediate, high, and very high CV risk, respectively. Moderate-intensity statins were the most frequently used medication across all CV risk categories. High-intensity statins were used in 5% and 10% of high and very high CV risk patients, respectively. Ezetimibe was used in 6% and 10% of high and very high CV risk patients, respectively. LDL-C targets were achieved in 44%, 27%, 7%, and 3% of low, intermediate, high, and very high CV risk patients, respectively. For uncontrolled patients in the high and very high CV risk categories, a median LDL-C reduction of 44% and 53%, respectively, would be required to meet LDL-C targets. There are clear opportunities to optimize LDL-C management in routine clinical practice. The prescription of LLT according to CV risk represents an important missed treatment opportunity.

Abstract 13703: Sex Differences on Cardiovascular Outcomes of Pcsk9-Inhibitors: A Meta-Analysis

Background: LDL-Cholesterol (LDLC) lowering therapies have been proven to significantly lower major adverse cardiovascular events (MACE) in patients with cardiovascular disease. Ideal LDL-C target levels are often not achieved using a high-dose statin and ezetimibe. The proprotein convertase subtilisin/kexin type-9 (PCSK-9) inhibitors can further reduce LDL-C and MACE, yet gender differences in LDL-C reduction remains unclear. We sought to determine if there are sex differences in efficacy outcomes of PCSK-9 inhibitors. Method: A comprehensive literature search was performed, and ongoing studies were identified using ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We used a PRISMA, Preferred Reporting Items for a Review and Meta-analysis and RevMan version 5.4 software to conduct a meta-analysis, heterogeneity test, and sensitivity analysis on the included studies. We established the significance level for all outcomes at a P-value of &lt;0.05. Statistical heterogeneity was identified through forest plots and a standard Chi-squared test with a significant level of p&lt;0.1. The extent of heterogeneity was based on the I 2 statistic, wherein a value of more than 50% was interpreted as substantial heterogeneity. Fixed-effects analysis was applied in this meta-analysis. Results: There was a significant reduction in MACE in PCSK9 inhibitor arm vs. placebo in both males (HR 0.85, 95% CI 0.80 to 0.91, p&lt;0.0001, and females (HR 0.86, 95% CI 0.76 to 0.96, p=0.009) (Figure). Furthermore, there was a similar significant reduction in LDLC with PCSK-9 inhibitors compared to placebo and ezetimibe for both sexes. Lastly, there was a significant reduction in LDL-C seen in both sexes when analyzed as to the frequency of PCSK9 inhibitor administration and the type of PCSK9 inhibitor given. Conclusion: This meta-analysis found no sex differences and similar efficacy in women and men in reducing MACE using PCSK-9 inhibitors.