High-intensity Lipid-lowering Therapy Research Articles

Association of Use and Dose of Lipid-Lowering Therapy Post Acute Myocardial Infarction With 5-Year Survival in Older Adults.

Older people are underrepresented in randomized trials. The association between lipid-lowering therapy (LLT) and its intensity after acute myocardial infarction and long-term mortality in this population deserves to be assessed. The FAST-MI (French Registry of Acute ST-Elevation or Non-ST-Elevation Myocardial Infarction) program consists of nationwide French surveys including all patients admitted for acute myocardial infarction ≤48 hours from onset over a 1- to 2-month period in 2005, 2010, and 2015, with long-term follow-up. Numerous data were collected and a centralized 10-year follow-up was organized. The present analysis focused on the association between prescription of LLT (atorvastatin ≥40 mg or equivalent, or any combination of statin and ezetimibe) and 5-year mortality in patients aged ≥80 years discharged alive. Cox multivariable analysis and propensity score matching were used to adjust for baseline differences. Among the 2258 patients aged ≥80 years (mean age, 85±4 years; 51% women; 39% ST-segment elevation myocardial infarction; 58% with percutaneous coronary intervention), 415 were discharged without LLT (18%), 866 with conventional doses (38%), and 977 with high-dose LLT (43%). Five-year survival was 36%, 47.5%, and 58%, respectively. Compared with patients without LLT, high-dose LLT was significantly associated with lower 5-year mortality (adjusted hazard ratio, 0.78 [95% CI, 0.66-0.92]), whereas conventional-intensity LLT was not (adjusted hazard ratio, 0.93 [95% CI, 0.80-1.09]). In propensity score-matched cohorts (n=278 receiving high-intensity LLT and n=278 receiving no statins), 5-year survival was 52% with high-intensity LLT at discharge and 42% without statins (hazard ratio, 0.78 [95% CI, 0.62-0.98]). In these observational cohorts, high-intensity LLT at discharge after acute myocardial infarction was associated with reduced all-cause mortality at 5 years in an older adult population. These results suggest that high-intensity LLT should not be denied to patients on the basis of old age. URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00673036, NCT01237418, and NCT02566200.

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.

Intensity of and adherence to lipid-lowering therapy as predictors of goal attainment and major adverse cardiovascular events in primary prevention

The effectiveness of lipid-lowering therapy (LLT) for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in routine care may depend on treatment intensity and adherence. Observational study of adults with newly initiated LLT for primary prevention of ASCVD in Stockholm, Sweden, during 2017-2021. Study exposures were LLT adherence [proportion of days covered (PDC)], LLT intensity (expected reduction of LDL cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity were calculated during the previous 12 months, and the patients estimated ASCVD risk was categorized. Study outcomes were major adverse cardiovascular events (MACE) and LDL-C goal attainment. Thirty-six thousand two hundred eighty-three individuals (mean age 63 years, 47% women, median follow-up 2 years), with a baseline low-moderate (40%), high (49%), and very-high (11%) ASCVD risk started LLT. Increases in LLT adherence, intensity, or adherence-adjusted intensity of 10% over 1 year were associated with lower risks of MACE (with hazard ratios of 0.95 [95% CI, 0.93-0.98]; 0.93 [0.86-1.00]; and 0.90 [0.85-0.95], respectively) and higher odds of attaining LDL goals. Patients with good adherence (≥80%) had similar risks of MACE and similar odds ratios for LDL-C goal attainment with low-moderate and high-intensity LLT. Treatment discontinuation was associated with increased MACE risk. The relative and absolute benefits of good adherence were greatest in patients with very high ASCVD risk. In routine-care primary prevention, better adherence to LLT was associated with a lower risk of MACE across all treatment intensities. Improving adherence is especially important among patients with very high ASCVD risk.

Association between high-intensity lipid-lowering therapy and atherosclerotic plaque content changes assed by iMAP-IVUS and near-infrared spectroscopy in patients with premature atherosclerosis

Abstract Background/Introduction The benefits of lipid-lowering drug treatment for the secondary prevention of coronary heart disease have been well-established by randomized, controlled trials. More evidence has now emerged to support the use of high-intensity low-density lipoprotein cholesterol (LDL-C) –lowering therapy including statine, ezetimibe, and PCSK9 inhibitors. Intravascular imaging, such as near-infrared spectroscopy (NIRS) can detect lipid-rich plaques. Virtual histology iMAP-Intravascular ultrasound (iMAP-IVUS) can classify tissue characteristics into 4 major components fibrotic, lipidic, necrotic, and calcified. Purpose Our study aimed to evaluate atherosclerotic plaque composition in very high cardiovascular-risk patients, who received high-intensity lipid-lowering therapy for 15 months. Methods Our study included stable coronary artery disease patients receiving statin and/or ezetimibe in maximum tolerated dose for at least one month, who were scheduled for PCI. In case LDL-C was >1.8 mmol/l, inclisiran was added to the therapy at the time of inclusion and continued for 15 months. The region of interest was a proximal or middle segment with angiographic evidence of nonobstructive de novo atherosclerosis >20% and <50%, evaluated by NIRS and iMAP-IVUS at baseline and 15 months later. After 15 months patients were classified into two groups – those who reached the European Society of Cardiology LDL-C target <1.8 mmol/L and those who did not. Statistical analysis was carried out with SPSS Statistics software, defining a significance level of 0.05. Results 37 eligible patients had undergone IVUS/NIRS investigation. The mean patient age was 53 years. After 15 months the mean LDL-C level decreased from 2.70 mmol/L to 1.79 mmol/l and 25 patients reached a target of <1.8 mmol/L. In the patient group that reached target - 4mm plaque lipid core burden index (LCBImax4mm) decreased from 184.00 (±160.07) to 62.72 (±142.19) with p=0.001 and total LCBI changed from 37.04 (± 40.80) to 15.60 (± 27.87) with p = 0.007. In patients with LDL-C >1.8 mmol/L, LCBImax4mm changed from 211.16 (±167.76) to 125.04 (±152.21) with no statistically significant difference p = 0.074. Similarly, the total LCBI was from 40.33 (± 43.38) to 22.41 (± 24.97) with p = 0.086. In iMAP-IVUS results necro-lipidic core in the <1.8 mmol/L group changed from 78.50 mm3 (±42.77) to 84.77 mm3 (±46.03) p = 0.422. Yet, second group's necro-lipidic core changed from 97.43 mm3 (±58.04) to 89.40 mm3 (±49.03), with no statistically significant difference p = 0.066. Additionally in both groups were significant changes in fibrotic tissues, for the target group from 139.50 mm3 (±69.86) to 147.32 mm3 (±73.56) p = 0.002 and from 149.71 mm3 (±82.79) to 160.09 mm3 (±89.01) p = 0.008 in second group. Conclusion Our study showed that after 15 months of high-intensity lipid-lowering therapy, patients that reached LDL-C levels <1.8 mmol/L, showed lower LCBImax4mm and total LCBI.

Dyslipidaemia and its management in patients with type 2 diabetes across the Middle East and Africa: the PACT-MEA study

Abstract Background There is a scarcity of high-quality epidemiological data on the clinical burden of type 2 diabetes (T2D) and cardiovascular risk (CV) in the Middle East and Africa due to under-representation of these regions in contemporary diabetes and cardiovascular trials. Multiple risk factors, including dyslipidaemia, increase CV risk in patients with T2D and established atherosclerotic cardiovascular disease (eASCVD) and those at risk for ASCVD. According to the European Society of Cardiology (ESC) 2021 Guidelines, target low-density lipoprotein cholesterol (LDL-C) for patients with T2D is <1.8 mmol/L (<1.4 mmol/L in patients with eASCVD or at very high risk). Purpose To establish the status of dyslipidaemia and its management in patients with T2D and eASCVD or high/very high ASCVD risk across the Middle East and Africa. Methods Adult patients with T2D participating in a cross-sectional, observational study in seven Middle East and African countries were included in the analysis. Laboratory and medication data were collected from medical charts of patients attending a routine health visit in 2022. Descriptive statistics were used to characterize the lipid profile and management of patients with T2D by age, diabetes duration, body mass index, HbA1c, microvascular complications, estimated glomerular filtration rate (eGFR), and urinary albumin to creatinine ratio (UACR). Results There were 3726 patients in the overall study sample (mean age, 58 ± 12; male, 53%), almost all of whom were at high (69%)/very high (30%, includes eASCVD) risk according to ESC 2021 guidelines. In patients for whom data was available in the medical record, median LDL-C (n=2525) was 2.2 mmol/L (IQR, 1.7 to 3.0), HDL-C (n=2453) was 1.1 mmol/L (IQR, 0.9 to 1.3), and triglycerides (n=2488) were 1.6 mmol/L (IQR, 1.2 to 2.3). Of the patients with high/very high ASCVD risk (n=2313), 30% met the ESC guideline-recommended target for LDL-C of <1.8 mmol/L and 16% met the target of <1.4mmol/L. Most patients were on statin therapy (77%, range across countries: 60%-87%, Table 1), with use increasing with age and duration of diabetes. More patients with T2D for ≥10 years were on high intensity statin therapy than those with T2D <10 years (37% vs 33%). A similar pattern was observed for patients with HbA1c levels ≥7% (37% vs 31%, Table 2). Most patients with nephropathy were on statins (87%); use increased with lower eGFR and higher UACR levels. Very few patients were on Ezetimibe (6.4%), fibrates (4.8%), fish oil (including icosapent ethyl) (1.4%), or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (0.5%). Conclusions Utilization of moderate intensity statin therapy (less than 50% LDL reduction) despite high and very high CV risk leads to failure to achieve cardioprotective LDL targets in most patients. Given the high burden of ASCVD in patients with T2D, prioritization of high intensity lipid lowering therapy is recommended.Table 1Table 2

Frequency, predictors and clinical outcomes of AMI patients with triple regression of coronary atherosclerosis: A sub-analysis of the PACMAN AMI trial

Abstract Background Recent studies have shown that coronary artery disease regression is not limited to atheroma reduction but also includes plaque stabilization in patients treated with high-intensity lipid-lowering therapy. The frequency and characteristics of patients who simultaneously show atheroma volume reduction and plaque stabilization defined as reduction in plaque lipid content and increase in fibrous cap thickness (i.e., triple regression) are unknown. Purpose This study sought to determine the percentage and determinants of both plaque volume reduction and plaque stabilization in patients with acute myocardial infarction (MI) and treated wiTh alirocumab or placebo added to high-intensity statin therapy. Methods The PACMAN-AMI trial employed serial intravascular ultrasound, near-infrared spectroscopy and optical coherence tomography to compare the effects of alirocumab vs. placebo (1:1) in 265 patients (537 non–infarct-related coronary arteries) receiving high-intensity statin therapy. Triple regression was defined by the combined presence of reduction in percent atheroma volume (PAV), reduction in maximum lipid core burden index (maxLCBI4mm) and increase in minimal fibrous cap thickness (FCT). Clinical outcomes of patients with or without triple regression were assessed at one year follow-up. Results Overall, 199 (75.1%) patients showed PAV reduction, 180 (67.7%) maxLCBI4mm reduction and 172 (77.6%) minimal FCT increase, with a total of 84 (31.7%) patients having triple regression (40.8% in the alirocumab group vs. 23.0% in the placebo group, p=0.002). The percentage of patients with triple regression was similar among the groups with PAV reduction, maxLCBI4mm reduction or minimal FCT thickening (42%, 51% or 49%, respectively, p=0.30). Similar baseline clinical features and a higher reduction in low-density lipoprotein cholesterol (LDL-C, -27.1 [37.7 to -16.6] mg/dl, p<0.001) and apolipoprotein B levels (-18.5 [-26.0 to -11.0] p<0.001) were observed patienst with vs. without triple regression. A higher reduction in PAV (-1.54 [-2.14 to -0.95] %, p<0.001), maxLCBI4mm (-111.24 [-140.46 to -82.02], p<0.001) and a higher increase in minimal FCT (56.39 [38.67 to 74.11] µm, p<0.001) were found in patients with triple regression. At multivariable analysis, factors independently associated with triple regression included higher baseline maxLCBI4mm (1.03, 1.01 to 1.06, p=0.013) and alirocumab treatment (2.83, 1.57 to 5.16, p=0.001). The composite clinical endpoint of death, MI and ischemia-driven revascularization occurred less frequently in patients with versus without triple regression (8.3% vs 18.2%, p=0.042). Conclusions Triple regression occurred among one third of acute AMI patients receiving high-intensity lipid lowering therapy. Alirocumab treatment and higher baseline lipid accumulation were independent predictors of triple regression. Triple regression was associated with a reduced rate of adverse cardiovascular events.

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 <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<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 <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 <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.

Abstract 13186: Factors Associated With Dysglycemia and Type 2 Diabetes Mellitus Onset in Familial Hypercholesterolemia

Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant monogenic disorder characterized by high blood LDL-C and cardiovascular disease (CVD). Type 2 diabetes mellitus (T2DM) is an independent cause of CVD and there is evidence that FH is associated with a lower frequency of its development. On the other hand, lipid lowering therapy (LLT) may increase T2DM risk. Goals: Evaluate the risk of dysglycemia and T2DM development in a cohort of molecularly proven FH individuals. Methods: This is a prospective analysis of a population enrolled on a genetic cascade screening program evaluated from March 2011 to January 2022. FH diagnosis was confirmed by molecular testing of variants in LDLR, APOB and PCSK9. Dysglycemia and T2DM diagnoses were done according to the ADA Criteria or use of any antidiabetic drugs. Results: 790 FH patients were included (age 45.5±15.0 years, 56.8% female, baseline LDL-C 198±74 mg/dL), 96.6% had LDLR variants. The prevalence of T2DM was 13.3% and 67.4% were taking LLT at baseline . There were 206 (26%) new cases of T2DM or dysglycemia after a median 51-month follow-up . In multivariate Cox regression analysis age (HR:1.026, CI95%: 1.014-1.038, p=0.000) , body mass index (HR: 1.062, CI95%: 1.035-1.090, p=0.000) and current smoking (HR: 2.005, HR: 1.337-3.008, p=0.001) were independently associated with T2DM and dysglycemia, while metformin use was associated with a lower risk (HR: 0.147, CI95%: 0.076-0.284, p=0.000). History of previous CVD, use of lipid lowering therapy at baseline, high intensity LLT , or type of molecular defect were not associated with higher T2DM/dysglycemia risk. Conclusions: In this cohort of molecularly proven FH subjects, T2DM affected more than 1 in 10 people at baseline. Previous CVD and classical risk factors but neither molecular defects nor lipid lowering therapy were associated with T2DM/dysglycemia onset.

Concomitant Coronary Atheroma Regression and Stabilization in Response to Lipid-Lowering Therapy

BackgroundThe frequency, characteristics, and outcomes of patients treated with high-intensity lipid-lowering therapy and showing concomitant atheroma volume reduction, lipid content reduction, and increase in fibrous cap thickness (ie, triple regression) are unknown. ObjectivesThis study was designed to investigate rates, determinants, and prognostic implications of triple regression in patients presenting with acute myocardial infarction and treated with high-intensity lipid-lowering therapy. MethodsThe PACMAN-AMI (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients with Acute Myocardial Infarction) trial used serial intravascular ultrasound, near-infrared spectroscopy, and optical coherence tomography to compare the effects of alirocumab vs placebo in patients receiving high-intensity statin therapy. Triple regression was defined by the combined presence of percentage of atheroma volume reduction, maximum lipid core burden index within 4 mm reduction, and minimal fibrous cap thickness increase. Clinical outcomes at 1-year follow-up were assessed. ResultsOverall, 84 patients (31.7%) showed triple regression (40.8% in the alirocumab group vs 23.0% in the placebo group; P = 0.002). On-treatment low-density lipoprotein cholesterol levels were lower in patients with vs without triple regression (between-group difference: −27.1 mg/dL; 95% CI: −37.7 to −16.6 mg/dL; P < 0.001). Triple regression was independently predicted by alirocumab treatment (OR: 2.83; 95% CI: 1.57-5.16; P = 0.001) and a higher baseline maximum lipid core burden index within 4 mm (OR: 1.03; 95% CI: 1.01-1.06; P = 0.013). The composite clinical endpoint of death, myocardial infarction, and ischemia-driven revascularization occurred less frequently in patients with vs without triple regression (8.3% vs 18.2%; P = 0.04). ConclusionsTriple regression occurred in one-third of patients with acute myocardial infarction who were receiving high-intensity lipid-lowering therapy and was associated with alirocumab treatment, higher baseline lipid content, and reduced cardiovascular events. (Vascular Effects of Alirocumab in Acute MI-Patients [PACMAN-AMI]; NCT03067844)

The efficacy of intensive lipid-lowering therapies on the reduction of LDLc and of major cardiovascular events

Statins are the cornerstone of lipid-lowering therapy (LLT) for reduction of low-density lipoprotein cholesterol (LDLc) levels and high percentage of patients require LLT combinations or alternative treatments for adequate LDLc control. We performed an intention-to-treat meta-analysis of published data of phase III trials evaluating LLT efficacy on major adverse cardiovascular events (MACE). The primary endpoint was MACE incidence, as reported in each trial, and secondary analyses included myocardial infarction, stroke and mortality. Eleven clinical trials and 135,688 patients were included; seven trials tested high intensity LLT and 4 LLT combinations. Intensive LLT reduced MACE risk by 15% (12.03%vs. 13.79%, HR: 0.85 95% CI 0.80-0.90; p<0.001). The number needed to treat was 56 patients. Meta-regression analyses showed a linear correlation between absolute LDLc reductions and the risk of MACE. Significant reductions in myocardial infarction (HR: 0.83, 95% CI 0.80-0.86) and stroke (HR: 0.81, 95% CI 0.75-0.87) were observed. Cardiovascular death rate was 3.32% in LLT treatment arm vs. 3.56% in controls, resulting in a HR: 0.94 (95% CI 0.88-0.99; p=0.03); no effect on all-cause mortality was observed (HR: 0.97 95% CI 0.93-1.01; p=0.09). The sensitivity analyses verified the lack of heterogeneity, except for MACE that was mainly driven by the divergent results of the 2 trials. Small study effect was detected for the assessment of mortality. Current evidence consistently supports the efficacy of available intensity LLT for LDLc decrease on MACE and cardiovascular mortality reduction.

Lipid-lowering therapy after acute coronary syndromes in Europe: can we do better?

Abstract Funding Acknowledgements Type of funding sources: None. Background Recent guidelines on acute coronary syndromes (ACS) recommend initiating lipid-lowering therapy (LLT) as soon as possible in order to obtain &amp;gt;50% LDL-cholesterol reduction with a low-density-lipoprotein-cholesterol (LDL-c) &amp;lt;1.4 mmol/L. Aim To define the current LLT policy in Europe after an ACS and to assess whether in hospital initiation of combination therapy of high potency (HP) statin with or without ezetimibe improves the adherence rate to target LDL-c levels as compared to a step-by-step LLT approach. Methods and results Data on LLT and lipid levels during and up to one year after hospitalisation were gathered retrospectively for 286 ACS patients who were admitted in 28 hospitals (70% academic) across 16 European countries between the years 2021 and 2022. Patients (median age 61 years, 75.9% men) were mostly admitted in dedicated cardiology departments/intensive cardiac care units (96.8%). A total 59% had ST-elevation myocardial infarction and 88% were treated with percutaneous coronary intervention. At baseline 69.9% of the patients had dyslipidaemia, 35 (14.6%) were on HP statin, 5 (3.9%) were on ezetimibe, and 6 (2.2%) were on HP statin/ezetimibe combination therapy. The median LDL-c on admission was 3.27 [interquartile range (IQR): 2.4-4.1] mmol/L. HP statin only was the predominant LLT during hospitalisation (62%) and was primarily initiated within 24h from admission (figure). During hospitalization, HP statin/ezetimibe combination therapy was administered in 24.0% of the cases. Combination therapy in hospital was given more frequently in high income countries (n=8) as compared to middle income countries (34.0% vs 10.8%, p&amp;lt;0.001). After one year, LLT up titration to combination therapy with ezetimibe or with PCSK9 inhibition was observed among 40 patients (14%, to a total of 37.4%) and 3 patients (1.6%), respectively. At follow-up, median LDL-c level was 1.6 (IQR 1.3-2.0) mmol/L and the median relative LDL-c reduction was 45.4% (IQR 27.2-64.0). Adherence to target LDL-c with &amp;gt; 50% reduction was achieved in 17.8% of the total population, in 22.4% of the high-income countries and in 12.3% of the middle-income countries (p=0.04). Patients treated with combination therapy at discharge had a higher relative LDL-c reduction than those with HP statin therapy only at discharge (median 52.5% vs 43.8%, p=0.007) and had a numerically higher target lipid status (23.9% vs 17.2%, p=0.24) Conclusions Despite high rates of high intensity LLT during hospitalisation, target LDL-c with &amp;gt; 50% LDL reduction was achieved only in 17.8%. Greater, yet insufficient, LDL-c reduction was observed when combination therapy of high dose statin with ezetimibe was initiated during the index hospitalisation.

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.

Suboptimal lipid management in patients with acute ischemic stroke

ObjectiveLipid-lowering drugs are among the most widely used drugs in cardiovascular prevention. Statins are often abandoned due to side effects, or under dosed, leading to unreached LDL-cholesterol goals and increased occurrence of cardiovascular events. MethodsWe included hospitalized patients with an ischemic stroke or transient ischemic attack. Of 92 patients, low density lipoprotein cholesterol (LDL-C) levels and lipid lowering therapy at admission and discharge were assessed. Based on their cardiovascular risk before the current event according to the most recent European guidelines, LDL-C targets were determined. Low, moderate, high and very high risk corresponded with LDL-C targets below 116, 100, 70 and 55 mg/dL respectively. ResultsBefore current event, 59 (64%) were very high, 21 (23%) high, 11 (12%) moderate and 1 low risk patients and eight patients were treated with low, 23 moderate, and 21 high intensity lipid-lowering therapy. Upon admission, 75 patients had insufficiently managed LDL-cholesterol levels, yet 39 of them were taking lipid lowering therapy. Only eight of the 21 patients on high intensity lipid lowering therapy reached their LDL-C target. During hospitalization 40 patients were switched to a high-intensity statin. Thirty-three patients switched from no treatment or a lower-intensity to a moderate-intensity lipid lowering therapy. Three were dismissed with low-intensity lipid lowering therapy, and five in association with Ezetimibe. Three patients had documented statin-intolerance. ConclusionIn this study, LDL-cholesterol was insufficiently managed according to international guidelines for prevention of ischemic stroke. Further optimization of lipid management in primary and secondary prevention and the use of higher intensity lipid lowering therapy in clinical practice is mandatory.

Use of optimal medical therapy in patients with diabetes and atherosclerotic cardiovascular disease: Insights from a prospective longitudinal cohort study.

To examine improvement in the use of optimal medical therapy (OMT) for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD) and diabetes. Patients with ASCVD (coronary, cerebrovascular, peripheral) and low-density lipoprotein-cholesterol of 70 mg/dl or higher were enrolled from December 2016 to July 2018 from 107 US sites/physicians (47% cardiology, 41% primary care, 12% other) and prospectively followed for 2 years (current analysis restricted to subgroup with diabetes). OMT was defined as high-intensity lipid-lowering (high-intensity statin, any statin + ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitor), antithrombotic (antiplatelet or anticoagulant), angiotensin-converting enzyme-inhibitor/angiotensin II receptor blocker/angiotensin receptor neprilysin inhibitor (ACE-I/ARB/ARNI) (excluding glomerular filtration rate [GFR] < 30 ml/min/1.73m2 ) and sodium-glucose co-transporter-2 inhibitor (SGLT2i)/glucagon-like peptide-1 receptor agonist (GLP-1 RA) (excluding GFR < 30 ml/min/1.73m2 and type 1 diabetes). Among 1590 patients with ASCVD and diabetes (96% type 2 diabetes), 58% were on high-intensity lipid-lowering therapy at the end of follow-up, 87% antithrombotic, 71% ACE-I/ARB/ARNI and 17% SGLT2i/GLP-1 RA. Overall, 11% of patients received comprehensive OMT, which modestly improved over time (vs. 8% at baseline; P=.002). Patients treated by cardiologists (vs. non-cardiologists) were more likely to be on high-intensity lipid lowering, but less likely to be on an SGLT2i/GLP-1 RA, and thus had lower rates of composite OMT (7.8% vs. 13.7%, P < .001). In a hierarchical multivariable model, older age was associated with lower odds of OMT (OR 0.74 per 10 years, 95% CI 0.60-0.90), whereas private insurance (OR 1.93, 95% CI 1.32-2.84) and coronary disease (OR 1.62, 95% CI 1.01-2.61) were associated with higher odds. The median odds ratio was 1.82 (95% CI 1.03-7.32), indicating a moderate variability in OMT use, independent of patient factors. We found suboptimal use of secondary prevention in US patients with ASCVD and diabetes, with minimal improvement over time. Further efforts are needed to improve the use of secondary prevention therapies in these patients with high residual risk.

Prevalent use of high-intensity statin therapy and LDL-C target attainment among PAD patients undergoing angioplasty.

Background: The global burden of peripheral arterial disease (PAD) is substantial. Reducing the major modifiable risk factors for noncommunicable disease, including dyslipidaemia, represents a public health priority. Aim is to evaluate the prevalent adequate use of lipid-lowering therapy (LLT) and low-density lipoprotein cholesterol (LDL-C) attainment among patients with PAD of the lower extremities undergoing percutaneous transluminal angioplasty. Patients and methods: We screened PAD patients treated at the University Hospital Zurich (January 2012-December 2018). We excluded patients <18 years, without classifiable severity of PAD, or with missing LDL-C or medication data. In this cross-sectional study, we studied the prevalent LLT use and LDL-C values in target according to the most recent European guidelines. Available clinical data included demographic information, lipid profile, type and dose of LLT, characteristics of the artery obstruction and angioplasty. Results: A total of 2,148 angioplasties were performed in 956 patients: 614 (64%) were men; the mean age was 70.6 (SD 11.4) years. A total of 608 (64%) had a non-critical PAD (Fontaine stage I-IIb), whereas the remaining had a critical limb ischemia or a diabetic foot syndrome. Their median LDL-C value was 2.00 (Q1-Q3: 1.50-2.60) mmol/L. In accordance to the 2016 and 2019 European Society of Cardiology guidelines, the LDL-C target of 1.8 and 1.4 mmol/L was not reached in 63% (n=599) and in 79% (n=760) of patients, respectively. Only 41% (n=390) of patients were on high-intensity statin therapy. Conclusions: The attainment of LDL-C targets, as recommended by current European guidelines, and the use of high-intensity LLT were unsatisfactory in the majority of PAD patients.

Exploring Contemporary Data on Lipid-Lowering Therapy Prescribing in Patients Following Discharge for Atherosclerotic Cardiovascular Disease in the South of Italy.

Current international guidelines strongly recommend the use of high-intensity lipid-lowering therapy (LLT) after hospitalization for atherosclerotic cardiovascular disease (ASCVD) events. With this study, our aim was to evaluate LLT prescribing in a large Italian cohort of patients after discharge for an ASCVD event, exploring factors associated with a lower likelihood of receiving any LLT and high-intensity LLT. Individuals aged 18 years and older discharged for an ASCVD event in 2019–2020 were identified using hospital discharge abstracts from two local health units of the Campania region. LLT treatment patterns were analyzed in the 6 months after the index event. Logistic regression models were developed for estimating patient predictors of any LLT prescription and to compare high-intensity and low-to-moderate-intensity LLT. Results: A total of 8705 subjects were identified. In the 6 months post-discharge, 56.7% of patients were prescribed LLT and, of those, 48.7% were high-intensity LLT. Female sex, older age, and stroke/TIA or PAD conditions were associated with a higher likelihood of not receiving high-intensity LLT. Similar predictors were found for LLT prescriptions. LLT utilization and the specific use of high-intensity LLT remain low in patients with ASCVD, suggesting a substantial unmet need among these patients in the contemporary real-world setting.

Intensity of and Adherence to Lipid-Lowering Therapy as Predictors of Major Adverse Cardiovascular Outcomes in Patients With Coronary Heart Disease.

Background The effectiveness of lipid-lowering therapy (LLT) is affected by both intensity and adherence. This study evaluated the associations of LLT intensity, adherence, and the combination of these 2 aspects of LLT management with the risk of major adverse cardiovascular events (MACE) in people with coronary heart disease. Methods and Results This is an observational study of all adults who suffered a myocardial infarction or had coronary revascularization during 2012 to 2018 and initiated LLT in Stockholm, Sweden. Study exposures were LLT adherence (proportion of days covered), LLT intensity (expected reduction of low-density lipoprotein cholesterol), and the combined measure of adherence and intensity. At each LLT fill, adherence and intensity during the previous 12 months were calculated. The primary outcomes were MACE (nonfatal myocardial infarction or stroke and death); secondary outcomes were low-density lipoprotein cholesterol goal attainment and individual components of MACE. We studied 20 490 patients aged 68±11 years, 75% men, mean follow-up 2.6±1.1 years. Every 10% increase in 1-year adherence, intensity, or adherence-adjusted intensity was associated with a lower risk of MACE (hazard ratio [HR], 0.94 [95% CI, 0.93-0.96]; HR, 0.92 [95% CI, 0.88-0.96]; and HR, 0.91 [95% CI, 0.89-0.94], respectively) and higher odds of attaining low-density lipoprotein cholesterol goals (odds ratio [OR],1.12 [95% CI, 1.10-1.15]; OR, 1.42 [95% CI, 1.34-1.51], and OR, 1.16 [95% CI, 1.19-1.24], respectively). Among patients with good adherence (≥80%), the risk of MACE was similar with low-moderate and high-intensity LLT despite differences in the low-density lipoprotein cholesterol goal attainment with the treatment intensities. Discontinuation ≥1 year increased the risk markedly (HR,1.66 [95% CI, 1.23-2.22]). Conclusions In routine care, good adherence to LLT was associated with the greatest benefit for patients with coronary heart disease. Strategies that improve adherence and use of intensive therapies could substantially reduce cardiovascular risk.

ACHIEVING THERAPEUTIC GOAL ON LDL IN HIGH AND VERY HIGH RISK PATIENTS IN A DEDICATED OUTPATIENT CLINIC

Objective: High LDL cholesterol levels represent an important risk factor for development of cardiovascular disease. The reduction of LDL reduces cardiovascular risk. Current guidelines (ESC 2019) recommend ambitious LDL levels for high and very high risk patients. But, in clinical practice, just a part of these patients achieve the ESC 2019 goals (DA VINCI Study). Design and method: We evaluated, in the first 152 patients, at high and very high cardiovascular risk, consecutively afferent to our dedicated clinic for hyperlipidaemia (Lipid Center CS), the achievement of the therapeutic goal of LDL according to ESC 2019 guidelines. All patients were on lipid-lowering drug treatment from at least twelve months and the last blood tests were no less recent than three months. Results: Of all patients, 82 were female. The mean age was 65.24 ± 10.33 years. Thirty patients were in secondary prevention. Of all patients, 70% reached the therapeutic goal (77% with very high risk and 68% with high risk). Fifty nine% were taking high-intensity lipid-lowering therapy. Seventy one% were taking combination therapy. Thirty four% were treated with PCSK9 inhibitors. Conclusions: Taking note of the limited number of the sample, our therapeutic achieved results are higher than that got in the DA VINCI study in which only 60% of patients, from west Europe, reached the therapeutic goal. A dedicated clinic for hyerlipidaemia and the high use of combination therapy with intensive drugs and extensive use of PCSK9 inhibitors may justify the results of our study. Our center did not participated in the DA VINCI study.

Lipid-lowering treatment intensity, persistence, adherence and goal attainment in patients with coronary heart disease

BackgroundTo examine patterns of lipid-lowering therapy (LLT) use, and persistence and adherence among patients with coronary heart disease and their associations with lipoprotein cholesterol (LDL-C) goal attainment. MethodsObservational study among 26,768 patients who had suffered a myocardial infarction or had been revascularized in Stockholm during 2012 to 2018, and followed up through 2019. Outcomes included initiation of LLT, discontinuation, re-initiation, adherence to treatment and LDL-C goal attainment according to the European dyslipidaemia guidelines from 2011 and 2016 (mainly LDL-C <1.8 mmol/L). Results82% of patients commenced or continued LLT within 90 days after discharge. Of those, 71% were dispensed an LLT prescription within 30 days (62% of them for high-intensity LLT). High-intensity LLT prescribing increased over time, from 12% in 2012 to 78% in 2018. During a median follow-up of 3 (IQR 2-5) years 73% continued to fill prescriptions for a statin, 26.3% temporarily or permanently discontinued, and 0.5% changed to non-statin LLT. Only 1.3% discontinued statin treatment permanently. Throughout observation, about 80% of patients showed good statin adherence (proportion of days covered ≥80%). LDL-C target attainment was 52% the first year and <50% during subsequent years. LDL-C goal attainment was highest among patients receiving high-intensity statin treatment and showing good treatment adherence. ConclusionIn secondary prevention for patients with established coronary heart disease, the proportion of LDL-C target attainment was low throughout the time period of the study, despite increasing use of high-intensity LLT and good treatment persistence and adherence.

P359 ACHIEVING THERAPEUTIC GOAL ON LDL IN HIGH AND VERY HIGH RISK PATIENTS IN A DEDICATED OUTPATIENT CLINIC

Abstract Background High LDL cholesterol levels represent an important risk factor for development of cardiovascular disease. Reduction of LDL reduces cardiovascular risk. Current guidelines (ESC 2019) recommend ambitious LDL levels for high and very high risk patients. But, in clinical practice, just a part of these patients achieve the ESC 2019 goals (DA VINCI Study). Patients and Methods We evaluated, in the first 152 patients, at high and very high cardiovascular risk, consecutively afferent to our dedicated clinic for hyperlipidaemia (Lipid Center CS), the achievement of the therapeutic goal of LDL according to ESC 2019 guidelines. All patients were on lipid–lowering drug treatment from at least twelve months and the last blood tests were no less recent than three months. Results Of all patients, 82 were female. The mean age was 65.24±10.33 years. Thirty patients were in secondary prevention. Of all patients, 70% reached the therapeutic goal (77% with very high risk and 68% with high risk). Fifty nine% were taking high–intensity lipid–lowering therapy. Seventy one% were taking combination therapy. Thirty four% were treated with PCSK9 inhibitors. Discussion Taking note of the limited number of the sample, our therapeutic results achieved are higher than that achieved in the DA VINCI study in which only 60% of patients from west Europe reached the therapeutic goal. A dedicated clinic for hyerlipidaemia and the high use of combination therapy with intensive drugs and extensive use of PCSK9 inhibitors may justify the results of our study. Our center did not participated in the DA VINCI study.