Addition Of Ezetimibe Research Articles

Pragmatic Trial of Messaging to Providers About Treatment of Hyperlipidemia (PROMPT-LIPID): A Randomized Clinical Trial.

Lipid-lowering therapy (LLT) is underutilized for very high-risk atherosclerotic cardiovascular disease. PROMPT-LIPID (PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia) sought to determine whether electronic health record (EHR) alerts improve 90-day LLT intensification in patients with very high-risk atherosclerotic cardiovascular disease. PROMPT-LIPID was a pragmatic trial in which cardiovascular and internal medicine clinicians within Yale New Haven Health (New Haven, CT) were cluster-randomized to receive an EHR alert with individualized LLT recommendations or no alert for outpatients with very high-risk atherosclerotic cardiovascular disease and LDL-C (low-density lipoprotein cholesterol), ≥70 mg/dL. The primary outcome was 90-day LLT intensification (change to high-intensity statin and addition of ezetimibe or PCSK9i [proprotein subtilisin/kexin type 9 inhibitors]). Secondary outcomes included LDL-C level, proportion of patients with LDL-C of <70 or < 55 mg/dL, rate of major adverse cardiovascular events, ED visit incidence, and 6-month mortality. Results were analyzed using logistic and linear regression clustered at the provider level. The no-alert group included 47 clinicians and 1370 patients (median age, 71 years; 50.1% female, median LDL-C, 93 mg/dL); the alert group included 49 clinicians and 1130 patients (median age, 72 years; 47% female, median LDL-C 91, mg/dL). The primary outcome was observed in 14.1% of patients in the alert group as compared with 10.4% in the no-alert group. There were no differences in any secondary outcomes at 6 months. Among 542 patients whose clinicians (n=46) did not dismiss the EHR alert recommendations, LLT intensification was significantly greater (21.2% versus 10.4%, odds ratio, 2.33 [95% CI, 1.48-3.66]). With a real-time, targeted, individualized EHR alert as compared with usual care, the proportion of patients with atherosclerotic cardiovascular disease with LLT intensification was numerically higher but not statistically significant. Among clinicians who did not dismiss the alert, there was a > 2-fold increase in LLT intensification. EHR alerts, coupled with strategies to reduce clinician dismissal, may help address persistent gaps in LDL-C management. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04394715, https://www.clinicaltrials.gov/ct2/show/study/NCT04394715.

Pharmacist optimization of lipid therapy in patients with peripheral vascular disease.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. American College of Cardiology/American Heart Association guidelines recommend high-intensity statin therapy and consideration for nonstatin therapy for patients with peripheral vascular disease (PVD); however, utilization rates remain suboptimal. The primary objective of this study was to determine whether pharmacist intervention for patients with PVD could improve the percentage of patients discharged on a high-intensity statin. The study used a single-center pre/post design and included patients with PVD who underwent peripheral bypass during their admission. Postintervention patients managed with an order set including a preselected consult for a pharmacy lipid protocol were compared to preintervention patients managed using the order set without the consult. The primary outcome was the percentage of patients discharged on a high-intensity statin. Secondary outcomes included intensification of statin therapy, the addition of ezetimibe, and referral to an outpatient lipid clinic. A total of 175 patients were included in the analysis, with 94 patients in the preintervention group and 81 patients in the postintervention group. The primary outcome met statistical significance, with an increase in the percentage of patients discharged on a high-intensity statin in the postintervention group (70.4%) compared to the preintervention group (38.3%) (P < 0.001; 95% confidence interval, 1.37-2.46). Secondary outcomes that met statistical significance included an increase in the percentage of patients with any increase in statin intensity (35.8% vs 20.2%; P = 0.02). The addition of a pharmacist consult led to an increase in the percentage of patients discharged on a high-intensity statin and an increase in overall statin intensification.

Pathophysiology and Clinical Management of Dyslipidemia in People Living with HIV: Sailing through Rough Seas.

Infections with human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst HAART regimens, darunavir and atazanavir, tenofovir disoproxil fumarate, nevirapine, rilpivirine, and especially integrase inhibitors have demonstrated the most favorable lipid profile, emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug-drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates, or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options.

Combined lipid lowering therapy, including ezetimibe, in the post-infarction period

Aim. To study the effect of 48-week therapy with atorvastatin and ezetimibe on laboratory parameters, structural and functional arterial characteristics and heart failure markers in the post-infarction period.Material and methods. A total of 87 patients with acute myocardial infarction were included. In the first 24 hours, atorvastatin 80 mg/day was prescribed. During hospitalization, after 5-6, 24, 48 weeks, clinical and paraclinical examinations were performed. In the level of low-density lipoprotein cholesterol (LDL-C) &gt;1,4 mmol/l and the decrease &lt;50% at one of the follow-up visits, ezetimibe 10 mg/day was additionally prescribed.Results. Eighty participants (93%) completed the study. Patients were divided into following groups: group 1 (n=32) — atorvastatin monotherapy; group 2 (n=49) — ezetimibe and atorvastatin therapy. In group 1, LDL-C decreased after 48 weeks by 53% (p&lt;0,001), while in group 2 by 63,2% (p&lt;0,001). According to carotid ultrasound in group 2, a decrease in the intima media thickness after 24 and 48 weeks was revealed by 9,1% (p&lt;0,001) and 10,5% (p&lt;0,001) compared to the baseline value, while in group 1 — by 4,5% only on the 24th week (p=0,012). When analyzing endothelial function, there was an increase in flow-dependent vasodilation only in group 2 from 9,1 (5,6; 11,8)% to 14,3±6,8% after 48 weeks (p&lt;0,001). With the addition of ezetimibe, there was a regression of the N-terminal pro-brain natriuretic peptide after 24 weeks by 69,6% (p=0,005), after 48 weeks — by 72,4% (p=0,009). In group 2, it decreased by 75,5% by the end of follow-up (p=0,010).Conclusion. The results rationale adding ezetimibe to statins in very high-risk patients due to the most pronounced lipid lowering effect, improvement of the structural and functional properties of the common carotid arteries, endothelial function and clinical and laboratory heart failure markers.

Effects of astepwise, structured LDL-C lowering strategy in patients post-acute coronary syndrome.

Low-density lipoprotein cholesterol (LDL-C) lowering constitutes acornerstone of secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet aconsiderable number of patients do not achieve guideline-recommended LDL‑C targets. The 2016 European guidelines recommended titration of LDL‑C lowering medication in aset number of steps, starting with oral medication. We aimed to investigate the effects of this stepwise approach in post-acute coronary syndrome (ACS) patients. In amulticentre, prospective, non-randomised trial, we evaluated athree-step strategy aiming to reduce LDL‑C to ≤ 1.8 mmol/l in post-ACS patients with prior ASCVD and/or diabetes mellitus. Steps, undertaken every 4-6weeks, included: 1)start high-intensity statin (HIST); 2)addition of ezetimibe; 3)addition of proprotein convertase subtilisin/kexin type9 inhibitors (PCSK9i). The primary outcome was the proportion of patients achieving LDL-C ≤ 1.8 mmol/l after Steps1 and2 (using oral medications alone). Secondary outcomes examined the prevalence of meeting the target throughout all steps ( https://onderzoekmetmensen.nl/nl/trial/21157 ). Out of 999 patients, 84% (95% confidence intervals (CI): 81-86) achieved the LDL‑C target using only statin and/or ezetimibe. In an intention-to-treat analysis, the percentages of patients meeting the LDL‑C target after each step were 69% (95% CI: 67-72), 84% (95% CI: 81-86), and 87% (95% CI: 85-89), respectively. There were protocol deviations for 23,38 and 23patients at each respective step. Through stepwise intensification of lipid-lowering therapy, 84% of very high-risk post-ACS patients achieved an LDL‑C target of ≤ 1.8 mmol/l with oral medications alone. Addition of PCSK9i further increased this rate to 87% (95% CI: 85-89).

Trends in Hyperlipidemia Treatments: Summary of Recommendations for Statin and Non-Statin Options

Several treatment options and recommendations exist to guide a primary care provider to reduce overall cardiac morbidity and mortality risk through lipid control. The wealth of data from large studies, the choices of agents with varying mechanisms of action, and differing guidelines result in a challenge to keep abreast of this rapidly changing landscape. In this literature review the latest data regarding lipid management are reviewed and summarized. Current US and international cholesterol treatment guidelines recommend lifestyle modification followed by statin as first-line of therapy in management of hyperlipidemia. After optimizing statin dose if LDL remains above target goal, then the addition of ezetimibe provides added reductions in morbidity and mortality. Fibrates can be considered as an adjunct to statins therapy particularly in the diabetic population with persistent triglyceride elevations and provide modest reductions in coronary artery disease. PCSK9 inhibitors can reduce morbidity and mortality in a high-risk population when a statin or statin+ezetimibe does not bring LDL below the target goal. Some newer agents (ANGPTL3/ACL/MTP Inhibitors) are reserved for patients with a predisposition to ASCVD due to a familial genetic dyslipidemia. Cost for these adjunctive therapies is a concern for the patient and clinician and patient education along with a shared decision approach are warranted. To date, evidence for these agents is limited. Finally, there remains unclear guidance on the value between a “treat to dose” versus a “treat to target” approach to lipid management. Further research is needed to provide clarity on which strategy proves optimal for primary prevention of MACEs.

Expected eligibility for PCSK9i therapy in secondary prevention, ESC/EAS guidelines vs Irish reimbursement criteria in post PCI patients

Abstract Introduction Reimbursement of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) in Ireland is determined by the national center for pharmacoeconomics (NCPE) managed access protocol. To be eligible for a PCSK9i, patients must have had a myocardial infarction or CABG, LDL of &amp;gt;3.5mmol/L, be treated with a high dose statin and ezetimibe. In contrast, the 2019 ESC/EAS dyslipidemias guidelines recommend that patients at ‘very high risk’ with an LDL-C of &amp;gt;1.4mmol/L on a maximally tolerated dose of a statin and ezetimibe, be considered for PCSK9i. In this study, we aimed to define the proportion of patients who are potentially suitable for a PCSK9i at follow-up outpatient post-percutaneous coronary intervention (PCI). Method We retrospectively analysed data on patients who had PCI in University Hospital Limerick (UHL) between January 2016 to December 2019, with follow-up complete lipid profiles at baseline and at 6 - 8 weeks during outpatient review. We sought to compare the potential PCSK9i eligible population in our cohort based on guideline recommendations vs Irish reimbursement criteria. We performed a hierarchal analysis of patients on high dose statin therapy with an LDL-C &amp;gt;1.4mmol/L at follow-up, who could potentially be eligible for a PCSK9i based on expected LDL-C. Expected LDL-C in these patients was calculated based on a 25% reduction in LDL-C with the addition of ezetimibe. Results Our analysis includes 1817 patients, with baseline characteristics; mean age 63.65years, 78.26% male, 40.01% smokers, 20.09% Diabetes Mellitus. 844 (46.45%) patients had a history of MI making them eligible for a PCSK9i based on NCPE clinical criteria. 12 patients (0.66%) in this group were on a high dose statin, and would have an expected LDL-C of &amp;gt;3.5mmol/L with the addition of ezetimibe, therefore making them eligible for a PCSK9i as per NCPE MAP criteria. In contrast to the NCPE MAP criteria all 1817 patients were deemed eligible for a PCSK9i based on ESC/EAS clinical criteria of "very high risk". 1275 patients (70.17%) had an LDL-C level &amp;gt;1.4mmol/L, 6 - 8 weeks post PCI despite high dose statin therapy. Only a minority of patients in this cohort were on ezetimibe, 57/1817 (3.14%). The addition of ezetimibe to patients with an LDL-C &amp;gt;1.4mmol/L, would result in 784 (43.14%) potentially being eligible for a PCSK9i based on current ESC guidelines, results are summarized in figure 1. Discussion Our data highlights the discrepancy between current ESC/EAS guidelines and reimbursement criteria for PCSK9i in Ireland. Based on expected attainable LDL-C minimal patients with coronary artery disease are eligible for reimbursement of a PCSK9i in Ireland for secondary prevention. Our findings also highlight that the majority of patients with established coronary disease do not meet their LDL-C goal at early follow-up. The addition of ezetimibe, would still result in over 40% of our cohort still having a significant lipid burden.

Cost impact of the ESC/EAS 2019 dyslipidemia guidelines recommended use of PSCK9i in very-high-risk patients with an LDL &amp;lt;1.8mmol/L for secondary prevention

Abstract ESC/EAS 2019 dyslipidemia guidelines give a class 1 recommendation to achieve a goal LDL-C of 1.4mmol/L in patients deemed very high risk. It is recommended to use a high dose statin and ezetimibe as first/second line therapies(1). In secondary prevention a class 1 recommendation is given for the addition of a PCSK9 inhibitors, if an LDL-C of 1.4mmol/L is not achieved. ODYSSEY and FOURIER used an LDL-C of &amp;gt;1.8mmol/l for trial inclusion, mean baseline LDL-C 2.25mmol/L and 2.38mol/l respectively(2, 3). Current Irish reimbursement criteria limit availability of PCSK9i due to high cost. Our aim was to determine the cost of PCSK9i therapy in patients post-PCI with an LDL-C of 1.5 – 1.8mmol/L and the potential cardiovascular benefit of a 1mmol/L reduction in LDL-C in this cohort. Methods We retrospectively analyzed patients at 6 - 8 weeks post-PCI in University Hospital Limerick (UHL) between January 2016 to December 2019. The cost analysis was based on a hierarchal analysis of patients on high dose statin, with an LDL-C &amp;gt;1.4mmol/L. Due to a low rate of prescribed ezetimibe we calculated the expected LDL-C, in patients on high dose statin with a presumed 25% reduction in LDL-C with the addition of ezetimibe. PCSK9i cost was based on the cohort of patients who would have an expected LDL-C &amp;gt;1.4 &amp; &amp;lt;1.8mmol/L despite treatment with high dose statin and ezetimibe. Cost was based on current pack reimbursement price of evoculmab, €8117.17 yearly. To calculate the benefit of a 1mmol/L LDL-C reduction in secondary prevention with PCSK9i therapy, we used a number needed to treat (NNT) of 21 over 5 years to prevent 1 CV death or myocardial infarctions based on meta-analysis data(4). Results A total of 784 patients were included in our analysis, who would be potentially eligible for a PCSK9i based on current ESC/EAS 2019 dyslipidemia guidelines with an expected LDL-C &amp;gt;1.4mmol/L. Baseline characteristics, mean age 63.6years, male 76.8%, 64.28% hypertension, 51.4% diabetes mellitus, smoking history 23.5%. Of the 784 patients potentially eligible for a PCSK9i, 375/784 (47.8%) had LDL-C of between 1.4mmol/L – 1.8mmol/L. Current cost for PSCK9i therapy for this patient cohort at our institution would result in potential total cost of €3,043,938.75 per year. In comparison expected cost of statin therapy in this group is €81,883.2 per year. 5 years of treatment with PCSK9i, assuming at least 1mmol/L reduction in LDL-C would be expected to prevent 17.8 CV deaths or MI’s in our cohort or €171,007.79 per event. In comparison the cost of statin therapy in this total cohort is €81,883.2 per year. Discussion Current cost of PCSK9i therapy in relation to first/second line lipid therapies makes prescribing prohibitive for patients with an LDL-C &amp;lt;1.8mmol/L. Additionally, the estimated cost of PCSK9i therapy to prevent one CVD/MI, limits the ability for this to become standard practice in Ireland, within the cohort of post-PCI patients with an LDL 1.4 – 1.8mmol/L.

FRI102 A Case Of Subclavian Artery Stenosis: Utility Of Lipoprotein (a) In Secondary Prevention Of Atherosclerotic Vascular Disease

Abstract Disclosure: F. Iqbal: None. R.A. Haas: None. Introduction: Atherosclerosis is the most common cause of upper extremity peripheral arterial disease (PAD). Prevalence of subclavian artery stenosis in the general population is approximately 2% with one study reporting a prevalence of 6.8% in those with diabetes mellitus (DM). We present a case of symptomatic upper extremity PAD in a patient with well controlled Type 1 DM and LDL-cholesterol at goal, but significantly elevated Lp(a). Clinical Case: 57-year-old Caucasian female with Type 1 DM (on CSII), hypothyroidism, obesity (BMI:43), hypertension and hyperlipidemia presented with several month history of left arm pain and cramping worsened by activity. At presentation, HbA1c was 6.1% and TSH 1.036 uIU/mL. She had been on atorvastatin, 40 mg once daily for several years with the addition of ezetimibe two years prior following an elevated coronary calcium score of 63. She underwent a left upper arm arterial duplex which showed 50-99% left subclavian and left axillary artery stenosis along with bilateral ICA stenosis. Lipid profile showed Total-C 112 mg/dL, LDL-C 59 mg/dL and HDL-C 34 mg/dL. She denied any symptoms of TIA or CVA. Vascular surgery recommended medical management with aspirin and risk factor modification. Cardiology advised CT chest-angiogram which showed moderate left subclavian stenosis and mild wall thickening of the great vessels and descending thoracic aorta. Work-up for arteritis was negative. A stress Echocardiogram showed inducible apical wall ischemia however no significant coronary artery disease was seen on angiogram. Her atorvastatin dose was increased to 80 mg once daily but as her diffuse atherosclerosis was out of proportion to her risk factors an Lp(a) level was checked and came back elevated at 356 nmol/L (desirable &amp;lt;75). She was continued on statin therapy, ezetimibe discontinued and Evolocumab (PCSK-9 inhibitor) was commenced. At follow-up (after 6 months of evolucamab treatment), she reported improvement in symptoms and repeat lipid profile was notable for Total-C 90, LDL-C 33, HDL38 and a 41% reduction in Lp(a) to 209. Conclusion: Lipoprotein (a) is an atherogenic, pro-inflammatory LDL-cholesterol like particle, the concentration of which is largely genetically determined. While the association between elevated Lp(a) and coronary artery disease has been well studied, there are few studies describing its relevance in peripheral artery disease. In our patient with symptomatic subclavian stenosis, the high Lp(a) served as marker of her diffuse atherosclerosis and elevated ASCVD risk. Although targeted Lp(a) lowering therapies are currently under investigation with promising initial results, currently the focus of management remains LDL-cholesterol lowering. PCSK9 inhibitors lower Lp(a) by 25%-40% and are a valuable treatment option. Presentation: Friday, June 16, 2023

Optimal implementation of the 2019 ESC/EAS dyslipidaemia guidelines in patients with and without atherosclerotic cardiovascular disease across Europe: a simulation based on the DA VINCI study.

The impact of the stepwise implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) treatment algorithm on low-density lipoprotein cholesterol (LDL-C) goal attainment was simulated in patients from the DA VINCI study. Monte Carlo simulation was used to evaluate treatment optimisation scenarios, based on a patient's risk category: statin intensification (step 1), addition of ezetimibe (step 2), and addition of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (step 3). Residual cardiovascular risk and predicted relative and absolute risk reduction (RRR and ARR) in cardiovascular events were assessed. In DA VINCI, 2482 patients did not achieve their 2019 ESC/EAS LDL-C goals and were included in the simulation. In patients without atherosclerotic cardiovascular disease (ASCVD) (n=962), 27.0% (n=259) and 57.0% (n=548) are likely to achieve their LDL-C goals at step 1 and step 2, respectively. Of those at very high risk without ASCVD (n=74), 88.1% (n=65) are likely to achieve their LDL-C goals at step 3. In patients with ASCVD (n=1520), 12.0% (n=183), 42.1% (n=641) and 93.2% (n=1416) are likely to achieve their LDL-C goals at steps 1, 2 and 3, respectively. In patients with and without ASCVD, treatment optimisation may result in mean simulated RRR of 24.0% and 17.7%, respectively, and ARR of 8.1% and 2.6%, respectively. Most patients at high cardiovascular risk are unlikely to achieve LDL-C goals through statin optimisation and ezetimibe, and will require a PCSK9 inhibitor, leading to greater reduction in cardiovascular risk. Amgen.

The Effectiveness and Safety of Intensive Lipid-Lowering with Different Rosuvastatin-Based Regimens in Patients at High Cardiovascular Disease Risk: A Nonblind, Randomized, Controlled Trial.

A statin alone or non-statins as add-ons have been introduced to intensive low-density lipoprotein cholesterol (LDL-C) -lowering therapy in patients at risk for high cardiovascular disease (CVD). The purpose of this study was to evaluate the effectiveness and safety of different rosuvastatin-based regimens for patients at high risk. Three hundred patients at high CVD risk were randomly assigned to the statin group (rosuvastatin, 20 mg/d), statin_EZ group (statin 10 mg/d + ezetimibe 10 mg/d), statin_pcsk group (statin 10 mg/d + alirocumab 75 mg/2 weeks) or combine3 group (statin 10 mg/d + ezetimibe 10 mg/d + alirocumab 75 mg/2 weeks). The primary outcome measure was cholesterol levels after 24 weeks of follow-up. Secondary outcomes included safety markers and the proportion of patients achieving the 70 mg/dL (1.8 mmol/L) target for LDL-C. A logistic regression model was performed to explore the factors affecting lipid target achievement. The total cholesterol (TC) and LDL-C levels in the four groups after treatment were significantly lower than those before treatment. TC and LDL-C levels after treatment were significantly different among the four groups (p 0.05). The levels in both the combine3 and statin_pcsk9 groups were significantly lower than those in the statin and statin_EZ groups (p 0.05), but there was no significant difference between the combine3 and statin_pcsk9 groups. Fifty-one participants (69%) in the statin_pcsk9 group and 56 participants (78%) in the combine3 group achieved the target. Body mass index (BMI) and hypertensive status were related to LDL-C target achievement. The incidence of adverse events in the four groups was low. The combination of a statin and a PCSK9 inhibitor was safe and more effective for the treatment of high-risk CVD patients, while the addition of ezetimibe was unable to significantly lower lipid levels any further. The rate of achieving the target was higher in patients with hypertension and a low BMI. Chinese Clinical Trial Registry, Identifier: ChiCTR2200058389, Date of Registration: 2022-04-08.

Simulation of bempedoic acid and ezetimibe in the lipid-lowering treatment pathway in Austria using the contemporary SANTORINI cohort of high and very high risk patients.

The low-density lipoprotein cholesterol goals in the 2019 European Society of Cardiology/European Atherosclerosis Society dyslipidaemia guidelines necessitate greater use of combination therapies. We describe areal-world cohort of patients in Austria and simulate the addition of oral bempedoic acid and ezetimibe to estimate the proportion of patients reaching goals. Patients at high or very high cardiovascular risk on lipid-lowering treatments (excluding proprotein convertase subtilisin/kexin type9 inhibitors) from the Austrian cohort of the observational SANTORINI study were included using specific criteria. For patients not at their risk-based goals at baseline, addition of ezetimibe (if not already received) and subsequently bempedoic acid was simulated using aMonte Carlo simulation. Acohort of patients (N = 144) with amean low-density lipoprotein cholesterol of 76.4 mg/dL, with 94% (n = 135) on statins and 24% (n = 35) on ezetimibe monotherapy or in combination, were used in the simulation. Only 36% of patients were at goal (n = 52). Sequential simulation of ezetimibe (where applicable) and bempedoic acid increased the proportion of patients at goal to 69% (n = 100), with adecrease in the mean low-density lipoprotein cholesterol from 76.4 mg/dL at baseline to 57.7 mg/dL overall. The SANTORINI real-world data in Austria suggest that aproportion of high and very high-risk patients remain below the guideline-recommended low-density lipoprotein cholesterol goals. Optimising use of oral ezetimibe and bempedoic acid after statins in the lipid-lowering pathway could result in substantially more patients attaining low-density lipoprotein cholesterol goals, likely with additional health benefits.

Potential Cardiovascular Events Avoided with Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination Compared with Ezetimibe Alone in Patients with Atherosclerotic Cardiovascular Disease Taking Maximally Tolerated Statins.

Patients with atherosclerotic cardiovascular disease who require additional low-density lipoprotein cholesterol (LDL-C) lowering despite maximally tolerated statins have a significant unmet medical need and are at increased risk of future cardiovascular events and a reduced quality of life. We aimed to estimate the percentage of cardiovascular events avoided following treatment with a fixed-dose combination of bempedoic acid plus ezetimibe (BA+EZE FDC) versus ezetimibe (EZE) in patients with atherosclerotic cardiovascular disease receiving maximally tolerated statins across a range of baseline LDL-C levels. A Markov cohort simulation model estimated major adverse cardiovascular events avoided over a lifetime horizon among patients with atherosclerotic cardiovascular disease and baseline LDL-C levels from 80 to >200 mg/dL. BA+EZE FDC was compared with EZE based on mean percent LDL-C reductions versus placebo reported in a phase III trial. Health outcomes for the average patient were extrapolated to a US population of 100,000 persons using evidence on contemporary LDL-C levels from the National Health and Nutrition Examination Survey. Among patients with atherosclerotic cardiovascular disease not at the LDL-C goal with maximally tolerated statins, the addition of BA+EZE FDC compared with the addition of EZE was predicted to provide incremental absolute reductions in major adverse cardiovascular events dependent on baseline LDL-C levels at the population level. For those with baseline LDL-C of 101-110 mg/dL (n = 15,237), there were 4.9% (744) fewer events predicted, while for patients with baseline LDL-C of >200 mg/dL (n = 1689), 10.9% (184) fewer events were predicted through the addition of BA+EZE FDC versus EZE. Further LDL-C reductions through the addition of BA+EZE FDC to maximally tolerated statins are predicted to reduce major adverse cardiovascular events compared with the addition of EZE. Benefits are potentially greater among those with higher starting LDL-C.

Simulation of bempedoic acid in the lipid-lowering treatment pathway using the European contemporary SANTORINI cohort of high- and very high-risk patients

Abstract Background Lowering LDL-C treatment goals in the 2019 ESC/EAS guidelines necessitates greater use of combination therapies (1). Cost of PCSK9 inhibitors (PCSK9i) and efficacy of ezetimibe alone as add on therapies limit population level achievement of LDL-C goals. Purpose This simulation study assessed the addition of oral bempedoic acid (BA) to ezetimibe in the treatment pathway in a real-world cohort of patients in order to assess the proportion of patients who might reach goal. Methods SANTORINI is a cohort study of European patients at high or very-high CV risk. Patients who were receiving any known LLT regimen with available data on LDL-C at baseline were eligible for this analysis. For patients not at risk-based LDL-C goals, the following treatment algorithm was applied (Figure 1), first the addition of ezetimibe and subsequently BA for those on statins, or addition of BA for those on ezetimibe and not at goal. Patients on PCSK9i remained in the cohort but no simulation was done. LDL-C reductions associated with ezetimibe and BA treatment were based on probabilistic distributions sourced from clinical trial efficacies based on prior studies (2–3). The effect of treatment on LDL-C levels was simulated through a Monte Carlo simulation run 10,000 times. No statin intensification was simulated as we assumed statin therapy was at maximum tolerated dose. Results At baseline (N=6252), mean age was 66 years and mean baseline LDL-C was 80.6 mg/dL with 1444 patients (23%) at goal; 93% (n=5797) were very high risk and 7% (n=455) high risk, of whom 84% (n=5227) were on statins, 23% (n=1447) on ezetimibe and 9% (n=546) on PCSK9i. Out of 4486 patients entering the simulation, 3419 received ezetimibe add-on with a third of those predicted to be achieving their risk-based goal (32%, n=1078/3419). Of those on ezetimibe and not at goal, the addition of BA would be predicted to result in another 36% goal achievement (n=1218/3408). Overall, the number of patients at goal would be expected to increase from 1444 (23%) at baseline to 2522 (40%) and 3740 (60%) after addition of ezetimibe and BA, sequentially. The mean LDL-C for the whole cohort would be expected to fall through this pathway from 80.6 mg/dL at baseline to 69.2 mg/dL and 61.1 mg/dL, respectively. Conclusion Few patients in the SANTORINI cohort were at goal at baseline and few would have LDL-C eligible for PCSK9i use. Optimising use of ezetimibe and BA after statins in the ESC/EAS 2019 LLT pathway could result in significantly more patients attaining lipid goals with likely additional health benefits. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH

Contemporary National Patterns of Eligibility and Use of Novel Lipid-Lowering Therapies in the United States.

Background The emergence of PCSK9i (proprotein convertase subtilisin kexin type 9 inhibitor) and icosapent ethyl (IPE) has expanded the role of lipid-lowering therapies beyond statins. Despite recommendations by clinical practice guidelines, their national eligibility and use rates remain unclear. Methods and Results In the National Health and Nutrition Examination Survey data from 2017 to 2020, we assessed eligibility and the use of statins, PCSK9i, and IPE among US adults according to American College of Cardiology/American Heart Association guideline recommendations. Eligibility for PCSK9i and IPE were determined in the following 2 scenarios: (1) assuming existing lipid-lowering therapy as the maximum tolerated before assessing eligibility for novel therapies and (2) assessing eligibility after assuming initiation and maximal escalation of preexisting lipid-lowering therapies and accounting for expected lipid improvements. Of 2729 sampled individuals, representing 149.3million adults, 1376 had indications for statins, representing 65.8million or 44.0% (95% CI, 40.9%-47.2%) of adults. Current statin use was 45% of those eligible and was low across demographic groups. A total of 9.7 and 11.6million adults would benefit from PCSK9i and IPE, respectively, based on lipid profiles and existing therapies. Assuming maximal escalation of statins and addition of ezetimibe, 4.1% (95% CI, 2.8%-5.4%) of adults or 6.1million would benefit from PCSK9i and 6.8% (95% CI, 5.4%-8.3%) or 10.2million from IPE. Conclusions Six and 10 million individuals have clinical profiles whereby PCSK9i and IPE, respectively, would be expected to improve cardiovascular outcomes even after maximum escalation of statins and ezetimibe use, but remain undertreated with lipid-lowering therapies. Optimal use of lipid-targeted agents that include these novel agents is needed to improve population health outcomes.

Bempedoic acid and PCSK9 inhibitor eligibility in a contemporary population with atherosclerotic cardiovascular disease

Abstract Funding Acknowledgements Type of funding sources: None. Background and Purpose The reduction of low-density lipoprotein cholesterol (LDL-C) in patients with established coronary heart disease (CHD) reduces the risk of atherosclerotic cardiovascular disease (ASCVD) events.(1) Many CHD patients fail to achieve guideline-recommended LDL-C targets without prohibitively expensive proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9 inhibitors).(2, 3, 4) This study aims to assess the impact that bempedoic acid may have on PCSK9 inhibitor eligibility in a population with CHD and ascertain whether its universal adoption would lead to overall cost-savings and a cost-effective reduction in ASCVD events. Methods and Results This retrospective analysis included 635 participants from the iASPIRE study, which recently assessed secondary prevention in an Irish cohort of CHD patients. We applied the 2019 ESC/EAS dyslipidaemia guideline LDL-C target of &amp;lt;1.4mmol/L and simulated the average treatment effect of improved lipid-lowering therapy with statins, ezetimibe and bempedoic acid. 86.3% of iASPIRE participants did not have LDL-C control and qualified for treatment intensification. Optimisation of statin therapy would allow 24.4% of patients to achieve their LDL-C goal, while the addition of ezetimibe would improve this to 55.7% leaving 44.3% eligible for a PCSK9 inhibitor. Utilising bempedoic acid would further reduce the proportion eligible to 18.7%. Based on current market prices and the universal application of ESC/EAS recommendations,(1, 5) the adoption of bempedoic acid would reduce the annual treatment costs associated with PCSK9 inhibitor use by almost 50% and result in cost savings per prevented CVD event. Conclusions The vast majority of CHD patients currently fail to achieve the recommended LDL-C target in everyday clinical practice. Ezetimibe and optimised statin therapy would enable most patients to meet their LDL-C goal. Employing bempedoic acid in patients with poor LDL-C control would significantly reduce the requirement for PCSK9 inhibitors and lead to cost savings per prevented CVD event.

Lipid-Lowering and Anti-Thrombotic Therapy in Patients With Peripheral Arterial Disease: European Atherosclerosis Society/European Society of Vascular Medicine Joint Statement

An updated evidence-based consensus of the Joint Task Force from the European Atherosclerosis Society and European Society of Vascular Medicine. The guidelines for patients with peripheral arterial disease (PAD) include a low-density lipoprotein cholesterol (LDL-C) goal of a >50% reduction from baseline and <1.4 mmol/L (<55 mg/dL). Lowering LDL-C reduces the incidence of cardiovascular events and major adverse limb events, including amputations, by 25%. The addition of ezetimibe or a PCSK9 (proprotein convertase subtilisin/kexin type 9 serine protease) inhibitor will further decrease the risk of cardiovascular events (the latter has been associated with a reduction in the risk of major adverse limb events by 40%). Statin-based treatment improved patients’ walking distance. Daily clopidogrel 75 mg or the combination of aspirin 100 mg and rivaroxaban (2 × 2.5 mg) is indicated to prevent cardiovascular events and should be used after lower extremity revascularization (with consideration of the bleeding risk). Adherence with these recommendations for lipid-lowering and antithrombotic therapy will improve the morbidity and mortality of patients with PAD.

Reduction of High Cholesterol Levels by a Preferably Fixed-Combination Strategy as the First Step in the Treatment of Hypertensive Patients with Hypercholesterolemia and High/Very High Cardiovascular Risk: A Consensus Document by the Italian Society of Hypertension.

The primary and secondary prevention strategies of atherosclerotic cardiovascular disease (ASCVD) largely rely on the management of arterial hypertension and hypercholesterolemia, two major risk factors possibly linked in pathophysiological terms by the renin-angiotensin system activation and that often coexist in the same patient synergistically increasing cardiovascular risk. The classic pharmacologic armamentarium to reduce hypercholesterolemia has been based in the last two decades on statins, ezetimibe, and bile acid sequestrants. More recently numerous novel, additive resources targeting different pathways in LDL cholesterol metabolism have emerged. They include drugs targeting the proprotein convertase subtilisin/kexin type 9 (PCSK9) (inhibitory antibodies; small-interfering RNAs), the angiopoietin-like protein 3 (inhibitory antibodies), and the ATP-citrate lyase (the inhibitory oral prodrug, bempedoic acid), with PCSK9 inhibitors and bempedoic acid already approved for clinical use. With the potential of at least halving LDL cholesterol levels faster and more effectively with the addition of ezetimibe than with high-intensity statin alone, and even more with the addition of the novel available drugs, this document endorsed by the Italian Society of Hypertension proposes a novel paradigm for the treatment of the hypertensive patient with hypercholesterolemia at high and very high ASCVD risk. Our proposal is based on the use as a first-line of a preferably fixed combination of lipid-lowering drugs, under the motto “Our goal: achieve control. No setback: combine and check”.

Ezetimibe- A Novel Add on Treatment Strategy to Achieve Targeted LDL in Patients with Uncontrolled LDL Levels on High Dose Statin Alone

Background: The lowering of low-density lipoprotein cholesterol (LDL-C) is the primary target of therapy in the primary and secondary prevention of cardiovascular events. Statins are the most prescribed lipid-lowering drugs, but many patients fail to achieve the target low-density lipoprotein (LDL) level with statin alone or at higher doses. The add-on therapy of 'Ezetimibe' to statin monotherapy has resulted in a synergistic effect in reducing LDL levels and achievements of lipid targets. Cholesterol comes from two sources. endogenous and exogenous. Rather than inhibiting one source, it is better to inhibit two sources. While statins inhibit endogenous production, Ezetimibe decreases absorption of cholesterol. Indian patients are also observed to have low HDL which is another risk factor for heart diseases. We aimed to assess the efficacy of the combination of atorvastatin plus ezetimibe in Indian patients with dyslipidemia and to see whether it can reduce LDL levels and Improve HDL and triglyceride levels. Objective: (1) To find out LDL reduction by addition of ezetimibe in combination with statin in Indian patients. (2) To find out increase in HDL levels by adding ezetimibe in combination with statin along with the reduction in triglyceride levels in Indian patients. Methods: The retrospective data from EMR of the patients diagnosed with a high level of LDL and satisfying the study's inclusion criteria were collected. The patients at the baseline were given monotherapy. Those who did not achieve the desired LDL were given treatment with Atorvastatin high dose (40 mg and 80 daily) and were allocated to the add-on therapy with Ezetimibe at 10 mg/day after 3 months. The groups (monotherapy and combined therapy) were compared at baseline and subsequent follow-up visits. Data were analyzed using R studio 1.2.1335 and Microsoft Excel. Statistical significance was considered at p&lt;0.05. Results: The LDL level showed a significant decrease after 18 months from baseline till the subsequent follow-up visits. The reduction observed in the serum concentration of LDL was from 167.95 ± 12.85 mg/dL to 91.9 ± 10.39 mg/dL (p &lt; 0.001) in 40 mg group and from 164.76 ± 9.9 mg/dL to 106.71 ± 17.17 mg/dL (p &lt; 0.001) in 80 mg group. Furthermore, the rate of achieving an LDL level &lt;100 mg/dL increased from 0% to 45.28% in the 40 mg group and from 0% to 35.24% in 80 mg group and showed significantly greater improvement (p = 0.001). Conclusion: Compared with high doses of statin, the combination of statin with Ezetimibe not only achieves targeted serum lipid levels, suggesting that combination therapy should be a priority when statin resistance or poor efficacy occurs with the higher dose of statin monotherapy. Keyword: LDL; HDL; Triglycerides; Atorvastatin; Ezetimibe

Abstract 11524: Ezetimibe Consistently Reduces LDL-C with Little Interindividual Variability in 14,970 Patients Post-ACS

Introduction: Ezetimibe (EZE) added to statin further reduces LDL-C and CV events. Prior studies demonstrated large inter-individual variability in LDL-C reduction with statins. Whether similar variability exists with EZE has not been reported in a large study. Methods: We assessed the placebo (PBO)-adjusted LDL-C reduction from randomization to 4 months in IMPROVE-IT, a double-blind RCT of EZE vs placebo (PBO) added to simvastatin (SIMVA) post-ACS. Inter-individual variation in % LDL-C reduction was calculated via rank-ordered subtraction of PBO/SIMVA from EZE/SIMVA. Patients not on study drug or with missing LDL-C values at either timepoint were excluded. Using the overall distribution of PBO-adjusted LDL-C reductions with EZE, we modelled the % of patients anticipated to achieve guideline-recommended LDL-C targets at 4 months with the addition of EZE across a range of baseline LDL-C values. Results: In 14,970 pts, the median baseline LDL-C in both groups was 80 mg/dL (IQR 65-96). The median change from baseline at 4 months was -37% (IQR -20% to -51%) in the EZE/SIMVA arm and -14% (IQR +7% to -31%) with PBO/SIMVA ( Panel A ). The PBO-adjusted median change in LDL-C at 4 months with EZE/SIM was -23% with low variability (IQR -19 to -27%; Panel A) . Based on this distribution, modelling predicts that fewer than half of patients would achieve the U.S. and European targets of &lt;70 and &lt;55 mg/dL when the baseline LDL-C is &gt;91 mg/dL and &gt;72 mg/dL, respectively, with the addition of EZE to statin therapy ( Panel B ). Conclusions: Addition of EZE to statin therapy results in a consistent median 23% reduction in LDL-C, with 75% of patients achieving at least a 19% reduction. The distribution of LDL-C reduction can be used to estimate how likely a patient will be to achieve guideline LDL-C targets with the addition of EZE to statin therapy.