Evolocumab Group Research Articles

Asia-Pacific Real-World Evolocumab Use, LDL-C Reduction, Physician Goals, and Patient Perceptions: HALES Observational Study.

Real-world data are needed to understand the effectiveness of new therapeutic options for low-density lipoprotein cholesterol (LDL-C) reduction in Asia-Pacific clinical practice. Description of evolocumab use among adults with establisHed Atherosclerotic cardiovascuLar diseasE or hypercholesterolemia in ASia-Pacific region (HALES) was performed to better understand characteristics of and clinical decision-making for adults with established atherosclerotic cardiovascular disease/hypercholesterolemia after local evolocumab approval. The HALES observational study, conducted at 33 sites (Hong Kong, Thailand, South Korea, Singapore, Taiwan, and Australia) comprised (1) chart review of patients who received evolocumab, a proprotein convertase subtilisin/kexin type9 inhibitor (PCSK9i), and (2) physician/patient survey and one-time data collection of patients with high cardiovascular risk initiating evolocumab or initiating/continuing non-PCSK9i lipid-lowering therapy. Patients could only enroll in (1) or (2). Chart review included 724 very high-risk patients initiating evolocumab from regulatory approval to 2021. From median baseline LDL-C of 3.2mmol/L (123.7mg/dL), patients had a median percent change in LDL-C of - 60.8% at 1-6months. Goal achievement increased from 7.9% to 69.8% for < 1.8mmol/L (< 70mg/dL) and 4.4% to 57.8% for < 1.4mmol/L (< 55mg/dL) from baseline to 12months. In the one-time data collection, more patients had ≥ 1.8mmol/L (≥ 70mg/dL) baseline LDL-C in the evolocumab vs non-PCSK9i group (95.2% and 48.5%, respectively). Surveys found that physicians applied guideline-recommended treatment targets, and patients demonstrated gaps in understanding cardiovascular risk. Real-world, Asia-Pacific data showed that LDL-C reduction after initiating evolocumab was consistent with that observed in other clinical trials and patient populations. Graphical abstract available for this article.·.

Efficacy of Alirocumab, Evolocumab, and Inclisiran in Patients with Hypercholesterolemia at Increased Cardiovascular Risk.

Background and Objectives: Lowering low-density lipoprotein (LDL-C) levels is critical for preventing atherosclerotic cardiovascular disease, yet some patients fail to reach the LDL-C targets despite available intensive lipid-lowering therapies. This study assessed the effectiveness and safety profile of alirocumab, evolocumab, and inclisiran in lipid reduction. Materials and Methods: A cohort of 51 patients (median (Q1-Q3) age: 49.0 (39.5-57.5) years) was analyzed. Eligibility included an LDL-C level > 2.5 mmol/L while on the maximum tolerated dose of statin and ezetimibe, a diagnosis of familial hypercholesterolemia, or a very high risk of cardiovascular diseases following myocardial infarction within 12 months prior to the study. Follow-ups and lab assessments were conducted at baseline (51 patients), 3 months (51 patients), and 15 months (26 patients) after the treatment initiation. Results: Median initial LDL-C levels 4.1 (2.9-5.0) mmol/L, decreasing significantly to 1.1 (0.9-1.6) mmol/L at 3 months and 1.0 (0.7-1.8) mmol/L at 15 months (p < 0.001). Total cholesterol also reduced significantly compared to baseline at both intervals (p < 0.001). No substantial differences in LDL-C or total cholesterol levels were observed between 3- and 15-month observations (p > 0.05). No statistically significant differences were noted in cholesterol reduction among the alirocumab, evolocumab, and inclisiran groups at 3 months. The safety profile was favorable, with no reported adverse cardiovascular events or significant changes in alanine transaminase, creatinine, or creatine kinase levels. Conclusions: Alirocumab, evolocumab, and inclisiran notably decreased LDL-C and total cholesterol levels without significant adverse effects, underscoring their potential as effective treatments in patients who do not achieve lipid targets with conventional therapies.

Efficacy of single-dose evolocumab injection in early-phase acute myocardial infarction: a retrospective single-center study.

Achieving rapid reduction of low-density lipoprotein cholesterol (LDL-C) levels below 55 mg/dL in patients with acute myocardial infarction (AMI) can be challenging with statins alone. This single-center, retrospective study aimed to assess the impact of single-dose injection of evolocumab 140 mg on LDL-C levels during the peri-percutaneous coronary intervention (PCI) period in patients with AMI. A total of 95 patients with AMI who underwent PCI were divided into the evolocumab (n = 50) and non-evolocumab (n = 45) groups. The percentage change of LDL-C level at 1-3 weeks from baseline was 78.4 ± 13.4% reduction in the evolocumab group versus 45.6 ± 22.6% in the non-evolocumab group, with a mean difference of -33.5% between the groups (95% CI: -42.6 to -24.5%; p < 0.001). The achievement rate of LDL-C levels below 55 mg/dL at 1-3 weeks was significantly higher in the evolocumab group than in the non-evolocumab group (97.7% vs. 60.0%, p < 0.001). Patients with AMI who received single-dose injection of evolocumab 140 mg during the peri-PCI period had a significantly greater LDL-C reduction and higher proportion of patients achieved the target LDL-C level in the early phase AMI than those who did not receive evolocumab.

Detection and Stabilisation of Vulnerable Plaques in the Coronary Arteries

Vulnerable atherosclerotic plaques (AP) can be assessed by coronary artery imaging techniques. Intravascular ultrasound allows real-time assessment of the longitudinal and transverse dimensions of the vessel, the severity of its remodelling, and the size and structure of the AP. The resolution of optical coherent tomography makes it possible to accurately identify vulnerable APs according to the following characteristic parameters: a large necrotic nucleus, a thin fibrous capsule, neoangiogenesis and inflammatory changes in the AP cap. Percent atheroma volume, total atheroma volume, maximum lipid core burden index within 4 mm, minimal fibrous cap thickness, maximum lipid arc, lipid length and macrophage grade are the main characteristics of vulnerable AP. Lipid-lowering therapy (LLT) has a stabilising effect on AP. Databases searched were PubMed and Web of Science up to April 2023. In total, eight relevant articles (original clinical studies) were selected. In the ODISSEY J-IVUS study, there was a decrease of total AP volume by 3.1% in the monotherapy group and 4.8% in the combined LLT group (p=0.23). In the GLAGOV trial, atheroma volume decreased by 0.9 mm3 in the placebo group and 5.8 mm3 in the evolocumab group (p&lt;0.001). Plaque regression was observed in 64.3% of patients in the evolocumab group and 47.3% in the placebo group. The dynamics of the minimum thickness of the fibrous cap varied within 18.0–62.67 µm on combined LLT and 13.2–33.19 µm on monotherapy (PACMAN-AMI). Regression of the lipid arc was also observed in the HUYGENS study. The development of cardiovascular imaging has made it possible to expand understanding of the morphology of vulnerable AP.

Evolocumab Treatment in Dyslipidemic Patients Undergoing Coronary Artery Bypass Grafting: One-Year Safety and Efficacy Results.

Background: The inhibition of PCSK9 lowered LDL cholesterol levels, reducing the risk of cardiovascular events. However, the effect on patients who have undergone surgical myocardial revascularization has not yet been evaluated. Methods: From January 2017 to December 2022, 180 dyslipidemic patients who underwent coronary artery bypass were included in the study. Until December 2019, 100 patients optimized therapy with statin ± ezetimibe (SG). Since January 2020, 80 matched patients added treatment with Evolocumab every 2 weeks (EG). All 180 patients were followed-up at 3 and 12 months, comparing outcomes. Results: The two groups are homogenous. At 3 months and 1 year, a significant decrease in the parameter mean levels of LDL cholesterol and total cholesterol is detected in the Evolocumab group compared to the standard group. No mortality was detected in either group. No complications or drug discontinuation were recorded. In the SG group, five patients (5%) suffered a myocardial infarction during the 1-year follow-up. In the EG group, two patients (2.5%) underwent PTCA due to myocardial infarction. There is no significant difference in overall survival according to the new treatment (p-value = 0.9), and the hazard ratio is equal to 0.94 (95% C.I.: [0.16-5.43]; p-value = 0.9397). Conclusions: The use of Evolocumab, which was started immediately after coronary artery bypass graft surgery, significantly reduced LDL cholesterol and total cholesterol levels compared to statin treatment alone and is completely safe. However, at one year of follow-up, this result did not have impact on the reduction in major clinical events.

PCSK9 inhibitor in acute ischemic stroke patient receiving mechanical thrombectomy: early outcomes and safety.

Lipid-lowering therapies are mainstays in reducing recurrence after acute ischemic stroke (AIS). Evolocumab, a Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, is a promising lipid-lowering agent known to decrease LDL cholesterol and mitigate vascular events alongside statins. However, its effects on the early functional outcomes post-mechanical thrombectomy (MT) remain unclear. This study aimed to assess the short-term effects and incidence of bleeding events after the early, off-label use of PCSK9 inhibitors in AIS patients undergoing MT. We retrospectively analyzed patients who had MT at a Regional Stroke Center from December 2018 to April 2023. Our primary outcome was discharge functional outcomes. Secondary outcomes included early neurologic deterioration (END), symptomatic intracerebral hemorrhage (sICH), 3-month functional outcomes, 3-month recurrence rate, and lipid profiles. Of 261 patients (mean age 69.2 ± 11.7, men 42.9%), 42 were administered evolocumab peri-procedurally. While baseline characteristics were similar between the two groups, evolocumab group demonstrated improved discharge outcomes, with a lower mean NIHSS (8.8 ± 6.8 vs. 12.4 ± 9.8, p = 0.02) and a higher percentage of patients with discharge mRS ≤ 3 (52.4% vs. 35.6%, p = 0.041). The 3-month follow-up show a non-significant trend toward an improved outcome in the evolocumab group. Multivariable analysis indicated that evolocumab had a potential impact on favorable discharge outcomes (aOR 1.98[0.94-4.22] for mRS ≤ 3 and 0.47[0.27-0.84] for lower ordinal mRS). Notably, evolocuamb users exhibited fewer instances of END and sICH, although they do not reach statistical significance. Additionally, the evolocumab group demonstrated potential benefits in LDL cholesterol reduction over time. Early use of evolocumab in AIS patients undergoing MT appeared to be safe and associated with better early functional outcomes. The potential benefit of the PCSK9 inhibitor shown here warrants further prospective studies.

Inhibition of PCSK9 with evolocumab modulates lipoproteins and monocyte activation in high-risk ASCVD subjects

BackgroundMechanistic studies suggest that proprotein convertase subtilisin/kexin type 9 inhibitors can modulate inflammation. MethodsDouble-blind, placebo-controlled trial randomized 41 ASCVD subjects with type 2 diabetes with microalbuminuria and LDL-C level >70 mg/dL on maximum tolerated statin therapy received subcutaneous evolocumab 420 mg every 4 weeks or matching placebo. The primary outcomes were change in circulating immune cell transcriptional response, lipoproteins and blood viscosity at 2 weeks and 12 weeks. Safety was assessed in all subjects who received at least one dose of assigned treatment and analyses were conducted in the intention-to-treat population. ResultsAll 41 randomized subjects completed the 2-week visit. Six subjects did not receive study medication consistently after the 2-week visit due to COVID-19 pandemic suspension of research activities. The groups were well-matched with respect to age, comorbidities, baseline LDL-C, white blood cell counts, and markers of systemic inflammation. Evolocumab reduced LDL-C by −68.8% (p < 0.0001) and −52.8% (p < 0.0001) at 2 and 12 weeks, respectively. There were no differences in blood viscosity at baseline nor at 2 and 12 weeks. RNA-seq was performed on peripheral blood mononuclear cells with and without TLR4 stimulation ("Stress" transcriptomics). "Stress" transcriptomics unmasked immune cell phenotypic differences between evolocumab and placebo groups at 2 and 12 weeks. ConclusionsThis trial is the first to demonstrate that PCSK9 mAB with evolocumab can modulate circulating immune cell properties and highlights the importance of "stress" profiling of circulating immune cells that more clearly define immune contributions to ASCVD.

Association between evolocumab use and slow progression of aortic valve stenosis.

No medications have been reported to inhibit the progression of aortic valve stenosis (AS). The present study aimed to investigate whether evolocumab use is related to the slow progression of AS evaluated by serial echocardiography. This was a retrospective observational study from 2017 to 2022 at Yokohama City University Medical Center. Patients aged ≥ 18 with moderate AS were included. Exclusion criteria were (1) mild AS; (2) severe AS defined by maximum aortic valve (AV) velocity ≥ 4.0m/s; and/or (3) no data of annual follow-up echocardiography. The primary endpoint was the association between evolocumab use and annual changes in the maximum AV-velocity or peak AV-pressure gradient (PG). A total of 57 patients were enrolled: 9 patients treated with evolocumab (evolocumab group), and the other 48 patients assigned to a control group. During a median follow-up of 33months, the cumulative incidence of AS events (a composite of all-cause death, AV intervention, or unplanned hospitalization for heart failure) was 11% in the evolocumab group and 58% in the control group (P = 0.012). Annual change of maximum AV-velocity or peak AV-PG from the baseline to the next year was 0.02 (-0.18 to 0.22) m/s per year or 0.60 (-4.20 to 6.44) mmHg per year in the evolocumab group, whereas it was 0.29 (0.04-0.59) m/s per year or 7.61 (1.46-16.48) mmHg per year in the control group (both P < 0.05). Evolocumab use was associated with slow progression of AS and a low incidence of AS events in patients with moderate AS.

Effect of combining evolocumab with statin on carotid intraplaque neovascularization in patients with premature coronary artery disease (EPOCH)

Background and aimsWe aimed to explore the effect of PCSK9 inhibitor based on the background of statin on carotid intraplaque neovascularization (IPN) assessed by serial contrast-enhanced ultrasound (CEUS) analysis in Chinese patients with premature coronary artery disease (PCAD). Methods41 patients were included to receive treatments with biweekly evolocumab (n = 22) or placebo (n = 19) in addition to statin therapy for 52 weeks. All patients were newly diagnosed with PCAD and treatments were initiated at baseline of the observations. Baseline and 52-week CEUS were acquired to measure the max plaque height (MPH) and IPN. The primary outcome was the 52-week IPN changes, the secondary endpoints included the 52-week MPH changes and major adverse cardiovascular events. ResultsThe mean ± SD age of the participants was 46.76 ± 8.56 years, and 61% (25/41) of patients were on statins before the start of the study. There was no statistically significant difference in the history of statins treatment and the initiated lipid-lowering therapy of atorvastatin and rosuvastatin between groups (p > 0.05). At 52 weeks, the evolocumab group showed a lower LDL level (0.84 ± 0.45 mmol/L vs. 1.58 ± 0.51 mmol/L, p < 0.001) and a greater decrease in percent reduction of LDL-C level (−65% vs. −32%) and a higher percent of achieving lipid-lowering target (95% vs. 53%, p < 0.05) compared with the placebo group. At 52 weeks, IPN (evolocumab group: 0.50 ± 0.60 vs. 1.50 ± 0.80, p < 0.001; placebo group: 0.79 ± 0.54 vs. 1.26 ± 0.65, p < 0.05) and MPH (evolocumab group: 2.01 ± 0.44 mm vs. 2.57 ± 0.90 mm, p < 0.05, placebo group: 2.21 ± 0.58 mm vs. 2.92 ± 0.86 mm, p < 0.05) reduced significantly in both groups from baseline to 52-week follow-up. IPN and MPH were decreased by both treatments. Still, there was no significant difference in delta (52 weeks - baseline) MPH by an ANOVA analysis between the two groups [evolocumab group: −0.56 mm (2.01 mm–2.57 mm); placebo group: −0.71 mm (2.21 mm–2.92 mm), p > 0.05]. In the evolocumab group, the change in the mean reduction of IPN from baseline [-1.00 (0.50–1.50) vs. −0.47 (0.79–1.26), p < 0.05] and the incidence of patients with carotid IPN decrease were significantly greater reduction (90% vs. 58%, p < 0.05). ConclusionsIf compared to placebo, the PCSK9 inhibitor evolocumab combined with statins resulted in a greater decrease in LDL-C and plaque neovascularization in Chinese patients with PCAD.

Proprotein convertase subtilisin/kexin type 9 inhibitors protect against contrast-associated acute kidney injury in patients with atherosclerotic cardiovascular disease.

Contrast-associated acute kidney injury (CA-AKI) may occur in patients undergoing medical procedures involving x-rays and radiocontrast media, potentially resulting in prolonged renal impairment. However, no effective treatments are available. Therefore, this study aimed to investigate the efficacy of evolocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, in reducing CA-AKI incidence among patients with atherosclerotic cardiovascular disease (ASCVD) undergoing percutaneous coronary intervention. This retrospective cohort study included patients who underwent percutaneous coronary intervention between January 2020 and December 2021 at Tianjin Chest Hospital. The study endpoint was CA-AKI incidence, and the impact of selection bias and other potential confounding factors was mitigated using bias matching. Overall, 1,642 patients were included in this study: 821 patients received evolocumab treatment before contrast agent application, and 821 did not receive such treatment. CA-AKI incidence was 6.21% and 8.04% in the evolocumab and control groups, respectively. After propensity-score matching, the incidence rate was 5.09% and 14.16% in the evolocumab and control groups, respectively. Evolocumab treatment significantly reduced CA-AKI incidence (p < 0.001). Consistent findings were obtained in the subgroups of individuals with type II diabetes mellitus, chronic heart failure, and hypertension. Evolocumab exhibited a significantly greater protective effect in the high- and extremely high-risk populations than in the low- and middle-risk populations (p < 0.001). Evolocumab administration significantly reduced CA-AKI incidence among patients with ASCVD. Notably, this effect was more prominent within the subset of high- and extremely high-risk individuals who were already experiencing CA-AKI.

Real-world effectiveness and safety of evolocumab in very high-risk atherosclerotic cardiovascular disease patients with acute ischemic stroke.

We investigated evolocumab's real-world effectiveness and safety on a background of statin therapy in the acute phase of ischemic stroke (IS) patients with a very high-risk of atherosclerotic cardiovascular disease (ASCVD). A real-world, single-center, retrospective study was conducted in the neurology department at Tianjin Huanhu Hospital in China. Patients were divided into two groups: evolocumab treatment (140mg every two weeks) or the standard of care (SOC) group. The primary efficacy outcome of the study was the achievement of a targeted lipid control rate and the incidence of major adverse cardiovascular events (MACE) by the end of the follow-up. MACE was defined as a composite of various cardiovascular events, cerebrovascular events such as stroke or TIA, and event-related deaths. Propensity score matching (PSM) analysis was utilized to account for confounding factors between groups. Survival analyses were performed using the Kaplan-Meier method and COX regression modeling. 1080 AIS patients with very high-risk ASCVD were recruited. After PSM, there were 528 individuals, with 206 in the evolocumab group and 322 in the SOC group. At 12 months of follow-up, the proportion of LDL-C < 1.4mmol/L and ≥ 50% reduction was 44.91% in the evolocumab group, compared with only 3.12% of SOC-treated patients (p < 0.01). The median follow-up time for clinical events was 15 months. The evolocumab group was associated with a lower risk of cerebrovascular events compared to the SOC group (HR, 0.45; 95% CI, 0.23-0.89; p = 0.02). This real-world study suggested that evolocumab on a background of statin reduced the LDL-C levels significantly and lowered the incidence of recurrent cerebrovascular events in the very high-risk ASCVD patients with AIS in China.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition with evolocumab decreases myocardial inflammation in individuals with acute coronary syndrome (ACS)

Abstract Background/Introduction Although inflammation is commonly present and often beneficial in the period following tissue injury, prolonged inflammation may impair healing and repair following acute ischemic injury. In addition to its impact on cholesterol metabolism PCSK9 is elevated in patients with inflammatory diseases and is thought to be a pro-inflammatory mediator. The presence and early trajectory of myocardial inflammation, and the impact of PCSK9 inhibition on that trajectory, in patients with an acute myocardial infarction have not been characterized. Purpose Our goals were to assess myocardial inflammation in patients with an acute myocardial infarction using 18F-FDG-PET scans obtained at the time of hospitalization for the infarction and at 30-days following the infarction and the impact of PCSK9 inhibition with evolocumab on inflammation in a placebo-controlled, randomized trial. Methods Fifty-five participants from the Evolocumab in Acute Coronary Syndrome trials, with a NSTEMI and a troponin-I of &amp;gt; 5 ng/ml or with a STEMI were randomized to placebo (n=30) or to 420 mg SQ of evolocumab (n=25) within 24 hours of admission. 18F-FDG-PET scans were performed within five days (2 [1-4]) of randomization and at 30 days. The myocardial mean Standardized Uptake Value (SUV) in the two randomized groups at baseline and the changes from baseline to 30 days were compared. All participants received guideline-directed therapies for acute infarction. Results Mean±SD age of the cohort was 57±13 years, 22% were African American, and 36% were women. There were no significant differences in demographic or clinical characteristics between the two groups. Mean SUV at baseline did not differ between the placebo (2.4±0.5) and the evolocumab (2.7±0.7) groups, p=0.25 for the between groups comparison. Mean SUV decreased in both groups, from 2.4±0.5 to 2.1±0.7 in the placebo group (p=0.05) and from 2.7±0.7 to 1.9±0.5 in the evolocumab group (p &amp;lt;0.0001), and the decrease was less in the placebo group, p=0.039 for the between groups comparison. The percent-change in the placebo group (-10.4%±36%) was also less than the percent change in the evolocumab group (-26.7%±20%), p = 0.04 for the between groups comparison. In addition, the percent of participants in whom the mean SUV units decreased was lower in the placebo group (60%) than in the evolocumab group (88%,), p=0.03 for the between groups comparison. Conclusion Myocardial inflammation assessed using 18F-FDG-PET decreases but is still present 30 days following an acute myocardial infarction. PCSK9 inhibition with evolocumab given within the first 24 hours of admission improves resolution of the inflammation. In addition to its marked impact on lipid levels, PCSK9 inhibition has significant anti-inflammatory effects in the early post-infarction setting.

Effect of evolocumab on platelet function in patients with acute coronary syndromes. An analysis of the randomized, double-blind, placebo-controlled EVOPACS Trial

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors substantially lower levels of low-density lipoprotein cholesterol (LDL-C) and favourably impact clinical outcomes in patients with acute coronary syndromes (ACS). Although PCSK9 inhibitors have been suggested in ex vivo studies to suppress platelet activation, the impact of evolocumab on platelet function in ACS patients receiving potent antiplatelet therapy remains largely unknown. Methods The EVOPACS trial was a randomized, double-blind, placebo-controlled trial assessing the use of evolocumab initiated in the acute phase of ACS. Patients presenting with ST-elevation myocardial infarction (STEMI) or Non-ST-elevation ACS (NSTE-ACS) were randomly allocated in a 1:1 ratio to either evolocumab 420mg SC or matching placebo at baseline (during hospitalization for index ACS event) and after 4 weeks. All patients received atorvastatin 40mg daily. Dual antiplatelet therapy consisting of aspirin and a potent P2Y12 inhibitor was initiated according to STEMI / NSTE-ACS guidelines, unless a less potent treatment was indicated (e.g. due to concomitant use of oral anticoagulation). Platelet function was measured at baseline (during index hospitalization) and after 8 weeks, using the Multiplate analyser. The main outcome for this analysis was the change from baseline to 8 weeks in adenosine diphosphate (ADP)-induced platelet aggregation. Results Serial platelet function measurements were available in 260 of all 308 enrolled patients, 124 in the evolocumab and 136 in the placebo group. Mean age was 60.2±11.0 years and 83% were men. Baseline clinical characteristics were well balanced between the two treatment groups. At discharge, the proportion of patients treated with ticagrelor, prasugrel, and clopidogrel was 73%, 11%, and 9% respectively, without differences between groups. Evolocumab significantly reduced LDL-C compared to placebo at 8 weeks (difference in mean percentage change -40.75%, 95% CI -45.39 to -36.11; p&amp;lt;0.001). Change in ADP-induced platelet aggregation between baseline and 8-week follow-up was -5.6±23.5 U (from 24.1±19.8 to 29.7±25.6 U) in the evolocumab group vs. -1.7±198.7 U (from 23.0±14.7 U to 24.7±19.1 U) in the placebo group (p=0.13). Similar results were found in a subgroup of 189 patients (86 in the evolocumab and 103 in the placebo group) treated with ticagrelor at discharge, showing a change in ADP-induced platelet aggregation of -2.7±19.5 U with evolocumab vs. -2.4±19.9 U with placebo (p=0.80). Conclusions In this randomized trial of ACS patients largely treated with a potent P2Y12 inhibitor, evolocumab initiated during index hospitalization on top of high-intensity statin therapy had no measurable effect on ADP-induced platelet aggregation. These findings suggest that the early therapeutic benefit of PCSK9 inhibitors in ACS patients is likely related to plaque regression/stabilization rather than changes in platelet activity.

Early Addition of Evolocumab to Statin Treatment in Patients with Acute Coronary Syndrome and Multivessel Disease Undergoing Percutaneous Coronary Intervention.

Evolocumab has been demonstrated to significantly reduce ischemic cardiovascular events in patients with stable coronary heart disease. However, it is currently unclear whether this benefit extends to patients with acute coronary syndrome (ACS) and multivessel disease (MVD) undergoing percutaneous coronary intervention (PCI). The objective of this study was to assess the safety, efficacy and feasibility of the early addition of evolocumab to statin treatment for ACS patients with MVD undergoing PCI. The authors conducted a multicenter, retrospective cohort study involving 1199 ACS patients with MVD undergoing PCI and with elevated low-density lipoprotein cholesterol (LDL-C) levels. Patients were divided into an evolocumab group or a standard-of-care group based on evolocumab use or not. The 18-month primary efficacy endpoint was a composite of ischemic stroke, death from cardiac causes, recurrent myocardial infarction (MI), unplanned coronary revascularization or unstable angina requiring hospitalization. The principal secondary efficacy endpoint was a composite of ischemic stroke, death from cardiac causes or recurrent MI. After propensity score matching, the addition of evolocumab to statin treatment lowered LDL-C levels by 42.62% compared with statin therapy alone at 18 months, from a mean baseline level of 3.37-0.75 mmol/L (p 0.001). Relative to standard therapy, evolocumab added to statins was associated with significant reductions in the primary efficacy endpoint (8.3% vs. 13.3%; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.39 to 0.91; p = 0.017) and the principal secondary efficacy endpoint (6.1% vs. 10.2%; adjusted HR, 0.61; 95% CI, 0.37 to 0.99; p = 0.048) after multivariable Cox regression adjustment. The treatment effect of evolocumab was consistent across all prespecified subgroups. There were no significant between-group differences in terms of adverse events. In ACS patients with MVD taken for PCI, early initiation of evolocumab along with statin treatment was associated with a significant reduction in LDL-C levels and a reduced risk of recurrent cardiovascular events. Chinese Clinical Trials Registry, identifier ChiCTR2000035165. Date: 2 August 2020. URL: https://www.chictr.org.cn/.

Evolocumab has no effects on heart failure with reduced ejection fraction injury biomarkers: The EVO-HF trial.

Patients with heart failure with reduced ejection fraction (HFrEF) have not been shown to benefit from statins. We hypothesized that, by limiting disease progression in stable HFrEF of ischaemic etiology, the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab could reduce circulating troponin levels, a surrogate biomarker of myocyte injury and atherosclerosis progression. The EVO-HF multicentre prospective randomized trial compared evolocumab (420 mg/month administered subcutaneously) plus guideline-directed medical therapy (GDMT; n = 17) versus GDMT alone (n = 22) for 1 year in patients with stable coronary artery disease and left ventricular ejection fraction (LVEF) <40%, ischaemic aetiology, New York Heart Association class II, N-terminal pro-B-type natriuretic peptide (NT-proBNP) ≥400 pg/ml, high-sensitivity troponin T (hs-TnT) >10 pg/ml, low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl. The primary endpoint was change in hs-TnT concentration. Secondary endpoints included NT-proBNP, interleukin-1 receptor-like 1 (ST2), high-sensitivity C-reactive protein (hs-CRP), LDL, low-density lipoprotein receptor (LDLR), high-density lipoprotein cholesterol (HDL-C), and PCSK9 levels at 1 year. Patients were mainly Caucasian (71.8%), male (79.5%), relatively young (mean age 68.1 ± 9.4 years), with a mean LVEF of 30.4 ± 6.5%, and managed with contemporary treatments. No significant changes in hs-TnT levels were observed in any group at 1 year. NT-proBNP and ST2 levels decreased in the GDMT plus evolocumab group (p = 0.045 and p = 0.008, respectively), without changes in hs-CRP, HDL-C, or LDLR. Total and LDL-C decreased in both groups, significantly higher in the intervention group (p = 0.003), and PCSK9 levels increased in the intervention group. This prospective randomized pilot trial, although with the limitation of the small sample size, does not support the benefit of evolocumab in reducing troponin levels in patients with elevated LDL-C levels, history of coronary artery disease, and stable HFrEF.

Evolocumab attenuate pericoronary adipose tissue density via reduction of lipoprotein(a) in type 2 diabetes mellitus: a serial follow-up CCTA study

BackgroundPericoronary adipose tissue (PCAT) density is a biomarker of vessel inflammation, which is supposed to be increased in patients with type 2 diabetes mellitus (T2DM). However, whether the coronary inflammation revealed by this novel index could be alleviated after evolocumab treatment in T2DM remains unknown.MethodsFrom January 2020 to December 2022, consecutive T2DM patients with low-density lipoprotein cholesterol ≥ 70 mg/dL on maximally tolerated statin and taking evolocumab were prospectively included. In addition, patients with T2DM who were taking statin alone were recruited as control group. The eligible patients underwent baseline and follow-up coronary CT angiography with an interval of 48-week. To render patients with evolocumab as comparable to those controls, a propensity-score matching design was used to select the matched pairs with a 1:1 ratio. Obstructive lesion was defined as the extent of coronary artery stenosis ≥ 50%; the numbers inside the brackets were interquartile ranges.ResultsA total of 170 T2DM patients with stable chest pain were included [(mean age 64 ± 10.6 [range 40–85] years; 131 men). Among those patients, 85 were in evolocumab group and 85 were in control group. During follow-up, low-density lipoprotein cholesterol (LDL-C) level (2.02 [1.26, 2.78] vs. 3.34 [2.53, 4.14], p < 0.001), and lipoprotein(a) (12.1 [5.6, 21.8] vs. 18.9 [13.2, 27.2], p = 0.002) were reduced after evolocumab treatment. The prevalence of obstructive lesions and high-risk plaque features were significantly decreased (p < 0.05 for all). Furthermore, the calcified plaque volume were significantly increased (188.3 [115.7, 361.0] vs. 129.3 [59.5, 238.3], p = 0.015), while the noncalcified plaque volume and necrotic volume were diminished (107.5 [40.6, 180.6] vs. 125.0 [65.3, 269.7], p = 0.038; 0 [0, 4.7] vs. 0 [0, 13.4], p < 0.001, respectively). In addition, PCAT density of right coronary artery was significantly attenuated in evolocumab group (− 85.0 [− 89.0, − 82.0] vs. − 79.0 [− 83.5, − 74.0], p < 0.001). The change in the calcified plaque volume inversely correlated with achieved LDL-C level (r = − 0.31, p < 0.001) and lipoprotein(a) level (r = − 0.33, p < 0.001). Both the changes of noncalcified plaque volume and necrotic volume were positively correlated with achieved LDL-C level and Lp(a) (p < 0.001 for all). However, the change of PCATRCA density only positively correlated with achieved lipoprotein(a) level (r = 0.51, p < 0.001). Causal mediation analysis revealed Lp(a) level mediated 69.8% (p < 0.001) for the relationship between evolocumab and changes of PCATRCA.ConclusionsIn patients with T2DM, evolocumab is an effective therapy to decrease noncalcified plaque volume necrotic volume, and increase calcified plaque volume. Furthermore, evolocumab could attenuate PCAT density, at least in part, via the reduction of lipoprotein(a).

The addition of evolocumab to maximal tolerated statin therapy improves walking performance in patients with peripheral arterial disease and intermittent claudication (Evol-PAD study)

ObjectiveTo test the hypothesis that in patients with peripheral arterial disease (PAD) and claudication, treated with maximal tolerated statin therapy, the addition of a monthly subcutaneous injection of evolocumab for 6 months improves treadmill walking performance. BackgroundLipid lowering therapy improves walking parameters in patients with PAD and claudication. Evolocumab decreases cardiac and limb adverse events in patients with PAD; however, the effect of evolocumab on walking performance is not known. MethodsWe performed a double-blind, randomized, placebo-controlled study to compare maximal walking time (MWT) and pain free walking time (PFWT) in patients with PAD and claudication treated with monthly subcutaneous injections of evolocumab 420 mg (n = 35) or placebo (n = 35). We also performed measurements of lower limb perfusion, brachial flow mediated dilatation (FMD), carotid intima media thickness (IMT), and serum biomarkers of PAD disease severity. ResultsAfter six-months of treatment with evolocumab MWT increased by 37.7 % (87.5 ± 24 s) compared to 1.4 % (−21.7 ± 22.9 s) in the placebo group, p = 0.01. PFWT increased by 55.3 % (67.3 ± 21.2 s) in the evolocumab group compared to 20.3 % (8.5 ± 20.3 s) in the placebo group, p = 0.051. There was no difference in lower extremity arterial perfusion measurements. FMD increased by 42.0 ± 73.9 % (1.01 ± 0.7 %) in the evolocumab group and decreased by 16.29 ± 20.06 % (0.99 ± 0.68 %) in the placebo group (p < 0.001). IMT decreased by 7.16 ± 4.6 % (0.06 ± 0.04 mm) in the evolocumab group and increased by 6.68 ± 4.9 % (0.05 ± 0.03 mm) in the placebo group, (p < 0.001). ConclusionsThe addition of evolocumab to maximal tolerated statin therapy improves maximal walking time in patients with PAD and claudication, increases FMD, and decreases IMT. Condensed abstractPeripheral arterial disease (PAD) impairs quality of life by causing lower extremity intermittent claudication, rest pain, or amputation. Evolocumab is a monthly injectable monoclonal antibody medication that reduces cholesterol. In this study, we randomly treated patients with PAD and claudication, and on background statin therapy, with evolocumab or placebo, and found that evolocumab improves walking performance on a treadmill test by increasing maximal walking time. We also found that evolocumab decreases plasma MRP-14 levels, a marker of PAD severity.

Effect of in-hospital evolocumab therapy on lipoprotein(a) in patients with acute myocardial infarction: a retrospective cohort study and a propensity score matching analysis.

This retrospective cohort analysis included a total of 467 AMI patients with LDL-C level >2.6 mmol/L upon admission, among whom 132 received in-hospital evolocumab (140 mg every 2 weeks) plus statin (20 mg atorvastatin or 10 mg rosuvastatin per day) and the remaining 335 received statin only. Lipid profiles at 1-month follow-up were compared between the two groups. A propensity score matching analysis was also conducted based on age, sex, and baseline lipoprotein(a) at a 1:1 ratio using a 0.02 caliper. At the 1-month follow-up, the lipoprotein(a) level decreased from 27.0 (17.5, 50.6) mg/dL to 20.9 (9.4, 52.5) mg/dL in evolocumab plus statin group, but increased from 24.5 (13.2, 41.1) mg/dL to 27.9 (14.8, 58.6) mg/dL in statin only group. The propensity score matching analysis included 262 patients (131 in each group). In subgroup analysis of the propensity score matching cohort stratified by the baseline lipoprotein(a) at cutoff values of 20 and 50 mg/dL, the absolute change in lipoprotein(a) was -4.9 (-8.5, -1.3), -5.0 (-13.9, 1.9), -0.2 (-9.9, 16.9) mg/dL in three subgroups in evolocumab plus statin group, and 0.9 (-1.7, 5.5), 10.7 (4.6, 21.9), 12.2 (2.9, 35.6) mg/dL in three subgroups in statin only group. In comparison to statin only group, evolocumab plus statin group had lower lipoprotein(a) level at 1 month in all subgroups (P < 0.05). In-hospital initiation of evolocumab on a background statin therapy reduced lipoprotein(a) level at 1-month follow-up in patients with AMI. Evolocumab plus statin therapy inhibited the increase in lipoprotein(a) in statin only therapy, regardless of the baseline lipoprotein(a) level.

516 SAFETY OF PCSK9I IN A SINGLE COUNTRY, MULTICENTER, OBSERVATIONAL STUDY: A POST-HOC ANALYSIS OF THE AT-TARGET-IT STUDY

Abstract Introduction PCSK9 inhibitors (PCSK9i) significantly decrease LDL cholesterol (LDL-C), either as monotherapy or in addition to the maximally tolerated dose of statin and/or ezetimibe. Yet, few data are available in real-world observations. Purpose AT-TARGET-IT is an Italian multicenter registry involving 9 Italian centers, designed to assess efficacy, adherence, and persistence of PCSK9i, as well as prescribing doctors’ behavior in patients with atherosclerotic cardiovascular disease (ASCVD) or familial hypercholesterolemia (FH). The aim of the present analysis was to assess differences between evolocumab and alirocumab on safety in patients on PCSK9i in a real-world single country observational study. Methods From June through November 2021, we enrolled patients with PCSK9i first prescription from 6 months before inclusion through starting of PCSK9i use. Clinical and demographic characteristics, concomitant therapies, blood chemistry, were recorded at the time of first prescription and at the latest observation preceding inclusion in the study. Results Of 798 patients enrolled, 566 (70.9%) patients took Evolocumab and 232 (29.1%) Alirocumab (of them, 117 patients Alirocumab 75 mg and 115 Alirocumab 150 mg). The LDL-C values reductions did not significantly differ between Evolocumab and Alirocumab groups (65.1% for Evolocumab; 64.5% for Alirocumab, p=ns). Regarding safety events, after a median observation period of 19.3 months (6; 57), 19 patients (2.4%) had acute coronary syndrome, 18 (2.3%) hospitalization for CV causes, 3 (0.4%) stroke, 6 (0.8%) new-onset heart failure (HF) and 68 (4.9%) the composite endpoints of ACS, CV hospitalization, new onset HF, new onset chronic kidney disease, stroke and cerebrovascular insufficiency. Comparing events between patients in Alirocumab and in Evolocumab, no significant difference was found between the two groups. Combined endpoint of adverse events occurred more frequently in patients in Alirocumab (27; 11.6%), in comparison with those in Evolocumab (41; 7.2%) (p=0.044) (Figure). Conclusion AT-TARGET-IT study shows that between evolocumab and alirocumab there was a statistically significant difference on the combined endpoint of adverse events.

Restoring mortality data in the FOURIER cardiovascular outcomes trial of evolocumab in patients with cardiovascular disease: a reanalysis based on regulatory data

ObjectiveThe FOURIER trial showed a benefit of the PCSK9 inhibitor evolocumab over placebo with respect to cardiovascular outcomes in patients with cardiovascular disease. However, we observed some inconsistencies between the...