scholarly journals What is the potential cardiovascular risk reduction associated with achieving LDL-C levels recommended in the ESC/EAS guidelines for very high-risk patients? Data from 18 European countries

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K Ray ◽  
S Bray ◽  
A.L Catapano ◽  
N Poulter ◽  
G Villa
Keyword(s):  
High Risk ◽  
Risk Reduction ◽  
Absolute Risk ◽  
European Countries ◽  
Lipid Lowering ◽  
Funding Source ◽  
Lipid Lowering Therapy ◽  
Cardiovascular Risk Reduction ◽  
Private Company ◽  
Very High

Abstract Background/Introduction For patients at very-high risk of cardiovascular (CV) events, the 2016 ESC/EAS dyslipidaemia guidelines recommended lipid-lowering therapy (LLT) to achieve an LDL-C level below 70 mg/dL. This was lowered to an LDL-C level below 55 mg/dL in the 2019 guidelines. Purpose To assess: 1) the risk profile of European patients with established atherosclerotic CV disease (ASCVD) receiving LLT; and 2) the treatment gap between the estimated risk and the population benefits if all patients were to achieve LDL-C levels of 70 mg/dL and 55 mg/dL. Methods We used data from Da Vinci, an observational cross-sectional study conducted across 18 European countries. Data were collected at a single visit between June 2017 and November 2018, for consented adults who had received any LLT in the prior 12 months and had an LDL-C measurement in the prior 14 months. LDL-C level was assessed at least 28 days after starting the most recent LLT (stabilised LLT). For each patient with established ASCVD receiving stabilised LLT, we: 1) calculated their absolute LDL-C reduction required to achieve LDL-C levels of 70 mg/dL and 55 mg/dL; 2) predicted their 10-year CV risk using the REACH score based on demographic and medical history; 3) simulated their relative risk reduction (RRR) by randomly sampling from the probability distribution of the rate ratio per 38.7 mg/dL (1 mmol/L) estimated by the Cholesterol Treatment Trialists Collaboration meta-analysis; and 4) calculated their absolute risk reduction (ARR) achieved by meeting LDL-C levels of 70 mg/dL and 55 mg/dL. Results A total of 2039 patients with established ASCVD were included in the analysis. Mean (SD) LDL-C was 83.1 (35.2) mg/dL. 40.4% and 19.3% of patients achieved LDL-C levels of 70 mg/dL and 55 mg/dL, respectively. Mean (SD) 10-year CV risk calculated using the REACH score was 36.3% (15.4%). Mean absolute LDL-C reductions of 19.6 mg/dL and 30.4 mg/dL were needed to reach LDL-C levels of 70 mg/dL and 55 mg/dL, respectively. When adjusted for the LDL-C reduction required to achieve an LDL-C level of 70 mg/dL, mean ARR was 3.0%, leaving a mean (SD) residual 10-year CV risk of 33.3% (15.5%). When adjusted for the LDL-C reduction required to achieve an LDL-C level of 55 mg/dL, mean ARR was 4.6%, leaving a mean (SD) residual 10-year CV risk of 31.7% (15.2%). Conclusion(s) In a contemporary European cohort with ASCVD receiving LLT, the 10-year risk of CV events is high and many patients do not achieve LDL-C levels of 55 mg/dL or even of 70 mg/dL. Moreover, even if all patients were to achieve recommended LDL-C levels, they would still remain at a high residual risk of CV events. These data suggest these patients require even more intensive LLT. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

scholarly journals What potential risk reduction could be achieved with evolocumab treatment? A simulation based on observational data from a cohort of users in 10 European countries

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K Ray ◽  
I Bridges ◽  
E Bruckert ◽  
B Van Hout ◽  
M Sibartie ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Risk Reduction ◽  
Potential Risk ◽  
Real World ◽  
European Countries ◽  
Lipid Lowering ◽  
Funding Source ◽  
Lipid Lowering Therapy ◽  
Simulation Based

Abstract Background/Introduction The FOURIER trial enrolled very high-risk patients with a mean LDL-C of 2.5 mmol/L, and demonstrated that evolocumab reduced major cardiovascular events by 1.5% in absolute terms over 2.2 years. Further research may be conducted to understand the potential benefits of evolocumab in the real world. Purpose Predict/simulate baseline CV risk and assess potential risk reduction among a large European cohort of evolocumab users. Methods We used interim data from an observational study of patients initiating evolocumab across 10 European countries from August 2015 with follow-up through October 2019. Demographic and clinical characteristics, lipid-lowering therapy (LLT) and lipid values were collected from routine medical records (6 months prior to evolocumab initiation through 30 months post initiation). For each patient, we 1) predicted/simulated their 10-year CV risk using three different approaches: i) a prediction using REACH score, ii) a simulation based on FOURIER trial patients, iii) a simulation based on real-world FOURIER-like patients from a published obervational study; 2) calculated their absolute LDL-C reduction on evolocumab treatment; 3) simulated their relative risk reduction (RRR) by randomly sampling from the probability distribution of the rate ratio per 1 mmol/L from the key secondary endpoint in the FOURIER trial landmark analysis; 4) calculated their absolute risk reduction (ARR). Results Our analysis included 779 patients initiating evolocumab in clinical practice per local reimbursement criteria, with up to 18 months follow-up. Mean (SD) age was 62.7 (9.6) years and mean (SD) baseline LDL-C was 3.85 (1.39) mmol/L. Mean (SD) absolute LDL-C reduction on evolocumab was 2.1 (1.2) mmol/L. Predicted/simulated 10-year CV risk, RRR and ARR are presented in Table 1. Simulated probability distributions (based on FOURIER) for 10-year CV risk before and after evolocumab treatment are shown in Figure 1. Conclusion(s) This cohort of evolocumab users in clinical practice had an almost 2-fold higher baseline LDL-C than patients enrolled in FOURIER trial, which translated to higher baseline CV risk. For that reason, the estimated 10-year absolute benefit in this cohort was larger than expected based on FOURIER trial results. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

scholarly journals Pooled safety and efficacy of inclisiran in patients with statin intolerance (ORION-10 and ORION-11)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
R.S Wright ◽  
D Kallend ◽  
F.J Raal ◽  
R Stoekenbroek ◽  
W Koenig ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Therapeutic Option ◽  
Lipid Lowering ◽  
Funding Source ◽  
Lipid Lowering Therapy ◽  
Statin Intolerance ◽  
Private Company ◽  
Phase 3 ◽  
Absolute Reduction ◽  
Secondary Endpoints

Abstract Introduction Statin-associated side effects prevent a substantial proportion of patients from being adequately treated with statin therapy and achieving adequate LDL-C reductions. Phase 3 trials showed that inclisiran, a new siRNA, durably lowers LDL-C by ≥50% on top of maximally tolerated statin therapy. Purpose To evaluate inclisiran's tolerability and LDL-C lowering effects among individuals who were not receiving statin therapy mainly because of statin intolerance. Methods The Phase 3 ORION-10 and ORION-11 trials randomized patients with established ASCVD (or risk-equivalents) with LDL-C >70 mg/dl despite maximally tolerated statins to inclisiran or placebo (1:1). Inclisiran sodium 300 mg was administered s.c. at baseline, three months later, then every six months. The primary efficacy endpoints were % change in LDL-C from baseline to Day 510 and time adjusted % change in LDL-C from baseline after Day 90 and up to Day 540. Absolute LDL-C reductions were secondary endpoints. This analysis included individuals who were not on statin therapy at baseline. Results The trials included 252 (7.9% of the pooled trial populations; mean age 68; male 62%; lipid-lowering therapy 28%). AE rates and LDL-C reductions are shown in the Table. Overall, 12 (4.7%) patients had myalgia (4.8% in the inclisiran groups, 4.7% in the placebo groups). There were 8 discontinuations in the inclisiran groups (6.5%) and 3 in the placebo groups (2.3%). The placebo-adjusted mean reduction in LDL-C at Day 510 was 45.8%, an absolute reduction of 68.0 mg/dL (p<0.0001). Conclusion Among statin intolerant individuals in ORION-10 and 11, inclisiran potently and durably lowered LDL-C with an adverse event profile comparable to placebo. Inclisiran may represent a new and potent therapeutic option for patients with elevated LDL-C unable to tolerate statins. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): The Medicines Company

Do European patients with peripeheral arterial disease receive optimal lipid lowering therapy and achieve LDL-C goals? Results from the DA VINCI study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K Ray ◽  
M Feudjo Tepie ◽  
A.L Catapano ◽  
P Giovas ◽  
S Bray ◽  
...  
Keyword(s):  
Da Vinci ◽  
Arterial Disease ◽  
Lipid Lowering ◽  
Moderate Intensity ◽  
Funding Source ◽  
Lipid Lowering Therapy ◽  
Private Company ◽  
Cerebral Disease ◽  
Study Visit ◽  
Lowering Therapy

Abstract Background 2016 and 2019 EAS/ESC dyslipidemia guidelines recommend lipid lowering therapy (LLT) to reduce LDL-C in patients with peripheral arterial disease (PAD) with or without established cardiovascular (CV) disease, and recommend target LDL-C goals based on individual CV risk. Data regarding the implementation of these guidelines in clinical practice across Europe is currently lacking. Purpose Describe LLT and achievement of the target LDL-C goals recommended in EAS/ESC dyslipidemia guidelines in patients with PAD. Methods The cross-sectional Da Vinci study enrolled consenting adults who had received LLT in the 12 months prior to the study visit and had at least one LDL-C measurement in the 14 months prior to the study visit, seen in a primary or secondary care setting across 18 European countries. Patients with coronary, peripheral and cerebral disease were enrolled at a ratio of 1:2:2. FH patients with prior CV events were excluded. Data were collected from medical records at a single visit between Jun '17–Nov '18, including LLT and most recent LDL-C. Primary outcome was LDL-C goal attainment ≥28 days after starting most recent LLT (treatment-stabilised LLT). Results Of 5888 patients enrolled, 2794 met our definition of atherosclerotic cardiovascular disease (ASCVD). Of these ASCVD patients, 1036 (37%) had PAD. 31% (323/1036) of PAD patients were female and mean (SD) age was 69 (9.4) years. Concomitant CV risk factors included diabetes mellitus (473/1036 patients [46%]), hypertension (809/1036 [78%]) and smoking (794/1036 [77%]). 26% (271/1036) of patients with PAD also had coronary vascular disease and 12% (122/1036) also had cerebrovascular disease. At the visit date, approximately half (497/1036 [48%]) of all PAD patients were receiving moderate intensity statins and 41% (421/1036) were receiving high intensity statins. 818 (73%) of the PAD patients had a treatment-stabilised LDL-C measurement (median, 2.20 mmol/L), of whom 40% (326/818) achieved the 2016 EAS/ESC LDL-C goal of 1.8 mmol/L and only 19% (159/818) achieved the 2019 goal of 1.4mmol/L. Conclusions European patients with PAD are not treated as per EAS/ESC recommendations, with a large proportion receiving suboptimal LLT and fewer than half achieving target LDL-C levels. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

Abstract 13117: Incorporation of High-Sensitivity Troponin Along With the AHA/ACC Cholesterol Guidelines for Improved Risk Stratification and Targeted PCSK9 Inhibition in Atherosclerotic Cardiovascular Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nicholas A Marston ◽  
Kazuma Oyama ◽  
Minao Tang ◽  
Petr Jarolim ◽  
Peter S Sever ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Reduction ◽  
Lower Risk ◽  
Absolute Risk ◽  
High Sensitivity ◽  
Absolute Risk Reduction ◽  
Pcsk9 Inhibitors ◽  
High Sensitivity Troponin ◽  
Cholesterol Guidelines ◽  
Very High

Introduction: The 2018 AHA/ACC cholesterol guidelines only recommend PCSK9 inhibitors in patients with very high risk ASCVD. However, high-sensitivity troponin (hsTn) can reclassify some lower risk patients as very high risk, identifying a subgroup who may benefit from PCSK9 inhibitors. Methods: We performed a nested prospective biomarker substudy including 22,224 patients enrolled in the FOURIER trial, which tested the PCSK9 inhibitor evolocumab. Per the guidelines, patients were assigned to ASCVD risk categories of “very high risk” or “not very high risk” (lower risk), followed by classification based on hsTnI (Abbott ARCHITECT) using an a priori risk threshold of 6 ng/L. The primary endpoint was a composite of CV death, MI, stroke, unstable angina, or coronary revascularization. The median follow-up was 2.2 years. Results: Clinical ASCVD categories alone identified a gradient of risk from 7.1% to 12.3% (HR 1.83, p<0.0001). Adding hsTnI further risk stratified patients by 1.5- to 2-fold in both the lower and very high risk ASCVD categories (HR 1.73, p=0.017 & HR 1.81, P<0.0001). Among patients with lower risk ASCVD, 25% had an elevated hsTnI and carried a similar risk (10.5%) to patients with very high risk ASCVD and low hsTnI (9.8%). Very high risk ASCVD patients receiving evolocumab had an absolute risk reduction of 1.9% (0.98-2.72). A similar absolute risk reduction was seen in the 25% of patients in the lower risk group with elevated hsTnI (ARR 2.0%, Figure). Conclusions: Either hsTn or ASCVD clinical criteria can identify patients who benefit from evolocumab. Specifically, hsTnI identifies a significant cohort of nominally lower risk ASCVD patients who are actually at greater risk than appreciated and may derive absolute risk reductions on par with very high risk ASCVD patients.

scholarly journals Management of High and Very High-Risk Subjects with Familial Hypercholesterolemia: Results from an Observational Study in Bulgaria

Folia Medica ◽  
2018 ◽  
Vol 60 (3) ◽  
pp. 389-396 ◽  
Author(s):  
Ivo S. Petrov ◽  
Arman Sh. Postadzhiyan ◽  
Mariya P. Tokmakova ◽  
Lyudmila G. Kitova ◽  
Svetlin N. Tsonev ◽  
...  
Keyword(s):  
High Risk ◽  
Observational Study ◽  
Genetic Disorder ◽  
Physician Education ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Mean Values ◽  
Premature Cardiovascular Disease ◽  
Very High ◽  
Observation Period

Abstract Background: Familial hypercholesterolaemia (FH) is a genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease (CVD). This retrospective observational study examined the clinical characteristics and management of FH subjects in Bulgaria over a 12-month period. Materials and methods: Twelve cardiology sites participated in this study from May 2015 to May 2016. Eligible subjects had at least two routine low-density lipo-protein cholesterol (LDL C) measurements and a prescription for lipid-lowering therapy (LLT) at the start of the observation period. Mean values for gender, age and cardiovascular (CV) event history at baseline and LDL-C over time were estimated. Results: Of the 220 eligible subjects, 196 fulfilled the criteria for FH diagnosis: 27 definite, 94 probable and 75 possible. Mean age at enrolment was 54.4 years and 64.1% of subjects were male. Mean CV risk classification at baseline was 26.8% high-risk (HR) and 73.2% very high-risk (VHR). Mean LDL-C was 5.6 mmol/L at enrolment and 4.1 mmol/L at last observation visit (12 months). The ESC/EAS Guideline LDL-C targets (applicable at the time of the study) were achieved by 14.5% of HR and 5.0% of VHR subjects. Most subjects (n=219) received statins. One subject was statin intolerant (ezetimibe therapy). Intensive statin treatment (atorvastatin 40–80 mg/daily and rosuvastatin 20–40 mg/daily) was used in 38.6% of individuals during the observation period and 10% of subjects received combination therapy (statin plus ezetimibe or other LLT). Conclusions: Most subjects with FH do not reach the ESC/EAS defined LDL-C targets. Early identification and physician education may improve FH management.

scholarly journals Residual Risk of Cardiovascular Complications in Case of Adequate Lipid-Lowering Therapy

2018 ◽  
Vol 3 (2) ◽  
pp. 19-25
Author(s):  
VV V Simerzin ◽  
OV V Fatenkov ◽  
IV V Gagloeva ◽  
MA A Galkina ◽  
YaA A Panisheva
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Cardiovascular Complications ◽  
Residual Risk ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Target Level ◽  
Lowering Therapy ◽  
Risk Patients ◽  
Very High

This article is devoted to the problems of residual risk of cardiovascu1ar comp1ications deve1opment for high and very high risk patients under adequate lipid-fowering pharmacotherapy in spite of c^lestera! and tow-density 1ipoproteins target level achievement. Afong with classic risk factors the special atte^ton is given to 1ipoprotein (a) [LP (a)] as the most aggressive factor of cardwvascular system atherosclerotic diseases devetopment and their comp1ications. Great importance is attached to 1ipidopheresis.

scholarly journals Evolocumab use in Europe: clinical guidelines vs. reimbursement thresholds – results from the HEYMANS study

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
K K Ray ◽  
E Bruckert ◽  
P Filardi ◽  
C Ebenbichler ◽  
A Vogt ◽  
...  
Keyword(s):  
Clinical Guidelines ◽  
Clinical Characteristics ◽  
Lipid Lowering ◽  
Moderate Intensity ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Private Company ◽  
Statin Monotherapy ◽  
Very High

Abstract Background 2019 ESC/EAS guidelines recommend a 50% lowering in untreated LDL-C and use of PCSK9 inhibitors (PCSK9i) for patients (pts) at very high cardiovascular (CV) risk when LDL-C goals of &lt;1.4mmol/L are not met despite maximally tolerated statins and ezetimibe. However, the LDL-C threshold at which PCSK9i are reimbursed are higher than the goals recommended in clinical guidelines. Purpose This prospective observational cohort study describes clinical characteristics and LDL-C control among pts initiating evolocumab across 12 EU countries. Methods Pts are followed from evolocumab initiation (baseline). Demographic/clinical characteristics, lipid lowering therapy (LLT) and lipid values are being collected from medical records (6 months before evolocumab up to 30 months post initiation). We report interim data from pts initiating evolocumab from August 2015 followed-up until July 2020. Results Of the 1,952 pts in whom evolocumab was initiated as per local reimbursement criteria, most (1844 [94%]) had 12 months follow-up, 785 (40%) had 24 months follow-up; mean follow-up: 20 months. Mean (SD) age was 60 (10.8) years; 85% of pts had a history of CV disease, 45% had familial hypercholesterolemia, 19% had type 2 diabetes, 65% were hypertensive, 7% had chronic kidney disease and 51% were prior/current smokers. At evolocumab initiation, 60% reported statin intolerance and 41% were on no background LLT. Fewer than half (846 [43%]) were receiving a statin (± ezetimibe); of these, most received a high/moderate intensity (68%/22%), with 13% receiving statin monotherapy. Median (Q1, Q3) baseline LDL-C was 3.98 (3.17, 5.07) mmol/L. Within 3 months of initiation median LDL-C fell by 58% to 1.63mmol/L. This reduction was maintained over time (Figure 1). Overall, 58% of pts achieved at least one LDL-C &lt;1.4mmol/L during follow-up. Among pts receiving background statins ± ezetimibe at evolocumab initiation, 67% (710/1053) achieved at least one LDL-C &lt;1.4mmol/L, versus 44% (317/714) of pts not receiving background statins/ezetimibe. During follow-up background oral LLT did not materially change; 40–45% pts received no LLT, 41–44% received statin ± ezetimibe, 12–14% received statin monotherapy. Conclusion In Europe, pts initiated on evolocumab had baseline LDL-C levels almost 3x higher than the present threshold for PCSK9i use recommended in guidelines reflecting disparities between local reimbursement criteria and guidelines. Although evolocumab led to a &gt;50% reduction in LDL-C, only ∼50% pts achieved an LDL-C &lt;1.4mmol/L, as approximately 41% received only evolocumab as monotherapy. LDL-C goal attainment was however higher among pts receiving evolocumab with background LLT. Therefore, lowering the LDL-C threshold for PCSK9i reimbursement, would result in more patients receiving combination therapy with oral LLT plus PCSK9i, thus increasing the likelihood of more pts achieving very-high risk LDL-C goals. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Amgen Europe GmbH

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

2021 ◽  
Vol 10 (24) ◽  
pp. 5938
Author(s):  
Jean Ferrières ◽  
François Roubille ◽  
Michel Farnier ◽  
Patrick Jourdain ◽  
Denis Angoulvant ◽  
...  
Keyword(s):  
High Risk ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Real Life ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Cholesterol Goal ◽  
Very High

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

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