scholarly journals The impact of the revised ESC Dyslipidaemia Guidelines on lipid-lowering therapy: simulating the need for PCSK9 inhibition in a contemporary ASCVD cohort

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
C Blaum ◽  
F.J Brunner ◽  
F Kroeger ◽  
J Braetz ◽  
B Bay ◽  
...  
Keyword(s):  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Treatment Target ◽  
Pcsk9 Inhibitor ◽  
Lowering Therapy ◽  
Artery Disease ◽  
Pcsk9 Inhibition ◽  
The Impact

Abstract Introduction The recently updated ESC guidelines on the management of dyslipidaemias recommend a more intense LDL-cholesterol (LDL-C) reduction. For patients with atherosclerotic cardiovascular disease (ASCVD) the LDL-C goal has been revised to ≤55 mg/dl with a concomitant class IA upgrade for cost intensive PCSK9 inhibitors. Purpose We aim to quantify the need for PCSK9 inhibitors to achieve the revised LDL-C target compared to former ESC recommendations in ASCVD patients Methods We included all patients with ASCVD (angiographically documented coronary artery disease, history of peripheral artery disease or stroke) from an observational cohort study ongoing since 2015. A simulation treatment algorithm adding sequentially a high intensity statin, ezetimibe and a PCSK9 inhibitor in case of a missed treatment target was applied with consideration of both partial and total statin intolerance. The need for PCSK9 inhibitors was calculated for 3 recommendations: 1. LDL-C treatment target ≤55 mg/dl (ESC 2019 Guidelines), 2. LDL-C treatment target ≤70 mg/dl (ESC 2016 Guidelines) and 3. risk-based use of PCSK9 inhibitors restricted to patients with a residual LDL-C >140 mg/dl or >100 mg/dl with clinical/angiographic risk factors (ESC consensus update 2017). Results We included 1936 patients (mean age 69 years, 74% male). Median LDL-C at inclusion was 86 mg/dl, with 60% of patients taking lipid lowering medication (55% statin only, 4% statin + ezetimibe, 1% ezetimibe only). Table 1 shows the distribution of medications required to meet recommendations 1–3. After simulated stepwise intensification of lipid lowering therapy 99% of patients achieved the revised LDL-C target of ≤55 mg/dl, with a need of 23.5% for a PCSK9 inhibitor. For the former LDL-C target of ≤70 mg/dl the need for PCSK9 inhibitors was 10.5%. Restricting the use of PCSK9 inhibitors to the highest risk patients according to the ESC 2017 consensus statement reduced the need for PCSK9 inhibition to only 1.4% with slightly fewer patients achieving their LDL-C target (78% for ≤55 mg/dl and 91% for ≤70 mg/dl respectively). Conclusion The revised LDL-C treatment goals substantially increase the projected need for PCSK9 inhibitors with an unclear health economic impact. Identification of ASCVD patients with a reasonable benefit/cost-ratio of PCSK9 inhibition remains to be investigated urgently. Funding Acknowledgement Type of funding source: None

scholarly journals Lower is better: ezetimibe and PCSK9 inhibition join the mainstream of lipid‑lowering therapy

2016 ◽  
Vol 7 (1) ◽  
pp. 17-25
Author(s):  
Cezary Wójcik
Keyword(s):  
Statin Therapy ◽  
Heart Association ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Level Of Evidence ◽  
Cholesterol Guidelines ◽  
Pcsk9 Inhibition ◽  
Current Guidelines

The focus of 2013 cholesterol guidelines to prevent atherosclerotic cardiovascular disease (ASCVD) released by American College of Cardiology (ACC) and American Heart Association (AHA) is the administration of high intensity statin therapy to specific four groups of patients, which were found to benefit the most from such therapy. They no longer promote achieving specific LDL-C goals with a combination therapy involving statins and other drugs, as advocated by the former ATP-III guidelines as well as current guidelines of European Atherosclerosis Society, International Atherosclerosis Society or National Lipid Association. Such approach has been dictated by the strict reliance on randomized controlled trials as the only acceptable level of evidence. However, since publication of the 2013 ACC/AHA guidelines, cardiovascular benefits of ezetimibe added to statin therapy have been established. Moreover, the advent of PCSK9 inhibitors, providing a powerful supplement and/or alternative to statin therapy, further complicates the therapeutic horizon in dyslipdiemias. It is very likely that a new set of ACC/AHA guidelines will be published in 2016, with a return of specific LDL-C and Non-HDL-C goals of therapy as well as integration of drugs other than statins. As the treatment of dyslipidemias becomes more complex, the need for the subspecialty of clinical lipidology to be officially recognized becomes more evident.

Effect of evolocumab on acute arterial events across all vascular territories : results from the FOURIER trial

2021 ◽  
Author(s):  
Kazuma Oyama ◽  
Robert P Giugliano ◽  
Minao Tang ◽  
Marc P Bonaca ◽  
Jeffrey L Saver ◽  
...  
Keyword(s):  
Statin Therapy ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Limb Ischaemia ◽  
Lipid Lowering Therapy ◽  
Peripheral Vascular ◽  
Pcsk9 Inhibitor ◽  
Acute Limb Ischaemia ◽  
The Impact ◽  
Over Time

Abstract Aims We assessed the impact of the proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitor evolocumab on acute arterial events across all vascular territories, including coronary, cerebrovascular, and peripheral vascular beds, in patients with established atherosclerotic cardiovascular disease (ASCVD). Methods and results In the FOURIER trial, 27 564 patients with stable ASCVD on statin therapy were randomly assigned to evolocumab or placebo. Acute arterial events were a composite of acute coronary (coronary heart disease death, myocardial infarction, or urgent coronary revascularization), cerebrovascular (ischaemic stroke, transient ischaemic attack, or urgent cerebral revascularization), or peripheral vascular (acute limb ischaemia, major amputation, or urgent peripheral revascularization) events. Of the 2210 first acute arterial events, 74% were coronary, 22% were cerebrovascular, and 4% were peripheral vascular. Evolocumab reduced first acute arterial events by 19% (hazard ratio [HR] 0.81 [95% confidence interval 0.74–0.88]; P < 0.001), with significant individual reductions in acute coronary (HR 0.83 [0.75–0.91]), cerebrovascular (HR 0.77 [0.65–0.92]), and peripheral vascular (HR 0.58 [0.38–0.88]) events. There were 3437 total events (first plus recurrent), with evolocumab reducing total events by 24% (incidence rate ratio 0.76 [0.69–0.85]). The magnitude of reduction in acute arterial events with evolocumab numerically increased over time, with a 16% reduction (HR 0.84 [0.75–0.95]) in the first year followed by a 24% reduction (HR 0.76 [0.67–0.85]) thereafter. Conclusion The addition of the PCSK9 inhibitor evolocumab to statin therapy reduced acute arterial events across all vascular territories with a robust effect over time, indicating a pan-vascular impact of aggressive lipid-lowering therapy on these acute and clinically meaningful events. Clinical Trial Registration URL: https://www.clinicaltrials.gov. Unique identifier: NCT01764633.

Genetic testing for familial hypercholesterolemia: Impact on diagnosis, treatment and cardiovascular risk

2019 ◽  
Vol 26 (12) ◽  
pp. 1262-1270 ◽  
Author(s):  
Seohyuk Lee ◽  
Leo E Akioyamen ◽  
Sumayah Aljenedil ◽  
Jean-Baptiste Rivière ◽  
Isabelle Ruel ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Confidence Interval ◽  
Familial Hypercholesterolemia ◽  
Odds Ratio ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Increased Risk ◽  
The Impact

Aims Familial hypercholesterolemia (FH) is the most common genetic disorder in medicine, with a prevalence of 1/250. Affected individuals have elevated low-density lipoprotein cholesterol (LDL-C) and an increased lifetime risk of atherosclerotic cardiovascular disease (ASCVD). The diagnosis of FH is based on algorithms that include LDL-C levels, physical manifestations, family history of high LDL-C and premature ASCVD, and, more recently, genetic testing. We sought to determine the impact of genetic testing on the: 1) diagnosis of ‘definite familial hypercholesterolemia’, 2) initiation and adherence of lipid-lowering therapy and 3) risk of ASCVD. Methods We performed a systematic review and meta-analysis, pooling odds ratios and 95% confidence intervals for ASCVD from studies comparing risk estimates in individuals harboring FH-causing variants and unaffected individuals. Results After screening 3304 unique publications, 56 studies were included in the analysis. 1) Genetic testing provided confirmation of FH in 28–80%, over clinical criteria alone, depending on the diagnostic algorithm and the method of analysis. In two large population-based studies comprising 76,751 individuals, an FH-causing variant was identified in only 1.7–2.5% of subjects with an LDL-C > 4.9 mmol/L (190 mg/dL). 2) A confirmed molecular diagnosis increased lipid-lowering therapy adherence (five studies, n = 4181 definite FH). 3) Loss-of-function variant of the LDLR were at a markedly increased risk of myocardial infarction (odds ratio 6.77, 95% confidence interval 4.75–9.66), and patients with a milder (hypomorphic) pathogenic LDLR change had a 4.4-fold increase in risk (odds ratio 4.4, 95% confidence interval 2.34–8.26), compared with controls. Conclusion DNA sequencing confirms the diagnosis of FH but has a poor yield in unselected patients whose sole criterion is an elevated LDL-C. Initiation and adherence to treatment is improved. The risk of ASCVD is 4.4- to 6.8-fold increased in patients with an FH-causing variant compared with controls, depending on the severity of the DNA change.

Dyslipidaemia management in the cardiac rehabilitation clinic of a tertiary referral centre; analysis of the impact of new ESC guidance on LDL-C target achievement

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
C Mccaughey ◽  
D Ranganathan ◽  
G Murphy ◽  
M Kerins ◽  
R Murphy
Keyword(s):  
High Risk ◽  
Cardiac Rehabilitation ◽  
High Intensity ◽  
Lipid Lowering ◽  
Relative Reduction ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Lowering Therapy ◽  
Esc Guidelines ◽  
The Impact

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiac rehabilitation (CR) programs provide an opportunity to measure low density lipoprotein cholesterol (LDL-C) levels and optimise lipid lowering therapy (LLT) accordingly. New ESC guidelines released in August 2019 recommend lower absolute LDL-C target levels and an >50% reduction from baseline in those at the highest risk. Purpose This study investigated the proportion of those patients who finished CR in 2019 that reached both their absolute and relative reduction in LDL-C levels, before and after the introduction of these new guidelines. We also analysed the choice and appropriateness of LLT.  Methods A retrospective chart review of 163 patients who completed CR in 2019. A database was created containing baseline patient characteristics and LDL-C levels both prior and post CR; as well as the patient’s contemporary LLT. Those patients who did not have a previous diagnosis of atherosclerotic cardiovascular disease (ASCVD) were risk stratified as per ESC guidance.  Baseline LDL-C levels were recorded, where possible, and otherwise calculated using pre-CR LDL profile with an adjustment made based on the projected effects of their LLT. Results Mean (SD) patient age was 62 (10) years, 123/163 (75%) were male and 142 (87%) patients had established ASCVD. 90/142 (63%) of very high-risk patients were treated with a high intensity LLT and 5/163 overall (3%) were prescribed ezetimibe. Overall, 96/163 (59%) patients in 2019 met their absolute LDL-C targets; 62% of applicable patients achieved an >50% reduction in LDL-C levels. 104 (64%) of patients were treated in compliance with their contemporary guidelines. Both pre (n = 112) and post (n = 51) September 2019 cohorts were well matched. Fewer patients who were treated under the August 2019 guidelines reached their absolute LDL-C (51% v 63%, p < 0.005) targets; achieved a >50% reduction in LDL-C from baseline (48% vs 61%, p < 0.005), or were compliant with the guidelines for their risk category (43% vs 73%, p < 0.005). Conclusions Both high intensity statin therapy and ezetimibe are under-prescribed. Fewer patients are meeting the lower absolute LDL-C targets set out in the 2019 ESC guidelines. For those at high risk, determining the reduction in LDL-C from baseline reveals that even those meeting their absolute LDL-C targets may still be undertreated. LDL-C Target Achievement N Mean LDL Pre-CR (95% CI) Mean LDL-C Post CR (95% CI) Absolute LDL-C Target Met (%) Mean % LDL-C Reduction from Baseline (95% CI) > 50% Reduction (% of applicable patients) Guidelines Achieved Pre-Sept"20 112 2.7 (2.46-2.93) 1.64 (1.49- 1.79) 70 (63) 61 (56-66) 50 (65) 82 (73) Post Sept 20 51 2.83 (2.41-3.25) 1.83 (1.41-2.25) 26 (51) 48 (37-59) 11 (34) 22 (43) Total 163 2.72 (2.52- 2.91) 1.69 (1.57-1.82) 96 (59) 57 (52- 62) 61 (52) 104 (64 LDL-C targets met, stratified by contemporary guidelines followed. Abstract Figure. Choice of lipid lowering therapy in 2019

scholarly journals Application of the 2019 ESC/EAS dyslipidaemia guidelines to nationwide data of patients with a recent myocardial infarction: a simulation study

2020 ◽  
Vol 41 (40) ◽  
pp. 3900-3909 ◽  
Author(s):  
Ali Allahyari ◽  
Tomas Jernberg ◽  
Emil Hagström ◽  
Margrét Leosdottir ◽  
Pia Lundman ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
High Intensity ◽  
Low Density Lipoprotein ◽  
Monte Carlo Model ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Recent Myocardial Infarction ◽  
Lowering Therapy

Abstract Aims To estimate the proportion of patients with a recent myocardial infarction (MI) who would be eligible for additional lipid-lowering therapy according to the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias, and to simulate the effects of expanded lipid-lowering therapy on attainment of the low-density lipoprotein cholesterol (LDL-C) target as recommended by the guidelines. Methods and results Using the nationwide SWEDEHEART register, we included 25 466 patients who had attended a follow-up visit 6–10 weeks after an MI event, 2013–17. While most patients (86.6%) were receiving high-intensity statins, 82.9% of the patients would be eligible for expanded lipid-lowering therapy, as they had not attained the target of an LDL-C level of <1.4 mmol and a ≥50% LDL-C level reduction. When maximized use of high-intensity statins followed by add-on therapy with ezetimibe was simulated using a Monte Carlo model, the LDL-C target was reached in 19.9% using high-intensity statin monotherapy and in another 28.5% with high-intensity statins and ezetimibe, while 50.7% would still be eligible for proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. When use of alirocumab or evolocumab was simulated in those who were eligible for PCSK9 inhibitors, around 90% of all patients attained the LDL-C target. Conclusion  Our study suggests that, even with maximized use of high-intensity statins and ezetimibe, around half of patients with MI would be eligible for treatment with PCSK9 inhibitors according to the 2019 ESC/EAS guidelines. Considering the current cost of PCSK9 inhibitors, the financial implications of the new guidelines may be substantial.

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