Association of PCSK9 Variants with the Risk of Atherosclerotic Cardiovascular Disease and Variable Responses to PCSK9 Inhibitor Therapy

2021 ◽  
pp. 101043
Author(s):  
Chayakrit Krittanawong ◽  
Muzamil Khawaja ◽  
Robert S Rosenson ◽  
Christopher I. Amos ◽  
Vijay Nambi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Inhibitor Therapy ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitor

Management in der Gefäßmedizin – Therapie mit PCSK9-Inhibitoren derzeit unwirtschaftlich für US-Gesundheitssystem

2017 ◽  
Vol 22 (03) ◽  
pp. 126-126
Author(s):  
Gabriele Dobler
Keyword(s):  
Cardiovascular Disease ◽  
Cost Effectiveness ◽  
Familial Hypercholesterolemia ◽  
Inhibitor Therapy ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitor ◽  
Heterozygous Familial Hypercholesterolemia

Kazi DS et al. Cost-effectiveness of PCSK9 Inhibitor Therapy in Patients With Heterozygous Familial Hypercholesterolemia or Atherosclerotic Cardiovascular Disease. JAMA 2016; 316: 743–753 PCSK9-Inhibitoren wurden kürzlich in den USA für Patienten mit familiärer Hypercholesterinämie (FH) oder atherosklerotischer kardiovaskulärer Erkrankung (ASCVD) zugelassen, die trotz Maximaldosen von Statinen eine weitere Senkung des LDL-Cholesterins benötigen. Langfristig könnten sie wichtig bei der ASCVD-Prophylaxe werden. Die Autoren untersuchten die langfristige Wirtschaftlichkeit und potentiellen Kosten für das US-Gesundheitssystem.

scholarly journals Real-world use of PCSK9 inhibitors: A single-center experience

2018 ◽  
Vol 47 (1) ◽  
pp. 265-270 ◽  
Author(s):  
Sinan Sarsam ◽  
Abeer Berry ◽  
George Degheim ◽  
Robby Singh ◽  
Marcel Zughaib
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Profile ◽  
Real World ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
The Impact

Objective Hyperlipidemia is an important risk factor for atherosclerotic cardiovascular disease. Many patients are intolerant to or have limited benefit from statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been approved for treating hyperlipidemia in these patients. We sought to investigate the impact of these medications in a real-world cardiology practice. Methods This was a retrospective study of 17 patients with either heterozygous familial hypercholesterolemia or established atherosclerotic cardiovascular disease with low-density lipoprotein cholesterol (LDL-C) levels above the treatment target despite maximally tolerated statins. Baseline lipid profile was compared with a repeat lipid profile obtained 4 to 6 weeks after initiating treatment with a PCSK9 inhibitor. Results The average duration of PCSK9 inhibitor treatment was 10.7 months. Lipid profile comparison showed that total cholesterol decreased from 243 ± 72 to 148 ± 39 (mg/dL) (39% reduction), triglycerides decreased from 185 ± 86 to 149 ± 62 (mg/dL) (19.5% reduction), high-density lipoprotein cholesterol increased from 56 ± 20 to 62 ± 26 (mg/dL) (10.7% increase), and LDL-C decreased from 154 ± 30 to 57 ± 32 (mg/dL) (63% reduction) from baseline. Conclusions PCSK9 inhibitors as add-on therapy to maximally tolerated statins resulted in an approximately 63% reduction in LDL-C.

Abstract 15913: Two-year Results of the Getting to an Improved Understanding of Low-density Lipoprotein Cholesterol and Dyslipidemia Management (GOULD) Registry of Patients With Atherosclerotic Cardiovascular Disease (ASCVD)

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Christopher P Cannon ◽  
James A De Lemos ◽  
Christie M Ballantyne ◽  
Robert S Rosenson ◽  
Shushama Alam ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Statin Therapy ◽  
Treatment Guidelines ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitor ◽  
Statin Dose

Background: Atherosclerotic cardiovascular disease (ASCVD) treatment guidelines recommend intensive statin therapy and adding non-statin therapy if LDL-C ≥70 mg/dL. Methods: We designed the GOULD registry to assess lipid-lowering therapy (LLT) over time: At 120 U.S. centers, 5006 ASCVD patients on any (LLT) were enrolled in 1 of 3 cohorts: 1) currently on PCSK9 inhibitor (PCSK9i), 2) no PCSK9i and LDL-C ≥100 mg/dL, and 3) no PCSK9i and LDL-C 70-99 mg/dL. Results: Over the two years, only 16.8% had some type of LLT intensification, In the cohorts of patients with baseline LDL-C ≥ 100 and 70-99 mg/dL, LLT intensification was present in 21.9% and 14.3% respectively: statin dose was intensified in 6.1% and 6.1%, ezetimibe was added in 6.8% and 4.3% and PCSK9i was added in 6.3% and 2.2% respectively. Conversely, out of the total population, statins were discontinued in 246/4275 (5.8%), ezetimibe in 81/535 (15.1%), and PCSK9i in 47/544 (8.6%). At 24 months, 83.7% were on statin (43.4% high-intensity), with 14.2% on ezetimibe. Lipid panels were measured in 73% by 1 year and 84% by 2 years. Among Pts in the LDL-C ≥100 and 70-99 mg/dL cohorts, 18.6% and 30.4% achieved an LDL-C <70 mg/dL by 1 year, with little further change by 2 years: 21.3% and 33.5% respectively. In the PCSK9 cohort, 53.2% had LDL-C<70 mg/dl. Overall, only 31.7% had LDL-C <70 mg/dL at 2 years (an increase from 6.7% at baseline), while 25.0% had LDL-C >100 mg/dL. Conclusion: Of ASCVD patients with suboptimal LDL-C at baseline, even after 2 years of follow up, strikingly only 16% had LLT intensification, and thus most remained uncontrolled. Further intensive efforts are needed to achieve optimal LDL management in patients with ASCVD.

ID: 19: ELIGIBILITY FOR PCSK9 TREATMENT IN 734 HYPERCHOLESTEROLEMIC PATIENTS REFERRED TO A REGIONAL CHOLESTEROL TREATMENT CENTER WITH LDL CHOLESTEROL ≥70 MG/DL DESPITE MAXIMAL TOLERATED CHOLESTEROL LOWERING THERAPY

2016 ◽  
Vol 64 (4) ◽  
pp. 931.2-932
Author(s):  
P Shah ◽  
CJ Glueck ◽  
N Goldenberg ◽  
V Jetty ◽  
A Kumar ◽  
...  
Keyword(s):  
Conventional Treatment ◽  
Ldl Cholesterol ◽  
Inhibitor Therapy ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Cholesterol Lowering ◽  
Commercial Insurance ◽  
Pcsk9 Inhibitor ◽  
Lowering Therapy ◽  
Insurance Criteria

BackgroundLDL cholesterol (LDLC) lowering has been revolutionized by PCSK9 inhibitors, Alirocumab (Praluent) and Evolocumab (Repatha), which have approved indications as an adjunct to diet-maximally tolerated cholesterol lowering therapy in heterozygous (HeFH) or homozygous (HoFH) familial hypercholesterolemia, and/or clinical atherosclerotic cardiovascular disease (CVD) where LDLC lowering is insufficient despite maximal tolerated therapy.MethodsWe applied FDA approved and commercial insurance eligibility criteria for PCSK9 inhibitor use in 734 patients serially referred over 3 years who then received ≥2 months maximally tolerated LDLC lowering diet-drug therapy with follow up LDLC ≥70 mg/dl, as well as in 37 patients approved by commercial insurance for PCSK9 inhibitors. We obtained estimates of the percentage of patients with HeFH and/or CVD who meet FDA and commercial insurance eligibility for PCSK9 inhibitors using LDLC goal-based guidelines.ResultsOf the 734 patients with LDLC ≥70 mg/dl after ≥2 months maximally tolerated LDLC lowering therapy, 220 (30%) had HeFH and/or CVD events with LDLC >100 mg/dl, meeting both FDA and commercial insurance criteria for PCSK9 inhibitor therapy. Sixty-six (9%) patients were statin intolerant, without HeFH or CVD events. Of the 37 patients whose PCSK9 inhibitor therapy was approved for coverage by medical insurance carriers, 34 (92%) had LDLC>100 mg/dl after ≥2 months on maximally tolerated LDLC lowering therapy. Sixteen (43%) of these 37 patients had HeFH without CVD (LDLC on maximally tolerated conventional treatment 181±48 mg/dl), 11 (30%) had CVD without HeFH (LDLC on maximally tolerated conventional treatment 122±22 mg/dl), and 8 (22%) had both HeFH and CVD (LDLC on maximally tolerated conventional treatment 204±56 mg/dl).ConclusionOf the 734 patients referred for high LDLC treatment, with LDLC ≥70 mg/dl after ≥2 months on maximally tolerated therapy, 220 (30%) had HeFH and/or CVD with LDLC >100 mg/dl, meeting both FDA and insurance criteria for PCSK9 inhibitor therapy. If 30% of patients with high LDLC and HeFH-CVD are eligible for PCSK9 inhibitors, then specialty pharmaceutical pricing models (∼$14,300/year) will collide with an estimated 16–21 million HeFH-CVD patients. Although the costs for PCSK9 inhibitors given to an estimated 16 to 21 million patients are extraordinary ($228–300 billion), we speculate that, when weighed against direct and indirect costs of CVD, on balance, the cost to society might be either none, or that society would, in fact, save money by an anticipated 50% reduction of CVD events with PCSK9 inhibitors. Whether the health care savings arising from the anticipated reduction of CVD on the PCSK9 inhibitors justify the broad population use of these agents remains to be determined.

scholarly journals Trends in PCSK9 Inhibitor Prescriptions before and after the Price Reduction in Patients with Atherosclerotic Cardiovascular Disease

2021 ◽  
Vol 10 (17) ◽  
pp. 3828
Author(s):  
Alex Smith ◽  
Drew Johnson ◽  
Joshua Banks ◽  
Scott W. Keith ◽  
Dean G. Karalis
Keyword(s):  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Prescribing Patterns ◽  
Price Reduction ◽  
High Price ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Pcsk9 Inhibitor ◽  
Before And After

Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors reduce low-density lipoprotein (LDL) cholesterol and cardiovascular event rates, yet due to their high price remain underutilized and difficult to prescribe in clinical practice. In March 2018, their price was significantly reduced. We evaluated whether the price reduction would improve prescribing patterns of PCSK9 inhibitors in eligible patients with atherosclerotic cardiovascular disease (ASCVD). Methods: We identified the number of eligible ASCVD patients and those prescribed a PCSK9 inhibitor for each year between July 2015 and December 2019. Patient demographics and clinical characteristics for those prescribed a PCSK9 inhibitor were extracted from their electronic health record. Results: In total 1059 patients of eligible patients received a new prescription for a PCSK9 inhibitor. From 2015 to 2019, the rate of new prescriptions among eligible patients increased from 0.5 to 3.3% (p < 0.001) and continuation rates increased from 18 to 60% (p < 0.001). Following the price reduction, patients who were prescribed a PCSK9 inhibitor were younger and more likely to be female, but less likely to have Medicare insurance. Conclusions: Despite the reduction in the cost of PCSK9 inhibitors, most eligible patients are not prescribed one. The reduction in cost has improved adherence, primarily in patients with commercial insurance. Older patients and those on Medicare still face significant barriers in accessing a PCSK9 inhibitor. Further reductions in the price of the PCSK9 inhibitors are needed as is further study of the barriers that exist in prescribing one.

scholarly journals Attainment of the 2019 ESC/EAS recommended LDL-C goal in Greek patients with established atherosclerotic cardiovascular disease

2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
A Ioannidis ◽  
A Pechlevanis ◽  
M Paraskelidou
Keyword(s):  
Cardiovascular Disease ◽  
Phone Call ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
The Novel ◽  
High Potency ◽  
Northern Greece ◽  
Observation Study ◽  
Pcsk9 Inhibitor

Abstract Funding Acknowledgements Type of funding sources: None. Introduction The novel 2019 ESC/EAS Guidelines on lipids recommend a more intensive reduction on LDL-C for patients with established atherosclerotic cardiovascular disease (ASCVD) in comparison with the 2016 edition. Purpose This cross-sectional observation study aims to assess whether patients on lipid lowering therapy, as a secondary prevention measure, are aware of the new set goals and if they achieved them. Methods Patients with known ASCVD, taking currently any statin, visiting the Emergency Department of a tertiary hospital in northern Greece were invited to participate by answering a short questionnaire followed by a phone call to provide the exact lab results or other details. Data were analyzed with the SPSS software version 20.0 for Windows (SPSS Inc., Chicago, Illinois, USA) Results In total 459 eligible patients (37.9% female) were enrolled from January to October 2020 (mean age 68 ± 12 years old). Mean duration of statin prescription was about 11 years (11.2 ± 6 years). The majority (431, 93.9%) of the patients reported lab tests yearly. The majority of the participants (406, 88.5%) were taking a statin as monotherapy of either low (11, 2.4%), medium (174, 37.9%) or high (221, 48.1%) potency. One tenth (50, 10.9%) were prescribed a combination of ezetimibe with a medium or high potency statin. Lastly, only three patients (0.7%) were prescribed a PCSK9 inhibitor. Approximately, one out of six patients had a LDL-C lower than 55mg/dL (78, 17.0%). As expected, the higher the potency of the statin, the higher the percentage of patients reaching the goal: low (1 of 11 patients, 9.1%), medium (21 of 174 patients, 12.1%) and high potency (45 of 221 patients, 20.4%). Moreover, nine out of the fifty the patients (18.0%) on ezetimibe combination therapy achieved the LDL-C goal. Lastly, two of the three patients (66.7%) on a PCSK9 inhibitor had attained the desired LDL-C level. No information could be collected regarding why patients not reaching the goal were not offered a statin of higher potency and/or dosing, a combination with ezetimibe or a PCSK9 inhibitor, accordingly. Disturbingly enough, none of the patient was aware that the LDL-C goals recommended by scientific societies had been lowered in 2019, although 71 patients (15.5%) could recall discussing LDL-C goals with their physician, even though none of the patients recalled the limit of 55mg/dL. The majority of the patients (427, 93.0%) reported that they would like to know their personal LDL-C goal. Conclusions Greek patients with established ASCVD taking statins are overall unaware of the novel set LDL-C goals. Hardly acceptable attainment of the LDL-C goal was observed. Further research is warranted to assess the barriers that obstruct a satisfactory goal achievement. Abstract Figure. Patients achieving LDL-C goal

scholarly journals Inclisiran—Silencing the Cholesterol, Speaking up the Prognosis

2021 ◽  
Vol 10 (11) ◽  
pp. 2467
Author(s):  
Sylwester Rogula ◽  
Ewelina Błażejowska ◽  
Aleksandra Gąsecka ◽  
Łukasz Szarpak ◽  
Milosz J. Jaguszewski ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cholesterol Metabolism ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
General Information ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cardiovascular Risk Reduction ◽  
Speaking Up ◽  
Pcsk9 Inhibitor

The reduction of circulating low-density lipoprotein-cholesterol (LDL-C) is a primary target in cardiovascular risk reduction due to its well-established benefits in terms of decreased mortality. Despite the use of statin therapy, 10%–20% of high- and very-high-risk patients do not reach their LDL-C targets. There is an urgent need for improved strategies to manage dyslipidemia, especially among patients with homozygous familial hypercholesterolemia, but also in patients with established cardiovascular disease who fail to achieve LDL goals despite combined statin, ezetimibe, and PCSK9 inhibitor (PCSK9i) therapy. Inclisiran is a disruptive, first-in-class small interfering RNA (siRNA)-based therapeutic developed for the treatment of hypercholesterolemia that inhibits proprotein convertase subtilisin–kexin type 9 (PCSK9) synthesis, thereby upregulating the number of LDL receptors on the hepatocytes, thus lowering the plasma LDL-C concentration. Inclisiran decreases the LDL-C levels by over 50% with one dose every 6 months, making it a simple and well-tolerated treatment strategy. In this review, we summarize the general information regarding (i) the role of LDL-C in atherosclerotic cardiovascular disease, (ii) data regarding the role of PCSK9 in cholesterol metabolism, (iii) pleiotropic effects of PCSK9, and (iv) the effects of PCSK9 silencing. In addition, we focus on inclisiran, in terms of its (i) mechanism of action, (ii) biological efficacy and safety, (iii) results from the ORION trials, (iv) benefits of its combination with statins, and (v) its potential future role in atherosclerotic cardiovascular disease.

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