Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors, Reality or Dream in Managing Patients with Cardiovascular Disease

2019 ◽  
Vol 20 (1) ◽  
pp. 72-82 ◽  
Author(s):  
Mohammad Alkhalil
Keyword(s):  
Cardiovascular Disease ◽  
Monoclonal Antibodies ◽  
Cardiovascular Events ◽  
Cost Effective ◽  
Lipid Lowering ◽  
High Dose ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Ldl Receptors ◽  
Coa Reductase

Background: Statins have been a major keystone in the management of patients with atherosclerotic cardiovascular disease. The benefits of inhibiting HMG CoA reductase, via statins, were translated into reduction in LDL-c with proportionate decrease in cardiovascular events in response to the magnitude of LDL-c reduction. Despite major advances in pharmacological treatments, including the use of high-dose statins, there are urgent need to further reduce future cardiovascular risk. This is in particularly important since 1 out of 5 high-risk atherosclerotic patients who achieve low LDL-c return with a second cardiovascular event within five years. Although this residual risk post-statin is largely heterogeneous, lowering LDL-c beyond ‘normal’ or guidelines-recommended level using novel therapies has resulted in further reduction in cardiovascular events. </P><P> Objective: The current review will discuss the use of PCSK9 inhibitors in patients with atherosclerotic disease. PCSK9 inhibitors are a new class of lipid-lowering drugs that are either fully human monoclonal antibodies (evolocumab and alirocumab) or humanised monoclonal antibodies (bococizumab) that effectively reduce LDL-c to unprecedented level. By blocking circulating PCSK9, these drugs would preserve LDL receptors and prevent them from cellular degradation. This process promotes recycling of LDL receptors back to hepatocytes surface, leading into further reduction of LDL-c. Combining PCSK9 inhibitors with statin have led into lower LDL-c, reduction in plaque volume and more importantly reduction in future cardiovascular events. Conclusion: These drugs are very promising, nonetheless, the unselective approach of applying these monoclonal antibodies may not prove to be cost-effective and potentially exposing some patients to unnecessary side effects.

Prescribing high-dose lipid-lowering therapy early to avoid subsequent cardiovascular events: is this a cost-effective strategy?

2011 ◽  
Vol 19 (3) ◽  
pp. 474-483 ◽  
Author(s):  
R Ara ◽  
A Pandor ◽  
J Stevens ◽  
R Rafia ◽  
SE Ward ◽  
...  
Keyword(s):  
Primary Care ◽  
Cardiovascular Events ◽  
Cost Effective ◽  
Effective Alternative ◽  
Lipid Lowering ◽  
High Dose ◽  
Lipid Lowering Therapy ◽  
Coronary Syndrome ◽  
Cost Effective Alternative ◽  
The Cost

Background: While evidence shows high-dose statins reduce cardiovascular events compared with moderate doses in individuals with acute coronary syndrome (ACS), many primary care trusts (PCT) advocate the use of generic simvastatin 40 mg/day for these patients. Methods and results: Data from 28 RCTs were synthesized using a mixed treatment comparison model. A Markov model was used to evaluate the cost-effectiveness of treatments taking into account adherence and the likely reduction in cost for atorvastatin when the patent expires. There is a clear dose–response: rosuvastatin 40 mg/day produces the greatest reduction in low-density lipoprotein cholesterol (56%) followed by atorvastatin 80 mg/day (52%), and simvastatin 40 mg/day (37%). Using a threshold of £20,000 per QALY, if adherence levels in general practice are similar to those observed in RCTs, all three higher dose statins would be considered cost-effective compared to simvastatin 40 mg/day. Using the net benefits of the treatments, rosuvastatin 40 mg/day is estimated to be the most cost-effective alternative. If the cost of atorvastatin reduces in line with that observed for simvastatin, atorvastatin 80 mg/day is estimated to be the most cost-effective alternative. Conclusion: Our analyses show that current PCT policies intended to minimize primary care drug acquisition costs result in suboptimal care.

scholarly journals Cardiovascular outcomes trials with statins in diabetes

2018 ◽  
Vol 18 (1) ◽  
pp. 7-13 ◽  
Author(s):  
Fariha Naeem ◽  
Gerard McKay ◽  
Miles Fisher
Keyword(s):  
Cardiovascular Disease ◽  
Side Effects ◽  
Primary Prevention ◽  
Secondary Prevention ◽  
Statin Therapy ◽  
Cardiovascular Events ◽  
Atherosclerotic Disease ◽  
Lipid Lowering ◽  
High Dose ◽  
Drug Side Effects

Treatment with statins is one of the most effective ways of reducing cardiovascular events in those with diabetes. Many studies containing thousands of subjects with diabetes have demonstrated that statins reduce cardiovascular events when there is no known cardiovascular disease (primary prevention) and in those with confirmed atherosclerotic disease (secondary prevention). High-dose statins appear to be even more effective in established cardiovascular disease, but at the expense of increased drug side effects. In this paper we review the evidence for the benefits of statins in diabetes. In a second review we will examine the evidence for possible benefits of other lipid-lowering therapies when these are added to background statin therapy in diabetes.

scholarly journals Cardiovascular outcomes trials with non-statin lipid-lowering drugs in diabetes

2018 ◽  
Vol 18 (3) ◽  
pp. 101-105
Author(s):  
Fariha Naeem ◽  
Gerard McKay ◽  
Miles Fisher
Keyword(s):  
Statin Therapy ◽  
Cardiovascular Events ◽  
Ldl Cholesterol ◽  
Lipid Lowering ◽  
High Dose ◽  
Large Trial ◽  
Pcsk9 Inhibitors ◽  
Vascular Events ◽  
Lipid Lowering Drugs ◽  
Cardiovascular Morbidity And Mortality

Statin therapy is proven to reduce cardiovascular morbidity and mortality in people with diabetes, and high-dose statins are recommended for people with established atherosclerotic vascular disease. In two dedicated studies in people with diabetes, fibrates did not significantly reduce cardiovascular events and were associated with serious side effects. A similar lack of benefit was seen in two large studies of niacin. Ezetimibe, when added to statins, may further reduce LDL cholesterol and non-fatal vascular events. The PCSK9 inhibitors are a new class of subcutaneous lipid- lowering drugs which cause profound reductions in LDL cholesterol when added to statins. Evolocumab reduced non-fatal cardiovascular events when added to background statin therapy in a larger group of subjects and the benefits were confirmed in a diabetes subgroup. In another large trial alirocumab reduced major adverse cardiovascular events and total mortality. The clinical use of ezetimibe and PCSK9 inhibitors is currently limited by cost.

PCSK9 Inhibitors: From Nature’s Lessons to Clinical Utility

2020 ◽  
Vol 20 (6) ◽  
pp. 840-854
Author(s):  
Frederick J. Raal ◽  
Robert Chilton ◽  
Naresh Ranjith ◽  
Virendra Rambiritch ◽  
Rory F. Leisegang ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Absolute Risk ◽  
Lipid Lowering ◽  
Major Adverse Cardiovascular Events ◽  
Tolerability Profile ◽  
Atherosclerotic Cardiovascular Disease ◽  
Lipid Lowering Therapy ◽  
Pcsk9 Inhibitors ◽  
Ldl Receptors ◽  
Coronary Syndrome

Background: Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors are a novel class of non-statin lipid lowering therapy that reduce LDL-cholesterol by 50 - 60%. PCSK9 inhibitors decrease LDL-cholesterol by preventing intracellular degradation of LDL receptors; subsequently, a greater number of LDL-receptors are available on the cell surface to extract circulating LDL. Objective: To describe the origins of PCSK9 inhibitors and their current use in clinical practice. Methods: We performed a narrative review of the PCSK9 inhibitor class of drugs. Results: Current data indicate that PCSK9 inhibitors effectively reduce LDL-cholesterol and are well tolerated and safe. PCSK9 inhibitors have also been shown to reduce cardiovascular event rates in patients with stable atherosclerotic cardiovascular disease and in patients with a recent (up to one year) acute coronary syndrome. Given the costs, chronicity of the treatment and the potential budget impact, PCSK9 inhibitors are often limited to patients with the highest absolute risk for major adverse cardiovascular events despite optimal treatment with high-intensity statin and ezetimibe. Conclusion: PCSK9 inhibitors have a favorable safety, efficacy and tolerability profile. Postmarketing safety surveillance and real-world studies are needed to further support the long-term safety profile of this class of medicine.

scholarly journals Therapeutic Potential of Quercetin as an Antiatherosclerotic Agent in Atherosclerotic Cardiovascular Disease: A Review

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Qian Deng ◽  
Xiao Xue Li ◽  
Yanting Fang ◽  
Xin Chen ◽  
Jingui Xue
Keyword(s):  
Cardiovascular Disease ◽  
Therapeutic Potential ◽  
Antioxidant Properties ◽  
Blood Lipid ◽  
Cost Effective ◽  
Medical Community ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Surgical Interventions ◽  
Wide Range

Atherosclerotic cardiovascular disease (ASCVD) is one of the diseases with the highest morbidity and mortality globally. It causes a huge burden on families and caregivers and high costs for medicine and surgical interventions. Given expensive surgeries and failures of most conventional treatments, medical community tries to find a more cost-effective cure. Thus, attentions have been primarily focused on food or herbs. Quercetin (Qu) extracted from food, a flavonoid component, develops potentials of alternative or complementary medicine in atherosclerosis. Due to the wide range of health benefits, researchers have considered to apply Qu as a natural compound in therapy. This review is aimed to identify the antiatherosclerosis functions of Qu in treating ASCVD such as anti-inflammatory, antioxidant properties, effects on endothelium-dependent vasodilation, and blood lipid-lowering.

scholarly journals A real-world assessment of treatment patterns in patients with atherosclerotic cardiovascular disease with hypercholesterolemia: a retrospective database analysis in Germany

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
I Gouni-Berthold ◽  
D Seshagiri ◽  
R Studer ◽  
S Klebs ◽  
A Achouba ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Real World ◽  
Treatment Patterns ◽  
Lipid Lowering ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Private Company ◽  
General Physician ◽  
Statin Monotherapy ◽  
The Mean

Abstract Background The European Society of Cardiology (ESC) guidelines suggest that greater absolute reduction in low-density lipoprotein cholesterol (LDL-C) leads to greater cardiovascular risk reduction. Several lipid-lowering treatments (LLTs) are available in Germany; however, the research on treatment patterns and LDL-C outcomes among patients (pts) receiving LLTs in real-world setting is limited. Purpose To characterize the pts characteristics, treatment patterns and LDL-C outcomes of pts with atherosclerotic cardiovascular disease (ASCVD) with hypercholesterolemia (ASCVD-H) in Germany. Methods This is a descriptive, non-interventional, retrospective cohort study of ASCVD-H pts identified from general physician (GP) practices available in the electronic medical record (EMR) database Disease Analyzer (January 1992-June 2020) in Germany. ASCVD-H pts were included if they had a recorded diagnosis, were prescribed LLTs or had LDL-C levels of ≥55 mg/dL anytime within 6 months before and 3 months after the index date (ID), as per the data recorded by the participating physician. The first encounter of ASCVD after hypercholesterolemia during the identification period (1/07/2015–30/06/2019) was considered as the ID. Persistence was measured as the duration (in days) with allowed gap of 60 days and adherence as proportion of days covered (PDC) within 12 and 24 months after ID. Results We included 147,905 pts with ASCVD-H (57.2% male; mean age: 70.6 yrs; ≥75 yrs-old: 43.3%; mean BMI: 29.0 kg/m2). Coronary artery disease was the most common index diagnosis (73.2%), followed by cerebrovascular disease (31.7%) and peripheral vascular disease (21.5%). Hypertension (83.5%) and diabetes (27.6%) were the most common comorbidities among these pts. At ID, statin monotherapy (58.6%) was the most commonly prescribed LLT, with simvastatin being the most common drug (36.4%). The use of PCSK9 inhibitors, ezetimibe and fibrates was very limited (&lt;1%; Table 1). Of note, LDL-C measurements (6 months prior and 3 months post index) were available for 50.7% of pts. In pts with uncontrolled LDL-C (≥55 mg/dL), 47.9% were receiving statin monotherapy (28.6% were on simvastatin), whereas there was no LLT prescribed in 48.0% of pts. The mean (SD) persistence and adherence to statins monotherapy within 24 months follow-up was 522 (260) days and 0.721 (0.345), respectively, with 60% of pts being adherent (PDC ≥0.80) to statins monotherapy. Conclusions Pts with ASCVD-H in Germany treated by GPs are elderly pts with multiple cardiovascular comorbidities. LDL-C was measured in nearly half of the pts, and almost all had LDL-C ≥55 mg/dL at ID. Findings indicate low prescription of LLTs in GP setting, particularly non-statin LLTs. The mean adherence (PDC) to statin monotherapy was 72% within the 24-month after ID. Data suggest the need for newer therapies with potential to control LDL-C levels. FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis Pharma AG, Basel, Switzerland.

Statins and Inflammation in Cardiovascular Disease

2018 ◽  
Vol 23 (46) ◽  
pp. 7027-7039 ◽  
Author(s):  
Georgia Vogiatzi ◽  
Evangelos Oikonomou ◽  
Gerasimos Siasos ◽  
Sotiris Tsalamandris ◽  
Alexandros Briasoulis ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Lipid Lowering ◽  
Hmg Coa Reductase ◽  
Ample Evidence ◽  
Reductase Inhibitors ◽  
Immune System Activation ◽  
Hmg Coa Reductase Inhibitors ◽  
Anti Inflammatory ◽  
Artery Disease ◽  
Coa Reductase

Background: Chronic inflammation and immune system activation underlie a variety of seemingly unrelated cardiac conditions including not only atherosclerosis and the subsequent coronary artery disease but also peripheral artery disease, hypertension with target organ damage and heart failure. The beneficial effects of HMG-CoA reductase inhibitors or statins are mainly attributed to their ability to inhibit hepatic cholesterol biosynthesis. Beyond their lipid lowering activity, ample evidence exists in support of their potent anti-inflammatory properties which initiate from the inhibition of GTPase isoprenylation, activating a cataract of secondary pathways and extend to the inhibition and blocking of immune cell activation and interaction. </P><P> Objective: To summarize the anti-inflammatory mechanisms of statins in clinical and experimental settings in cardiovascular disease. </P><P> Methods: A systematic search of PubMed and the Cochrane Database was conducted in order to identify the majority of trials, studies, current guidelines and novel articles related to the subject. </P><P> Results: In vitro, statins have immuno-modulatory and anti-inflammatory effects, and they can exert antiatherosclerotic effects independently of their hypolipidemic actions. In addition, positive results have emerged from mechanistic and experimental studies on the active role of HMG-CoA reductase inhibitors in HF. By extrapolating those data in clinical setting, we further understand how HMG-CoA reductase inhibitors can beneficially affect not only systolic but also diastolic HF. </P><P> Conclusion: In this review article, we present the basic pathophysiologic data supporting the anti-inflammatory actions of statins in clinical and experimental settings and we link these mechanisms with confirmatory clinical data on the potent non lipid lowering effects of HMG-CoA reductase inhibitors.

How many CCS- and ACS-patients might reach the newly recommended LDL-C-target <55mg/dl in clinical practice if guidelines were applied – an estimate from the DYSIS II study population

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.K Gitt ◽  
M Horack ◽  
D Lautsch ◽  
R Zahn ◽  
J Ferrieres
Keyword(s):  
Clinical Practice ◽  
Real Life ◽  
Statin Treatment ◽  
Lipid Lowering ◽  
High Risk Population ◽  
High Dose ◽  
Funding Source ◽  
Pcsk9 Inhibitors ◽  
Target Values ◽  
Coronary Syndromes

Abstract Background The 2019 ESC guidelines for the management of dyslipidemia even further lowered the LDL-C-target values for the very high-risk population from &lt;70mg/dl to &lt;55mg/dl. Population based studies already had shown that the previous target was difficult to reach. It is yet unclear how many patients in clinical practice might be treated to the new target. Methods The Dyslipidemia International Study (DYSIS II) prospectively collected data of patients with chronic coronary syndromes (CCS) and acute coronary syndromes (ACS) (all on statins) in 18 countries in Europe, the Middle East, South- and East Asia to document patient characteristics, medication and a current lipid profile from 2012 to 2014 under real life conditions in physicians' offices and hospitals. We took these real-life lipid profiles and data on the kind/dose of used statins to estimate how treatment escalation such as changing statin treatment to a high dose (atorvastatin ≥40mg / rosuvastatin≥20mg), adding ezetimibe and adding a PCSK9-inhibitor might help to bring LDL-C-levels to the recommended &lt;55mg/dl target. Results A total of 7,865 patients were enrolled into DYSIS II, 6,794 had CCS and 1,071 ACS. Under the documented statin treatment in DYSIS only 12.7% of patients reached an LDL-C &lt;55mg/dl. Putting all patients on high dose statins in combination with ezetimibe, 64.1% would reach the target. If PCSK9-inhibitors would be used in the remaining patients not at goal a total of 94.0% would match the goal. Conclusion Our analysis indicates that in real life practice the use available lipid-lowering medications would substantially increase the percentage of CCS- and ACS-patients reaching the newly recommended 2019 ESC guideline LDL-C-target of &lt;55 mg/dl from less than 20% to more than 90% of the population. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): MSD

The Impact of Atherosclerotic Cardiovascular Risk on Graft Failure in Deceased-Donor Renal Transplantation

2021 ◽  
pp. 152692482110246
Author(s):  
Grace Hsu ◽  
Tracy M. Sparkes ◽  
Brent N. Reed ◽  
Stormi E. Gale ◽  
Brian E. Crossley ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiovascular Disease ◽  
Cardiovascular Risk ◽  
Renal Transplant ◽  
Cardiovascular Events ◽  
Graft Failure ◽  
Deceased Donor ◽  
Low Risk ◽  
Major Adverse Cardiovascular Events ◽  
Atherosclerotic Cardiovascular Disease

Introduction: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. Research question: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. Design: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. Results: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; ( P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. Discussion: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.

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