scholarly journals Statins Alone or in Combination with Ezetimibe or PCSK9 Inhibitors in Atherosclerotic Cardiovascular Disease Protection

2020 ◽  
Author(s):  
Marija Vavlukis ◽  
Ana Vavlukis
Keyword(s):  
Cardiovascular Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors

Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?

2021 ◽  
pp. 107424842110236
Author(s):  
Ruihai Zhou ◽  
George A. Stouffer ◽  
Sidney C. Smith
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Outcomes ◽  
Mechanism Of Action ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Blood Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Cholesterol Lowering ◽  
Cholesterol Levels

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as “bad” cholesterol and high-density lipoprotein cholesterol (HDL-C) as “good” cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.

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.

scholarly journals Effectiveness and Tolerability of Alternative Statin Dosing in Daily Statin Intolerant Patients in the Era of PCSK9 Inhibitors

2020 ◽  
pp. 1-4
Author(s):  
Anthony P. Morise ◽  
Anthony P. Morise ◽  
Jennifer A. Tennant
Keyword(s):  
Cardiovascular Disease ◽  
Baseline Level ◽  
Ldl Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Statin Intolerance ◽  
Lipid Clinic ◽  
Cholesterol Goal ◽  
Pcsk9 Inhibition ◽  
Clinic Population

Background: Intolerance to the daily use of statins can be dealt with by the use of Proprotein Catylase Subtilisin Kexin Type 9 (PCSK9) inhibitors. Alternative statin dosing has previously been utilized in patients with statin intolerance. Methods: Since the introduction of PCSK9 inhibitors for clinical use in 2015, we evaluated the effectiveness of alternative statin dosing in patients with daily statin intolerance defined as the inability to tolerate the daily use of any dose of statin. Alternative statin dosing was defined as weekly, twice weekly, or every other day atorvastatin or rosuvastatin. From our lipid clinic population of 505 patients with primary hypercholesterolemia (71% with atherosclerotic cardiovascular disease), 338 (67%) had daily statin intolerance. Alternative statin dosing was agreed to by 122 patients of these 338. At the time of this analysis, 87 patients (59% with atherosclerotic cardiovascular disease) could be assessed concerning the effectiveness of alternative statin dosing to achieve their LDL-cholesterol goal. Results: Of the 87 patients undergoing alternative statin dosing with or without ezetimibe, 30 (34%) achieved their goal. An additional 22 patients had a >30% reduction in LDL-cholesterol with oral therapy alone. Twenty-nine of the 87 patients later received PCSK9 inhibition with 27 achieving either their goal or a >30% reduction in LDL cholesterol. The baseline LDL-cholesterol of those achieving their goal LDLcholesterol with alternative statin dosing (154 + 40 mg/dL) could not be distinguished (p=0.79) from those who later required PCSK9 inhibition to achieve their goal (157 + 41 mg/dL). Intolerance to alternative statin dosing was seen in 24 of the 87 (28%) patients. Conclusion: In conclusion, prior to initiating PCSK9 inhibition in patients with daily statin intolerance, a trial of alternative statin dosing should be attempted. The success of alternative statin dosing cannot be predicted by the baseline level of LDL-cholesterol.

PCSK9 inhibitors for prevention of atherosclerotic cardiovascular disease

2018 ◽  
Vol 12 (4) ◽  
pp. 835-843 ◽  
Author(s):  
Vera A. Bittner ◽  
Robert P. Giugliano ◽  
Eliot A. Brinton ◽  
John R. Guyton
Keyword(s):  
Cardiovascular Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors

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.

PCSK9 in cholesterol metabolism: from bench to bedside

2018 ◽  
Vol 132 (11) ◽  
pp. 1135-1153 ◽  
Author(s):  
Allison B. Reiss ◽  
Neal Shah ◽  
Dalia Muhieddine ◽  
Juan Zhen ◽  
Jennifer Yudkevich ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cholesterol Metabolism ◽  
Treatment Options ◽  
Low Density Lipoprotein ◽  
Regulatory Protein ◽  
Density Lipoprotein ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Adequate Treatment ◽  
First Line Therapy

Dyslipidemia, and specifically elevated low-density lipoprotein (LDL) cholesterol, is one of the most important cardiovascular risk factors. Statins are considered first line therapy for the primary and secondary prevention of cardiovascular disease. However, statins may not be adequate treatment for elevated circulating LDL levels and are ineffective in certain familial hypercholesterolemias. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9), a regulatory protein that affects LDL receptors, offers a new alternative for these patients. Moreover, gain-of-function PCSK9 mutations were discovered to be the root cause of familial autosomal dominant hypercholesterolemia. Inhibition of PSCK9 reduces plasma LDL levels, even in patients for whom statins are ineffective or not tolerated. Alirocumab and evolocumab, human monoclonal antibodies that inhibit PCSK9, have been approved to lower LDL levels. While there are drawbacks to these treatments, including adverse events, administration by subcutaneous injection, and high cost, these drugs are indicated for the treatment of atherosclerotic cardiovascular disease and familial hypercholesterolemia as adjunct to diet and maximally tolerated statin therapy. PCSK9 inhibitors may work synergistically with statins to lower LDL. Novel approaches to PCSK9 inhibition are currently in development with the aim of providing safe and effective treatment options to decrease cardiovascular event burden, ideally at lower cost and with oral bioavailability.

Recent Updates on the Use of PCSK9 Inhibitors in Patients with Atherosclerotic Cardiovascular Disease

2019 ◽  
Vol 21 (5) ◽  
Author(s):  
Dave L. Dixon ◽  
Lauren G. Pamulapati ◽  
John D. Bucheit ◽  
Evan M. Sisson ◽  
Shawn R. Smith ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors
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