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Volume 19, Supplement 1 - 2018

Volume 19, Supplement 1 - 2018

Table of Contents

Identifying Patients for Nonstatin Therapy Nonstatin Decision Making
Statins are first-line therapy for reducing atherosclerotic cardiovascular disease (ASCVD) risk. Some patients remain at high ASCVD risk despite maximizing statin therapy. Ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs) have been shown to reduce ASCVD events in randomized trials and may be of benefit in selected high-risk patients with cardiovascular disease (CVD) or familial hypercholesterolemia (FH). Number-needed-to-treat (NNT) to prevent one ASCVD event can help identify groups of patients who may gain a net benefit from added nonstatin therapy. Patient groups with NNTs <25 (in whom PCSK9 mAbs may approach cost effectiveness with discounting) include extremely high-risk patients (those with CVD with FH, polyvascular disease, or recurrent ASCVD events) with lowdensity lipoprotein cholesterol (LDL-C) levels ≥70 mg/dL, very high-risk patients (those with CVD with diabetes [and no polyvascular disease], chronic kidney disease, or acute coronary syndromes, or CVD or FH with poorly controlled risk factors) with LDL-C levels ≥100 mg/dL, and high-risk patients (those with CVD or FH with well-controlled risk factors) with LDL-C ≥130 mg/dL. Ezetimibe, which is generic in the United States, is reasonable for patient groups with NNTs <30, the level considered reasonable by most patients. This includes extremely high-risk patients with LDL-C levels ≥130 mg/dL, or very high-risk patients with LDL-C ≥190 mg/dL. All guidelines recommend statin therapy for the prevention of ASCVD. [Rev Cardiovasc Med. 2018;19(suppl 1):S1-S8 doi: 10.3909/ricm19S1S0004] © 2018 MedReviews®, LLC
Statin Intolerance Nonstatin Decision Making
Statins are critical medications to prevent and treat cardiovascular disease2 and they are generally very well tolerated. In some instances, however, statin intolerance may limit use of these lifesaving medications. Statin intolerance has many definitions but is commonly diagnosed when a patient is unable to continue statin therapy due to perceived, or objectively documented, adverse effects. A very high rate of discontinuation of statin therapy warrants a closer look at the implications from the standpoint of cardiovascular risk in statin-intolerant patients, as well as an evaluation of the available options to help patients maintain their statin therapy and understand the potential benefits of such therapy. [Rev Cardiovasc Med. 2018;19(suppl 1):S9-S19 doi: 10.3909/ricm19S1S0005] © 2018 MedReviews®, LLC
Can We Cure Atherosclerosis? Nonstatin Decision Making
Cardiovascular disease mortality rates have begun to rise in the United States. Based on the large body of supportive evidence, we propose a proof-of-concept, first-in-human trial to cure atherosclerosis: CURing Early ATHEROsclerosis (CURE ATHERO). This trial is based on a model of intensive induction therapy for extensive, if not complete, plaque regression, followed by intermittent maintenance therapy. An extensive body of evidence has demonstrated the causal role of apolipoprotein B lipoproteins in atherosclerosis progression and data suggest intensive low-density lipoprotein cholesterol (LDL-C) lowering may have a substantial impact on earlier stages of atherosclerosis. Compared with lifetime treatment to prevent atherosclerosis progression, this induction–intermittent treatment model will minimize costs and maximize adherence and safety. [Rev Cardiovasc Med. 2018;19(suppl 1):S20-S24 doi: 10.3909/ricm19S1S0003] © 2018 MedReviews®, LLC
Familial Hypercholesterolemia: Although Identification Advances, Appreciation and Treatment Lag Nonstatin Decision Making
Familial hypercholesterolemia is one of the most common autosomal dominant inherited genetic disorders, yet it is frequently undiagnosed, leading to a markedly increased risk for cardiovascular events. Understanding the pathophysiology of the disease as well as the importance of cascade screening is critical to appropriate treatment of patients. Though the mainstay of therapy for heterozygous familial hypercholesterolemia remains statins, many patients require additional therapy including ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies to achieve adequate low-density lipoprotein cholesterol (LDL-C) lowering. Access to PCSK9 inhibitors remains a significant clinical problem. [Rev Cardiovasc Med. 2018;19(suppl 1):S25-S30 doi: 10.3909/ricm19S1S0001] © 2018 MedReviews®, LLC
PCSK9 Inhibitors: Mechanism of Action, Efficacy, and Safety Nonstatin Decision Making
Low-density lipoprotein (LDL) receptors on the surface of liver hepatocytes are the primary way that humans regulate serum LDL cholesterol levels. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a proteolytic enzyme that indirectly regulates serum LDL cholesterol (LDL-C) by causing the destruction of LDL receptors. Less LDL receptors result in increased LDL-C in the bloodstream but inhibiting or binding the circulating PCSK9 results in increased LDL receptors with the resultant decrease in serum LDL-C. Two PCSK9 inhibitors are currently approved for use: alirocumab and evolocumab. Both are fully human monoclonal antibodies that bind free PCSK9. Herein we discuss the mechanism of action, efficacy, and safety of PCSK9 inhibitors. [Rev Cardiovasc Med. 2018;19(suppl 1):S31-S46 doi: 10.3909/ricm19S1S0002] © 2018 MedReviews®, LLC
Access to PCSK9 Inhibitors Nonstatin Decision Making
[Rev Cardiovasc Med. 2018;19(suppl 1):S47-S50 doi: 10.3909/ricm19S1S0006] © 2018 MedReviews®, LLC