Cardiovascular disease remains the leading cause of death and disability in the United States and globally. Disease burden continues to escalate despite technological advances associated with improved life expectancy and quality of life. As a result, longer life is associated with multiple chronic cardiovascular conditions.
View Article and Find Full Text PDFPatients with homozygous familial hypercholesterolemia (FH) have severe hypercholesterolemia from birth and if untreated may experience very early onset of coronary artery disease in childhood or young adulthood with an aggressive course resulting in early death. Early initiation of aggressive low-density lipoprotein cholesterol (LDL-C) lowering is the mainstay of treatment, which requires the use of a multidrug treatment regimen, often in combination with lipoprotein apheresis, but LDL-C goal achievement is frequently unattainable due to the severity of baseline hypercholesterolemia and hyporesponsiveness to many LDL-C-lowering medications. Evinacumab, a monoclonal antibody that sequesters angiopoietin-like 3 protein and lowers LDL-C by an average of 49% in patients with homozygous FH, was approved by the Food and Drug Administration in February 2021 and is a major advance in treatment of these high-risk patients.
View Article and Find Full Text PDFStatin-associated muscle symptoms (SAMS) are the most common form of statin intolerance and are associated with increased risk of cardiovascular events that manifest from statin underutilization and discontinuation. The reported frequencies of SAMS are divergent in the literature. The writing group estimates the prevalence of SAMS, namely all muscle symptoms temporally related to statin use but without regard to causality, to be about 10% (range 5% to 25%), and the prevalence of pharmacological SAMS, specifically muscle symptoms resulting from pharmacological properties of the statin, to be about 1-2% (range 0.
View Article and Find Full Text PDFBackground: Lipid management for prevention and treatment of cardiovascular disease remains insufficient for many with currently available therapies.
Objective: Evaluate real-world use of bempedoic acid.
Methods: Retrospective study of patients in our Center for Preventive Cardiology who were prescribed bempedoic acid between February 2020 and July 2021.
Background: Monoclonal antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9i) lower LDL-C by up to 60% and increase plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels by 10-fold.
Objectives: The authors studied the reasons behind the robust increase in plasma PCSK9 levels by testing the hypothesis that mechanisms beyond clearance via the low-density lipoprotein receptor (LDLR) contribute to the regulation of cholesterol homeostasis.
Methods: In clinical cohorts, animal models, and cell-based studies, we measured kinetic changes in PCSK9 production and clearance in response to PCSK9i.
Heart failure with reduced ejection fraction (HFrEF) is a debilitating disease that is associated with substantial morbidity, mortality, and societal costs. The past three decades have brought about significant advancements in the pharmacologic management of HFrEF, and a corresponding reduction in morbidity and mortality. However, the progress to improve clinical outcomes in real-world settings has stalled in recent years, largely due to underutilization of guideline directed medical therapies (GDMT).
View Article and Find Full Text PDFObjective: To determine the real-world use of pharmacotherapy with new evidence-based cardiovascular indications in an academic Preventive Cardiology Clinic.
Methods: A retrospective study of patients seen in our Center for Preventive Cardiology (CPC) and who received a new prescription, according to Food and Drug Administration (FDA) approved indications, for one of the following pharmacotherapies with new evidence-based cardiovascular indications from May 2019 to May 2020: proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), eicosapentaenoic acid (EPA), sodium-glucose cotransporter 2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA). Treatment endpoints were prescription patterns, medication access, patient out-of-pocket expenses, medication tolerability, and clinical cardiovascular events while on these therapies.
: Familial hypercholesterolemia (FH) is characterized by lifelong elevation of low-density lipoprotein cholesterol (LDL-C), early onset coronary atherosclerosis, and premature death. FH is underdiagnosed and undertreated, but requires aggressive LDL-C-lowering to prevent complications. Current treatment strategies such as lifestyle modification and numerous LDL-C-lowering medications are often insufficient to achieve lipid goals in FH.
View Article and Find Full Text PDFJ Cardiovasc Pharmacol
August 2021
Hypercholesterolemia is a leading cause of cardiovascular morbidity and mortality. Accordingly, efforts to lower apolipoprotein B-containing lipoproteins in plasma are the centerpiece of strategies for cardiovascular prevention and treatment in primary and secondary management. Despite the importance of this endeavor, many patients do not achieve appropriate low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) goals, even among those who have experienced atherosclerotic cardiovascular disease.
View Article and Find Full Text PDFObjective: To characterize unusual responses to PCSK9 inhibitor (PCSK9i) therapy in a real-world setting, given their extremely low prevalence in clinical trials.
Methods: A retrospective study of patients seen in a structured academic PCSK9i clinic who had LDL-C measurements before and after initiation of PCSK9i (up to 12 months). Unusual response was defined as: (1) no response: no changes in LDL-C level at all time points; (2) delayed response: <30% LDL-C reduction by the third dose, but achieving this threshold at a later time; (3) reduced response: <30% LDL-C reduction at all time points; and (4) lost response: ≥30% LDL-C reduction by the third dose, but displaying <30% reduction at a later time.
Background: Chylomicronemia syndrome (CS) is a metabolic condition characterized by severely elevated plasma triglycerides (>880 mg/dL) and high rates of morbidity and mortality. The syndrome can be classified into two major groups: monogenic familial chylomicronemia syndrome (FCS) and multifactorial chylomicronemia syndrome (MCS), the frequencies of which are ill-defined.
Objective: The objective of the study was to characterize the prevalence of the most common and rarest subsets of this syndrome, MCS and FCS, respectively, in a single-center, real-world setting.
Standard lipid-lowering therapies in solid organ transplantations pose challenges due to interactions with immunosuppressants. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a new class of lipid-lowering therapies with potential promise in this population. We describe PCSK9i as an efficacious and safe option for management of hypercholesterolemia in solid organ transplantations.
View Article and Find Full Text PDFCurr Cardiol Rep
September 2019
Purpose Of Review: To review the clinical trial data and underlying mechanistic principles in support of the robust cardiovascular (CV) benefits, in particular, heart failure (HF) outcomes association with sodium-glucose co-transporter-2 (SGLT2) inhibitors.
Recent Findings: Several large CV outcome trials in patients with type 2 diabetes mellitus (T2DM) and with either established atherosclerotic CV disease (ASCVD) or at high risk for ASCVD reveal that SGLT2 inhibitors cause reductions in CV and HF endpoints. The reduction in ASCVD appears to be confined to those with established ASCVD on the order of ≈ 14%, as does the mortality benefit-all-cause and CV-related.
Until 1990, lipid clinics in the United States existed only in academic medical centers, generally in close relationship with laboratory-based research programs. The advent of statin therapy, the success of major clinical trials to prevent or stabilize atherosclerotic cardiovascular disease, and organizational efforts highlighted by regional Lipid Disorders Training Centers and the newly formed National Lipid Association boosted the formation of lipid clinics and preventive cardiology clinics in private and academic settings. This roundtable discussion with 4 experts examines multiple aspects of lipid clinic operations: obtaining referrals, adapting to either the academic or community setting, organizing a team of providers, incorporating diet and lifestyle counseling as well as medication, establishing the pharmacist role, and gaining financial stability.
View Article and Find Full Text PDFBackground: Perioperative bridging in atrial fibrillation (AF) is associated with low thromboembolic rates but high bleeding rates. Recent guidance cautions the practice of bridging except in high risk patients. However, the practice of bridging varies widely and little data exist regarding appropriate anticoagulation intensity when using intravenous unfractionated heparin (UFH).
View Article and Find Full Text PDFAnn Pharmacother
December 2019
Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide. In response, a multidisciplinary team approach, which includes clinical pharmacists, is recommended to improve patient outcomes. The purpose of the study was to describe interventions associated with integration of a clinical pharmacist, with an emphasis on pharmacist-generated patient cost avoidance.
View Article and Find Full Text PDFTrends Cardiovasc Med
April 2020
Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) has revolutionized our understanding of cholesterol homeostasis and added to our arsenal against atherosclerotic cardiovascular disease (ASCVD). In a span of approximately 15 years, PCSK9 has morphed from an esoteric and rare cause of familial hypercholesterolemia (FH) into the most efficient cholesterol-lowering target ever known, with the completion of two large scale cardiovascular outcome trials showing positive results. Current Food and Drug Administration (FDA) approved modalities to inhibit PCSK9 are in the form of monoclonal antibodies which display an unparalleled degree of low-density lipoprotein cholesterol (LDL-C) lowering and expand upon the notion that lower LDL-C is better for ASCVD risk reduction.
View Article and Find Full Text PDFBackground: Lipoprotein(a) [Lp(a)] is an atherogenic lipoprotein associated with atherosclerotic cardiovascular disease. Niacin and proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) both lower Lp(a).
Objective: The objective of the study was to determine if addition of PCSK9i to background niacin therapy further lowers Lp(a).
Solid organ transplantation (SOT) has revolutionized treatment of end-stage disease. Improvements in the SOT continuum of care have unmasked a significant burden of cardiovascular disease, manifesting as a leading cause of morbidity and mortality. Although several risk factors for development of post-transplant cardiovascular disease exist, dyslipidemia remains one of the most frequent and modifiable risks.
View Article and Find Full Text PDFPCSK9i (protein convertase subtilisin/kexin type 9 inhibitors) are set to revolutionize the treatment of hypercholesterolemia in the management of atherosclerotic risk, but numerous reports have detailed unprecedented barriers to access for these drugs. To overcome these challenges, our group created a model to facilitate provision of this new therapy for patients who qualify according to Food and Drug Administration criteria. This report details the real-world follow-up experience of PCSK9i use in a large patient cohort structured to ensure rigor in data collection, analysis, and interpretation.
View Article and Find Full Text PDFBleeding events and life-threatening hemorrhage are the most feared complications of warfarin therapy. Prompt anticoagulant reversal aimed at replacement of vitamin K-dependent clotting factors is essential to promote hemostasis. A retrospective cohort study of warfarin-treated patients experiencing a life-threatening hemorrhage treated with an institution-specific warfarin reversal protocol (postimplementation group) and those who received the prior standard of care (preimplementation group) was performed.
View Article and Find Full Text PDFPurpose: The impact of a pharmacy-managed program for providing education and discharge instructions for patients with heart failure (HF) was evaluated.
Methods: A before-and-after quasiexperimental design was used to quantify the effect of a pharmacist-managed HF medication education and discharge instruction program on the incidence of 30-day readmission rates and adherence to targeted Joint Commission core measures for HF (the provision of discharge instructions and the prescribing of an angiotensin-converting-enzyme inhibitor [ACEI]/angiotensin II receptor blocker [ARB] at discharge or documentation of the reason if therapy was not prescribed). Adult patients admitted to Oregon Health and Science University's cardiology unit with systolic HF exacerbation as their primary diagnosis between December 2010 and March 2011 were included.