Barbara S. Wiggins

2017 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways

James L. Januzzi, Jr, MD, FACC, Chair Luis C. Afonso, MBBS, FACC Brendan Everett, MD, FACC Adrian F. Hernandez, MD, FACC William Hucker, MD, PhD Hani Jneid, MD, FACC Dharam J. Kumbhani, MD, SM, FACC Joseph E. Marine, MD, FACC Pamela Bowe Morris, MD, FACC Robert Piana, MD, FACC Karol E.

Recommendations for Management of Clinically Significant Drug-Drug Interactions With Statins and Select Agents Used in Patients With Cardiovascular Disease: A Scientific Statement From the American Heart Association

A drug-drug interaction (DDI) is a pharmacokinetic or pharmacological influence of 1 medication on another that differs from the known or anticipated effects of each agent alone.1 A DDI may result in a change in either drug efficacy or drug toxicity for 1 or both of the interacting medications.2 Pharmacokinetic DDIs result in altered absorption, distribution, metabolism, or excretion of a medication. A pharmacodynamic DDI occurs when 1 medication modifies the pharmacological effect of another in an additive, a synergistic, or an antagonistic fashion. It is estimated that ≈2.8% of hospital admissions occur as a direct result of DDIs.3 However, the actual incidence of hospitalization secondary to clinically significant DDIs is likely to be highly underestimated because medication-related issues are more commonly reported as adverse drug reactions. Complex underlying disease states also may make recognizing a DDI more challenging, further contributing to a lower reported incidence. The overall clinical impact of a DDI can range from mild to life-threatening. Therefore, not all DDIs require a modification in therapy. The variability in the clinical significance of a DDI depends on both medication-specific and patient-specific factors. Medication-specific factors include the individual pharmacokinetic characteristics of each medication implicated in the DDI (eg, binding affinity, half-life [t1/2]), dose of the medications, serum concentrations, timing and sequence of administration, and duration of therapy. Patient-specific factors include age, sex, lifestyle, genetic polymorphisms causing differences in enzyme expression or activity, and disease impairment affecting drug metabolism (eg, hepatic or renal impairment, cardiac failure) or predisposition to differences in efficacy or safety (eg, statin intolerance in patients with a history of myopathy). Clinically significant DDIs are usually preventable. To optimize patient safety, healthcare providers must have an understanding of the mechanisms, magnitude, and potential consequences of any given DDI. Interpreting this information …

Reduced Anticoagulant Effect of Dabigatran in a Patient Receiving Concomitant Phenytoin

Dabigatran, a direct thrombin inhibitor, is an oral anticoagulant indicated for the prevention of stroke in patients with atrial fibrillation (AF) and for the treatment and prevention of deep vein thrombosis and pulmonary embolism. Dabigatran, as well as the other new anticoagulants—rivaroxaban, apixaban, and edoxaban—are substrates for P‐glycoprotein (P‐gp). Although the U.S. labeling for rivaroxaban and apixaban states to avoid concomitant use with phenytoin, a known P‐gp inducer, the U.S. labeling for dabigatran and edoxaban are less clear. We describe the first case report, to our knowledge, documenting a drug interaction between phenytoin and dabigatran by using laboratory measurements of dabigatran serum concentrations. A 45‐year‐old African‐American man was admitted to the inpatient cardiology service following defibrillations from his implantable cardioverter defibrillator. The patient was evaluated and received appropriate antitachycardia pacing for atrial tachyarrhythmias for an episode of ventricular tachycardia (VT), and antiarrhythmic therapy with sotalol was initiated to reduce both his AF and VT burden. On review of the patients medications for potential interactions, it was discovered that the patient was taking both dabigatran and phenytoin. To determine the magnitude of this drug interaction prior to making a change in his anticoagulation regimen, a dabigatran serum concentration was measured. This concentration was undetectable, indicating that phenytoin had a significant influence on dabigatrans metabolism and that this patient was at high risk for stroke. Clinicians should be aware of this interaction between phenytoin and dabigatran as well as with all other new oral anticoagulants. In patients taking phenytoin who require an anticoagulant, only warfarin should be prescribed to minimize the risk of stroke. In addition, the prescribing information for dabigatran should be updated to include other medications that result in a significant reduction in dabigatran serum concentrations, such as phenytoin.

Cardiovascular Drug Shortages Predominant Etiologies, Clinical Implications, and Management Strategies

Objective: To review the literature surrounding the incidence, significance, and management of cardiovascular (CV) drug shortages. Data Sources: A literature search was conducted using all available indexing databases from January 1996 to August 2013, coupled with assessments of the ASHP (American Society of Health System Pharmacists) and Food and Drug Administration Web sites designated to drug shortages. Data were also gathered through a review of listservs discussing this topic. Data Synthesis: CV drug shortages are among the top 5 national drug class shortages that are posing a threat to patient care and public health. When a drug shortage occurs, it requires modifications to prescribing and the method medications are processed by the pharmacy. These necessary yet cumbersome changes can potentially result in less-than-desirable prescribing options and increases in personnel time because of administrative and dispensing obstacles. Any one of these has the potential to increase costs and/or lead to worse outcomes. Several factors have been shown to contribute to these shortages, including manufacturing delays, increased demand, medication discontinuations, and lack of raw materials. In this article, we review 13 of the critical CV drug shortages, describe their role in therapy, discuss the reasons for the shortage, define their impact on patient care, and recommend alternative therapies. Conclusions: CV drug shortages are common and can potentially lead to deleterious patient outcomes. Institutions should develop plans for early identification, management, and resolution to minimize the clinical sequelae associated with drug shortages.

Recommendations for Managing Drug–Drug Interactions with Statins and HIV Medications

The discovery of antiretroviral therapy (ART) for the treatment of human immunodeficiency virus (HIV) has enabled individuals to live longer. As a result, HIV is now often considered a chronic condition. However, as a result of the increase in longevity or the HIV treatment modalities themselves, individuals with HIV are at high risk for the development of atherosclerotic cardiovascular disease. Therefore, these patients should be optimized with pharmacologic therapy to lower their cardiovascular risk through the addition of statin therapy to their regimen. Unfortunately, many medications utilized to treat HIV interact with this class of agents, making prescribing of statin therapy in these patients challenging. While several classes of ARTs do not pose an increased risk of drug–drug interactions with statins, HIV treatment often requires several combinations of medications, enhancing the complexity and drug–drug interaction risk. Clinicians should be aware of interactions with statins and ART and carefully review the degree and clinical significance of each particular medication. With this understanding, the appropriate statin as well as statin dose can be selected in order to optimize the treatment of this patient population, while minimizing the potential risk of adverse effects.

Evolocumab: Considerations for the Management of Hyperlipidemia

Purpose of ReviewTo review the efficacy, safety, pharmacology, and pharmacokinetics of evolocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor.Recent FindingsPCSK9 inhibitors are a class of lipid-lowering agents that significantly reduce low-density lipoprotein cholesterol (LDL-C) levels in patients with atherosclerotic cardiovascular disease and hyperlipidemia. Evolocumab is a monoclonal antibody that inhibits PCSK9 and has been evaluated in phase II and III studies as monotherapy, in combination with statins and other lipid-lowering therapies, in patients who are statin intolerant, and in patients with heterozygous and homozygous familial hypercholesterolemia. Data from these studies show that evolocumab significantly reduces LDL-C levels. Treatment with evolocumab also significantly improves levels of other lipid parameters (e.g., apolipoproteins A1 and B, lipoprotein(a), non–high-density lipoprotein cholesterol, and triglycerides). Recent results indicate that LDL-C reduction with evolocumab significantly reduces the risk of cardiovascular events and is also associated with atherosclerotic plaque regression. From a safety standpoint, rates of adverse events (AEs), serious AEs, and AEs leading to discontinuation were similar between evolocumab and controls in clinical trials, and no increase in AEs was observed when evolocumab was used in combination with statins.SummaryPatients with elevated LDL-C benefit from evolocumab treatment, suggesting that evolocumab could help meet an unmet medical need in high-risk patient populations with atherosclerotic cardiovascular disease and hyperlipidemia that are unable to reduce LDL-C levels sufficiently with statin therapy alone.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging: Best Practices for Safety and Effectiveness

WRITING COMMITTEE MEMBERS John W. Hirshfeld Jr., MD, FACC, FSCAI, Chair | Victor A. Ferrari, MD, FACC, Co-Chair | Frank M. Bengel, MD† | Lisa Bergersen, MD, MPH, FACC | Charles E. Chambers, MD, FACC, MSCAI‡ | Andrew J. Einstein, MD, PhD, FACC | Mark J. Eisenberg, MD, MPH, FACC | Mark A. Fogel, MD, FACC | Thomas C. Gerber, MD, FACC | David E. Haines, MD, FACC§ | Warren K. Laskey, MD, MPH, FACC, FSCAI | Marian C. Limacher, MD, FACC | Kenneth J. Nichols, PhD# | Daniel A. Pryma, MD | Gilbert L. Raff, MD, FACCk | Geoffrey D. Rubin, MD, MBA, FNASCI¶ | Donnette Smith** | Arthur E. Stillman, MD, PhD, FNASCI | Suma A. Thomas, MD, MBA, FACC | Thomas T. Tsai, MD, MSc, FACC | Louis K. Wagner, PhD | L. Samuel Wann, MD, MACC

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 2: Radiological Equipment Operation, Dose-Sparing Methodologies, Patient and Medical Personnel Protection.

The stimulus to create this document was the recognition that ionizing radiation‐guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure to clinical personnel. While the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. ACC leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel.

2018 ACC/HRS/NASCI/SCAI/SCCT Expert Consensus Document on Optimal Use of Ionizing Radiation in Cardiovascular Imaging-Best Practices for Safety and Effectiveness, Part 1: Radiation Physics and Radiation Biology: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways Developed in Collaboration With Mended Hearts.

The stimulus to create this document was the recognition that ionizing radiation‐guided cardiovascular procedures are being performed with increasing frequency, leading to greater patient radiation exposure and, potentially, to greater exposure for clinical personnel. Although the clinical benefit of these procedures is substantial, there is concern about the implications of medical radiation exposure. The American College of Cardiology leadership concluded that it is important to provide practitioners with an educational resource that assembles and interprets the current radiation knowledge base relevant to cardiovascular procedures. By applying this knowledge base, cardiovascular practitioners will be able to select procedures optimally, and minimize radiation exposure to patients and to clinical personnel.

Higher Maximum Doses and Infusion Rates Compared with Standard Unfractionated Heparin Therapy Are Associated with Adequate Anticoagulation without Increased Bleeding in Both Obese and Nonobese Patients with Cardiovascular Indications

To evaluate the time to achieve therapeutic activated partial thromboplastin time (aPTT) values and occurrence of bleeding based on standard unfractionated heparin (UFH) weight‐based dosing recommendations compared with an aggressive weight‐based UFH dosing strategy using higher maximum doses and infusion rates in both obese and nonobese patients who presented with non–ST‐segment elevation myocardial infarction or unstable angina (NSTEMI/UA) or atrial fibrillation.