Should direct oral anticoagulants be used to treat protein C or S deficiency?

ABSTRACT: Few studies have evaluated the use of direct oral anticoagulants (DOACs) in patients with major thrombophilias, such as protein C or S deficiency. The data related to use of DOACs in treating protein C or S deficiency are heterogeneous, consisting of various DOACs, inconsistent ranges of dosing, dissimilar patient demographics, and inconsistent clinical endpoints. Vitamin K antagonists and low-molecular-weight heparins are preferred until more robust data are available about using DOACs in patients with protein C or S deficiency.

Potential Failure of Vancomycin Dosing Using AUC/MIC in a Patient With Purulent Methicillin-Resistant Staphylococcus aureus Pericarditis.

Objective: The objective of this case report is to describe utilization of area under the curve (AUC)/minimum inhibitory concentration (MIC) vancomycin dosing with variable MIC results in a patient with methicillin-resistant Staphylococcus aureus (MRSA) purulent pericarditis. Case: A 57-year-old Caucasian male presented with cardiac tamponade and pulmonary emboli. Echocardiogram showed moderate-large pericardial effusion with signs of early tamponade physiology. Pericardiocentesis removed serosanguinous, straw yellow fluid. Blood and pericardial cultures revealed MRSA. Patient was then initiated on vancomycin with an initial AUC of 415. MIC of repeat blood cultures were inconsistent. After 8 days of persistent bacteremia, patient was transitioned to daptomycin and ceftaroline with blood culture clearance within 48 hours. Discussion/Conclusion: Guidelines recommend AUC/MIC vancomycin dosing in patients with MRSA bacteremia. Literature regarding treatment of MRSA purulent pericarditis is limited to case reports. Evidence shows variation in MIC results dependent on analysis methods. Further studies on obtaining accurate MIC values and use of AUC/MIC dosing for MRSA purulent pericarditis are prudent to provide appropriate therapy in these patients as mortality is high.

Rilonacept: A Newly Approved Treatment for Recurrent Pericarditis.

OBJECTIVE: To review the pharmacology, efficacy, and safety of rilonacept for the prevention and treatment of recurrent pericarditis (RP). DATA SOURCES: A MEDLINE search was conducted between January 2006 and April 2021 using the following terms: rilonacept, pharmacology, pericarditis, recurrent pericarditis, interleukin (IL) antagonist, and pharmacology; prescribing information was also used. STUDY SELECTION AND DATA EXTRACTION: English-language studies assessing pharmacology, efficacy, and safety of IL antagonists were reviewed. DATA SYNTHESIS: Rilonacept traps IL-1α and IL-1ß. In the Phase III trial, rilonacept was associated with a lower risk of recurrence, more persistent clinical response, and higher amount of days with no or minimal pericarditis symptoms, compared with placebo. The median time to pain response was 5 days, and median time to normalization of C-reactive protein was 7 days with rilonacept. All patients receiving rilonacept during the run-in period were able to be weaned off of standard background therapy, leading to transition to rilonacept monotherapy. The most common adverse effects were upper respiratory tract infections and injection site reactions. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: Rilonacept may be used for the prevention and treatment of multiple recurrences in patients receiving background therapy for RP, and reduction in risk of recurrence in adults and adolescents ≥12 years with elevated C-reactive protein. Rilonacept may be considered to wean patients from standard background therapy. CONCLUSION: Rilonacept is a safe, once weekly, subcutaneously administered IL-1 "trap," indicated for the treatment of RP, and reduction in risk of recurrent pericarditis in adults and children ≥12 years of age.

What is rilonacept's role in treating recurrent pericarditis?

ABSTRACT: The interleukin (IL)-1 antagonist rilonacept is approved by the FDA to treat recurrent pericarditis. In adults and adolescents with multiple recurrences of pericarditis, compared with placebo, rilonacept is associated with a lower risk of recurrent pericarditis, more persistent clinical response, normalized C-reactive protein within 7 days, and a higher number of days with no or minimal pericarditis symptoms. Patients receiving rilonacept could be weaned off of standard therapies for recurrent pericarditis and eventually be transitioned to rilonacept monotherapy. The most common adverse reactions to rilonacept include injection-site reactions, upper respiratory tract infections, and increased lipids. A loading dose of rilonacept is administered subcutaneously (SQ), along with weekly SQ maintenance dosing, which can be self-administered. Rilonacept is indicated for the treatment of recurrent pericarditis and reduction in risk of recurrence in patients age 12 years and older who have an elevated C-reactive protein level and significant disease burden.

Which SSRI is safest for patients with CVD and major depressive disorder?

ABSTRACT: Major depressive disorder is a common mood disorder and presents increased morbidity and mortality risks for patients with comorbid cardiovascular disease (CVD). Selective serotonin reuptake inhibitors (SSRIs) are a cornerstone of treatment for major depressive disorder, given their relative safety and affordability compared with other antidepressant classes, and SSRIs frequently are used in patients with CVD. However, clinicians should carefully weigh safety considerations before prescribing SSRIs in these patients. This article reviews the safety of SSRIs in patients with CVD and discusses SSRI selection.

Pharmacotherapeutic Management Strategies for Thyroid Disease-Induced Pericarditis.

Objective: To describe the various pharmacotherapeutic strategies in managing thyroid disease-induced pericarditis (TDIP). Considerations for both hypothyroid-induced and hyperthyroid-induced pericarditis will be discussed. Data Sources: A literature search of MEDLINE, including PubMed, was performed inclusive of all years, using the following search terms: thyroid disease, pericardial diseases, pericarditis, acute pericarditis, cholesterol pericarditis, hypothyroidism, hyperthyroidism, colchicine, corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, methimazole, propylthiouracil, and P-glycoprotein. Product monographs were reviewed as well. Study Selection and Data Extraction: Relevant English-language studies and data as well as the most current guidelines for diagnosis and management of thyroid and pericardial diseases were considered. Because of limited data regarding the subject matter, no date range limits were established during literature search. Data Synthesis: It is well documented that thyroid dysfunction can adversely affect cardiovascular function. Additionally, there are published guidelines on the diagnosis and management of pericarditis and, separately, thyroid disease. There are limited data, however, on managing TDIP. The sequela of untreated TDIP can be detrimental. Relevance to Patient Care and Clinical Practice: Strategies on managing TDIP are scarcely reported in the literature. This review provides clinicians with a single reference source for treatment strategies toward managing hypothyroidism-induced and hyperthyroidism-induced pericarditis as well as significant drug interactions that can potentially confound the management of hypothyroidism- and hyperthyroidism-induced pericarditis. Conclusions: Treatment of TDIP involves addressing both the thyroid disease as well as the pericarditis. Along with treatment strategies, clinicians should also consider potential drug-drug and drug-disease interactions that can potentially worsen clinical outcomes.

Managing acute and recurrent idiopathic pericarditis.

Pericarditis is the most common form of pericardial disease and may be associated with significant morbidity and mortality. Management of idiopathic pericarditis includes pharmacologic therapies, non-pharmacologic therapies, and surgery. This article describes the diagnosis and management of idiopathic causes of pericarditis, incorporating recommendations included in the European Society of Cardiology guidelines.

Pain management considerations in patients living with both pain syndromes and cardiovascular diseases and disorders.

Concomitant pain syndromes and cardiovascular disease (CVD) and disorders are associated with significant morbidity, impaired quality of life, and neuropsychiatric disorders. There is an interplay between the mechanisms of pathophysiology of both CVD and pain syndromes. Patients with CVD (and/or disorders) as well as pain syndromes have an increased propensity for drug-drug/disease interactions. Therefore, an understanding of how to use pharmacotherapy to treat pain syndromes, in the context of patients who have diagnoses of CVD and/or disorders, is paramount to patients' success in achieving adequate pain control and appropriately managing CVD and/or disorders, all while decreasing the risk of adverse events (AEs) both from pharmacotherapy to treat pain and CVD (and/or disorders). Based on the appraisal of literature and authors' clinical expertise, it was determined that gabapentinoids, opioids, skeletal muscle relaxants, tricyclic antidepressants, clonidine, serotonin norepinephrine-reuptake inhibitors, dronabinol, carbamazepine, second-generation antipsychotics, non-steroidal anti-inflammatory drugs, aspirin, corticosteroids, and topical anesthetics have the most evidence for use in patients with CVD and/or disorders. However, the literature surrounding the use of pharmacotherapy for pain management is limited to retrospective studies and there is a lack of well-designed, prospective, randomized trials; this also includes head-to-head comparator studies. Unlike many CVD-related pharmacotherapy studies, data studying pain management in patients with CVD lacks standardized outcomes that are consistent among the pool of data. Overall, the decision to prescribe specific pain management therapies in patients with CVD and/or disorders should include assessment of pain severity, type of pain, drug-drug/disease interactions, adjuvant therapies required, and the risk or presence of AEs.

Key Articles and Guidelines in the Management of Pericardial Syndromes.

Over the past two decades, emerging literature has shaped the management of pericardial syndromes and has evolved abundantly towards the creation of European guidelines for the diagnosis and management of pericardial diseases. However, since the publication of the European guidelines in 2015, more data surrounding the management of pericardial syndromes have been published. Comprehensive reference materials with the most updated literature are warranted and can be pivotal in helping pharmacists make evidence-based and clinical decisions for patients diagnosed with pericardial syndromes. This compilation of key articles and guidelines will serve as a resource for pharmacists who are responsible for the care of patients with pericardial syndromes.

A systematic review of the drug-drug interaction between statins and colchicine: Patient characteristics, etiologies, and clinical management strategies.

Colchicine and statins are frequently co-prescribed for prevention and treatment of cardiovascular diseases, auto-inflammatory diseases, and gout. Both are substrates and inhibitors of the cytochrome P-450 (CYP) 3A4 isozyme and P-glycoprotein so that taken together, they represent a clinically significant interaction. Data suggest the interaction may be associated with potentially life-threatening myopathies and rhabdomyolysis. The purposes of this systematic review (SR) were to gather and appraise evidence surrounding the statin-colchicine drug interaction and discuss related risk-mitigation strategies. An electronic literature search was performed. Twenty-one articles met the protocol to be included in the qualitative analysis: 18 case reports/series, 2 retrospective observational cohort studies, and 1 retrospective case-control study. Thirty-eight patients developed an adverse drug event (ADE) receiving statin-colchicine combination therapy; 25 (66%) patients developed myopathy; 10 (26%) patients developed rhabdomyolysis, and three (8%) patients developed neuromyopathy. Over 70% of patients developed ADEs on simvastatin or atorvastatin, and 80% of studies reported moderate-to-high intensity statins. Colchicine dosing varied but ranged between 0.5 to 1.5 mg daily. Sixty-two percent of patients in the case reports/series had comorbid renal disease. Seven studies (33% of all included studies) reported patients taking concomitant interacting medications at the CYP3A4 and/or P-glycoprotein efflux pump. Seventeen studies (81% of all included studies) reported ADEs leading to hospitalization. A multivariate analysis from one case-control study identified risk factors prognosticating myopathy ADEs in patients taking statin-colchicine therapy: comorbid renal disease and/or cirrhosis, colchicine doses 1.2 mg daily or greater, and concomitant interacting medications. Clinicians must be cognizant that the statin-colchicine drug interaction may lead to patient harm and thus should employ risk-mitigation strategies for statin-associated muscle symptoms. Future studies are warranted to validate clinically relevant risk factors that are strongly associated with the complications owing to the statin-colchicine drug interaction.

Management of Idiopathic Viral Pericarditis in the Pediatric Population.

Idiopathic (viral) pericarditis (IP) is one of the most common etiologies of acute and recurrent pericarditis in children. IP is associated with significant morbidity, and recurrence rates of IP are high and require treatment to decrease risk of recurrence and pericarditis-related chest pain. Despite significant morbidity, sparse guidance exists to comprehensively address management of IP in children. The purpose of this review is to provide an overview of the pharmacotherapy of IP in children, including clinical pearls for managing pediatric patients. Clinicians should consider using the combination of colchicine and nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy, in order to reduce the risk of recurrence and foster symptom improvement in IP. Colchicine dosing may vary depending on patient age, weight, concomitant pharmacotherapies, and disease states. Choice of NSAID should be based on cost, tolerability, and adverse drug events (ADEs). Children should receive higher NSAID attack dosing for >1 week to ensure a reduction in high sensitivity C-reactive protein concentrations and symptom relief. Corticosteroids should be considered last-line for treatment of IP in children, because they increase the risk of recurrence. Immunotherapies may be considered for children with multiple recurrences related to IP despite the use of NSAIDs, colchicine, and/or corticosteroids. Similar to adults, diligent monitoring should be implemented, to prevent drug-drug interactions, drug-disease interactions, and/or ADEs in children.

Clinical and economic outcomes associated with hospitalizations for acute idiopathic pericarditis in the United States.

BACKGROUND: Outcomes-based data regarding the management of hospitalized U.S. patients with acute idiopathic pericarditis (AIP) are lacking. OBJECTIVES: This study sought to elucidate the clinical and economic outcomes associated with the inpatient care of AIP. METHODS: Cohort study of adults with AIP; multivariable analyses of clinical and economic outcomes (inpatient mortality, surgical or medical complications, length of stay, and medical charges). RESULTS: Surgical or medical complications, pericardiocentesis, and pericardiotomy were each independently associated with a significantly higher odds of inpatient mortality (p<0.05). Pericardiocentesis, pericardiotomy, and pericardiectomy were also independently associated with significantly higher odds for complications (p<0.001) and, overall, surgical or medical complications were associated with longer lengths of stay and higher charges (p < 0.001). A higher odds of inpatient mortality was associated with micropolitan or rural patient residence, Medicaid payor, and African American race (p<0.05). CONCLUSIONS: U.S. inpatient cases of AIP are associated with significant use of healthcare resources, disparities, morbidity, and mortality.

Current pharmacotherapy management of children and adults with pericarditis: Prospectus for improved outcomes.

Pericarditis is the most common inflammatory pericardial disease in both children and adults. Since the 2015 European Society of Cardiology Guidelines for the diagnosis and management of pericardial disease were published, there have been significant updates to management. Pharmacotherapy has been historically reserved for idiopathic pericarditis (IP). However, there has been increasing use of pharmacotherapies, such as anti-inflammatory therapies, colchicine, and immunotherapies for other causes of pericarditis, such as post-cardiac injury syndromes (PCIS). Nevertheless, the quality of data varies depending on PCIS or idiopathic etiologies, as well as the adult and pediatric population. High-dose anti-inflammatory therapies should be used to manage symptoms associated with either etiology of pericarditis in both adults and children, but do not ameliorate the inflammatory disease process. Choice of anti-inflammatory should be guided by drug-drug/disease interactions, cost, tolerability, patient age, and should be tapered accordingly over several weeks to months. Colchicine should be added as adjuvant therapy to anti-inflammatory therapies in adults and children with IP, as it has been shown to lower the risk of recurrence, reduce pericarditis symptoms, and improve morbidity. Colchicine is also reasonable to add to adults and children with pericarditis secondary to PCIS. Systemic glucocorticoids increase risk of recurrence in adults and children with IP and are reserved for second-line treatment in acute and recurrent IP; they are generally avoided in PCIS. Immunotherapies are regarded as third-line for recurrent IP in adults and children. Limited evidence exists to support their use in patients with pericarditis from PCIS. Pharmacovigilance strategies, such as C-reactive protein and adverse drug event monitoring, are also important toward balancing efficacy and safety of the various strategies used to manage pericarditis in adults and children.

Pharmacists' Role in the Management of Acute and Recurrent Pericarditis: Inpatient and Outpatient Perspectives.

Pharmacists are qualified to provide valued care to patients inflicted with cardiovascular-related disorders. Although the role of pharmacists regarding the care of patients with cardiovascular disease has been previously described, there is currently no literature describing the role of pharmacists in the management of patients with pericarditis, specifically in patients with viral or idiopathic etiologies of pericarditis. Much of the management of idiopathic pericarditis, whether acute or recurrent, is a combination of pharmacotherapy, consisting of aspirin, nonsteroidal anti-inflammatory therapies, colchicine, corticosteroids, and/or immunotherapies. Therefore, pharmacists in any practice setting (ie, inpatient or outpatient) have the opportunity to provide an integral role in ensuring adherence to guideline-based care related to the management of acute or recurrent idiopathic pericarditis, optimizing patients' use of pharmacotherapy, preventing adverse drug events such as drug-drug and drug-disease interactions, resolving managed care-related issues, providing care transitions activities that emphasize medication reconciliation and patient education, and evaluating the cost-effectiveness of the pharmacotherapies used to treat acute and recurrent idiopathic pericarditis. This review describes the role of pharmacists in the management of acute and recurrent idiopathic pericarditis within the inpatient and outpatient practice settings, with an emphasis on specialty practice areas, such as the emergency department, intensive care and medicine units within the hospital, ambulatory care-based practices, community pharmacy, and managed care pharmacy.

Management of Acute Idiopathic (Viral) Pericarditis in the Emergency Department: A Review for the Nursing Professional.

Acute pericarditis is an inflammatory disorder that contributes to chest pain admissions in the emergency department (ED). Nursing professionals can play a vital role in the differential, triage and management of acute pericarditis in the ED. First-line pharmacotherapy to specifically treat acute pericarditis of viral or idiopathic origin is paramount in improving patients' quality of life and reducing the risk of further recurrences of pericarditis and consists of combination therapy with aspirin (acetylsalicylic acid [ASA]) or a nonsteroidal anti-inflammatory drug (NSAID), in combination with colchicine. Corticosteroids should not be initiated as first-line therapy in idiopathic (viral) pericarditis, as they increase the risk of recurrences. Nursing professionals are also pivotal in monitoring pharmacotherapy with respect to safety and efficacy. Overall, the nursing professional can facilitate timely administration and monitoring of medications, provide patient education, promote adherence, and assist in transitions of care for patients diagnosed with acute idiopathic (viral) pericarditis in the ED.

Optimal Medical Therapy Prescribing Patterns and Disparities Identified in Patients with Acute Coronary Syndromes at an Academic Medical Center in an Area with High Coronary Heart Disease-Related Mortality.

BACKGROUND: Coronary heart disease (CHD)-related mortality is high in the southern United States. A five-drug pharmacotherapy regimen for acute coronary syndromes (ACS), defined as optimal medical therapy (OMT), can decrease CHD-related mortality. Studies have indicated that OMT is prescribed 50-60% of the time. Assessment of prescribing could provide insight into the potential etiology of disparate mortality. OBJECTIVE: The aim was to evaluate prescribing of OMT at discharge in patients presenting with an ACS event at an academic medical center and identify patients at risk of not receiving OMT. METHODS: A single-center, retrospective cohort of patients with ACS diagnosis between July 2013 and July 2015 was investigated, and a multivariable regression analysis conducted to identify populations at risk of not receiving OMT. RESULTS: A total of 864 patients were identified by International Classification of Diseases, Ninth Revision (ICD-9) codes, with 533 excluded and 331 analyzed. OMT was prescribed in 69.79%. Patients ≥ 75 years of age [p = 0.003; odds ratio (OR) 0.30; 95% confidence interval (CI) 0.136-0.673], unstable angina presentation (p = 0.042; OR 0.55; 95% CI 0.307-0.977), and surgical management (p = 0.001; OR 0.22; 95% CI 0.095-0.519) were less likely to receive OMT. CONCLUSIONS: The percentage of patients prescribed OMT exceeded the reported global percentage of prescribed OMT. However, disparities exist among specific populations.

Career Skills Assessment in a Doctor of Pharmacy Curriculum.

Objective. To assess students' knowledge of, perceived importance of, and confidence in six career skills areas (curriculum vitae/resume writing, interviewing skills/business attire, phone interviews, thank you notes, business/dining etiquette, and networking) before, immediately after, and six months after participating in a career skills workshop. Methods. All students in a senior-level seminar course participated in the same simulation/performance-based workshop that was coupled with verbal or rubric-based feedback for each of the areas. Results. Ninety-one students participated in the study and all students' knowledge significantly increased over the study as determined by study baseline, conclusion, and six-month follow-up assessments. At study follow-up, knowledge increased an average of +7.1 percentage points from baseline. Multivariate analysis indicated significant increases in confidence from baseline to follow-up ranging from +0.15 to +0.29 across the six workshop areas, with resume/CV preparation having the highest increase. From study onset to follow-up, students perceived that the six career skills areas were above the average importance midpoint (3.0). Conclusion. The workshop was effective in increasing students' knowledge and confidence of essential career skills vital to pursuing post-graduate employment. These career skills are important for helping students distinguish themselves in a competitive job market.

Treatment of Adults with Idiopathic Recurrent Pericarditis: Novel Use of Immunotherapy.

Idiopathic recurrent pericarditis (IRP) can be challenging to treat. Even after guideline-directed first-line treatment consisting of aspirin (ASA) or a nonsteroidal antiinflammatory drug (NSAID) in combination with colchicine therapy, recurrences still occur in greater than 20% of patients. Many patients then require treatment with long-term corticosteroids, which is not a favorable option due to their short- and long-term adverse effects. Because it is theorized that the pathophysiology of IRP may possess autoimmune sequelae, the use of immunotherapy for the treatment of IRP has emerged. In this review, we describe the literature associated with immunotherapy used to treat IRP in an adult population as well as provide an overview of the safety and monitoring parameters for each agent. The most common immunotherapies used after patients have had multiple recurrences of IRP are anakinra, intravenous immunoglobulin (IVIG), and azathioprine. In most cases, these immunotherapies are adjunctive therapy, with the goal of tapering and discontinuing immunosuppressive corticosteroids. After reviewing the data, anakinra resulted in more patients discontinuing corticosteroids and prevented further recurrences of pericarditis. IVIG resulted in symptom resolution and no further recurrences in most of the patients. Azathioprine was associated with more than half of patients becoming recurrence free; however, many patients required a restart of corticosteroids due to recurrence. Clinicians should be aware of the adverse effects of immunotherapy, ranging from mild gastrointestinal events to risk of infection and serious blood dyscrasias that may require diligent monitoring. The use of immunotherapy for the treatment of adults with IRP should be restricted to patients who have multiple recurrences. Ideally, immunotherapy would be adjunctive to first-line combination therapy with ASA/NSAID plus colchicine, with the goal of tapering and discontinuing immunosuppressive corticosteroids. Furthermore, clinicians should consider cost, drug-drug and drug-disease interactions, and safety, as well as the quality of the retrospective evidence before considering any immunotherapy.

Pharmacotherapy of Vasospastic Angina.

Vasospastic angina is a diagnosis of exclusion that manifests with signs and symptoms, which overlap with obstructive coronary artery disease, most often ST-segment elevation myocardial infarction. The pharmacotherapy that is available to treat vasospastic angina can help ameliorate angina symptoms. However, the etiology of vasospastic angina is ill-defined, making targeted pharmacotherapy difficult. Most patients receive pharmacotherapy that includes calcium channel blockers and/or long-acting nitrates. This article reviews the efficacy and safety of the pharmacotherapy used to treat vasospastic angina. High-dose calcium channel blockers possess the most evidence, with respect to decreasing angina incidence, frequency, and duration. However, not all patients respond to calcium channel blockers. Nitrates and/or alpha1-adrenergic receptor antagonists can be used in patients who respond poorly to calcium channel blockers. Albeit, evidence for use of nitrates and alpha1-adrenergic receptor antagonists in vasospastic angina is not as robust as calcium channel blockers and can exacerbate adverse effects when added to calcium channel blocker therapy. Despite having a clear benefit in patients with obstructive coronary artery disease, the benefit of beta-adrenergic receptor antagonists, statins, and aspirin remains unclear. More data are needed to elucidate whether or not these agents are beneficial or harmful to patients being treated for vasospastic angina. Overall, the use of pharmacotherapy for the treatment of vasospastic angina should be guided by patient-specific factors, such as tolerability, adverse effects, drug-drug, and drug-disease interactions.