The clinical significance of colchicine in the treatment of acute idiopathic (viral) pericarditis (IP) was only elucidated less than a decade ago. Multiple trials have shown the benefit of colchicine in decreasing the rate of recurrence, primarily in the European population. However, the colchicine formulation used in these trials is not available in Western countries such as the USA. In the USA, two formulations are available: the 0.6 mg capsule and the 0.6 mg tablet. As a result, higher doses than administered in the European trials must be utilized to treat IP. However, the use of these dosage forms has never been studied in the treatment of IP. Pharmacokinetic and pharmacodynamic knowledge of colchicine germane to clinicians such as drug disposition and drug-drug or drug-disease interactions have not been extensively reviewed in recent years. Furthermore, the safety of colchicine in the treatment of IP has not been extensively studied, and literature regarding adverse drug events originates from data in patients treated for familial Mediterranean fever and gout. This review will help the clinician understand pharmacotherapeutic considerations and thereby optimize therapy and ensure patient safety when using colchicine to treat IP.
Aspirin (ASA) and non-steroidal anti-inflammatory drugs (NSAIDs) are a mainstay of therapy for the treatment of idiopathic pericarditis (IP). A comprehensive review consisting of pertinent clinical literature, pharmacokinetic, and pharmacodynamic considerations, has not been released in recent years. This review will facilitate the clinician’s understanding of pharmacotherapeutic considerations for using ASA/NSAIDs to treat IP. Data were compiled using clinical literature consisting of case reports, cohort data, retrospective and prospective studies, and manufacturer package inserts. ASA, ibuprofen, indometacin, and ketorolac relatively have the most evidence in the treatment of IP, provide symptomatic relief of IP, and should be tapered accordingly. ASA is the drug of choice in patients with coronary artery disease (CAD), heart failure (HF), or renal disease, but should be avoided in patients with asthma and nasal polyps, who are naïve to ASA therapy. Ibuprofen is an inexpensive and relatively accessible option in patients who do not have concomitant CAD, HF, or renal disease. Indometacin is not available over-the-counter in the USA, and has a relatively higher incidence of central nervous system (CNS) adverse effects. Ketorolac is an intravenous option; however, clinicians must be mindful of the maximum dose that can be administered. While ASA/NSAIDs do not ameliorate the disease process of IP, they are part of first-line therapy (along with colchicine), for preventing recurrence of IP. ASA/NSAID choice should be dictated by comorbid conditions, tolerability, and adverse effects. Additionally, the clinician should be mindful of considerations such as tapering, high-sensitivity CRP monitoring, bleeding risk, and contraindications to ASA/NSAID therapy.
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.
Idiopathic (viral) pericarditis is the most common form of pericardial disease in the Western world. Despite the combination of colchicine and nonsteroidal antiinflammatory drugs (NSAIDs) plus aspirin (ASA), considered first-line therapy, the incidence of recurrent pericarditis is ~20-30%. In addition, secondary recurrence without optimal first-line therapy is ~50%. This is due to the many clinical challenges, such as inappropriate NSAID/ASA duration of therapy, the use of corticosteroid therapy, contraindications or intolerances to therapy, adverse effects, and issues related to adherence. This review describes contemporary pharmacotherapeutic management of idiopathic (viral) pericarditis, with a particular emphasis on the role of colchicine. Emerging therapies and management strategies, such as high-sensitivity C-reactive protein-guided therapy and novel immunotherapies, are also reviewed. Ultimately, understanding appropriate treatment will assist the clinician in helping decrease the risk of recurrent, incessant, and refractory pericarditis.
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.
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 statincolchicine 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 statincolchicine 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.
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.
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/performancebased 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 17.1 percentage points from baseline. Multivariate analysis indicated significant increases in confidence from baseline to follow-up ranging from 10.15 to 10.29 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 postgraduate employment. These career skills are important for helping students distinguish themselves in a competitive job market.
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