(1)
Cardiology Department, Maria Vittoria Hospital and Department of Public Health and Pediatrics University of Torino, Torino, Italy
6.1 Overview
The therapy of pericardial and myopericardial syndromes should be targeted as much as possible at the underlying aetiology. Nevertheless, in clinical practice, many cases remain “idiopathic”, that is without a well-established aetiological diagnosis with a conventional diagnostic approach. Nothing is really “idiopathic”, but in the real world, considering a cost-effective diagnostic approach, as well as the potential risks of additional invasive investigations, it may be rationale and appropriate to provide empiric medical therapies to treat the most probable diagnosis. In developed countries with a low prevalence of tuberculosis, the most common presumed aetiology is viral or immune mediated.
The conventional diagnostic approach is essentially aimed at excluding significant causes, such as bacterial infections or cancer, that may have targeted and well-established therapies. On this basis, in this chapter, it will be reviewed the mechanism of action, indications, contraindications and usual doses of main medical drugs that are used in the common clinical management of pericardial syndromes. Specific therapies will be reviewed separately for each aetiology.
6.2 Aspirin and Non-steroidal Anti-inflammatory Drugs (NSAID)
Aspirin and NSAIDs are the mainstay of the treatment of pericardial and myopericardial inflammatory syndromes (pericarditis and pericardial effusions with evidence of systemic inflammation) [1, 2].
Mechanism of Action
The primary effect of NSAIDs is the inhibition of cyclooxygenase (COX) (prostaglandin synthase), thereby impairing the ultimate transformation of arachidonic acid to prostaglandins, prostacyclin and thromboxanes. There are two main described isoforms of COX: COX-1 and COX-2. COX-1 is expressed in most tissues and regulates normal cellular processes (such as gastric cytoprotection, vascular homeostasis, platelet aggregation and kidney function), and it is stimulated by hormones or growth factors. COX-2 is mainly expressed during inflammatory states (Fig. 6.1).
Fig. 6.1
Mechanism of action of NSAIDs. The main action is the inhibition of COX. Such effect explains the effect on inflammation and main side effects on gastrointestinal tract and kidney function
Indications
Any inflammatory pericardial syndrome.
Main Contraindications, Warnings, Precautions and Interactions
Allergy, to be used with caution in patients with platelet and bleeding disorders, dehydration and heavy ethanol use (>3 drinks/day) may increase bleeding risks and may enhance gastric mucosal damage, erosive gastritis or peptic ulcer disease and severe hepatic failure. To be used with caution in patients with mild-to-moderate renal impairment and to be avoided in severe impairment.
NSAIDs can interact with numerous drugs, including anticoagulants, antiplatelet agents, antihypertensive drugs, calcineurin inhibitors (cyclosporine and tacrolimus), digoxin, diuretics, glucocorticoids, lithium, selective serotonin reuptake inhibitors (SSRIs), methotrexate and other medications. The interaction of NSAIDs with methotrexate generally requires avoidance of NSAID use in patients receiving antineoplastic doses, while both may be used concurrently with standard doses in patients receiving low-dose methotrexate (e.g. in rheumatologic disorders).
Adverse Events
Aspirin and NSAID may affect haemostasis, thus causing bleeding. Haemorrhage may occur at virtually any site. Risk is dependent on multiple variables including dosage, concurrent use of multiple agents, which alter haemostasis, and patient susceptibility. Many adverse effects are dose related and are rare at low dosages. Other serious reactions are idiosyncratic, related to allergy or individual sensitivity. Main adverse events include agitation, confusion, dizziness, fatigue, headache, insomnia, Reye’s syndrome (children), skin rash, urticaria, gastrointestinal ulcer (5–30 %), duodenal ulcer, dyspepsia, epigastric distress, gastritis, gastrointestinal erosion, heartburn, nausea, stomach pain, vomiting, anaemia, blood coagulation disorder, haemorrhage, iron deficiency anaemia, prolonged prothrombin time, thrombocytopenia, hepatitis (reversible), hepatotoxicity, increased serum transaminases, hypersensitivity (anaphylaxis, angiooedema), acetabular bone destruction, rhabdomyolysis, weakness, hearing loss, tinnitus, increased blood urea nitrogen, increased serum creatinine, interstitial nephritis, renal failure (including cases caused by rhabdomyolysis), renal insufficiency, renal papillary necrosis, asthma, bronchospasm, dyspnoea, hyperventilation, laryngeal oedema, noncardiogenic pulmonary oedema, respiratory alkalosis and tachypnea.
Special Populations
Aspirin is contraindicated in children due to the possible risk of Reye’s syndrome and hepatotoxicity. Weight-adjusted doses are recommended for other NSAIDs (Table 6.1).
Table 6.1
Dosing of aspirin and NSAID in children
Drug | Dosing |
|---|---|
Aspirin | Contraindicated because of the risk of Reye’s syndrome and hepatotoxicity |
Ibuprofen | 30–50 mg/kg/24 h divided in doses every 8 h (not to exceed the maximal dose of 2.4 g/day) |
Indomethacin | To be considered for children >2 years. 1 to 2 mg/kg/day in 2–4 divided doses (not to exceed the maximal dose of 150–200 mg/day) |
Aspirin can be used at lower doses during pregnancy (e.g. 500–750 mg every 8 h) before the 20 weeks and should be avoided if >20 weeks [3–7].
In the elderly, it is recommended the use of the lowest recommended doses and frequency. All patients taking aspirin and NSAIDs should receive gastroprotection with a proton pump inhibitor [4].
Common Prescribed Drugs and Dosing
In literature, the most common reported drugs include aspirin, ibuprofen and indomethacin (Fig. 6.2) [1, 2, 4].
Fig. 6.2
Aspirin and commonly prescribed NSAID in pericardial syndromes
The selection of the drug should be individualized, taking into account the local availability and physician expertise, the previous history of the patient (favouring the choice of the drug proven to be most efficacious to control symptoms), concomitant therapies and disease (e.g. aspirin is the favourite choice in patients already on aspirin or with ischaemic heart disease, while corticosteroids may have less interference with patients on traditional oral anticoagulant therapy) [4].
A specific issue for clinical practice is how to use anti-inflammatory therapies in patients with ischaemic heart diseases. Aspirin should be the preferred choice in these patients: dose of aspirin up to 1500 mg/day has been demonstrated to be efficacious as antiplatelet therapy, while it is not demonstrated that higher doses (usually considered for anti-inflammatory effect) really attenuate or compromise its antiplatelet activity. Indomethacin and other NSAIDs should be avoided in patients with coronary heart disease. Most of them have a small risk of additional ischaemic events. For instance, ibuprofen and indomethacin significantly increase cardiovascular risk (RR 1–3), while naproxen (500 mg twice daily) probably is safer [8].
Additional issues to be considered are how to cope with aspirin, NSAIDs and traditional oral anticoagulant therapies. Essentially based on experts’ opinion, it is advisable to use low-dose corticosteroids (e.g. prednisone 0.2–0.5 mg/kg/day) and avoid aspirin and other NSAIDs. There are no data specifically for pericardial syndromes on the use of anti-inflammatory therapies and new oral anticoagulants (e.g. dabigatran, rivaroxaban, apixaban). These statements reflect the experts’ consensus provided by the 2015 European Society of Cardiology guidelines on pericardial diseases [8].
Common dosing for inflammatory pericardial syndromes is reported in Table 6.2. In order to achieve a better control of symptoms during 24 h, it is better to provide the drug every 8 h as three daily doses after meal ingestion [2, 4, 8, 9].
Table 6.2
Common dosing of aspirin and usual NSAIDs in pericardial inflammatory syndromes
Drug | Usual dosing as initial attack dose |
|---|---|
Aspirin | 750–1000 mg every 8 h |
Ibuprofen | 600 mg every 8 h |
Indomethacin | 25–50 mg every 8 h |
6.3 Colchicine
Colchicine is an ancient anti-rheumatic drug of plant origin that has been used for centuries for the treatment and prevention of gouty attacks. The term colchicum derives from “Colchis”, an ancient region and country on the Black Sea and indicates its origin. The plant source of colchicine, the autumn crocus (Colchicum autumnale), was described for treatment of rheumatism and swelling in the Ebers Papyrus (ca. 1500 B.C.), an Egyptian medical papyrus (Fig. 6.3). Colchicum extract was first described as a treatment for gout in De Materia Medica by Pedanius Dioscorides, in the first-century AD [10].
Fig. 6.3
Colchicine and its plant origin
Mechanism of Action
The main known mechanism of action is the capability of colchicine to concentrate in white blood cells (especially granulocytes) and block tubulin polymerization thus interfering with several cellular functions (e.g. phagocytosis, degranulation, chemotaxis) that are relevant to explain its anti-inflammatory properties (Fig. 6.4).
Fig. 6.4
Main mechanisms of action of colchicine and old and new emerging options for recurrent cases (azathioprine, human intravenous immunoglobulin and anakinra)
Following the successful use of the drug to treat and prevent poliserositis attacks (including pericarditis) in patients with familial Mediterranean fever (FMF), the first idea to use colchicine for pericarditis is due to Bayes-de-Luna et al. who proposed the use of colchicine to treat and prevent recurrent pericarditis in patients without FMF in 1987. Following the successful use in single cases, prospective studies, specific trials have been planned and performed in the last 10 years, definitely showing its safety and efficacy at the proposed low doses to treat and prevent pericarditis [10].
Indications
Any inflammatory pericardial syndrome to treat the acute episode. Colchicine may hasten the response to aspirin, NSAID and corticosteroids when added on top of these therapies and especially prevent recurrences.
Main Contraindications, Warnings, Precautions and Interactions
Hypersensitivity to colchicine. Colchicine should be avoided in patients with severe renal and liver impairment, pregnancy, lactation, as well as in patients with concomitant use of a strong P-glycoprotein (P-gp) or strong CYP3A4 inhibitor in presence of renal or hepatic impairment. The main drug interactions of colchicine are reported in Table 6.3.
Table 6.3
Major contraindications and interactions of colchicine
Feature | Data |
|---|---|
Major contraindications | Concomitant use of a P-glycoprotein (P-gp) or strong CYP3A4 inhibitor in presence of renal or hepatic impairment |
Severe renal impairment | |
Severe liver disease | |
Pregnancy
Related posts: Age and Gender Issues in the Management of Pericardial Diseases
Guidelines on the Management of Pericardial Diseases
 Acute Pericarditis: Specific Aetiologies (Non-viral, Non-idiopathic)
 Constrictive Pericarditis
 Pericardial Effusion
 Pericarditis Associated with Myocardial Involvement (Myopericarditis/Perimyocarditis)
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