ClinicalGeneticDrugs and Brugada syndrome patients: Review of the literature, recommendations, and an up-to-date website (www.brugadadrugs.org)
Introduction
Worldwide, the Brugada syndrome is recognized as an important cause of sudden cardiac death occurring in individuals at a relatively young age. Brugada syndrome is diagnosed in the presence of specific electrocardiographic (ECG) abnormalities (known as the type 1 Brugada syndrome ECG; Figure 1) seen in combination with an absence of gross structural abnormalities and several other criteria.1, 2 In addition, Brugada syndrome often shows familial aggregation.
The presence of the type 1 Brugada syndrome ECG in particular has been linked to an increased risk for ventricular tachyarrhythmias, cardiac arrest, and sudden death in patients with Brugada syndrome.3 Importantly, many drugs have been reported to induce the type 1 Brugada syndrome ECG and/or (fatal) arrhythmias in patients with Brugada syndrome (Figure 2). Therefore, patients with Brugada syndrome should be advised not to use these drugs or to use them only under controlled conditions.
Although the most appropriate treatment of Brugada syndrome is under discussion,4, 5 avoidance of potentially proarrhythmic drugs and treatment of fever (which is a well-known trigger of cardiac events in Brugada syndrome)6, 7 are generally accepted to be an important part of (prophylactic) treatment. However, some patients may (only) be appropriately treated with an implantable cardioverter-defibrillator. Some drugs may have an antiarrhythmic effect and thus may be used favorably in the acute or chronic setting.8, 9, 10 Because Brugada syndrome has a rather low prevalence (estimated at 1:2,000, varying in different regions around the world),1 these and other critical characteristics of Brugada syndrome may not be common knowledge for many physicians.11
With the aim of aiding all physicians who treat patients with Brugada syndrome, we discussed the interaction between drugs and Brugada syndrome, performed an extensive review of the literature, formed an international expert panel to produce a consensus recommendation for each drug, and initiated a website (www.brugadadrugs.org;Figure 3) to ensure worldwide online and up-to-date availability of this knowledge base.
Section snippets
Literature review
PubMed (Text: Brugada; MeSH terms: Chemicals and Drugs Category; only reports in English were considered) and expert knowledge was used to investigate drugs that have been associated with the type 1 Brugada syndrome ECG, with arrhythmias or with antiarrhythmic properties in Brugada syndrome patients. Although there is large variation in the extent to which different drugs have been associated with Brugada syndrome, we aimed to investigate the first reported drug–Brugada syndrome association for
Results
The PubMed search yielded 563 reports, including 506 written in English. The BrugadaDrugs.org Advisory Board selected approximately 15% of these reports as adding considerably to our knowledge and understanding of drug effects in Brugada syndrome. The drugs and accompanying recommendations are listed in Table 1, Table 2, Table 3, Table 4.
Discussion
In this study, we reviewed the literature on drug use in Brugada syndrome patients and made recommendations about their safety that were based on the literature and expert opinion. We also initiated a website (www.brugadadrugs.org) where these drugs and the recommendations can be accessed by all physicians who treat patients with Brugada syndrome and by other individuals with a possible interest (e.g., patients). On this website, we provide more detailed information on the drugs used in Brugada
Limitations
The principal limitation of the association between certain drugs, Brugada syndrome, and arrhythmias is the limited number of case reports and experimental studies suggesting an effect in Brugada syndrome. Furthermore, Brugada syndrome patients may show conflicting results and large variability in their response to certain drugs. This response may also vary in different conditions (e.g., with or without fever, drug in therapeutic range, overdose, or in combination with other drugs). Therefore,
Acknowledgments
We gratefully acknowledge CardioNetworks (a nonprofit organization based in The Netherlands that was founded in 2007 with the aim of providing unbiased and up-to-date medical knowledge to the global community) and particularly its chair Jonas S.S.G. de Jong, MD, for hosting the website. The inspiration for the website comes from www.qtdrugs.org, which contains lists of drugs associated with the long QT syndrome.
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This study was supported by The Netherlands Heart Foundation Grant 2005T024 to Dr. Postema; Fondation Leducq Trans-Atlantic Network of Excellence, Preventing Sudden Death Grant 05-CVD-01 to Dr. Wilde; CHU de Nantes, France, and Société Française de Cardiologie Grant P.H.R.C. 2004 R20/07 to Dr. Probst; and National Institutes of Health Grant HL65962 to Dr. Roden.