International Journal of Cardiology 124 (2008) 388 – 390 www.elsevier.com/locate/ijcard
Letter to the Editor
Contemporary use of adjunctive corticosteroids in tuberculous pericarditis☆ Charles S. Wiysonge a , Mpiko Ntsekhe a , Freedom Gumedze b , Karen Sliwa c , Kathleen Ngu Blackett d , Patrick J. Commerford a , Jimmy A. Volmink e,1 , Bongani M. Mayosi a,⁎ a
The Cardiac Clinic, Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa b Department of Statistical Sciences, University of Cape Town, Cape Town, South Africa c Department of Cardiology, Chris Hani Baragwanath Hospital, University of the Witwatersrand, Soweto, South Africa Faculty of Medicine and Biomedical Sciences, University of Yaoundé I and Centre Hospitalier et Universitaire, Yaoundé, Cameroon e Primary Health Care Directorate, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa Received 11 November 2006; accepted 31 December 2006 Available online 18 April 2007
Abstract There is controversy concerning the effectiveness of adjunctive corticosteroids in reducing mortality in tuberculous pericarditis. To assess the impact of this controversy on contemporary clinical practice, we studied the use of adjunctive corticosteroid in 185 consecutive patients with suspected pericardial tuberculosis from 15 hospitals in Cameroon, Nigeria, and South Africa. 109 (58.9%) patients received steroids with significant variation in corticosteroid use ranging from 0% to 93.5% per centre (P < 0.0001). The presence of clinical features of HIV infection was the independent predictor of the non-use of adjunctive corticosteroids (OR 0.39, 95% CI 0.20–0.75, P = 0.005). We have demonstrated marked variation in the use of corticosteroids by practitioners, with nearly half of all patients not receiving this intervention. Taken together with the statistical uncertainty regarding the effectiveness of adjunctive steroids in tuberculous pericarditis, these observations probably reflect a state of genuine uncertainty or clinical equipoise among practitioners who care for patients with tuberculous pericarditis in sub-Saharan Africa. These data provide a justification for the establishment of adequately powered randomised clinical trials to assess the effectiveness of adjunctive corticosteroids in patients with tuberculous pericarditis. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Tuberculous pericarditis; Adjunctive corticosteroids; Equipose
Tuberculous pericarditis is accompanied by a host inflammatory response that results in significant morbidity and mortality due to effusive and constrictive disease in
☆ Funding: this study was supported, in part, by grants from the Medical Research Council of South Africa, the National Research Foundation of South Africa, and the University of Cape Town. ⁎ Corresponding author. Department of Medicine, J Floor Old Main Building, Groote Schuur Hospital, Observatory 7925, Cape Town, South Africa. Tel.: +27 21 406 6200; fax: +27 21 448 6815. E-mail address: [email protected]
(B.M. Mayosi). 1 Present address: Faculty of Health Sciences, University of Stellenbosch, Tygerberg, South Africa.
0167-5273/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.12.060
spite of appropriate antitubercular chemotherapy . It has been suggested that the addition of anti-inflammatory drugs, such as corticosteroids, to antitubercular therapy may reduce complications and improve survival . In addition, active tuberculosis increases immune activation in human immunodeficiency virus (HIV) infected patients, accelerating progression of the acquired immunodeficiency syndrome and resulting in early death. Adjunctive corticosteroids may improve survival in tuberculosis patients co-infected with HIV by modulating this immunologic response . Several small clinical trials have examined the effectiveness of adjunctive steroids in both HIV infected and
C.S. Wiysonge et al. / International Journal of Cardiology 124 (2008) 388–390
Fig. 1. Regional distribution of adjunctive steroid use in sub-Saharan Africa. Yaoundé, Cameroon (0%); Guateng, South Africa (0%), Western Cape (W Cape), South Africa (37.1%); KwaZulu Natal 9KZN), South Africa (82.6%), Eastern Cape (E Cape), South Africa (82.8%); Ibadan, Nigeria (93.5%).
uninfected persons with tuberculous pericarditis, a metaanalysis of which shows a promising but inconclusive effect of this intervention on mortality . There is concern that adjunctive corticosteroids may increase the risk of malignancy and opportunistic infections in patients immunocompromised by HIV. However, some authors recommend routine use of adjunctive steroids in managing patients with tuberculous pericarditis . We conducted a cross-sectional analysis in the Investigation of the Management of Pericarditis in Africa (IMPI Africa) registry to assess contemporary use of adjunctive corticosteroids by physicians treating patients with suspected tuberculous pericarditis in Africa . The design and baseline characteristics of patients enrolled in the IMPI Africa registry have been described fully elsewhere . In brief, between 1 March 2004 and 31 October 2004 we enrolled consecutive cases of presumed tuberculous pericarditis from 15 referral hospitals in Cameroon, Nigeria, and South Africa. The management of each patient was at the discretion of the collaborating physician. We assessed the proportion of patients receiving adjunctive corticosteroids and the regional distribution of adjunctive steroid use. We also used logistic regression to assess factors associated with adjunctive steroid use. We enrolled 185 patients with median age 33 years (range 14–87), 56% of whom were men. All patients
received standard antitubercular drugs. A total of 109 (58.9%) patients were put on adjunctive corticosteroids. There was significant regional variation in steroid use; from no patient on steroids in participating hospitals in Yaoundé (Cameroon) and Guateng Province (South Africa), to 29/31 patients on steroids (93.5%) in Ibadan (Nigeria) (P < 0.0001) (Fig. 1). In univariate analysis, patients with clinical HIV disease, impaired New York Heart Association functional class, and active pulmonary tuberculosis were significantly less likely to receive steroids, and there was a trend towards fewer men receiving steroids than women (Table 1). Amongst these factors, having clinical features of HIV infection was the independent predictor for non-use of adjunctive corticosteroids. The IMPI Africa registry shows considerable regional variation in adjunctive corticosteroid use for patients with suspected tuberculous pericarditis across three sub-Saharan African countries; about half of the patients are not treated with adjunctive corticosteroids. There also appears to be variation in the type of patient who receives steroids, with patients having clinical features of HIV infection being less likely to be put on these drugs. There appears to be a selection for patients who are healthier, which may exaggerate the apparent clinical benefit of adjunctive steroid use . The apparent reluctance of clinicians to prescribe adjunctive corticosteroids to tuberculous pericarditis patients with clinical HIV disease most probably reflects concerns about the safety of these pharmacological agents in HIV-infected patients. Taken together with the statistical uncertainty regarding the effectiveness of adjunctive steroids in tuberculous pericarditis, [1,4] the non-use of adjunctive corticosteroids in nearly half of the patients probably reflects a state of genuine uncertainty or clinical equipoise among practitioners who care for patients with tuberculous pericarditis. These data provide a powerful justification for the establishment of adequately powered randomised clinical trials to assess the effectiveness of adjunctive corticosteroids in patients with tuberculous pericarditis .
Table 1 Logistic regression analyses for the association between patient characteristics and use of adjunctive steroids in tuberculous pericarditis Baseline characteristic
Age Male sex Clinical HIV disease Haemodynamic instability⁎ Active pulmonary tuberculosis Severe effort intolerance⁎⁎
Controlled for age and sex
Forward stepwise multiple logistic regression
1.02 0.59 0.37 0.58 0.50 0.51
0.99–1.04 0.33–1.08 0.20–0.68 0.30–1.11 0.25–0.97 0.28–0.92
0.10 0.09 0.001 0.10 0.04 0.03
– – 0.36 0.57 0.47 0.48
– – 0.18–0.68 0.29–1.11 0.23–0.94 0.26–0.89
– – 0.002 0.10 0.03 0.02
– 0.52 0.39 – 0.55 –
– 0.27–1.00 0.21–0.75 – 0.27–1.13 –
– 0.05 0.005 – 0.11 –
⁎Pulse rate more than 100 beats per minute and systolic blood pressure less than 100 mm Hg, and/or cardiac tamponade requiring pericardiocentesis. ⁎⁎New York Heart Association functional classes III or IV. (Age was analysed as a continuous variable in the model.)
C.S. Wiysonge et al. / International Journal of Cardiology 124 (2008) 388–390
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