The article by Betancourt and colleagues (2005) is refreshingly a good example of an active pharmacovigilance program. Although their numbers are not clearly stated the study involved many hospitals and clinicians who reported the cases.
However, based on the criteria they used for causality assessment, their conclusion that 94.9% of total ADRs are possibly associated with streptokinase needs to be revisited for the reasons stated below. In order to be concise, I limit my argument on one ADR: hypotension. The data presented show that 285 patients had hypotension, yet it is not stated how many of them are among the 943 patients who were co-medicated with beta-blockers, the agents that cause hypotension as well. From the literature, it is established that the incidence of hypotension may depend on the type of agent used. Though beta-blockers used in this study were not mentioned, it is reported that when used alone, hypotension occurs in 2-10%, 1-27.4%, 15-25%, and up to 50% in patients treated respectively with carvedilol, metoprolol, atenolol, and esmolol (Weist, 1995; Mitchell et al., 2002; Sanderson et al., 1999; Basile, 2003; Buck, 2005). Moreover, simultaneous use of streptokinase and a beta-blocking agent may have a protective effect as in the case of metoprolol. Herlitz and colleagues (1993) reported that hypotension occurs in 23% of patients co-medicated with streptokinase and metoprolol, as opposed to 47% of patients receiving streptokinase alone. Thus, because beta-blockers produce hypotension by themselves, and its incidence may be increased or decreased when associated with streptokinase, this relationship acts as a confounder on the results presented. A contingency table of patients on beta-blocking therapy versus those reported with hypotension while on streptokinase would shed more light on the correct figures from which more accurate estimates could be derived.
Ntambwe Malangu, BPharm MSc
References
Basile JN. Titration of beta-blockers in heart failure: How to maximize benefit while minimizing adverse events. Available at: http://www.postgradmed.com/issues/2003/03_03/basile3.htm. Accessed, 09 March, 2006.
Betancourt BY, Marrero-Miragaya MA, Jiménez-López G, Valenzuela-Silva C, García-Iglesias E et al. Pharmacovigilance program to monitor adverse reactions of recombinant streptokinase in acute myocardial infarction. BMC Clinical Pharmacology 2005, 5:5 doi:10.1186/1472-6904-5-5
Buck ML. Use of Carvedilol in Children With Cardiac Failure. Pediatr Pharm. 2005; 11 (2). Available at: http://www.medscape.com/viewarticle/500749
Herlitz J, Hartford M, Aune S, and Karlsson T. Occurrence of hypotension during streptokinase infusion in suspected acute myocardial infaction and its relation to prognosis and metoprolol therapy. Am J Cardiol 1993 May 1; 71(12): 1021-24.
Mitchell RG, Stoddard MF, Ben-Yehuda, Aggarwal KB et al. Esmolol in acute ischemic syndromes. Am. Heart J. 2002 Nov;144(5): E9.
Sanderson JE, Chan SK, Yip G, et al. Beta-blockade in heart failure: a comparison of carvedilol with metoprolol. J Am Coll Cardiol 1999;34(5):1522-8.
Weist D. Esmolol: A review of its therapeutic efficacy and pharmacokinetic characteristics. Clin Pharmacokinet. 1995 Mar;28(3): 190-202.
Confounding due to drug interactions
14 March 2006
Dear Editor
The article by Betancourt and colleagues (2005) is refreshingly a good example of an active pharmacovigilance program. Although their numbers are not clearly stated the study involved many hospitals and clinicians who reported the cases.
However, based on the criteria they used for causality assessment, their conclusion that 94.9% of total ADRs are possibly associated with streptokinase needs to be revisited for the reasons stated below. In order to be concise, I limit my argument on one ADR: hypotension. The data presented show that 285 patients had hypotension, yet it is not stated how many of them are among the 943 patients who were co-medicated with beta-blockers, the agents that cause hypotension as well. From the literature, it is established that the incidence of hypotension may depend on the type of agent used. Though beta-blockers used in this study were not mentioned, it is reported that when used alone, hypotension occurs in 2-10%, 1-27.4%, 15-25%, and up to 50% in patients treated respectively with carvedilol, metoprolol, atenolol, and esmolol (Weist, 1995; Mitchell et al., 2002; Sanderson et al., 1999; Basile, 2003; Buck, 2005). Moreover, simultaneous use of streptokinase and a beta-blocking agent may have a protective effect as in the case of metoprolol. Herlitz and colleagues (1993) reported that hypotension occurs in 23% of patients co-medicated with streptokinase and metoprolol, as opposed to 47% of patients receiving streptokinase alone. Thus, because beta-blockers produce hypotension by themselves, and its incidence may be increased or decreased when associated with streptokinase, this relationship acts as a confounder on the results presented. A contingency table of patients on beta-blocking therapy versus those reported with hypotension while on streptokinase would shed more light on the correct figures from which more accurate estimates could be derived.
Ntambwe Malangu, BPharm MSc
References
Basile JN. Titration of beta-blockers in heart failure: How to maximize benefit while minimizing adverse events. Available at: http://www.postgradmed.com/issues/2003/03_03/basile3.htm. Accessed, 09 March, 2006.
Betancourt BY, Marrero-Miragaya MA, Jiménez-López G, Valenzuela-Silva C, García-Iglesias E et al. Pharmacovigilance program to monitor adverse reactions of recombinant streptokinase in acute myocardial infarction. BMC Clinical Pharmacology 2005, 5:5 doi:10.1186/1472-6904-5-5
Buck ML. Use of Carvedilol in Children With Cardiac Failure. Pediatr Pharm. 2005; 11 (2). Available at: http://www.medscape.com/viewarticle/500749
Herlitz J, Hartford M, Aune S, and Karlsson T. Occurrence of hypotension during streptokinase infusion in suspected acute myocardial infaction and its relation to prognosis and metoprolol therapy. Am J Cardiol 1993 May 1; 71(12): 1021-24.
Mitchell RG, Stoddard MF, Ben-Yehuda, Aggarwal KB et al. Esmolol in acute ischemic syndromes. Am. Heart J. 2002 Nov;144(5): E9.
Sanderson JE, Chan SK, Yip G, et al. Beta-blockade in heart failure: a comparison of carvedilol with metoprolol. J Am Coll Cardiol 1999;34(5):1522-8.
Weist D. Esmolol: A review of its therapeutic efficacy and pharmacokinetic characteristics. Clin Pharmacokinet. 1995 Mar;28(3): 190-202.
Competing interests
NONE