Cardiovascular morbidity and the use of inhaled bronchodilators

Christine Macie, Kate Wooldrage, Jure Manfreda, Nicholas Anthonisen, Christine Macie, Kate Wooldrage, Jure Manfreda, Nicholas Anthonisen

Abstract

We used the Manitoba Health database to examine the relationship between use of inhaled respiratory drugs in people with chronic obstructive respiratory diseases and cardiovascular hospitalizations from 1996 through 2000. The drugs examined were beta agonists [BA], ipratropium bromide IB, and inhaled steroids (ICS). End points were first hospitalizations for supraventricular tachycardia, myocardial infarction, heart failure or stroke. A nested case control analysis was employed comparing people with and without cardiovascular events. Cases and controls were matched for gender and age, and conditional logistic regression was used in multivariate analysis considering other respiratory drugs, respiratory diagnosis and visit frequency, non-respiratory, non-cardiac comorbidities, and receipt of drugs for cardiovascular disease. In univariate analyses, BA, IB and ICS were all associated with hospitalizations for cardiovascular disease, but in multivariate analyses ICS did not increase risk while both BA and IB did. There were interactions between respiratory and cardiac drugs receipt in that bronchodilator associated risks were higher in people not taking cardiac drugs; this was especially true for stroke. There were strong interactions with specific cardiac drugs; for example, both BA and IB substantially increased the risk of supraventricular tachycardia in patients not anti-arryhthmic agents, but not in the presence of such agents. We conclude that bronchodilator therapy for chronic obstructive diseases is associated with increased cardiovascular risk, especially in patients without previous cardiovascular diagnoses, and that this is unlikely due to the severity of the respiratory disease, since risk was not increased with ICS.

References

    1. Anthonisen NR, Connett JE, Enright PL, et al. Hospitalizations and mortality in the Lung Health Study. Am J Respir Crit Care Med. 2002;166:333–9.
    1. Au DH, Curtis JR, Every NR, et al. Association between inhaled β-agonists and the risk of unstable angina and myocardial infarction. Chest. 2002;121:846–51.
    1. Au DH, Udris EM, Fan VS, et al. Risk of mortality and patients with known left ventricular systolic dysfunction. Chest. 2003;123:1964–9.
    1. Au DH, Udris EM, Curtis JR, et al. Association between chronic heart failure and inhaled β-2 adrenoceptor agonists. Am Heart J. 2004;148:915–20.
    1. Coleman AJ, Leary UP, Kaul DS. Hemodynamic effects of Sch 1000 in normal subjects. Postgrad Med J. 1975;51(Suppl 7):121.
    1. Coughlin SS, Metayer C, McCarthy EP, et al. Respiratory illness, β-agonists and risk of idiopathic dilated cardiomyopathy. Am J Epidemiol. 1995;142:395–403.
    1. Curkendall SM, DeLuise C, Jones JK, et al. Cardiovascular disease in patients with chronic obstructive lung disease, Saskatchewan Canada. Ann Epidemiol. 2006;16:63–70.
    1. Guite HF, Dundas R, Burney PGJ. Risk factors for death from asthma, chronic obstructive pulmonary disease, and cardiovascular disease after a hospital admission for asthma. Thorax. 1999;54:301–7.
    1. Hudson LD, Kurt TL, Petty TL, et al. Arrhythmias associated with acute respiratory failure in patients with chronic airway obstruction. Chest. 1973;63:661–5.
    1. Huzel L, Roos LL, Anthonisen NR, et al. Diagnosing asthma: the fit between survey and administrative database. Canad Respir J. 2002;9:407–12.
    1. Iskandar SB, Mathai MG, Byrd RP, et al. Myocardial injury during standard treatment of an adult with status asthmaticus. J Asthma. 2004;41:337–42.
    1. Kallergis EM, Manios EG, Kanoupakis EM, et al. Acute electrophysiologic effects of inhaled salbutamol in humans. Chest. 2005;127:2057–63.
    1. Kleiger RE, Senior RM. Long term electrocardiographic monitoring of ambulatory patients with chronic airway obstruction. Chest. 1974;65:483–7.
    1. Macie C, Wooldrage K, Manfreda J, et al. Inhaled corticosteroids and mortality in COPD. Chest. 2006;130:640–6.
    1. Ringbaek T, Viskum K. Is there any association between inhaled ipratropium and mortality in patients with COPD and asthma? Resp Med. 2003;97:264–72.
    1. Robin ED, McCauley R. Sudden cardiac death in bronchial asthma, and inhaled beta-adrenergic agonists. Chest. 1992;101:1699–702.
    1. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of β-agonists in patients with asthma and COPD. A meta-analysis. Chest. 2004;125:2309–21.
    1. Sin DD, Tu JV. Lack of association between ipratropium bromide and mortality in elderly patients with chronic obstructive airway disease. Thorax. 2000;55:194–7.
    1. Sin DD, Mann SFP. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? Circulation. 2003;107:1514–9.
    1. Sin DD, Wu L, Mann SFP. The relationship between reduced lung function and cardiovascular mortality. A population-based study and a systematic review of the literature. Chest. 2005;127:1952–9.
    1. Suissa S, Ernst P, Boivin JF, et al. A cohort analysis of excess mortality in asthma and the use of inhaled β-agonists. Am J Respir Crit Care Med. 1994;149:604–10.
    1. Suissa S, Hemmelgarn B, Blais L, et al. Bronchodilators and acute cardiac death. Am J Respir Crit Care Med. 1996;154:1598–602.
    1. Suissa S, Assimes T, Ernst P. Inhaled short acting β-agonist use in COPD and the risk of acute myocardial infarction. Thorax. 2003;58:43–6.
    1. [WHO] World Health Organisation. International classification of diseases, 9th revision. Geneva: WHO; 1978.
    1. [WHO] World Health Organization. World Health Organization’s Centre for Drug Statistics Methodology: Guidelines for ATC classification and DDD assignment. Oslo, Norway: WHO; 1995.

Source: PubMed

3
Abonnieren