Use of beta2 agonists and risk of acute myocardial infarction in patients with hypertension.
BACKGROUND
* Use of beta(2) agonists has been associated with tachycardia, an abnormal ECG and atrial fibrillation. * Previous observational studies of the association between use of beta(2) agonists and the risk of acute myocardial infarction (MI) have demonstrated conflicting results. * Instead of a causal effect, the positive association between beta(2) agonist use and MI may be explained by latent ischaemic heart disease, which has symptoms that appear similar to respiratory complaints in chronic obstructive pulmonary disease.


CONCLUSIONS
* The majority of beta(2) agonist users in our study population did not have an increased risk of nonfatal acute MI. * Only patients with ischaemic heart disease and who had recently started beta(2) agonists had an increased risk of acute MI. * It is likely that this increased risk was related to latent cardiovascular disease rather than direct effects of beta(2) agonists.


OBJECTIVE
Observational retrospective studies of the association between use of beta(2) agonists and the risk of acute myocardial infarction (MI) have demonstrated conflicting results, particularly among first-time users. The aim of this study was to examine the association between beta(2) agonist use and first nonfatal acute MI.


METHODS
We conducted a case-control study (2476 cases) nested in a cohort of antihypertensive drug users in the Dutch PHARMO RLS database. PHARMO RLS consists of drug dispensing linked to the national hospitalizations register. Each case of nonfatal acute MI was matched with up to 12 control patients by gender, age and region. Drug and disease history and the severity of the underlying respiratory disease were adjusted for.


RESULTS
Risk of acute MI was increased in current beta(2) agonist users [crude odds ratio (OR) 1.36, 95% confidence interval (CI) 1.15, 1.61]. However, this excess risk was reduced after adjustment for severity of asthma and chronic obstructive pulmonary disease (adjusted OR 1.18, 95% CI 0.93, 1.49). The risk was highest in patients with ischaemic heart disease and low cumulative dose of beta(2) agonists (adjusted OR 2.47, 95% CI 1.60, 3.82).


CONCLUSIONS
Most users of beta(2) agonists did not have an increased risk of acute MI. Only patients with ischaemic heart disease with low cumulative exposure to beta(2) agonists had an increased risk of acute MI. It is likely that this increased risk was related to latent cardiovascular disease rather than to the direct effects of beta(2) agonists.
de Vries
Frank
F
Utrecht Institute for Pharmaceutical Sciences, Division of Pharmacoepidemiology and Pharmacotherapy, Universiteit Utrecht, Utrecht, The Netherlands. f.devries@uu.nl
Pouwels
Sander
S
Bracke
Madelon
M
Lammers
Jan-Willem
JW
Klungel
Olaf
O
Leufkens
Hubert
H
van Staa
Tjeerd
T
D000318:Adrenergic beta-Agonists / Q000009:adverse effects*; D000368:Aged; D000959:Antihypertensive Agents / Q000009:adverse effects*; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced*; D012189:Retrospective Studies; D018570:Risk Assessment / Q000592:standards; D016896:Treatment Outcome
D000318:Adrenergic beta-Agonists; D000959:Antihypertensive Agents