Abstract
BackgroundAngiotensin converting enzyme inhibitor (ACEI) intolerance commonly occurs, requiring switching to an angiotensin-II receptor blocker (ARB). Angiotensin converting enzyme inhibitor intolerance may be mediated by bradykinin, potentially affecting airway hyperresponsiveness.ObjectiveTo assess the risk for switching to ARBs in asthma.MethodsWe conducted a new-user cohort study of ACEI initiators identified from electronic health records from the UK Clinical Practice Research Datalink. The risk for switching to ARBs in people with asthma or chronic obstructive pulmonary disease and the general population was compared. Adjusted hazard ratios (HRs) were calculated using Cox regression, stratified by British Thoracic Society (BTS) treatment step and ACEI type.ResultsOf 642,336 new users of ACEI, 6.4% had active asthma. The hazard of switching to ARB was greater in people with asthma (HR = 1.16; 95% confidence interval [CI], 1.14-1.18; P ≤ .001) and highest in those at BTS step 3 or greater (HR = 1.35, 95% CI, 1.32-1.39; and HR = 1.18, 95% CI, 1.15-1.22, P ≤ .001 for patients aged ≥60 and <60 years, respectively). Hazard was highest with enalapril (HR = 1.25, 95% CI, 1.18-1.34, P ≤ .001; HR = 1.44, 95% CI, 1.32-1.58, P ≤ .001 for BTS step 3 or greater asthma). No increased hazard was observed in chronic obstructive pulmonary disease or those younger than age 60 years at BTS step 1/2. The number needed to treat varied by age, sex, and body mass index (BMI), ranging between 21 and 4, and was lowest in older women with a BMI of 25 or greater.ConclusionsPeople with active asthma are more likely to switch to ARBs after commencing ACEI therapy. The number needed to treat varies by age, sex, BMI, and BTS step. Angiotensin-II receptor blocker could potentially be considered first-line in people with asthma and in those with high-risk characteristics.
Highlights
Asthma is a highly prevalent disease causing significant morbidity, mortality and healthcare cost.[1]Comorbidity in asthma is common, and 62.6% of people with asthma reported to have ≥1 comorbidity, and the likelihood of having coronary artery disease, congestive heart failure, peripheral vascular disease, cerebrovascular disease, hypertension, diabetes and chronic kidney disease are all significantly greater in people with asthma compared to the general population.[2,3] Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed medicines indicated for the management of these chronic diseases.[4]
The hazard of switching to angiotensin-II receptor blocker (ARB) was greater in people with asthma (HR1.16, 95%CI 1.14-1.18, p=
Hazard was highest with enalapril (HR1.25, 95%CI 1.18-1.34, p=
Summary
Asthma is a highly prevalent disease causing significant morbidity, mortality and healthcare cost.[1]Comorbidity in asthma is common, and 62.6% of people with asthma reported to have ≥1 comorbidity, and the likelihood of having coronary artery disease, congestive heart failure, peripheral vascular disease, cerebrovascular disease, hypertension, diabetes and chronic kidney disease are all significantly greater in people with asthma compared to the general population.[2,3] Angiotensin-converting enzyme inhibitors (ACEI) are commonly prescribed medicines indicated for the management of these chronic diseases.[4]. Whilst ACEI have beneficial effects in the management of these chronic diseases, many patients are intolerant of longterm ACEI the most common reason of which is a dry persistent cough. This adverse drug reaction is thought to occur in around 10% of people treated with ACEI and may be related to increased levels of bradykinin.[5] This adverse reaction is considered a class effect of ACEI, suggesting that even low doses may alter bradykinin levels in susceptible patients. Angiotensin converting enzyme inhibitor (ACEI) intolerance commonly occurs requiring switching to an angiotensin-II receptor blocker (ARB). ACEI intolerance may be mediated by bradykinin potentially affecting airway hyper-responsiveness
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