Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors - a nationwide registry-based cohort study

Eva Rye Rasmussen, Anton Pottegård, Anette Bygum, Christian von Buchwald, Preben Homøe, Jesper Hallas

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Abstract

BACKGROUND: It has long been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (AT2s) have some degree of 'cross-reactivity' in causing angioedema. Therefore, caution has been advised when switching patients with ACEi-related angioedema to an AT2.

OBJECTIVES: To clarify whether AT2s can be used safely in patients with a history of angioedema during ACEi treatment and to estimate the incidence rate of angioedema in patients subsequently treated with other antihypertensive drugs (beta-adrenergic blockers, calcium channel blockers, thiazides and analogues) or no antihypertensives.

METHODS: This is a nationwide retrospective registry-based cohort study of the Danish population during the period 1994 to 2016, and it uses Danish health registries. Propensity score adjusted and conventional proportional hazards regression models have been employed.

RESULTS: A total of 1 106 024 ACEi users were identified. In total, 5 507 (0.5%) of these patients had experienced angioedema during ACEi treatment and were included in the study. The highest risk of angioedema recurrence was associated with continued ACEi use at an adjusted hazard ratio of 1.45 (95% CI, 1.19 to 1.78). An inverse association was found between AT2s and angioedema (adjusted hazard ratio, 0.39; 95% CI, 0.30 to 0.51) compared with other antihypertensives (adjusted hazard ratios, 0.77 to 0.97).

CONCLUSIONS: Compared with other antihypertensive drugs, AT2s do not increase the incidence of angioedema in patients with previous ACEi-related angioedema.

Original languageEnglish
JournalJournal of Internal Medicine
Volume285
Issue number5
Pages (from-to)553-561
ISSN0954-6820
DOIs
Publication statusPublished - May 2019

Fingerprint

Angiotensin Receptor Antagonists
Registries
Cohort Studies
Propensity Score
Adrenergic beta-Antagonists
Incidence
Proportional Hazards Models
Health

Keywords

  • Angioedema
  • angiotensin-converting enzyme
  • angiotensins
  • hypertension
  • therapeutics

Cite this

@article{5b6616f052194652abfd0fab7543ffdb,
title = "Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors - a nationwide registry-based cohort study",
abstract = "BACKGROUND: It has long been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (AT2s) have some degree of 'cross-reactivity' in causing angioedema. Therefore, caution has been advised when switching patients with ACEi-related angioedema to an AT2.OBJECTIVES: To clarify whether AT2s can be used safely in patients with a history of angioedema during ACEi treatment and to estimate the incidence rate of angioedema in patients subsequently treated with other antihypertensive drugs (beta-adrenergic blockers, calcium channel blockers, thiazides and analogues) or no antihypertensives.METHODS: This is a nationwide retrospective registry-based cohort study of the Danish population during the period 1994 to 2016, and it uses Danish health registries. Propensity score adjusted and conventional proportional hazards regression models have been employed.RESULTS: A total of 1 106 024 ACEi users were identified. In total, 5 507 (0.5{\%}) of these patients had experienced angioedema during ACEi treatment and were included in the study. The highest risk of angioedema recurrence was associated with continued ACEi use at an adjusted hazard ratio of 1.45 (95{\%} CI, 1.19 to 1.78). An inverse association was found between AT2s and angioedema (adjusted hazard ratio, 0.39; 95{\%} CI, 0.30 to 0.51) compared with other antihypertensives (adjusted hazard ratios, 0.77 to 0.97).CONCLUSIONS: Compared with other antihypertensive drugs, AT2s do not increase the incidence of angioedema in patients with previous ACEi-related angioedema.",
keywords = "Angioedema, angiotensin-converting enzyme, angiotensins, hypertension, therapeutics",
author = "Rasmussen, {Eva Rye} and Anton Potteg{\aa}rd and Anette Bygum and {von Buchwald}, Christian and Preben Hom{\o}e and Jesper Hallas",
note = "{\circledC} 2018 The Association for the Publication of the Journal of Internal Medicine.",
year = "2019",
month = "5",
doi = "10.1111/joim.12867",
language = "English",
volume = "285",
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journal = "Journal of Internal Medicine",
issn = "0954-6820",
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Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors - a nationwide registry-based cohort study. / Rasmussen, Eva Rye; Pottegård, Anton; Bygum, Anette; von Buchwald, Christian; Homøe, Preben; Hallas, Jesper.

In: Journal of Internal Medicine, Vol. 285, No. 5, 05.2019, p. 553-561.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Angiotensin II receptor blockers are safe in patients with prior angioedema related to angiotensin-converting enzyme inhibitors - a nationwide registry-based cohort study

AU - Rasmussen, Eva Rye

AU - Pottegård, Anton

AU - Bygum, Anette

AU - von Buchwald, Christian

AU - Homøe, Preben

AU - Hallas, Jesper

N1 - © 2018 The Association for the Publication of the Journal of Internal Medicine.

PY - 2019/5

Y1 - 2019/5

N2 - BACKGROUND: It has long been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (AT2s) have some degree of 'cross-reactivity' in causing angioedema. Therefore, caution has been advised when switching patients with ACEi-related angioedema to an AT2.OBJECTIVES: To clarify whether AT2s can be used safely in patients with a history of angioedema during ACEi treatment and to estimate the incidence rate of angioedema in patients subsequently treated with other antihypertensive drugs (beta-adrenergic blockers, calcium channel blockers, thiazides and analogues) or no antihypertensives.METHODS: This is a nationwide retrospective registry-based cohort study of the Danish population during the period 1994 to 2016, and it uses Danish health registries. Propensity score adjusted and conventional proportional hazards regression models have been employed.RESULTS: A total of 1 106 024 ACEi users were identified. In total, 5 507 (0.5%) of these patients had experienced angioedema during ACEi treatment and were included in the study. The highest risk of angioedema recurrence was associated with continued ACEi use at an adjusted hazard ratio of 1.45 (95% CI, 1.19 to 1.78). An inverse association was found between AT2s and angioedema (adjusted hazard ratio, 0.39; 95% CI, 0.30 to 0.51) compared with other antihypertensives (adjusted hazard ratios, 0.77 to 0.97).CONCLUSIONS: Compared with other antihypertensive drugs, AT2s do not increase the incidence of angioedema in patients with previous ACEi-related angioedema.

AB - BACKGROUND: It has long been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (AT2s) have some degree of 'cross-reactivity' in causing angioedema. Therefore, caution has been advised when switching patients with ACEi-related angioedema to an AT2.OBJECTIVES: To clarify whether AT2s can be used safely in patients with a history of angioedema during ACEi treatment and to estimate the incidence rate of angioedema in patients subsequently treated with other antihypertensive drugs (beta-adrenergic blockers, calcium channel blockers, thiazides and analogues) or no antihypertensives.METHODS: This is a nationwide retrospective registry-based cohort study of the Danish population during the period 1994 to 2016, and it uses Danish health registries. Propensity score adjusted and conventional proportional hazards regression models have been employed.RESULTS: A total of 1 106 024 ACEi users were identified. In total, 5 507 (0.5%) of these patients had experienced angioedema during ACEi treatment and were included in the study. The highest risk of angioedema recurrence was associated with continued ACEi use at an adjusted hazard ratio of 1.45 (95% CI, 1.19 to 1.78). An inverse association was found between AT2s and angioedema (adjusted hazard ratio, 0.39; 95% CI, 0.30 to 0.51) compared with other antihypertensives (adjusted hazard ratios, 0.77 to 0.97).CONCLUSIONS: Compared with other antihypertensive drugs, AT2s do not increase the incidence of angioedema in patients with previous ACEi-related angioedema.

KW - Angioedema

KW - angiotensin-converting enzyme

KW - angiotensins

KW - hypertension

KW - therapeutics

U2 - 10.1111/joim.12867

DO - 10.1111/joim.12867

M3 - Journal article

VL - 285

SP - 553

EP - 561

JO - Journal of Internal Medicine

JF - Journal of Internal Medicine

SN - 0954-6820

IS - 5

ER -