The impact of age and sex on the reporting of cough and angioedema with renin-angiotensin system inhibitors: a case/noncase study in VigiBase.

The purpose of this study was to assess the impact of age and sex on the reporting of cough and angioedema related to renin-angiotensin system (RAS) inhibitors. A case/noncase study was performed in VigiBase. Two case groups were identified, reports of cough and reports of angioedema, and noncases were all reports of all other adverse events. Logistic regression analysis was used to assess the association between reporting of cough and angioedema with each class of RAS inhibitors stratified by age/sex and to control for confounding. The reporting of cough with angiotensin-converting enzyme (ACE) inhibitors was significantly higher in women than in men [adjusted reporting odds ratio (ROR): 44.0, 95% CI (43.2-44.8) for women vs. 29.2, 95% CI (28.5-29.9) for men]. There was no difference in reporting of cough linked to angiotensin receptor blockers (ARBs) and aliskiren between men and women. In contrast, the reporting of angioedema with ACE inhibitors and ARBs was significantly higher in men than in women, but for aliskiren, women had a significantly higher ROR than men [adjusted ROR: 5.20, 95% CI (4.18-6.46) for women vs. 3.04, 95% CI (2.30-4.02) for men]. The reporting of cough with ACE inhibitors was increased with age until reaching a plateau at middle adulthood (40-59 years) and the reporting of angioedema with ACE inhibitors was increased with age until elderly (60-79 years). Age had only a slight effect on the reporting of cough and angioedema with ARBs and aliskiren. Both age and sex have substantial effects on the reporting of cough and angioedema with RAS inhibitors and in particular ACE inhibitors. Further study is needed to determine whether these differences mainly express different adverse drug reaction risks in subgroups or also can be explained by factors influencing reporting.

The impact of serum potassium-influencing antihypertensive drugs on the risk of out-of-hospital cardiac arrest: A case-control study.

AIMS: Sudden cardiac arrest (SCA) is a complex multifactorial event and most commonly caused by ventricular tachycardia/ fibrillation (VT/ VF). Some antihypertensive drugs could induce hypokalaemia or hyperkalaemia, which may increase susceptibility to VT/VF and SCA. OBJECTIVE: To assess the association between different classes of antihypertensive drugs classified according to their potential impact on serum potassium levels and the occurrence of out-of-hospital cardiac arrest (OHCA) based on VT/VF. METHODS: A case-control study was performed among current users of antihypertensive drugs. Cases were OHCA victims with electrocardiogram documented VT/VF drawn from the AmsteRdam REsuscitation STudies (ARREST) registry, and controls were non-OHCA individuals from the PHARMO database. Antihypertensive drugs were classified into: (i) antihypertensives with neutral effect on serum potassium levels; (ii) hypokalaemia-inducing antihypertensives; (iii) hyperkalaemia-inducing antihypertensives; (iv) combination of antihypertensives with hypo- and hyperkalaemic effects. RESULTS: We included 1345 cases and 4145 controls. The risk of OHCA was significantly increased among users of hypokalaemia-inducing antihypertensives [adjusted odds ratio (OR) 1.39; 95% confidence interval (CI) 1.10-1.76] and among users of a combination of antihypertensives with hypo- and hyperkalaemic effects (adjusted OR 1.42; 95%CI 1.17-1.72) vs. users of antihypertensives with neutral effect. There was no difference in OHCA risk between users of hyperkalaemia-inducing antihypertensives vs. users of antihypertensive drugs with neutral effect (adjusted OR 1.15; 95%CI 0.95-1.40). CONCLUSION: The risk of OHCA is significantly increased in patients who were current users of hypokalaemia-inducing antihypertensives and patients using a combination of antihypertensives with hypo- and hyperkalaemic effects.