Lisinopril

Additional information

Pharmacokinetics and dosing

A pharmacokinetic study (16 men, 16 women) examined the sex-related differences after a single 20 mg dose of lisinopril. There were no differences in plasma concentration between men and women, or in effects on blood pressure or heart rate [19]. No studies with a clinically relevant sex analysis regarding the dosing of lisinopril have been found and no sex differentiation in dosing has been recommended by the pharmaceutical company [6].

Effects

Heart failure

A European multicentre cohort study of patients with heart failure with reduced ejection fraction (HFrEF) (3609 men, 1114 women) found similar all-cause mortality for patients treated with ACE inhibitors (enalapril, lisinopril, or ramipril) given at equivalent doses. No differences between men and women or between age groups were seen [1].

In a large cohort study comparing angiotensin converting enzyme (ACE) inhibitors with angiotensin receptor blockers (ARBs) in patients with congestive heart failure (9 475 men, 10 223 women), women on ARBs had better survival than women on ACE inhibitors (HR 0.69, 95%CI 0.59-0.80) while men on ARBs had similar survival as men on ACE inhibitors (HR 1.10, 95%CI 0.95-1.30). However, other anti-hypertensive agents were more common in those on ARBs, especially women, leading to a larger blood pressure reduction and thus larger reduction in risk of death. Also, more of those on ARBs were hypertensive than those on ACE inhibitors, and more of those on ACE inhibitors had a history of myocardial infarction than those of ARBs [2]. Additional confounding by indication cannot be excluded.Clinical trials have shown that men and women have similar antihypertensive responses to lisinopril [20-22]. However, in the large ALLHAT study, black men responded better to lisinopril compared to amlodipine than black women when receiving the same dose [23, 24].

Pulse pressure (the difference between systolic blood pressure and diastolic pressure) is suggested to be a predictor of cardiovascular disease and may be influenced by genetics. A study examined whether RAS polymorphism had different impact on pulse pressure in men and women taking lisinopril showed no sex differences [25].

The dose-dependent antihypertensive efficacy of lisinopril seems to be similar in hypertensive boys and girls aged 6-16 years (n=115), despite patient’s age or ethnicity [6, 26]. 

 Hypertension

In general, the activity level of the endogenous renin-angiotensin system (RAS), which regulates blood pressure, is higher in men than in premenopausal women. Postmenopausal women have higher activity than premenopausal women. This suggests that the efficacy of an RAS inhibitor would be lower in premenopausal women. However, studies on sex differences in the effect of RAS inhibition are contradictory [3, 4]. It has been suggested that black hypertensive patients have a smaller antihypertensive efficacy of ACE inhibitors than non-blacks, possibly due to a higher prevalence of low renin state in black hypertensive patients [5-7].

Adverse effects

Several studies have reported a female predominance in the prevalence of ACE inhibitor induced cough [8-16]. The pathogenesis of the cough reaction is unknown. Different thresholds for coughing in men and women have been proposed [17], as well as ethnic differences in cough tendency [18]. One study suggests that sex hormones do not have any influence on cough, since most of the women in the study were postmenopausal [6].In a Norwegian double-blind multicenter study (206 men, 206 women), nearly three times more women than men spontaneously reported cough with lisinopril (12.6% vs. 4.4%) [16, 27].

A review has examined ACE inhibitor-associated angioedema/urticaria; the number of reports among patients taking lisinopril (mean dose 12 mg daily) were similar in men and women [28]. It is suggested that ACE inhibitors cause angioedema to a greater extent in black patients than in non-black patients [6].

Reproductive health issues

ACE inhibitors should not be used in pregnant women. Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).