https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840180435

Meeting report: International autoimmune hepatitis group

ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.

Angiotensin-Converting Enzyme Inhibitors

http://www.sportellodolore.info/public/sportello/genere/CARDIOVASCOLARE/Gender-differences-in-drug-responses_2007_Pharmacological-Research.pdf

Gender differences in drug responses

Angiotensin-converting enzyme inhibitor-induced cough: ACCP evidence-based clinical practice guidelines.

Although sex-specific differences in cardiovascular medicine are well known, the exact influences of sex on the effect of cardiovascular drugs remain unclear. Women and men differ in body composition and physiology (hormonal influences during the menstrual cycle, menopause, and pregnancy) and they present differences in drug pharmacokinetics (absorption, distribution, metabolism, and excretion) and pharmacodynamics, so that is not rare that they may respond differently to cardiovascular drugs. Furthermore, women are also less often treated with evidence-based drugs thereby preventing optimization of therapeutics for women of all ages, experience more relevant adverse drug reactions than men, and remain underrepresented in most clinical trials. Thus, current guidelines for prevention, diagnosis, and medical treatment for cardiovascular diseases are based on trials conducted predominantly in middle-aged men. A better understanding of these sex-related differences is fundamental to improve the safety and efficacy of cardiovascular drugs and for developing proper individualized cardiovascular therapeutic strategies both in men and women. This review briefly summarizes gender differences in the pharmacokinetics and pharmacodynamics of cardiovascular drugs and provides recommendations to close the gaps in our understanding of sex-specific differences in drug efficacy and safety.

/pdf/gender-differences-in-the-effects-of-cardiovascular-drugs-vla5qg339a.pdf

Gender differences in the effects of cardiovascular drugs

Female sex as an important determinant of lisinopril-induced cough.

Female preponderance for lisinopril-induced cough in hypertension.

In a randomized, parallel, double-blind study, lisinopril (n = 412; average dose 18.8 mg) reduced systolic and diastolic blood pressure (change = 20.2/13.8 mmHg; P less than 0.01/P less than 0.01) more than nifedipine (n = 416; average dose 37.4 mg; change = 13.3/11.2 mmHg) after 10-week treatment in patients, aged 40-70 years, with mild-to-moderate essential hypertension. Lisinopril was better tolerated than nifedipine. The withdrawals from treatment were fewer in the lisinopril-treated group (11 versus 46; P less than 0.01). The frequency of adverse experiences reported after a general question of discomfort was significantly lower for lisinopril than for nifedipine (P less than 0.01). When questioned on specific symptoms, frequency of coughing was higher with lisinopril (P less than 0.01), while flushing, edema, palpitations, dizziness, tiredness and rash were reported more frequently (P less than 0.01, for all) in the nifedipine-treated group. Quality of life was assessed by both patients and spouses. No significant changes in wellbeing were observed for either drug, except for the highest dose level of nifedipine which caused a deterioration.

Lisinopril and nifedipine in essential hypertension: a Norwegian multicenter study on efficacy, tolerability and quality of life in 828 patients.

Effect and tolerability of combining lovastatin with nifedipine or lisinopril.

BACKGROUND: The LIFE study (Losartan Intervention For Endpoint reduction in hypertension) is a randomized, double-blind comparison of losartan and atenolol-based treatment. The study hypothesis was that losartan would reduce cardiovascular morbidity and mortality more than traditional antihypertensive treatment with atenolol. MATERIAL AND METHODS: The study included 9193 patients in seven countries. RESULTS: By the end of the study, the mean dose was losartan 82 mg and atenonol 79 mg, whereas 94% of patients in both groups received additional hydrochlorothiazide. Blood pressure was reduced 30/17 mmHg by losartan and 29/17 mm Hg by atenolol. Despite the same reduction in blood pressure, the primary combined endpoint (cardiovascular mortality, non-fatal stroke and myocardial infarction) was reduced by 13.0% (p = 0.021) in the losartan group. Non-fatal and fatal strokes were reduced by 24.9% (p = 0.001). In two pre-specified subgroup analyses, cardiovascular mortality was reduced by 46% (p = 0.01) in patients with isolated systolic hypertension (n = 1326), and total mortality was reduced by 39% (p = 0.002) in patients with diabetes (n = 1159). INTERPRETATION: Losartan prevented more cardiovascular complications than atenolol for the same reduction in blood pressure and have positive additional effects beyond blood pressure control in patients with hypertension and left ventricular hypertrophy.

Kjell Gisholt

Papers

Female sex as an important determinant of lisinopril-induced cough.

Female preponderance for lisinopril-induced cough in hypertension.

Lisinopril and nifedipine in essential hypertension: a Norwegian multicenter study on efficacy, tolerability and quality of life in 828 patients.

Effect and tolerability of combining lovastatin with nifedipine or lisinopril.

Treatment of hypertension in patients with left ventricular hypertrophy