Valsartan

Additional information

Pharmacokinetics and dosing

According to the original manufacturer, pharmacokinetics of valsartan does not differ significantly between men and women [1] and no sex differentiation in dosing has been recommended [2].

Effects

Hypertension

The original manufacturer reports that the antihypertensive effect is independent of age, sex or race. However, antihypertensive drugs that affect the renin-angiotensin system (ACE inhibitors and angiotensin-II blockers) have generally been found to be less effective in low-renin hypertensives (more frequently blacks) than in high-renin hypertensives (frequently whites). [1]. Contrary to this, a subgroup analysis of the Belgian PREVIEW study (1525 men, 1665 women) showed that valsartan for 90 days resulted in fewer women than men reaching target SBP (36.3 vs 41.2%) and combined SBP-DBP target (32.4 vs 36.7%). Determinants for uncontrolled BP varied between men and women [3].

A subgroup analysis of the large randomized, double-blind VALUE trial (8777 men, 6469 women) studying valsartan and amlodipine in hypertensive patients, showed a higher risk of cardiac events in valsartan-treated women but not in valsartan-treated men (HR 1.21 vs 0.94) [4].

Combination therapyA post-hoc analysis of the COSIMA study explored the impact of patient’s age and sex on the antihypertensive effect of valsartan/hydrochlorothiazide (80/12.5 mg) compared to irbesartan/hydrochlorothiazide (150/12.5 mg) (252 men, 197 women). More patients achieved blood pressure control with irbesartan/HCTZ than valsartan/HCTZ and was achieved in all age group and in men and women [5].

Data from The China STATUS II study, including Chinese adults (6456 men, 4856 women) treated with valsartan/amlodipine (80/5 mg) showed that the effect on SBP was better in women [6].

Heart failure

The large randomized double-blind placebo-controlled Valsartan Heart Failure Trial (Val-HeFT) (4008 men, 1002 women) reported that the effects of valsartan in heart failure patients was similar across age groups and in men and women [1].

Myocardial infarction

Valsartan (target dose 160 mg x2) was compared to captopril (target dose 50 mg x3) and their combination in the large randomized, double-blind VALIANT study (10133 men, 4570 women). All-cause mortality was similar for valsartan and captopril based on sex, age, and race. Women, regardless of treatment, were more likely to experience the composite secondary outcome of cardiovascular death, myocardial infarction, heart failure, stroke, and resuscitation from cardiac arrest (HR 1.15), which could be explained by an increased risk of hospitalization for heart failure in women (HR 1.36) [7].

Adverse effects

In the post-hoc analysis of the COSIMA study mentioned above [5], the overall safety profile was similar in the two treatment groups and across age groups and in men and women. Non-serious adverse events occurred in 18% of women and 13% of men receiving valsartan/HCTZ (unknown if significant sex difference) [5].

According to controlled studies conducted by the manufacturer, the incidence of adverse effects in adult patients with hypertension was not associated with sex, age or race [2].

Reproductive health issues

Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).