Hypertension Knowledge Centre
Centrally Acting Drugs
Moxonidine in postmenopausal hypertensive women
After the menopause, systolic blood pressure increases such that the prevalence of hypertension in postmenopausal women is similar to, or higher than, that in men.52 The presence of several interlinked cardiovascular risk factors after the menopause has led to the concept of the ‘menopausal metabolic syndrome’, with comorbidities such as hypertension, abdominal obesity, insulin resistance, type 2 diabetes, and changes in the lipid profile.53,54 Some of the factors associated with the menopausal metabolic syndrome are shown in figure 16.55
Figure 16: Some of the interlinked factors associated with the menopausal metabolic syndrome. Adapted from55
The contribution of hormonal changes to increased blood pressure in postmenopausal women is unclear, but may include reduced elasticity of the arteries,56 reduced sensitivity of angiotensin II receptors,57 increased plasma renin activity,58 reduced nitric oxide activity,59 and increased sympathetic activity.60 After the menopause there is a shift in the autonomic control of the cardiovascular system towards an increased sympathetic tone which is, in part, independent from changes in body weight and glucose metabolism, but is in the long-term heightened by these metabolic changes.61
The prevalence of metabolic syndrome in postmenopausal hypertensive women has important implications for therapy, as some antihypertensive drugs may worsen the already altered metabolic profile of these patients while others may have a beneficial effect.61 The profile of moxonidine, with its desirable effects on sympathetic outflow and glucose metabolism, suggests it should be particularly useful in treating hypertension in postmenopausal women with metabolic syndrome.
Kaaja et al (2004)35 reported the results of a multicentre, doubleblind, prospectively randomised study comparing monotherapy with moxonidine (0.3mg twice-daily, n=57) versus atenolol (50mg oncedaily, n=55) in hypertensive postmenopausal women who were not taking hormone replacement therapy. Mean body mass index was 29.3 kg/m2 (moxonidine) and 30.9 kg/m2 (atenolol). A 4-week placebo run-in phase was followed by a double-blind 8-week therapy period.
Statistically significant reductions in systolic and diastolic blood pressure occurred in both treatment groups during the course of treatment, with the beta-blocker having a slightly more potent effect overall. Atenolol was associated with a significant decrease in heart rate (-8.1 beats per minute, p=0.035), whereas there was no significant change in heart rate in the moxonidine group.
Moxonidine demonstrated a beneficial effect on several metabolic parameters, in contrast to atenolol. As shown in figure 17, moxonidine produced statistically significant reductions in AUC and mean plasma glucose levels at one and two hours after an oral glucose tolerance test (p<0.01 versus pretreatment). Changes with atenolol were less marked and were not statistically significant from pretreatment values.
Figure 17: Changes versus baseline in plasma glucose during oral glucose tolerance test following treatment with moxonidine (0.3mg twice-daily) and atenolol (50mg once-daily) (intention to treat analysis, n=109). Adapted from35
Moxonidine also reduced mean plasma insulin values, whereas atenolol increased mean plasma insulin (figure 18). The differences between groups did not reach statistical significance, probably because of high variability of the response.
Figure 18: Changes versus baseline in plasma insulin during oral glucose tolerance test following treatment with moxonidine (0.3mg twice-daily) and atenolol (50mg oncedaily) (intention to treat analysis, n=109). Adapted from35
The effect of moxonidine on mean plasma insulin levels was even more pronounced in a subgroup of 43 patients with baseline insulin more than 10 mU/L (i.e., insulin-resistant patients); the between-group difference in AUC was not quite statistically significant (p=0.06).
There was a significant increase in uric acid after treatment with atenolol (p=0.048) but not with moxonidine.