Hypertension Knowledge Centre
Centrally Acting Drugs
Role of moxonidine in combination with other antihypertensives
Frei et al (1994)19 evaluated the efficacy of moxonidine and hydrochlorothiazide as monotherapy or in combination in a placebocontrolled study in 160 patients with mild-to-moderate hypertension. This was a double-blind, parallel group, prospectively randomised study in general practice, with a 4-week placebo run-in and an 8-week treatment period. Patients were newly diagnosed or had unsatisfactorily controlled blood pressure; their mean age was 55 years (range 28-73 years).
Monotherapy results were described in the ‘monotherapy’ section. Using the two drugs in combination gave a more marked reduction in blood pressure than either of the monotherapies (p<0.05) (figure 10).
Figure 10: Mean reduction in sitting diastolic blood pressure after eight weeks of treatment with moxonidine and hydrochlorothiazide (HCTZ) as monotherapy or in combination. Adapted from19
Overall response (defined as diastolic blood pressure ≤90 mmHg or ≥10 mmHg decrease in blood pressure) was 70% with monotherapy, 88% with combination therapy, and 44% with placebo (figure 11). After cessation of treatment, rebound hypertension did not occur in any group.
Figure 11: Percentage response for all patients (intent-to-treat analysis) following moxonidine and hydrochlorothiazide (HCTZ) as monotherapy or in combination. Adapted from19
Waters et al (1999)30 reported the results of the TOPIC study (Trial Of Physiotens® In Combination) which included patients aged 18-80 years with mild-to-moderate hypertension and a mean baseline BMI of 28.6 kg/m2. A 4-week placebo run-in phase was followed by eight weeks of monotherapy with moxonidine 0.2-0.4mg/day. Patients not responding to monotherapy were randomised to double-blind treatment with a daily dose of 0.4mg moxonidine plus either amlodipine 5mg,enalapril 10mg or HCTZ 12.5mg for a further four weeks.
In total, 253 patients were included in the double-blind ‘combination’ efficacy analysis.
Reductions in blood pressure were seen in all three combination groups, but the combination of moxonidine with amlodipine reduced sitting DBP (primary endpoint) and SBP to a significantly greater extent (p<0.05) than other combination therapies (figure 12). Response to therapy (sitting DBP normalisation or a reduction of ≥10 mmHg) occurred in significantly more moxonidine/amlodipine patients (46.9%) than moxonidine/HCTZ (21.1%) or moxonidine/enalapril (26.8%) patients (both p<0.05).
Figure 12: Mean change in systolic and diastolic blood pressure during four weeks of combination therapy in patients who had not responded to previous moxonidine monotherapy (TOPIC study). Adapted from30
A study of moxonidine used in combination with metoprolol in hypertensive patients with type 2 diabetes was reported by Jacob et al.34 This is described in the diabetes section.