Hypertension Knowledge Centre
Angiotensin II Antagonists
Eprosartan - effect on systolic blood pressure and pulse pressure
Eprosartan has been shown to be significantly more effective than enalapril in reducing raised SBP.
Sega (1999) compared eprosartan versus enalapril in 118 patients with severe hypertension (DBP 115-125mmHg).5 This was a randomised, parallel group study in which an 8-week double-blind titration phase was followed by a 2-week maintenance phase. The initial dosage of eprosartan was 400mg/day, which was increased to 600 or 800mg daily if necessary. The initial dosage of enalapril was 10mg/day, increased to 20 or 40mg if necessary. Hydrochlorothiazide (HCTZ) (25mg/day) was added at week 6 in patients not achieving target BP.
Eprosartan had a significantly greater effect than enalapril on both sitting and standing SBP, and had a comparable effect to enalapril on DBP. Figure 10 shows the change in blood pressure from baseline after 10 weeks of treatment. There was a reduction from baseline in SBP of 29.1mmHg with eprosartan, compared with a reduction of 21.2mmHg with enalapril (p=0.025).
Figure 10: Mean reduction from baseline of sitDBP and sitSBP, following treatment with eprosartan or enalapril in patients with severe hypertension. Adapted from 5
At study endpoint, the response rate was 69.5% for the eprosartan group and 54.2% for the enalapril group (not statistically significant, p=0.07). A similar proportion of patients in each group received additional HCTZ (37-39%). The authors concluded that eprosartan was highly effective in the treatment of patients with severe hypertension when used as monotherapy or in combination with hydrochlorothiazide.
Ruilope et al (2001) reported results of a 12-week, double-blind, randomised trial comparing eprosartan with enalapril in 334 patients aged >65 years with predominantly systolic hypertension.41 Starting doses were eprosartan 600mg once-daily or enalapril 5mg once-daily. After 3 weeks these doses could be titrated up to 800mg and 20mg once-daily to achieve a treatment target of SBP <140mmHg.
At study endpoint, eprosartan and enalapril reduced sitSBP to a similar extent (18.0 versus 17.4mmHg respectively). At week 3 (but not at endpoint) there were significantly more responders in the eprosartan group than in the enalapril group for SBP (30% versus 20%, p=0.033 respectively).
At study endpoint, eprosartan and enalapril reduced sitSBP to a similar extent (18.0 versus 17.4mmHg respectively). At week 3 (but not at endpoint) there were significantly more responders in the eprosartan group than in the enalapril group for SBP (30% versus 20%, p=0.033 respectively).
Punzi et al (2004) reported results of a double-blind, randomised, placebo-controlled study of eprosartan as monotherapy or in combination with HCTZ in 283 patients aged 60 years or older with isolated systolic hypertension.42 A 3-5 week placebo run-in period was followed by 13 weeks of double-blind treatment (6 weeks titration with eprosartan 600-1200mg/day or matched placebo), 3-week maintenance, and 4 weeks of combination therapy with HCTZ 12.5mg.
The results are summarised in figure 11. At monotherapy endpoint, eprosartan produced a statistically significant reduction in sitSBP (16.1 versus 8.4mmHg for placebo, p<0.0001). Eprosartan/HCTZ combination therapy was also statistically significantly more effective than placebo in reducing sitSBP (21.7 versus 14.4mmHg, p<0.002).
Figure 11: Mean change from baseline in sitSBP in elderly patients >60 years of age with isolated systolic hypertension, following 9 weeks of monotherapy with eprosartan or placebo and 4 weeks combination therapy with HCTZ. Adapted from 42
Changes in standing SBP paralleled those of sitSBP, with statistically significant differences being oberved after monotherapy (p<0.001) and combination therapy (p<0.03). There were no reductions in sitDBP of more than 4mmHg during the study. Subgroup analyses showed no statistically significant differences for age (<75 yrs versus ?75 yrs), gender or race.
Teitelbaum et al (2004) investigated the effects of eprosartan (600mg od, alone or with HCTZ) in patients aged 60-84 years old with isolated systolic hypertension (n=97) or with combined systolic-diastolic hypertension (n=98) in a 10-week, randomised, open-label multicentre study.43 Eprosartan significantly reduced SBP at study endpoint from baseline in both groups (-17.5 versus -20.6mmHg respectively, p<0.0001). The reduction in DBP was significantly greater in patients with combined systolic-diastolic hypertension than in those with ISH (12.2 versus 5.0mmHg, respectively, p<0.0001).
Effect on pulse pressure
Emerging data suggest that pulse pressure (the difference between SBP and DBP readings) is an independent predictor of stroke and several other cardiovascular events.44 Patients with isolated systolic hypertension have elevated pulse pressure, which may predispose them to greater risk than those with combined systolic-diastolic hypertension.45
In the study by Punzi et al, eprosartan monotherapy decreased mean pulse pressure by 16.9mmHg at study endpoint compared with a decrease of 9.1mmHg with placebo.42 In the study by Teitelbaum et al, eprosartan gave a statistically significant reduction in mean pulse pressure from baseline both in ISH and combined systolic-diastolic hypertension treatment groups (p<0.0001).43 However, there was a significantly greater reduction in the ISH group compared with the combined systolic-diastolic hypertension group (12.5 versus 8.4mmHg, p<0.05) (figure 12).
Figure 12: Mean pulse pressure during 10 weeks of treatment with eprosartan in patients with ISH or combined systolic-diastolic hypertension. Adapted from 43
An observational study by de la Sierra et al (2004) investigated the effect of 12 weeks of treatment with eprosartan (600mg/day, 87% monotherapy) on pulse pressure in 3,133 patients with essential hypertension in primary care centres.46 Patients were either newly diagnosed or unresponsive to their current treatment. Eprosartan gave a statistically significant reduction in pulse pressure at 12 weeks (mean reduction of 13.5mmHg from baseline, p<0.001). There was also a significant reduction in the ratio of pulse pressure/mean blood pressure, from 61.9% to 58.5%, p<0.05. This ratio is a means of taking into account the severity of hypertension, enabling the authors to conclude that the reduction in pulse pressure by eprosartan was, at least in part, independent of the overall severity of hypertension.
A subgroup analysis by the same authors of 895 patients with isolated systolic hypertension showed that eprosartan, given as monotherapy or in combination with HCTZ, significantly reduced mean SBP by 25.6mmHg (p<0.05) and pulse pressure by 22.5mmHg (p<0.05).47 However the decrease in DBP was only 3.1mmHg, compared with 16.7mmHg in a subset of patients with mixed systolic/diastolic hypertension.
Robles et al (2005) reported the results of a 16-week open-label study in the primary care setting, which assessed the effect of eprosartan 600mg/day on pulse pressure in patients with mild-to-moderate hypertension.48 Results were evaluable in 566 patients at the end of the study period. There were statistically significant reductions in mean blood pressure (-26/-13mmHg), mean pulse pressure (-13mmHg) and mean arterial pressure (-17.4mmHg), all p<0.0001 compared with pretreatment baseline (figure 13). As in the de la Sierra study, there was a statistically significant reduction in the ratio of pulse pressure/mean arterial pressure from 61% to 59%.
Figure 13: Reduction in mean pulse pressure, arterial pressure, systolic BP and diastolic BP in an open-label study in the primary care setting. Adapted from 48
Taken together, the results in this section indicate that treatment with eprosartan has a predominant effect on SBP and pulse pressure in subjects with ISH, and that the reduction in pulse pressure may be independent of the severity of hypertension.