Patients who have already suffered a stroke are at high risk of recurrence. Among those who survive a first stroke, 8% of patients suffer a further stroke within one year,56 and 17% of patients experience another event in the five-year period following initial stroke.57 Stroke survivors have a 15-fold increased risk of recurrence.3
Evidence is now emerging that treatment with antihypertensive agents can significantly lower the rate of recurrent stroke in patients.58
Morbidy and mortality after Stroke - Eprosartan compared with nitrendipine for Secondary prevention
MOSES was a controlled, multicentre study comparing eprosartan (n=710) versus the calcium channel blocker nitrendipine (n=695) in hypertensive patients who had experienced cerebral ischaemia/TIA/prolonged reversible ischaemic neurological deficit (PRIND) or intracerebral haemorrhage during the 24 months prior to study enrolment. All patients had a cerebral scan or MRI before inclusion. Nitrendipine was chosen as the comparator in this study because it had previously been tested against placebo in the Syst-Eur trial, where it reduced all strokes by 42% and all cardiovascular events by 31%.
Baseline characteristics for patients in the two groups were similar with respect to age (mean age 68 years), gender, weight, body mass index, SBP, DBP and baseline neurological scores. Less than a quarter of patients in each group had no concomitant disorders, ie. this population of patients could be described as being at a ‘high risk’ of recurrence.
The combined primary endpoint was a composite of total mortality plus the total number of cardiovascular and cerebrovascular events, including all recurrent events. Cerebral complications were defined as intracerebral haemorrhage, recurrence of stroke, TIAs or PRIND. Cardiovascular complications were defined as any cardiovascular event, including MI and new heart failure. Pre-defined secondary endpoints were the single components of the combined primary endpoint, as well as an assessment of functional status and cognitive function.
Mean follow-up of patients in the study was 2.5 years. The mean dosage of each drug used at the end of the study was 623mg eprosartan and 16mg nitrendipine. Approximately one-third of patients in each group received monotherapy; diuretics were the most frequently prescribed combination partner, followed by beta-blockers, ACE inhibitors or AIIAs, or calcium channel blockers.
Normotensive blood pressure was achieved in both groups after three months (figure 23). Overall, 76% of patients on eprosartan had their BP normalised. This was higher than in LIFE (46%) or VALUE (64%). At the study end, mean BP was 137.5/80.8mmHg in the eprosartan group and 136.0/80.2mmHg in the nitrendipine group. At the study end, 71.1% and 72.5% of patients in the eprosartan and nitrendipine group, respectively had normal SBP values and DBP<90mmHg.
Figure 23: Effect of treatment with eprosartan or nitrendipine on blood pressure in hypertensive patients with previous stroke/TIA/PRIND. Adapted from6
In total, 206 eprosartan patients suffered an event during the follow-up period, compared with 255 in the nitrendipine group (figure 24). This represents a statistically significant risk reduction of 21% with the eprosartan-based regimen (p=0.014). The difference emerged after one year and became more pronounced as the length of follow-up increased.
Figure 24: Reduction in total mortality, cardiovascular and cerebrovascular events during treatment with eprosartan or nitrendipine in hypertensive patients with previous stroke/TIA/PRIND. Adapted from 6
In an analysis of the secondary endpoints, eprosartan showed a significant reduction of 25% in fatal and non-fatal cerebrovascular events, including recurrent events (p=0.02) (figure 25). Eprosartan also showed a trend towards a reduced risk of having a fatal or non-fatal cardiac event, but this difference was not statistically significant (p=0.06). However, analysis of first occurrence of cardiovascular events showed a statistically significant difference in favour of eprosartan (p=0.03). In terms of overall mortality, there was no difference between the two groups.
There was no difference between groups in terms of functional status and cognitive function as assessed by MMSE, Barthel Index, and Rankin Scale scores.
Figure 25: Reduction in stroke recurrence during treatment with eprosartan or nitrendipine in hypertensive patients with previous stroke/TIA/PRIND. Adapted from6