Stroke Reduction with AIIA – Solvay

26 October 2006 (Last Updated October 26th, 2006 09:27)

With stroke such a serious problem, the ability to reduce the likelihood of cerebrovascular events is essential. There is evidence to suggest that the AIIA eprosartan can offer more than just effective blood pressure control.

Stroke represents a major health and economic problem globally, affecting over 20 million people every year. It is the third biggest cause of death worldwide after heart disease and cancer, with a mortality rate of 25%. High Blood Pressure (BP) contributes to over 12.7 million strokes worldwide and a substantial number of patients remain permanently disabled. Stroke survivors have a 15-fold risk of stroke recurrence compared with the general population.

Eprosartan, a new-generation Angiotensin II Antagonist (AIIA), exerts a unique dual mode of action on the Renin Angiotensin Aldosterone System (RAAS) and the Sympathetic Nervous System (SNS), which translates clinically into broad-spectrum anti-hypertensive actions with obvious implications beyond BP control.

EPROSARTAN CONTROL OF SYSTOLIC BLOOD PRESSURE

Recent data shows that eprosartan offers a very effective control of Systolic Blood Pressure (SBP). Both the RAAS and the SNS play important interlinked roles in the control of SBP. Elevated SBP is a powerful predictor of coronary artery, stroke and renal disease. Moreover, studies undertaken in primary care in different countries have shown that pulse pressure (the difference between SBP and diastolic BP readings) can be significantly reduced with eprosartan. Emerging data suggest that pulse pressure is an independent predictor of stroke and several other cardiovascular events.

The Morbidity and Mortality after Stroke, comparing Eprosartan with Nitrendipine for Secondary Prevention study (MOSES) has, for the first time, investigated two different active drugs. The rationale behind including these drugs was the cerebroprotective experimental effects of eprosartan and the positive results of the Syst-Eur trial, in which the calcium channel blocker nitrendipine reduced primary stroke by 42 per cent. A total of 1405 well-defined, high-risk hypertensives with
cerebral events during the last 24 months were randomised. The combined primary endpoint was a composite of total mortality plus the number of cardiovascular and cerebrovascular events, including all recurrent events.

BP reduction was the same for both groups, with normotensive values reached after three months. Around 75.5% of eprosartan-treated patients reached values of less than 140/90mmHg. This is a higher percentage than in other trials like Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) with 46% or Valsartan Antihypertensive Long-term Use Evaluation (VALUE) with 64%. Moreover, the percentage of patients treated with monotherapy was comparably high in MOSES: 34.4% and 33.1%
received eprosartan or nitrendipine, respectively. In LIFE it was 11% and 12%, while in VALUE it was 27% and 25%.

MORE THAN BP CONTROL

Beyond the very similar BP control achieved in MOSES, the eprosartan-based regimen lowered primary endpoints significantly more than the nitrendipine-based regimen, with a risk reduction of 21% in favour of eprosartan (p=0.014).

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). Eprosartan also showed a trend towards a reduced risk of having a fatal or non-fatal cardiac event, just under the level of significance (p=0.06). However, analysis of first occurrence of cardiovascular events revealed a statistically significant difference in favour of eprosartan (p=0.03). Overall, eprosartan offers additional end organ protection above that offered by BP reductions (Schrader et al. Stroke 2005;36:1218-26).

The mechanism for a superior stroke prevention of AIIAs compared with other antihypertensives most likely corresponds to the selective blockade of the AT1 receptor, while the effects mediated through the AT2 receptor are not affected or even enhanced. The AT2 receptor has a regenerative effect on the endothelium and the vessel structure, for example, by decreased inflammation and coagulation, and seems to prevent central ischemia.

Eprosartan has a placebo-like side-effect profile and does not involve the cytochrome P450 enzyme system, which reduces the potential for drug interactions. The inhibition of AT1 receptors by eprosartan is dose-dependent, indicating that the blockade represents true competitive antagonism. For patient convenience and compliance, the dose regimen of eprosartan is 600mg, once daily.