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In Reply: In response to Dr Fournier and colleagues and Dr Messerli and colleagues, we too are uncertain why losartan prevented stroke to such a greater extent than atenolol with the same level of blood pressure reduction, yet why the 2 regimens were equal in preventing myocardial infarction. Although our study did not address mechanisms, there are preclinical data in models such as the stroke-prone spontaneously hypertensive rat that show a benefit of angiotensin AT₁-receptor blockade with losartan on cerebrovascular structure and prevention of cerebral lesions in the absence of an effect on blood pressure.¹ In this context, AT₂-receptor stimulation in addition to AT₁-receptor blockade for greater selective cerebral protection seems intriguing.² In addition, pending results of mechanistic substudies of our study may potentially shed light on the cerebrovascular protective properties of losartan.³

Regarding the choice of the ₁-selective blocker atenolol as the comparator, this drug and . . . [Full Text of this Article]

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