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(Stroke. 2005;36:1225.)
© 2005 American Heart Association, Inc.

Original Contributions

Editorial Comment: Secondary Prevention of Stroke Is Important

But All Hypertensive Drugs Are Not Created Equal?

Timo E. Strandberg, MD, PhD

Helsinki University Central Hospital, Finland

The Morbidity and Mortality After Stroke—Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES) study¹ has 2 important messages. First, it consolidates the evidence that is beneficial to treat hypertension even after a cerebrovascular disorder (stroke or transient ischemic attack) has occurred. Second, and more intriguing, it supports the idea that antihypertensive drugs (specifically angiotensin receptor blocker [ARB] therapy) may have benefits beyond blood pressure lowering.

An overview of hypertension trials including stroke survivors suggested that antihypertensive treatment decreased recurrence of stroke by 28%.² The preliminary result of the Post-Stroke Antihypertensive Treatment Study (PATS) corroborated this finding by showing that indapamide monotherapy with a 5 mm Hg systolic blood pressure reduction lowered the risk of recurrent stroke by 29% compared with placebo.³ The large PROGRESS study further showed that compared with placebo, angiotensin convertase enzyme (ACE) inhibitor–based therapy decreased recurrent cardiovascular complications in stroke survivors.⁴ Interestingly, this effect was not seen in those patients on ACE inhibitor alone, only in those with indapamide and ACE inhibitor combined. This result again strengthened the view that thiazide diuretics may have special effects in stroke prevention.⁵ Now the MOSES study shows that ARB (eprosartan)-based therapy decreased recurrent events compared with calcium channel blocker (nitrendipine)–based therapy among patients with previous cerebrovascular disorders. Because MOSES did not include a placebo group, it is essential that nitrendipine has been tested previously against placebo in the Syst-Eur trial, and there it reduced stroke by 38% and coronary events by 26%.⁶ Consequently, MOSES suggests that with eprosartan, a substantial further decrease of vascular events can be achieved.

With all this evidence, it is clear that hypertensive patients with a history of cerebrovascular disorder (transient ischemic attack, PRIND, or stroke) must be treated effectively with antihypertensive drugs; they are high-risk patients. Also, other risk factors including dyslipidemia must be taken into account. It should be remembered that stroke survivors are at increased risk of other vascular diseases, such as coronary heart disease, as well. Studies with statins in the treatment of dyslipidemia have shown that high-risk patients benefit from the treatment irrespective of the baseline low-density lipoprotein cholesterol value.⁷ Similarly, in the PROGRESS study, stroke survivors actually benefited from the treatment whether they did or did not have hypertension at baseline.⁴

MOSES differs from PROGRESS because recruited participants had to have treatment-requiring hypertension. Despite identical blood pressure lowering, eprosartan reduced vascular events more than nitrendipine. Actually, the latter even lowered blood pressure somewhat better. In previous studies, ARBs have been shown to especially reduce strokes and heart failure.⁸ Furthermore, in the Losartan Intervention for Endpoint (LIFE) study, ARB losartan-based therapy reduced strokes better than ß-blocker–based therapy.⁹ However, in the VALUE study, valsartan was nonsignificantly worse than amlodipine in stroke prevention, but post hoc analyses¹⁰ suggested that this may have been attributable to less effective blood pressure control by valsartan during the first 6 months of the trial (4.0/2.1 mm|Hg difference in favor of amlodipine).

If ARBs were truly better than other antihypertensive drugs in stroke prevention, what could be the mechanism? According to the Fournier hypothesis, the reason may lie in the selective blocking by ARBs of the deleterious effects mediated through the angiotensin II type 1 (AT1) receptor, whereas the effects through the AT2 receptor are unaffected or even enhanced.¹¹ AT2 receptor seem to mediate beneficial effects on the endothelium through decreased coagulation and inflammation and altered vessel structure, and AT2 receptor also protects brain tissue from ischemia in experimental models.^12,13 However, direct proof of this in humans lacking. Also, other mechanisms may be operating. ARBs have been shown to prevent diabetes,¹⁴ and losartan prevented new-onset atrial fibrillation in the LIFE study.¹⁵ Diabetes and atrial fibrillation are important risk factors of stroke, but their possible role in the MOSES study has not been analyzed further.

Finally, the MOSES results do not corroborate the recent suspicions of increased myocardial infarction risk with ARBs.¹⁶ In these high-risk patients, cardiovascular events (including myocardial infarction) tended to be less frequent in the eprosartan group, even though nitrendipine, compared with placebo, prevented coronary events in the Syst-Eur trial.⁶

	References

Top References

 

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