Published online before print May 5, 2005, doi: 10.1161/01.STR.0000166044.06026.46
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(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?
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 |
|---|
- Schrader J, Luders S, Kulschewski A, et al. Morbidity and Mortality after Stroke—Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES). Stroke. 2005; 36: 1218–1226.
[Abstract/Free Full Text] - Gueyffier F, Boissel JP, Boutite F, Boissel JP, Boutitie F, Pocock S, Coope J, Cutler J, Ekbom T, Fagard R, Friedman L, Kerlikowske K, Perry M, Prineas R, Schron E. Effect of antihypertensive treatment in patients having already suffered from stroke. Gathering the evidence. The INDANA (Individual Data Analyses of Antihypertensive intervention trials) Project Collaborators. Stroke. 1997; 28: 2557–2562.
[Abstract/Free Full Text] - PATS Collaborating Group. Post-Stroke Antihypertensive Treatment Study. Chin Med J. 1995; 108: 710–717.[Medline] [Order article via Infotrieve]
- PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood pressure lowering regimen among 6105 individuals with previous stroke or transient ischemic attack. Lancet. 2001; 358: 1033–1041.[CrossRef][Medline] [Order article via Infotrieve]
- Messerli FH, Grossman E, Lever AF. Do thiazide diuretics confer specific protection against strokes? Arch Intern Med. 2003; 163: 2557–2560.
[Abstract/Free Full Text] - Staessen JA, Fagard R, Thijs L, Celis H, Arabidze GG, Birkenhager WH, Bulpitt CJ, de Leeuw PW, Dollery CT, Fletcher AE, Forette F, Leonetti G, Nachev C, O’Brien ET, Rosenfeld J, Rodicio JL, Tuomilehto J, Zanchetti A. Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst-Eur) trial investigators. Lancet. 1997; 350: 757–764.[CrossRef][Medline] [Order article via Infotrieve]
- Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360: 7–22.[CrossRef][Medline] [Order article via Infotrieve]
- Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively designed overviews of randomised trials. Lancet. 2003; 362: 1527–1535.[CrossRef][Medline] [Order article via Infotrieve]
- Dahlöf B, Devereux R, Kjeldsen SE, Julius S, Beevers G, de Faire U, Fyhrquist F, Ibsen H, Kristiansson K, Lederballe-Pedersen O, Lindholm LH, Nieminen MS, Omvik P, Oparil S, Wedel H; LIFE Study Group. LIFE Study Group. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002; 359: 995–1003.[CrossRef][Medline] [Order article via Infotrieve]
- Weber MA, Julius S, Kjeldsen SE, Brunner HR, Ekman S, Hansson L, Hua T, Laragh JH, McInnes GT, Mitchell L, Plat F, Schork MA, Smith B, Zanchetti A. Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial. Lancet. 2004; 363: 2032–2034.[CrossRef][Medline] [Order article via Infotrieve]
- Fournier A, Messerli F, Achard J, Fernandez L. Cerebroprotection mediated by angiotensin II: a hypothesis supported by recent randomised clinical trials. J Am Coll Cardiol. 2004; 43: 1343–1347.
[Abstract/Free Full Text] - Iadecola C, Gorelick PB. Hypertension, angiotensin, and stroke: beyond blood pressure. Stroke. 2004; 35: 348–350.
[Free Full Text] - Watanabe T, Barker TA, Berk BC. Angiotensin II and the endothelium: diverse signals and effects. Hypertension. 2005; 45: 163–169
[Abstract/Free Full Text] - Jandeleit-Dahm KA, Tikellis C, Reid CM, Johnston CI, Cooper ME. Why blockade of the renin-angiotensin system reduces the incidence of new-onset diabetes? J Hypertens. 2005; 23: 463–473.[Medline] [Order article via Infotrieve]
- Wachtell K, Lehto M, Gerdts E, Olsen MH, Hornestam B, Dahlöf B, Ibsen H, Julius S, Kjeldsen SE, Lindholm LH, Nieminen MS, Devereux RB. Angiotensin II receptor blockade reduces new-onset atrial fibrillation and subsequent stroke compared to atenolol: the Losartan Intervention For End Point Reduction in Hypertension (LIFE) study. J Am Coll Cardiol. 2005; 45: 712–719.
[Abstract/Free Full Text] - Verma S, Marty Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ. 2004; 329: 1248–1249.
[Free Full Text]
Related Article:
- Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention: Principal Results of a Prospective Randomized Controlled Study (MOSES)
- Joachim Schrader, Stephan Lüders, Anke Kulschewski, Frank Hammersen, Kerstin Plate, Jürgen Berger, Walter Zidek, Peter Dominiak, Hans Christoph Diener, and the MOSES Study Group
Stroke 2005 36: 1218-1224.[Abstract] [Full Text] [PDF]
This article has been cited by other articles:
 |
|
 |
|
  L. Lopez-Jimenez, M. Camafort, G. Tiberio, J. A. Carmona, C. Guijarro, F. Martinez-Penalver, M. Monreal, and FRENA Investigators Secondary Prevention of Arterial Disease in Very Elderly People: Results From a Prospective Registry (FRENA) Angiology, August 1, 2008; 59(4): 427 - 434. [Abstract] [PDF]
|
|
|
|
 |
|
 R. Oprisiu-Fournier, J.-M. Serot, J.-M. Achard, F. H. Messerli, S. E. Black, and A. Fournier AT1 Receptor Blockers for Cognition Decline After Cardiac Surgery? Stroke, November 1, 2006; 37(11): 2666 - 2666. [Full Text] [PDF]
|
|
|
|
|
|
A. Fournier, G. Choukroun, S. S. Modeliar, O. Godefroy, J.-M. Achard, J. Wang, and F. Messerli Does the MOSES Trial Establish Superiority of AT1-Receptor Blockers Over Dihydropyridine/Calcium Antagonists in Secondary Stroke Prevention? Stroke, February 1, 2006; 37(2): 336 - 337. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||