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(Stroke. 2006;37:338.)
© 2006 American Heart Association, Inc.

Letters to the Editor

MOSES Raises Questions

Martin H. Strauss, MD

Division of Cardiology, North York General Hospital, Toronto, Canada

Subodh Verma, MD, PhD

Division of Cardiac Surgery, St Micheal’s Hospital, Toronto, Canada

To the Editor:

The MOSES trial confirms both the safety and efficacy of eprosartan in hypertensive patients with cerebrovascular disease.¹ The authors’ conclusion that eprosartan provides "vascular protective effects" above that of nitrendipine, however, is not substantiated by the data. Mortality was not different (57 eprosartan versus 52 nitrendipine; P=0.725), nor was the first occurrence of a cebrovascular event (80 eprosartan versus 89 nitrendipine; P=0.42). Eprosartan did reduce total cerebrovascular events (102 versus 134; P=0.026) but did not result in improvement in either functional or cognitive parameters. Perhaps this is a reflection that nondisabling TIAs rather than stroke drove the benefit. Furthermore, the apparent benefit with eprosartan may have been spurious because a single patient, presumably on nitrendipine, had multiple events.

The cardiovascular end points in MOSES take on a more intriguing significance considering the results of the VALUE trial, which compared the same 2 classes of drugs. In VALUE, the ARB valsartan was associated with a 19% (P=0.02) increase in myocardial infarction (MI) compared with the calcium channel blocker (CCB) amlodipine. A highly controversial editorial addressed the increased MI rate in VALUE, suggesting that ARB as a class may not only lack vascular protection, but may possibly result in increased MI.² This hypothesis continues to be debated,³ and despite the ongoing analysis of the data,^4,5 some have already concluded that an ARB may not have the same "vascular protection" of an angiotensin converting enzyme inhibitor (ACEI).⁶

Eprosartan, although reducing first time cardiovascular events (CV; 60 versus 84; P=0.03), did not reduce total cardiovascular events. Acute coronary syndrome rates tended to be lower with eprosartan, which is encouraging, but the benefit with eprosartan on cardiovascular end points appears to be primarily related to a reduction in congestive heart failure (CHF). The reduction in CHF with eprosartan, surprisingly, did not correlate with a reduction in mortality. Considering the criterion for diagnosing CHF in MOSES was not reported, one has to wonder whether peripheral edema alone, a common side effect with CCB secondary to vasodilatation, led to an increase in the diagnosis of CHF in the nitrendipine patients. This, of course, would be erroneous in the absence of other symptoms or signs of CHF requiring treatment.

How should the results of MOSES influence clinical practice? Should ARB or CCB be first-line therapy in the hypertensive patient after cerebrovascular accident? Upwards of 64% of the patients in MOSES had a very strong indication for an ACEI becuase their premorbid diagnosis included coronary artery disease or diabetes mellitus.⁷ Current guidelines⁸ strongly recommend all patients with coronary artery disease receive ACEI independent of hypertension because of their unique "vascular protective" effects, the benefit which is above that of lowering blood pressure alone.⁹ Many patients with cerebrovascular disease have concomitant coronary artery disease, which even in the absence of symptoms, will statistically lead to the demise of the patient. Thus, ACEI can reasonably be viewed as the "preferred" cardio-protective agent for a MOSES patient. And finally, a MOSES patient requires aggressive intervention of all vascular risk factors. Only 32% of the hyperlipidemic patients in MOSES received a statin. This suggests a real opportunity for dramatically improving the prognosis of a MOSES patient with a more judicious prescribing of statins.

References

1. Schrader J, Luders S, Kulschewski A, Hammersen F, Plate K, Berger J, Zidek W, Dominiak P, Diener HC. Morbidity and Mortality after Stroke-Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES). Stroke. 2005; 36: 1218–1226.[Abstract/Free Full Text]
2. Verma S, Strauss M. Angiotensin receptor blockers and myocardial infarction. BMJ. 2004; 329: 1248–1249.[Free Full Text]
3. Strauss M, Verma S. Letters To The Editor. Angiotensin receptor blockers and myocardial infarction. BMJ. 2005; 330: 1269–1271.[Free Full Text]
4. Verma S, Leiter L, Lonn E, Strauss M. Perindopril in diabetes: perspectiv from the EUROPA substudy, PERSUADE. Eur Heart J. 2005; 26: 1347–1349.[Free Full Text]
5. Strauss MH, Verma S. Inhibition of the renin-angiotensin system in cardiovascular protection: Is it important to watch C’ARB ‘intake? Can J Cardiol. 2005; 21: 577–580.[Medline] [Order article via Infotrieve]
6. ARB and Myocardial Infarction. The Medical Letter. 2005; 47: 38–39.
7. Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. 2000; 342: 145–153.[Abstract/Free Full Text]
8. Lopez-Sendon J, Swedberg K, McMurray J, Tamargo J, Maggioni AP, Dargie H, Tendera M, Waagstein F, Kjekshus J, Lechat P, Torp-Pedersen C; Task Force on ACE-inhibitors of the European Society of Cardiology. Expert consensus document on angiotensin converting enzyme inhibitors in cardiovascular disease. The Task Force on ACE-inhibitors of the European Society of Cardiology. Eur Heart J. 2004; 25: 1454–1470.[Free Full Text]
9. Verdecchia P, Reboldi G, Angeli F, Gattobigio R, Bentivoglio M, Thijs L, Staessen JA, Porcellati C. Angiotensin-converting enzyme inhibitors and calcium channel blockers for coronary heart disease and stroke prevention. Hypertension. 2005; 46: 386–392.[Abstract/Free Full Text]

Response:

Joachim Schrader, MD; Stephan Lüders, MD; Anke Kulschewski, MD Frank Hammersen, MD

Department of Internal Medicine, St. Josefs Hospital, Cloppenburg, Germany

Kerstin Plate

Institute for Hypertension and Cardiovascular Research, Cloppenburg, Germany

Jürgen Berger, PhD

Medical Biometry and Epidemiology, University Hospital Hamburg-Eppendorf, Germany

Walter Zidek, MD

Department of Nephrology, Charité Campus Benjamin Franklin, Berlin, Germany

Peter Dominiak, MD

Department of Pharmacology and Toxicology, University of Lübeck, Germany

Hans Christoph Diener, MD

Department of Neurology, University of Essen, Germany

for the MOSES Study Group
Drs Strauss and Verma discussed several important aspects of the MOSES study results concerning the cardiovascular end points in comparison to other data, especially the increase of myocardial infarction in the valsartan group of the VALUE trial.¹ These results could not be supported by the MOSES data.² In this study, the number of acute coronary syndrome in the eprosartan group was even less than in the nitrendipine group (39 versus 48; but not significant) showing at least the safety of treatment with eprosartan in patients with cerebrovascular disease. Drs Strauss and Verma wondered if the diagnosis of heart failure in the MOSES study could be attributable to peripheral edema alone. This question is of course of great importance because the significant difference in first occurrence of cardiovascular events was attributable to heart failure.

To accept the diagnosis of CHF, more information like hospital demission-letters, echocardiography, chest x-ray, hospitalization and concomitant medication had to be documented and considered by the end point committee. Because of the limited number of words in the original article these methods could not be described in detail.

The benefit for the eprosartan group in terms of reducing cerebral events was not driven by a single patient with multiple events. There was a higher number of patients with >1 event in the same category of end points (TIA, ischemic stroke, acute coronary syndrome, CHF) in the nitrendipine group (16 versus 24; eprosartan versus nitrendipine).

References

1. Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L, Hua T, Laragh J, McInnes GT, Mitchell L, Plat F, Schork A, Smith B, Zanchetti A; VALUE trial group. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004; 363: 2022–2031.[CrossRef][Medline] [Order article via Infotrieve]
2. Schrader J, Luders S, Kulschewski A, Hammersen F, Plate K, Berger J, Zidek W, Dominiak P, Diener HC; MOSES Study group. Morbidity and Mortality after Stroke-Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES). Stroke. 2005; 36: 1218–1226.[Abstract/Free Full Text]

This Article Full Text (PDF) All Versions of this Article: 37/2/338    most recent 01.STR.0000199643.05768.8fv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Strauss, M. H. Search for Related Content PubMed PubMed Citation Articles by Strauss, M. H.