DÄ internationalArchive7/2008Secondary Stroke Prevention - Recent Advances: In Reply


Secondary Stroke Prevention - Recent Advances: In Reply

Dtsch Arztebl Int 2008; 105(7): 129. DOI: 10.3238/arztebl.2008.0129

Diener, H

LNSLNS 1. Letter by Lorenzl, Linnebank, and Stanger on B vitamins and cerebral ischemia:
In our article on the secondary prevention of stroke, we concentrated on large, randomized studies – for a good reason – and presented the evaluation of the primary end points defined in the study protocol for each of the studies. Within the constraints of an overview, it is not possible to include all post hoc analyses and letters to the editor about this topic. Furthermore, we are of the opinion that for therapeutic decisions mainly predefined end points of clinical studies should be considered – as is the case with licensing studies for new drugs.
2.Letter by Martin Gernken:
All meta-analyses published recently have shown that there is no relation between the dose of aspirin at doses >30 mg/day and the reduction in vascular end points. The aspirin dose in the ESPRIT study was therefore sufficiently high. An NNT of 80/year is clinically relevant, we think, when bearing in mind that for antihypertensive drugs, the NNT is 110 and for statins it is 230 to 250.
3.Letter by Günther Egidi:
3.1. At the time when the PROGRESS study was planned, the definition for hypertension still meant blood pressure measurements >160/90 mg Hg. What is relevant is the principle and not the threshold value by which hypertension is defined.
3.2. The MOSES study was not statistically powered to evaluate secondary end points such as death. It is irrelevant whether nitrendipine was underdosed in the author's opinion, since the blood pressure reduction was identical in both treatment groups. Of all hypertension studies that have been conducted so far, MOSES has the largest proportion of patients whose hypertension was being controlled in the context of the study.
3.3. A difference of normotensive patients in the LIFE study of 46% versus 49% is neither relevant nor does it reach significance.
3.4. The SPARCL study was the first prospective, randomized study that showed the benefit of a statin in secondary prevention of stroke. We kept the recommendation of atorvastatin in the subjunctive because of the drugs costs and licence, and we also explicitly pointed out that lowering cholesterol with a statin is more important than using a particular statin to do so.
3.5. As mentioned above, the aspirin doses in ESPS2 and ESPRIT are definitely effective.
3.6. The authors refute the idea of conflicting interests as mentioned by the first author. The recommendations from the UK National Institute for Health and Clinical Excellence (NICE), which is completely above any suspicion of representing the interests of the pharmaceutical industry, go even further than the authors' in this overview. NICE recommends the combination of aspirin and dipyramidole as first line secondary prevention in patients with ischemic stroke, independent of the risk of recurrence.
4. Professor Meyer from Groß-Rodensleben, in a letter directly to us, has pointed out an error. In table 1 in the ESPS2 study, the study end point was stroke. The corrected results should read for dipyramidole and ASA, 9.5%, for dipyramidole 12.8%, for ASA 12.5%, and for placebo 15.2%. Table 2 also has a mistake. The remarks regarding the comparison of ASA plus dipyramidole versus aspirin should say "the combination is significantly more effective than ASA." DOI: 10.3238/arztebl.2008.0129

Prof. Dr. Hans-Christoph Diener
Universitätsklinik für Neurologie
Hufelandstr. 55
45147 Essen, Germany

Conflict of interest statement
Prof. Dr. H.-C. Diener Professor HC Diener received honoraria for participation in clinical trials, as principal investigator, as advisory board member, or for presentations from: Abbott, AstraZeneca, Bayer Vital, Böhringer Ingelheim, D-Pharm, Fresenius, GlaxoSmith-Kline, Janssen Cilag, MSD, Novartis, Novo-Nordisk, Paion, Parke-Davis, Pfizer, Sanofi-Aventis, Sankyo, Servier, Solvay, Wyeth, Yamaguchi. Financial support for research projects was granted by: Astra/Zeneca, GSK, Böhringer Ingelheim, Novartis, Janssen-Cilag, Sanofi-Aventis. The Department of Neurology at the University Hospital in Essen is in receipt of research grants from the European Union, the German Research Foundation, the Federal Ministry of Education and Research, the Bertelsmann Foundation, and the Heinz-Nixdorf Foundation.