J Thromb ThrombolysisDOI 10.1007/s11239-006-9046-zThrombin generation in mesalazine refractory ulcerative colitisand the influence of low molecular weight heparinAnton A. Vrij Æ Ardi Oberndorff-Klein-Woolthuis Æ Gerard Dijkstra ÆAndrea E. de Jong Æ Rob Wagenvoord Æ Hendrik C. Hemker ÆReinhold W. Stockbru¨ggerÓ Springer Science+Business Media, LLC 2007differences were observed on the cl
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Ldr shaw.qxpRosiglitazone: the prescribing
From an editorial perspective it has been of considerable between the two TZDs. Although new prescribing already interest to observe the Pandora’s Box phenomenon that may have shifted in the light of these recent reports, such has followed the now much publicised meta-analysis a switch in existing usage takes the issue that one step paper1 in respect of rosiglitazone and possible increased further. A round-robin peer consensus enquiry suggests risk of myocardial infarction. Sensation-seeking head- that not everyone is yet ready to take this step, but in the lines have appeared within the popular press (‘Is true spirit of open debate we feel that it is important to Avandia the next Vioxx?’),2 whilst medical journals have publish Bob Ryder’s paper and will be interested to learn provided prominent coverage in news sections (‘Study of readers’ views on his recommendation.
links diabetes drug to heart deaths’).3 The intensity ofinterest has largely obscured any easy interpretation of the issue, particularly as the debate is far from concluded The whole episode will surely go down as a milestone in with uncertainties of actual risk still to be established.4 the way we introduce new drugs for diabetes. Issues con- Some prominent editorial leaders have attempted to cerning the adequacy of trial data provided for regula- maintain a measure of commonsense, arguing the need tory purposes and its relevance to the wider population for a ‘calmer and more considered approach’5 and cau- post licensing have rightly been highlighted. Certainly, tioning against ‘overreaction’,6 whilst our own commis- emphasising the ongoing need for careful surveillance sioned commentary favoured ‘a pragmatic approach’.7 of drug outcomes post marketing launch, both from further controlled studies as well as observation from open clinical practice, is essential. New treatments for Certainly, many questions remain unanswered, but it is diabetes are still much needed but perhaps the learning salutory to note how the use of relative changes in effect message from this experience is that new therapies, (so favoured in drug trials when positive and in subse- however welcome in principle, must be embraced with quent drug marketing) can work to disadvantage in this objective circumspection10 and a considered commit- negative context, when in reality the much smaller ment to our patients’ best interests. Ryder’s reminder of dimension of absolute change may be more meaningful.
‘primum non nocere’ is appropriate.
Current outstanding key questions are whether thereported adverse effects with rosiglitazone, if proven, are drug specific or whether they might be a drug class effect with implications for the other current alternative thia-zolidinedione (TZD), pioglitazone. So far the FDA has advised caution for both drugs, but this primarily rests 1. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of on an increased heart failure risk known to be common myocardial infarction and death from cardiovascular to both.8 The real immediate question from patients and causes. N Engl J Med 2007; 356: 2457–2471.
prescribers alike is ‘what to do?’: what are the real risks 2. Thottam J. Is Avandia the next Vioxx? Time 2007: 21 May.
with TZDs?; do the potential risks merit withdrawal of 3. Tanne JH. Study links diabetes drug to heart deaths. BMJ TZD prescribing?; and, if so, what are the alternative 2007; 334: 1073.
therapeutic options? Not forgetting the importance of 4. Diamond GA, Bax L, Kaul S. Uncertain effects of rosiglita- continued lifestyle attention, the tried and tested tradi- zone on the risk for myocardial infarction and cardio- tional therapies of metformin and second generation annals.org/cgi/content/full/0000605-200710160-00182 sulphonylureas still serve well in the oral treatment of VL (scheduled 16 October 2007: 147(8)).
type 2 diabetes, whilst the new DPP4 inhibitors, yet to be 5. Editorial. Rosiglitazone: seeking a balanced perspective.
fully evaluated in clinical practice, are another consider- Lancet 2007; 369: 1834.
ation in the available drug armamentarium. 6. Hirsch IB. TZDs: Where do we go from here? Diabetes, obe- We believe guidelines on drug prescribing are impor- sity and cardiovascular news. American Diabetes tant in supporting good clinical practice9 but recognise the need to revise recommendations in the light of new 7. Drummond R, Fisher M. Fractures, heart failure and fears evidence. To determine definitive guidance on TZD of myocardial ischaemia: has the record stuck for rosiglita- prescribing just at this moment in time is very difficult, zone and the thiazolidinediones? Pract Diabetes Int 2007; 24:
and professional bodies such as the Association of British 8. Singh H, Loke YK, Furberg CD. Thiazolidinediones and Clinical Diabetologists will now no doubt wait until there heart failure. Diabetes Care 2007; 30: 2148–2153.
is greater clarity. In the meantime, individual opinion will 9. Higgs ER, Krentz AJ, on behalf of the Association of British be held and championed such as by Bob Ryder, who has Clinical Diabetologists. ABCD position statement on glita- marshalled his arguments (see Personal Comment on zones. Pract Diabetes Int 2004; 21: 293–295.
page xxx) promoting a prescribing switch from rosiglita- 10. Nathan DM. Finding new treatments for diabetes – How zone to pioglitazone on the basis of reported differences many, how fast . how good? N Engl J Med 2007; 356: 437–440.
Pract Diab Int October 2007 Vol. 24 No. 8 Copyright 2007 John Wiley & Sons
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