Rapid Responses to:

PRACTICE: Cathie Sudlow Dipyridamole with aspirin is better than aspirin alone in preventing vascular events after ischaemic stroke or TIA BMJ 2007; 334: 901 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

No advantage of dipyridamole and aspirin versus aspirin alone

Manfred Gogol   (29 April 2007)

Don't forget the bleeding risk with Dipyridamole

Brendan A McGrath   (6 May 2007)

No change to recommend

Erika Baum   (21 May 2007)

No advantage of dipyridamole and aspirin versus aspirin alone 29 April 2007
Manfred Gogol, Head of Geriatric Department Krankenhaus Lindenbrunn, Lindenbrunn 1, D-31863 Coppenbruegge, Germany Send response to journal: Re: No advantage of dipyridamole and aspirin versus aspirin alone	I totally disagree with the recommendations by C Sudlow (1). The cited ESPRIT study (2) had lots of methodical limitations. First, during the study inclusion criteria changed from a three arm to a two arm design (3,4). Second, patients and physicians were not blinded to the treatment regime. The therefore resulting confounder canīt estimated. Third, possible lifestyle changes, co-morbidity and co-treatment were not under examination. During the study medication adherence in the dipyridamole/aspirin group were much less (2,6 fold) than in the aspirin group. The on-treatment analysis only showed a small significant benefit for the item bleeding complications (HR 0.58, 95%-CI 0.35-0.97). The analysis by the intention-to-treatment principle showed small benefits only in combined endpoints, which was driven by the only benefit in the occurrence of non-fatal strokes. The combined therapy showed no advantage in death. The new occurrence of disability was not reported. Furthermore the real benefit by a number needed to treat (NNT) of 104 (5) is small. To sum up there are doubts about effectiveness in general and cost- effectiveness in particular. In Germany the daily costs for dipyridamole/aspirin are Ī 1.40-1.60 compared to Ī 0.035-0.042 for 100 mg aspirin. In my view the published data of ESPRIT donīt alter the recommendations of the Antithrombotic Trialistsī Collaboration (6). 1.Sudlow C. Give dipyridamole with aspirin instead of aspirin alone to prevent vascular events after ischaemic stroke or TIA. BMJ 2007;334:901. 2.The ESPRIT study group. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): a randomised controlled trial. Lancet 2006;367:1665-73. 3.De Schryver ELLM, on behalf of the European/Australian stroke prevention in reversible ischaemia trial (ESPRIT) group. Design of ESPRIT: an international randomized trial for secondary prevention after non- disabling cerebral ischaemia of arterial origin. Cerebrovasc Dis 2000;10:147-50. 4.De Schryver ELLM. ESPRIT: Protocol changes. Cerebrovasc Dis 2001;11:286. 5.Tirschwell D. Aspirin plus dipyridamole was more effective than aspirin alone for preventing vascular events after minor cerebral ischemia. ACP Journal Club November/December 2006;145:57. 6.Antithrombotic Trialistsī Collaboration. Collaborative meta- analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ 2002;324:71-86. Competing interests: None declared
Don't forget the bleeding risk with Dipyridamole 6 May 2007
Brendan A McGrath, SpR Anaesthetics and Intensive Care Medicine Blackpool Victoria Hospital. FY3 8NR. UK Send response to journal: Re: Don't forget the bleeding risk with Dipyridamole	Cathie Sudlow presents her case for the benefits of adding Dipyridamole to Asprin for the prevention of vascular events after ischaemic stroke. Her recommendationas are to combine anti-platelet therapy as long as other 'lifestyle' measures are in place, but do not represent a balance of risks. There is well recognised risk of haemorrhage associated with dual anti-platelet therapy which can be very difficult to control, especially in the peri-operative setting. Many patients in the target age group will have pathology that may be a potential source of haemorrhage, and for anyone requiring surgery, dual anti-platelet therapy can lead to life- threatening bleeding. (Dipyridamole therapy also limits the choice of technique for the anaesthetist which can disadvantage the patient). Whilst in the elective situation, the Dipyridamole can be stopped for 7-10 days in line with current guidelines, for patients with a potential source of bleeding, blanket administration of dual anti-platelet therapy can be catastrophic. The balance of the risks of such bleeding must be considered before embarking on Dipyridamole therapy. References Harder S, Klinkhardt U, Alvarez JM. Avoidance of bleeding during surgery in patients receiving anticoagulant and/or antiplatelet therapy: pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinetics 2004; 43:963–81 Horlocker TT, et al. Regional anesthesia in the anticoagulated patient: Defining the risks (the second ASRA Consensus Conference on Neuraxial Anesthesia and Anticoagulation) Regional Anesthesia and Pain Medicine 2003: 28:172-197 Competing interests: None declared
No change to recommend 21 May 2007
Erika Baum, General Practitioner and Head of the Dep. of General Practice, University of Marburg, Germany 35444 Marburg, Robert-Koch-Str 5, Germany Send response to journal: Re: No change to recommend	Dear colleague, your recommendation fpr change to add dipyridamole to aspirin in patients after stroke or TIA is not based on good evidence. There is broad consensus and good evidence that standard treatment is 75-150 mg aspirin in these subjects. In the ESPRIT trial, you are referring to (ESPRIT Study group:Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial.Lancet. 2006 May 20;367(9523):1665-73.) half of the control group took aspirin in lower doses. So besides other shortcomings of that study, this cannot be the basis to change standard treatment. With my best regards Erika Baum Competing interests: None declared