Uncertainties About Thrombolysis for Stroke Should Be Addressed With Large-Scale Randomized Trials
To the Editor:
We agree with Professor Weintraub that there are uncertainties about the treatment of patients with recombinant tissue plasminogen activator (rtPA) for acute ischemic stroke. Many physicians are uncertain whether the benefits of treatment outweigh the potentials harms1 and so do not provide treatment in their areas. Hence, the provision of thrombolysis is patchy in some countries—in the UK only 33 centers provide rtPA to acute stroke patients on a regular basis.2 Countries with similar populations and healthcare systems may have remarkable differences in the use of thrombolysis; for example, Finland has entered 7 times as many patients as Denmark into the SITS register of stroke thrombolysis, despite their similarly sized populations.2
We believe the uncertainties about thrombolysis for acute stroke patients—and the consequent variations in clinical usage—can only be reduced by obtaining more reliable evidence on the balance of risk and benefit from large-scale randomized trials. The main areas of scientific uncertainty are being addressed in the Third International Stoke Trial (IST-3): does rtPA increase mortality?; is the net benefit in people aged over 80 worthwhile?; do patients with milder stroke or severe strokes gain useful benefit?; and is treatment of benefit between 3 and 6 hours? We urge those who share Dr Weintraub’s uncertainties about rtPA to recruit patients into one of the current thrombolysis trials such as IST-3. This will give patients, doctors and even the law courts more certainty when dealing with these difficult decisions in future.
IST-3 is an independent, investigator-led trial. It is supported by grants from: the UK Medical Research Council, the Health Foundation, the Stroke Association of the United Kingdom; Chest, Heart, and Stroke Scotland; University of Edinburgh; Norwegian Research Council; AFA Insurances (Sweden); The Swedish Heart Lung Fund, The Australian Heart Foundation, DesAcc; and the Dalhousie University Internal Medicine Research Fund (Canadian centre support). In the initial double-blind phase, drug and placebo for the first 300 patients were supplied by Boehringer Ingelheim.