Do Contrast Agents Impede Clot-Busting Drugs in Ischemic Stroke Patients?

April 20, 2012

By James E. Barone MD

NEW YORK (Reuters Health) Apr 18 - Radiologic contrast agents are known to blunt the effects of thrombolytic drugs, but doctors at the Calgary Stroke Program saw few clinical problems when they used dyes together with recombinant tissue plasminogen activators (rtPA) in patients with ischemic strokes.

In a retrospective study reported online in Stroke, they compared 111 patients who had computed tomographic angiography (CTA) with contrast before undergoing thrombolysis and 1,119 historical controls who did not undergo CTA.

The groups were similar at baseline except that the CTA group had significantly more extensive ischemia on non-contrast CT scans (p=0.049) and more control patients had received anti-platelet drugs before thrombolysis (p=0.001). Similar proportions of the two groups had favorable functional outcomes: 47.7% with CTA and 49.5% in controls.

Multivariate analysis revealed that CTA slightly reduced the odds of a favorable outcome (OR 0.62, p=0.049). Propensity score matching showed that CTA was associated with less favorable outcomes with a 10% treatment effect size. There was no significant difference in the number of parenchymal hematomas on follow-up CT scanning.

The paper concludes that the negative effects of x-ray contrast are clinically insignificant but cautions that prospective studies are needed to confirm this.

The fraction of stroke patients who have CTA prior to thrombolytic therapy worldwide is unknown. Lead author Dr. Imanuel Dzialowski, now at Dresden University Stroke Center in Germany, told Reuters Health by email that he is unaware of any published data on the topic. "However," he said, "from experience I can say that in our institution as well as in many academic stroke centers in Europe and North America almost every rtPA eligible patient receives contrast in order to demonstrate an intracranial arterial occlusion before thrombolysis is initiated."

With the use of CTA so common, Dr. Dzialowski thinks a prospective randomized study could be ethically accomplished. He said: "There is no evidence that performing CT angiography or a CT perfusion study before thrombolysis improves patient outcome. It improves our understanding of the individual vessel pathology and enhances individual therapeutic strategies such as endovascular treatment which again is not yet evidence based."

Dr. Keith Muir, SINAPSE Professor of Clinical Imaging & Consultant Neurologist at the Institute of Neurosciences & Psychology, University of Glasgow, told Reuters Health by email, "The appropriate randomized study needs to assess the balance of risks and benefits, and the bigger picture is what the additional information from the contrast studies might do for patients. All of the current evidence for the use of rtPA is based on a single non-contrast CT scan before treatment, so this is still the only standard of care that we can support."

Dr. Muir, who was not involved in Dr. Dzialowski's study, will begin a trial next year that randomizes patients to assessment by CT alone, or CT plus CTA and CT perfusion.

"On the positive side," Dr. Muir said, "better information on vasculature and brain perfusion might lead to more use of rtPA in suitable patients (probably mostly those with clinically mild symptoms but a large area of brain at risk, who often deteriorate) and less use in people in whom it may be dangerous (for example those with very severe hypoperfusion who might be at increased risk of bleeding). On the negative side, the CTA and CT perfusion examinations take longer to acquire and analyze, involve additional radiation and contrast exposure, and in theory, the contrast may reduce the effectiveness of rtPA. So it's the balance of these that is important, rather than simply the issue of contrast effect on rtPA action."

As for whether the current study reassures doctors that CTA before thrombolysis is safe, Dr. Dzialowski said, "As we pointed out, the retrospective study design carries multiple limitations so we have to be cautious in drawing strong conclusions. On the other hand, our simulation of a randomized trial suggested a possible effect size of up to 10% difference in outcome. If this magnitude of a negative effect would be confirmed, it indeed would pose a significant problem since the positive TPA effect is only around 10% as well."

Dr. Muir agreed. "The study used existing data to address the question, and that is always suboptimal since you probably wouldn't have designed a study that set out to look at this specific issue in quite the same way," he said. "It does offer some reassurance that at least any effect is unlikely to be very large."


Stroke 2012.


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