Does the Application of X-Ray Contrast Agents Impair the Clinical Effect of Intravenous Recombinant Tissue-Type Plasminogen Activator in Acute Ischemic Stroke Patients?

Abstract

Background and Purpose-Experimental data suggest a negative interaction between x-ray contrast agents and fibrinolytic efficacy of recombinant tissue-type plasminogen activator (rtPA). We hypothesized that the application of a contrast agent before intravenous thrombolysis with rtPA reduces its clinical efficacy in acute ischemic stroke. Methods-We retrospectively studied consecutive ischemic stroke patients receiving contrast agents for computed tomography angiography before intravenous treatment with rtPA. We compared functional outcomes with an historical control group from the Canadian Alteplase for Stroke Effectiveness Study who did not receive contrast agents before thrombolysis with rtPA. Primary end point was favorable functional outcome at 90 days defined as modified Rankin Scale scores 0 to 2. We performed logistic regression analysis and a propensity score matching analysis to estimate the effect size of contrast agent use as a negative predictor of outcome. Results-We identified 111 patients for the computed tomography angiography and 1119 patients for the control group.Proportions of favorable functional outcome were 47.7% (53/111 patients) for the computed tomography angiography group and 49.5% (542/1094 patients) for the control group (Pϭ0.77). Adjusted probabilities for favorable outcome were 0.48 (95% CI, 0.37-0.58) and 0.51 (95% CI, 0.47-0.54), respectively. Contrast use was associated with reduced odds of favorable outcome (OR, 0.62 ; 95% CI, 0.38 -0.99). Propensity score matching suggested a larger effect size (OR, 10.0%; 95% CI, 0.5%-19.3%). Conclusions-Our study did not show a significant negative clinical effect of x-ray contrast agents applied before intravenous thrombolysis with rtPA. However, to confirm a possible small negative interaction between contrast agents and rtPA, additional experimental and prospective clinical studies are needed. (Stroke. 2012;43:1567-1571.)

Recanalization and Clinical Outcome of Occlusion Sites at Baseline CT Angiography in the Interventional Management of Stroke III Trial

“…Another important finding of this analysis was the safety (4) of baseline vascular imaging in reperfusion treatment trials of IV tPA versus combined therapy. No differences in clinical outcome were seen in the trial subgroup that received IV tPA alone and underwent CT angiography versus those that did not, suggesting no evidence for impaired thrombolytic effect of radiographic contrast material on tPA activity as postulated in the cardiac literature (5,6).…”

Outcome Differences between Intra-Arterial Iso- and Low-Osmolality Iodinated Radiographic Contrast Media in the Interventional Management of Stroke III Trial

“…No comparative data in IV or IA IRCM use in human stroke are available to refute that hypothesis. 3 Mechanisms contributing to potential differences in IRCM efficacy and safety have been extensively analyzed under a variety of experimental conditions in vitro and in animal models, including coagulation, direct cytotoxic, neurotoxic, osmotic, hydrostatic, and direct vasomotor effects. Prior antiplatelet use of aspirin conferred neither clinical nor reperfusion benefit nor hemorrhagic risk in conjunction with IV rtPA in the National Institute of Neurological Disorders and Stroke trial, and none has previously been demonstrated in EVT.…”

“…34 While a meta-analysis investigating the fibrinolysis effect of IRCM of any type or route of administration (IV or IA) has suggested no difference in recanalization rates, 35 the wide range of fibrinolytic practices makes the study only marginally relevant to the potential effects of individual IRCM types with EVT of M1 occlusion in IMS III. Dzialowski et al 3 reported reduced odds of favorable outcome in patients receiving IV contrast for CT angiography before IV thrombolysis.…”

“…1 Iso-osmolal iodixanol (290 mOsm/kg H 2 O) infusion led to smaller infarcts and less ICH compared with both low-osmolal iopamidol and saline in a similar model. 2 Dzialowski et al 3 reported reduced odds of favorable outcome in patients receiving intravenous IRCM for CT angiography before IV thrombolysis.…”

Iodinated Contrast Prior to Thrombolysis Was Not Associated With Worse Intracranial Hemorrhage

“…However, concern exists regarding the adverse effects of the iodinated contrast agents used, particularly bleeding complications in the setting of intravenous (IV) thrombolysis with recombinant tissue-type plasminogen activator (rt-PA). [2][3][4] One hypothesized etiology relates to a direct toxic effect on the integrity of the blood-brain barrier. [5][6][7][8] Review of the Interventional Management of Stroke II (IMS-2) study suggested IV iodinated contrast agents increased intracranial hemorrhage (ICH).…”