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Low-osmolar ionic contrast media was better than nonionic media for ischemic complications of angioplasty

ACP J Club. 1996 Nov-Dec;125:62. doi:10.7326/ACPJC-1996-125-3-062

Source Citation

Grines CL, Schreiber TL, Savas V, et al. A randomized trial of low osmolar ionic versus nonionic contrast media in patients with myocardial infarction or unstable angina undergoing percutaneous transluminal coronary angioplasty. J Am Coll Cardiol. 1996 May;27:1381-6. [PubMed ID: 8626947]



To compare low-osmolar ionic and nonionic contrast media in patients having angioplasty for unstable ischemic syndromes.


1-month randomized controlled trial.


Hospital in Michigan, USA.


211 patients (mean age 63 y, 63% men) who had a high likelihood of a hypercoagulable state and had either unstable angina with chest pain and electrocardiographic evidence of ST- or T-wave changes in the past 48 hours, acute myocardial infarction (MI), or angina after an MI that had occurred during the present hospitalization. Exclusion criteria were contraindication to aspirin or heparin, receipt of streptokinase or anistreplase in the past 48 hours, angioplasty within the previous week, or any procedure using radiographic contrast media in the past 24 hours.


Patients were allocated to low-osmolar ionic contrast media (ioxaglate meglumine 39.3% and ioxaglate sodium 19.6% solution) (n = 106) or low-osmolar nonionic contrast media (iohexol 35%) (n = 105).

Main outcome measures

Primary end points were angiographic evidence of intermittent patency, thrombus formation, and distal embolization during angioplasty. Secondary end points were recurrent ischemia and need for repeat revascularization.

Main results

After balloon deflation, fewer patients who received ionic contrast media had decreased flow (reduction of ≥ 1 Thrombolysis in Myocardial Infarction [TIMI] grade compared with baseline) compared with patients who received nonionic contrast media (P = 0.04) (Table). At the completion of angioplasty, the ionic and nonionic groups did not differ for mean percentage diameter stenosis, success of the procedure, formation of thrombi, or distal embolization. After angioplasty, patients who received ionic contrast media had fewer recurrent ischemic events than did patients who received nonionic contrast media (P = 0.02) (Table). The difference in need for repeat revascularization did not reach statistical significance.


Patients who received ionic contrast media had fewer reductions in flow during angioplasty and fewer ischemic complications than did patients who received nonionic contrast media.

Source of funding: In part, Mallinckrodt Medical, Inc.

For article reprint: Dr. C.L. Grines, William Beaumont Hospital, Division of Cardiology, 3601 West Thirteen Mile Road, Royal Oak, MI 48073-6769, USA. FAX 248-551-8806.

Table. Low-osmolar ionic contrast media (CM) vs nonionic CM for ischemic complications of agioplasty*

Outcomes at 1 mo Ionic CM Nonionic CM RRR (95% CI) NNT (CI)
Decreased flow 8.1% 17.8% 53% (33 to 78) 10 (5 to 213)
Recurrent ischemic events 3.0% 11.4% 75% (21 to 92) 12 (6 to 54)

*Abbreviations defined in Glossary; RRR, NNT, and CI caluclated from data in article.


Use of nonionic contrast media has been promoted because of the reduction in the number of mild to moderate side effects associated with high-osmolar ionic contrast media. The reduction in side effects was associated with an additional hospital cost of US $186 when the nonionic contrast agent was used (1). Because of the high cost, it has been recommended that nonionic contrast media be used only in high-risk patients, such as those with low ejection fraction, congestive heart failure, and severe valvular disease (2). Several groups, however, have noted a clustering of thrombotic complications with the nonionic contrast media (2). 2 large randomized trials with > 400 patients each had conflicting results on the incidence of cardiac ischemic complications in low-risk patients when nonionic and ionic contrast media were compared (3, 4).

The study by Grines and colleagues is among the first to evaluate low-osmolar ionic contrast media in patients having angioplasty for unstable angina or acute MI. The hypothesis put forward is that ionic contrast media has an antithrombotic effect. This finding, however, is not consistent among in vivo and in vitro studies (1). In this study, no link was established between the proposed pathophysiology and the clinical outcomes, although several hematologic markers were measured.

Because the results are inconsistent with those of previous studies on contrast media in relation to "hard" clinical end points, such as repeat procedures or MI (3, 4), the data from the trial by Grines and colleagues do not support a change in clinical practice for all patients. While awaiting more definitive evidence, however, practicing cardiologists should seriously consider using low-osmolar ionic contrast media in patients with ongoing thrombosis or in those who have had acute MI.

Magnus Ohman, MD
Duke University Medical CenterDurham, North Carolina, USA


1. Hill JA, Grabowski EF. Relationship of anticoagulation and radiographic contrast agents to thrombosis during coronary angiography and angioplasty: are there real concerns? Cathet Cardiovasc Diagn. 1992;25:200-8.

2. Harding MB, Davidson CJ, Pieper KS, et al. Comparison of cardiovascular and renal toxicity after cardiac catheterization using a nonionic versus ionic radiographic contrast agent. Am J Cardiol. 1991;68:1117-9.

3. Lembo NJ, King SB 3d, Roubin GS, Black AJ, Douglas JS Jr. Effects of nonionic versus ionic contrast media on complications of percutaneous transluminal coronary angioplasty. Am J Cardiol. 1991;67:1046-50.

4. Hlatky MA, Morris KG, Pieper KS, et al. Randomized comparison of the cost and effectiveness of iopamidol and diatrizoate as contrast agents for cardiac angiography. J Am Coll Cardiol. 1990;16:871-7.