Safety and cost effectiveness of high-osmolality as compared with low-osmolality contrast material in patients undergoing cardiac angiography

N Engl J Med. 1992 Feb 13;326(7):425-30. doi: 10.1056/NEJM199202133260701.


Background and methods: Low-osmolality contrast agents produce fewer hemodynamic and electrophysiologic alterations during cardiac angiography, but they are 20 times more expensive than high-osmolality contrast agents. In a randomized, double-blind trial comparing a nonionic low-osmolality contrast agent (Omnipaque 350) with a high-osmolality agent that does not avidly bind calcium (Hypaque 76) in 505 patients undergoing cardiac angiography, we determined the incidence of minor, mild, moderate, and severe adverse reactions, identified risk factors for such reactions, and evaluated the cost effectiveness of various strategies for the use of contrast material.

Results: The 253 patients who received a high-osmolality contrast agent were three times more likely to have a moderate adverse reaction (95 percent confidence interval for the relative risk, 1.6 to 5.5) but no more likely to have a severe reaction (95 percent confidence interval, 0.2 to 2.3) than the 252 patients who received a low-osmolality agent. All 10 severe reactions occurred in patients who were older than 60 years or had unstable angina. Patients with these characteristics were also 3.5 times more likely (95 percent confidence interval, 1.8 to 6.8) to have a moderate reaction (44 of 310 patients, or 14 percent) than those without either characteristic (8 of 195 patients, or 4 percent). We estimated that the incremental cost of each moderate reaction avoided would be $1,698 with a strategy that involved giving a low-osmolality contrast agent only to patients who were over 60 years of age or had unstable angina, instead of giving a high-osmolality agent to all patients. The incremental cost per moderate reaction avoided by giving a low-osmolality contrast agent to all patients rather than only to those over 60 or with unstable angina would be $5,842.

Conclusions: The use of contrast agents with low rather than high osmolality during cardiac angiography reduces the risk of moderate, but not of severe, adverse reactions to the agent used. A strategy of reserving low-osmolality contrast agents for use in patients at high risk for adverse reactions would be more cost effective than one requiring their use in all patients.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Angina, Unstable
  • Contrast Media / adverse effects
  • Contrast Media / economics*
  • Coronary Angiography*
  • Cost-Benefit Analysis
  • Diatrizoate / adverse effects
  • Diatrizoate / economics
  • Double-Blind Method
  • Female
  • Humans
  • Iohexol / adverse effects
  • Iohexol / economics
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Process Assessment, Health Care*
  • Risk Factors


  • Contrast Media
  • Diatrizoate
  • Iohexol