Safety of dipyridamole testing in 73,806 patients

The Multicenter Dipyridamole Safety Study

Jean Lette, James L. Tatum, Sheila Fraser, Donald D Miller, David D. Waters, Gary Heller, Eric B. Stanton, Hee Seung Bom, Jeffrey Leppo, Stanley Nattel

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

Background: Dipyridamole imaging is widely used as an alternative to exercise testing to identify and risk stratify patients with coronary artery disease. Safety data on intravenous dipyridamole stress testing has been derived largely from individual institutional data. Methods and Results: Data were collected retrospectively by 85 coinvestigators from 73,806 patients who underwent intravenous dipyridamole stress imaging in 59 hospitals and 19 countries to determine the incidence of major adverse reactions during testing. The dose of dipyridamole infused was 0.56 mg/kg in 64,740 patients, 0.74 mg/kg in 6551 patients, and 0.84 mg/kg in 2515 patients. Combined major adverse events among the entire 73,806 patients included seven cardiac deaths (0.95 per 10,000), 13 nonfatal myocardial infarctions (1.76 per 10,000), six nonfatal sustained ventricular arrhythmias (0.81 per 10,000) ((ventricular tachycardia in two and ventricular fibrillation in four), nine transient cerebral ischemic attacks (1.22 per 10,000), (with speech or motor deficit), one stroke, and nine severe bronchospasms (1.22 per 10,000) (one intubation and eight near intubations). In addition to the safety data, detailed demographic, peripheral hemodynamic, side effect, and concomitant drug data were examined in a subgroup of 3751 patients. End points from subsets of patients were compared with those of the group as a whole. Multivariate analysis revealed that dipyridamole-induced chest pain was more common in patients less than 70 years old (p = 0.0017), those with a history of coronary revascularization (p = 0.002), or patients taking aspirin (p = 0.0001). Minor noncardiac side effects were less frequent among the elderly (p = 0.0053) and more frequent in women (p = 0.0001) and patients taking maintenance aspirin (p = 0.0034). When a patient was judged on the basis of the adequacy of hemodynamic response to be a dipyridamole "nonresponder" (< 10 mm Hg drop in systolic blood pressure and 10 beats/min increase in heart rate), the only significant predictor was angiotensin-converting enzyme inhibitor intake (p = 0.0025). Inferoposterior hypoperfusion was significantly more frequent in patients with dipyridamole-induced hypotension: 57% (44/77) (p < 0.0001) of those who had hypotension and 89% (8/9) (p = 0.0076) who had severe symptomatic bradyarrhythmias displayed inferoposterior defects on thallium scanning. Caffeine levels were determined in 391 consecutive patients: levels greater than 5 mg/L were observed in only eight patients (2%), suggesting that methylxanthine levels sufficients to alter the hemodynamic response to dipyridamole resulting in suboptimal hyperemic stress are unlikely when patients take nothing by mouth after midnight. Conclusion: The risk of serious dipyridamole-induced side effects is very low and is comparable to that reported for exercise testing in a similar patient population.

Original languageEnglish (US)
Pages (from-to)3-17
Number of pages15
JournalJournal of Nuclear Cardiology
Volume2
Issue number1
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

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Dipyridamole
Safety
Hemodynamics
Intubation
Aspirin
Controlled Hypotension
Exercise
Blood Pressure
Bronchial Spasm
Thallium
Transient Ischemic Attack
Ventricular Fibrillation
Bradycardia
Ventricular Tachycardia
Caffeine
Drug-Related Side Effects and Adverse Reactions
Chest Pain

Keywords

  • asthma
  • coronary heart disease
  • coronary hyperemia/vasodilation
  • dipyridamole
  • radionuclide imaging
  • stress testing

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

Safety of dipyridamole testing in 73,806 patients : The Multicenter Dipyridamole Safety Study. / Lette, Jean; Tatum, James L.; Fraser, Sheila; Miller, Donald D; Waters, David D.; Heller, Gary; Stanton, Eric B.; Bom, Hee Seung; Leppo, Jeffrey; Nattel, Stanley.

In: Journal of Nuclear Cardiology, Vol. 2, No. 1, 01.01.1995, p. 3-17.

Research output: Contribution to journalArticle

Lette, J, Tatum, JL, Fraser, S, Miller, DD, Waters, DD, Heller, G, Stanton, EB, Bom, HS, Leppo, J & Nattel, S 1995, 'Safety of dipyridamole testing in 73,806 patients: The Multicenter Dipyridamole Safety Study', Journal of Nuclear Cardiology, vol. 2, no. 1, pp. 3-17. https://doi.org/10.1016/S1071-3581(05)80003-0
Lette, Jean ; Tatum, James L. ; Fraser, Sheila ; Miller, Donald D ; Waters, David D. ; Heller, Gary ; Stanton, Eric B. ; Bom, Hee Seung ; Leppo, Jeffrey ; Nattel, Stanley. / Safety of dipyridamole testing in 73,806 patients : The Multicenter Dipyridamole Safety Study. In: Journal of Nuclear Cardiology. 1995 ; Vol. 2, No. 1. pp. 3-17.
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T1 - Safety of dipyridamole testing in 73,806 patients

T2 - The Multicenter Dipyridamole Safety Study

AU - Lette, Jean

AU - Tatum, James L.

AU - Fraser, Sheila

AU - Miller, Donald D

AU - Waters, David D.

AU - Heller, Gary

AU - Stanton, Eric B.

AU - Bom, Hee Seung

AU - Leppo, Jeffrey

AU - Nattel, Stanley

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N2 - Background: Dipyridamole imaging is widely used as an alternative to exercise testing to identify and risk stratify patients with coronary artery disease. Safety data on intravenous dipyridamole stress testing has been derived largely from individual institutional data. Methods and Results: Data were collected retrospectively by 85 coinvestigators from 73,806 patients who underwent intravenous dipyridamole stress imaging in 59 hospitals and 19 countries to determine the incidence of major adverse reactions during testing. The dose of dipyridamole infused was 0.56 mg/kg in 64,740 patients, 0.74 mg/kg in 6551 patients, and 0.84 mg/kg in 2515 patients. Combined major adverse events among the entire 73,806 patients included seven cardiac deaths (0.95 per 10,000), 13 nonfatal myocardial infarctions (1.76 per 10,000), six nonfatal sustained ventricular arrhythmias (0.81 per 10,000) ((ventricular tachycardia in two and ventricular fibrillation in four), nine transient cerebral ischemic attacks (1.22 per 10,000), (with speech or motor deficit), one stroke, and nine severe bronchospasms (1.22 per 10,000) (one intubation and eight near intubations). In addition to the safety data, detailed demographic, peripheral hemodynamic, side effect, and concomitant drug data were examined in a subgroup of 3751 patients. End points from subsets of patients were compared with those of the group as a whole. Multivariate analysis revealed that dipyridamole-induced chest pain was more common in patients less than 70 years old (p = 0.0017), those with a history of coronary revascularization (p = 0.002), or patients taking aspirin (p = 0.0001). Minor noncardiac side effects were less frequent among the elderly (p = 0.0053) and more frequent in women (p = 0.0001) and patients taking maintenance aspirin (p = 0.0034). When a patient was judged on the basis of the adequacy of hemodynamic response to be a dipyridamole "nonresponder" (< 10 mm Hg drop in systolic blood pressure and 10 beats/min increase in heart rate), the only significant predictor was angiotensin-converting enzyme inhibitor intake (p = 0.0025). Inferoposterior hypoperfusion was significantly more frequent in patients with dipyridamole-induced hypotension: 57% (44/77) (p < 0.0001) of those who had hypotension and 89% (8/9) (p = 0.0076) who had severe symptomatic bradyarrhythmias displayed inferoposterior defects on thallium scanning. Caffeine levels were determined in 391 consecutive patients: levels greater than 5 mg/L were observed in only eight patients (2%), suggesting that methylxanthine levels sufficients to alter the hemodynamic response to dipyridamole resulting in suboptimal hyperemic stress are unlikely when patients take nothing by mouth after midnight. Conclusion: The risk of serious dipyridamole-induced side effects is very low and is comparable to that reported for exercise testing in a similar patient population.

AB - Background: Dipyridamole imaging is widely used as an alternative to exercise testing to identify and risk stratify patients with coronary artery disease. Safety data on intravenous dipyridamole stress testing has been derived largely from individual institutional data. Methods and Results: Data were collected retrospectively by 85 coinvestigators from 73,806 patients who underwent intravenous dipyridamole stress imaging in 59 hospitals and 19 countries to determine the incidence of major adverse reactions during testing. The dose of dipyridamole infused was 0.56 mg/kg in 64,740 patients, 0.74 mg/kg in 6551 patients, and 0.84 mg/kg in 2515 patients. Combined major adverse events among the entire 73,806 patients included seven cardiac deaths (0.95 per 10,000), 13 nonfatal myocardial infarctions (1.76 per 10,000), six nonfatal sustained ventricular arrhythmias (0.81 per 10,000) ((ventricular tachycardia in two and ventricular fibrillation in four), nine transient cerebral ischemic attacks (1.22 per 10,000), (with speech or motor deficit), one stroke, and nine severe bronchospasms (1.22 per 10,000) (one intubation and eight near intubations). In addition to the safety data, detailed demographic, peripheral hemodynamic, side effect, and concomitant drug data were examined in a subgroup of 3751 patients. End points from subsets of patients were compared with those of the group as a whole. Multivariate analysis revealed that dipyridamole-induced chest pain was more common in patients less than 70 years old (p = 0.0017), those with a history of coronary revascularization (p = 0.002), or patients taking aspirin (p = 0.0001). Minor noncardiac side effects were less frequent among the elderly (p = 0.0053) and more frequent in women (p = 0.0001) and patients taking maintenance aspirin (p = 0.0034). When a patient was judged on the basis of the adequacy of hemodynamic response to be a dipyridamole "nonresponder" (< 10 mm Hg drop in systolic blood pressure and 10 beats/min increase in heart rate), the only significant predictor was angiotensin-converting enzyme inhibitor intake (p = 0.0025). Inferoposterior hypoperfusion was significantly more frequent in patients with dipyridamole-induced hypotension: 57% (44/77) (p < 0.0001) of those who had hypotension and 89% (8/9) (p = 0.0076) who had severe symptomatic bradyarrhythmias displayed inferoposterior defects on thallium scanning. Caffeine levels were determined in 391 consecutive patients: levels greater than 5 mg/L were observed in only eight patients (2%), suggesting that methylxanthine levels sufficients to alter the hemodynamic response to dipyridamole resulting in suboptimal hyperemic stress are unlikely when patients take nothing by mouth after midnight. Conclusion: The risk of serious dipyridamole-induced side effects is very low and is comparable to that reported for exercise testing in a similar patient population.

KW - asthma

KW - coronary heart disease

KW - coronary hyperemia/vasodilation

KW - dipyridamole

KW - radionuclide imaging

KW - stress testing

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