Sodium thiosulfate does not reduce infarct size vs. placebo after reperfusion for STEMI
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WASHINGTON — Sodium thiosulfate, administered before and after reperfusion for STEMI, did not improve infarct size between 4 months and 2 years compared with placebo, a speaker reported.
The GIPS-IV trial is the first to assess the use of sodium thiosulfate, or any hydrogen sulfide-donating compounds, for the treatment of STEMI in humans, according to a presentation at the American College of Cardiology Scientific Session.
Sodium thiosulfate, an antioxidant that produces hydrogen sulfide, is currently used to treat cyanide poisoning, calciphylaxis and adverse events of cisplatin, a chemotherapy drug. The compound may also have some anti-inflammatory, antioxidant, antiapoptotic, proangiogenic and antifibrotic effects and could improve vasodilation, endothelial function and preserve mitochondrial function, according to the study background.
Therefore, researchers evaluated whether administration of sodium thiosulfate before and after reperfusion for STEMI would improve risk for ischemia/reperfusion injury after 4 months and up to 2 years.
“The rationale of our study was based on a wealth of preclinical evidence that demonstrates that the administration of hydrogen sulfide or a hydrogen sulfide-donating compound prevents damage after a heart attack, in both small and larger animal models,” Marie-Sophie de Koning, MD, physician scientist and PhD candidate at University Medical Center Groningen in the Netherlands, said during a press conference.
Researchers enrolled adults presenting with ongoing STEMI with symptom onset within 12 hours before arrival in the catheterization laboratory. A total of 186 patients were randomly assigned to sodium thiosulfate and 187 were assigned to placebo (mean age, 62 years; 23% women; 97% white). Follow-up was completed in 116 participants in the sodium thiosulfate group and 110 in the placebo group. The primary outcome was infarct size measured using cardiac MRI after 4 months up to 2 years. Secondary outcomes included peak creatine kinase-MB during index hospitalization and left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide and safety endpoints, including major adverse CV events, by 4 months.
De Koning reported the researchers observed no significant difference in infarct size among patients with STEMI who received sodium thiosulfate at the time of revascularization compared with placebo up to 2 years later (sodium thiosulfate, 8%; placebo, 8.9%; P = .55).
Researchers also found no difference in peak CK-MB (P = .64), LVEF (P = .26) or NT-proBNP (P = .8) among patients who received sodium thiosulfate compared with placebo.
Incidence of major adverse CV events was also not different between treatment arms (P = .22); however, researchers noted an increase in new-onset nausea and vomiting among patients treated with sodium thiosulfate compared with placebo (P for both < .001).
“We did observe that sodium thiosulfate can be safely administered in patients presenting with a heart attack, but it did not reduce damage after the heart attack, despite promising preclinical evidence,” de Koenig said during the press conference. “Future studies should establish the role of hydrogen sulfide in protecting the heart against damage, since our results do not exclude hydrogen sulfide as a whole as a potential cardioprotective therapy. Our results combined with the results of other trials demonstrated that improving outcomes in countries with fast and effective treatment for heart attack remains challenging.”
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This was an interesting study of a somewhat novel agent, sodium thiosulfate. There have been reports that this may be a cardioprotective agent for patients who are having acute MI. There is some theoretical information that it has anti-inflammatory, antioxidant and other potentially helpful effects.
Sodium thiosulfate did not show any reduction in adverse events or infarct size as measured by cardiac MRI. It is interesting because this has been considered to be a possible agent to try and reduce infarct size in patients with heart attacks. Sodium thiosulfate was safe, but it did not reduce infarct size.
The researchers did say that these results do not exclude using it as a potential cardioprotective therapy, I guess because it is safe, but, unfortunately, it was not shown to have benefit to reduce heart attack size.
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de Koning MS, et al. Late-Breaking Clinical Trials V. Presented at: American College of Cardiology Scientific Session; April 2-4, 2022; Washington, D.C. (hybrid meeting).
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