2021Acute coronary syndromesArrhythmias & devices1900 patients

TTM2

Therapy group: Post-cardiac arrest care · Therapy: Hypothermia vs normothermia

Targeted hypothermia at 33°C after out-of-hospital cardiac arrest did not lower six-month mortality compared with normothermia with early fever treatment.

Published in N Engl J Med (2021)

Question: Does targeted hypothermia at 33°C improve survival in comatose patients after out-of-hospital cardiac arrest compared with normothermia with early treatment of fever?
Design: Open-label randomized trial with blinded outcome assessment, enrolling 1900 adults; 1850 were evaluated for the primary outcome.
Population: Adults in coma after an out-of-hospital cardiac arrest of presumed cardiac or unknown cause.
Intervention: Targeted hypothermia at 33°C followed by controlled rewarming (up to 28 hours per the registry).
Control: Targeted normothermia with early treatment of fever (body temperature ≥37.8°C) using active temperature control.
Primary outcome: Death from any cause at 6 months.
Results: At 6 months, 465 of 925 patients (50%) in the hypothermia group had died versus 446 of 925 (48%) in the normothermia group (relative risk 1.04; 95% CI 0.94 to 1.14; P = 0.37). Moderately severe disability or worse (modified Rankin scale ≥4) occurred in 55% in both groups (relative risk 1.00; 95% CI 0.92 to 1.09).
Safety: Arrhythmia with hemodynamic compromise was more common with hypothermia (24% vs. 17%, P<0.001); other adverse events did not differ significantly.
Conclusion: In comatose patients after out-of-hospital cardiac arrest, targeted hypothermia did not reduce 6-month mortality compared with targeted normothermia.
Why it matters: It challenged the benefit of routine cooling to 33°C and supported an approach of actively controlling temperature to avoid fever after cardiac arrest.

Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.

Generated on October 14, 2026

Sources

Original publication on PubMed (PMID 34133859) ↗Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest.
Journal article (DOI) ↗
ClinicalTrials.gov record (NCT02908308) ↗

Educational content only. CanduCardio is intended for healthcare professionals and CanduTV for the general public. It does not replace clinical judgment or professional consultation.