A synthetic drug called ularitide shows no promise for alleviating the destructive effects of acute cardiac arrest. The TRUE-AHF study evaluated its safety and efficacy via a randomized clinical trial conducted at more than 150 clinical centres.


It is reported that 5.7 million people suffer from cardiac arrests in the U.S., with the disease increasingly becoming a global public health issue. Some concrete facts about cardiac ailments are as follows –

  1. Underlying conditions such as diabetes, high blood pressure, and coronary heart disease substantially increase the risk of heart failure.
  2. Unhealthy lifestyle choices namely, smoking tobacco, sedentary lifestyle, obesity, and consuming cholesterol-rich foods increases the risk of heart failures.
  3. Shortness of breath, weight gain, swelling in legs and ankle, fatigue, are some signs and symptoms that can lead to a heart condition and eventually heart failure.

During an event leading to a cardiac arrest, a part of the heart is deprived of oxygen due to a blocked artery, and if not corrected quickly, that section of heart muscle sustains irreparable damage. During a cardiac event, if the heart skips a beat or it’s rhythm is disrupted, the vital blood-pumping organ can stop beating. This sudden stoppage is called an acute heart failure. The brain and body are deprived of oxygen, which without immediate medical intervention, can lead to death within minutes.

One such therapeutic intervention is the use of vasodilators. These agents increase the diameter of the arteries to encourage blood circulation without burdening the weakened heart. The body’s natural response is to release molecules such as cardiac troponin and the N-terminal pro-brain natriuretic peptide (NT-proBNP) to help reduce cardiac-wall stress. Researchers hypothesize that a vasodilator-treatment in the critical moments of heart failure could lead to positive outcomes.

A study called the Trial of Ularitide Efficacy and Safety in Acute Heart Failure (TRUE-AHF) tested the preceding hypothesis and was published in The New England Journal of Medicine. Having shown benefits in previous trials, the artificially synthetized ularitide – an analogue of the naturally occurring vasodilator urodilatin – was tested for its efficacy and safety in 2,157 randomly assigned patients with acute heart failure. Patients were randomly assigned to a treatment group (n=1072) that received 15 ng/kg/min of intravenous ularitide or a placebo group (n=1056). Medication was administered intravenously for 48 hours. The patients were monitored for the first 120 hours for worsening heart failure and physiological parameters such as blood pressure.

Death from cardiovascular causes occurred in 236 patient in the ularitide group and 225 in the placebo group, indicating no substantial benefit. However, the drug produced some favourable short-term effects such as a significant decrease in the systolic blood pressure compared to that of the placebo group. This is indicative of a reduction in cardiac-wall stress, thus having a meaningful cardiac decongestion. This study certainly raises doubts revolving around the theories of early intervention vasodilator-treatments for cardiac failures. Even though ularitide showed a favourable short-term physiological effect, it had no benefit on the primary outcome of mortality.


Written By: Akshita Wason, B. Tech, PhD

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