NOMI: Nitric Oxide May Do Wonders for STEMI But Not When Mixed with Nitroglycerin

BARCELONA, Spain—Inhalation of nitric oxide (NO) before and during percutaneous coronary intervention (PCI) does not reduce infarct size across the board vs placebo in patients with ST-segment elevation myocardial infarction (STEMI), reported researchers September 1, 2014, at the European Society of Cardiology Congress.

But results for the novel treatment were strengthened by removing patients who received nitroglycerin from the equation, said researcher Stefan P. Janssens, MD, PhD, of the University of Leuven (Leuven, Belgium). 

Methods
The NOMI trial enrolled 248 STEMI patients slated for PCI who presented within 2 to 12 hours. Patients were randomly assigned to receive either placebo (n = 122) or inhaled NO at 80 ppm (n = 126) prior to PCI and for up to 4 hours after the start of reperfusion. Baseline characteristics were well matched between groups, with a 46.5% rate of nitroglycerin use. There were no treatment-related complications during study drug administration.


At 48 to 72 hours, MRI showed no difference in infarct size (expressed as fraction of LV mass) between patients who received NO and those who did not. A prespecified subanalysis, however, showed an interaction with nitroglycerin (P = .0139), such that NO benefited nitroglycerin-naive patients only; in fact, there was a trend toward harm in patients receiving both agents (table 1). 

Table 1. Ratio of Infarct Size to LV mass

 

Control

NO

P Value

Overall

19.4%

18.0%

.44

With Nitroglycerine

15.1%

19.3%

.059

Without Nitroglycerin

22.4%

17.0%

.044

 

Overall, there were also signs of better recovery of LV function with NO at 48 to 72 hours. These differences reached significance by 4-month follow-up (table 2).

Table 2. LV Remodeling

 

Control

NO

P Value

At 48-72 Hours

    LV-ESVI, mL/m2

    LV-EDVI, mL/m2

 

44

82

 

41

79

 

.10

.21

At 4 Months

    LV-ESVI, mL/m2

    LV-EDVI, mL/m2

 

46

90

 

41

84

 

.048

.063

Abbreviations: LV-ESVI, left ventricular end-systolic volume index; LV-EDVI, left ventricular end-diastolic volume index.

On Kaplan-Meier analysis, the 4-month combined risk of death, recurrent MI, stroke, and hospitalization was 13.0% in the NO group and 20.4% in the control group (log-rank P = .1022). There were 5 deaths (4.1%) with NO and 8 deaths (6.3%) with control.

The potential benefit to nitroglycerin-naive patients, “together with a robust safety profile and promising clinical trends, needs independent corroboration in future studies,” Dr. Janssens concluded. 

‘Flavor of Effect,’ But Not Enough

Michael Marber, BSc, MBBC, PhD, of King’s College London (London, England), characterized the results of this effort to translate basic science into clinical application as “intriguing.” 

Importantly, “though there is a flavor of effect,” the trial was negative for the primary endpoint, Dr. Marber noted, adding that the interplay between nitroglycerin and NO complicates matters. “The problem is that there is a sweet spot,” he suggested. “A certain concentration of nitric oxide leads to these beneficial effects. Perhaps a high concentration leads to adverse free radical production and worsens cardiac injury.”

However, it is impossible to tease out this relationship, given that nitroglycerin administration was not randomized, he said. Also uncertain is how much reperfusion injury affects long-term clinical outcome. 

While worthy of further investigation, Dr. Marber said, trial design may prove difficult: “Would you mandate patients not get [nitroglycerin] or would you just do the study as a real-world study, on the background of organic nitrates?”

 


Source:
Janssens S. Nitric oxide for inhalation to reduce reperfusion injury in STEMI - NOMI. Presented at: European Society of Cardiology Congress; September 1, 2014; Barcelona, Spain.

 

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Disclosures
  • Dr. Janssens reports having a research contract to conduct a preclinical study in pigs.

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