‘Total Ischemic Time’ Key to Cutting NSTEMI Deaths With Invasive Strategy

Among patients presenting to the hospital with NSTEMI, an early invasive strategy based on symptom-to-catheter time is associated with a lower risk of all-cause mortality at 3 years, according to new prospective registry data.

While rapid intervention has proven to be beneficial in STEMI patients, who often clearly know when their symptoms began, opinions have been mixed on whether NSTEMI patients should be rushed to treatment, especially within the logistical constraints associated with cath lab operations during off hours.

“The point is that total ischemic time is the most important concept to reduce mortality in [all] acute myocardial infarction,” senior study authors Myung Ho Jeong, MD, PhD (Chonnam National University Hospital and Medical School, Gwangju, Republic of Korea), and Tae Hoon Ahn, MD (Chung-Ang University Gwangmyeong Hospital, Gyeonggi-do, Republic of Korea), told TCTMD in an email. “Therefore, the effort to reduce total ischemic time, such as [with an] early invasive strategy using EMS [emergency medical services], is essential to achieve reducing mortality for patients with NSTEMI as well as STEMI.”

Because of their observational nature, the findings—which show an almost halving of all-cause mortality for patients treated within, compared with after, 48 hours of symptom onset—may not be enough to sway entrenched practices for addressing NSTEMI, the authors note. However, they say, increased education efforts are warranted to encourage those with symptoms to visit the hospital as soon as possible, “and there is no doubt about the need for a rapid critical pathway protocol for [all] acute myocardial infarction in the hospital.”

Commenting on the study for TCTMD, Sorin Brener, MD (New York-Presbyterian Brooklyn Methodist Hospital, NY), said he thinks, by contrast, the findings are enough to change the guidelines, or at least to make them “more pragmatic.” Because it is hard for NSTEMI patients to pinpoint the exact duration of their symptoms, physicians are often left “scratching our heads” about how urgent they should be in sending patients to the cath lab, he said.

“The guidelines, in my mind, should say if you have high-risk criteria you should go right away, and if you don't have high risk criteria, you should go as early as possible,” Brener said, acknowledging that operators have to work within certain logistical constraints.

For example, if a patient with NSTEMI presents on a Friday, they should be sent to the cath lab on Saturday if it’s open to STEMI cases, as opposed to waiting until Monday, he argued, even though the guidelines suggest that waiting is appropriate. “Why would I wait? What is the benefit? What good thing would happen to them from marinating them more and more in this medication that usually doesn’t help and exposing them to risk?”

NSTEMI in Korean Registry

For the study, published in the January 9, 2023, issue of JACC: Cardiovascular Interventions, SungA Bae, MD (Chonnam National University Hospital and Medical School), Jeong, Ahn, and colleagues looked at 5,856 patients with NSTEMI (mean age 64.2 years; 72.0% male) enrolled in the Korea Acute Myocardial Infarction Registry–National Institutes of Health (KAMIR-NIH) between 2011 and 2015. Notably, the analysis did not include any patients considered to be at very high risk, defined as having cardiogenic shock, acute heart failure, life-threatening arrhythmia, or ST-segment depression > 1 mm in six leads plus ST-segment elevation in leads aVR and/or V1.         

Just over two-thirds (n = 3,919) of patients were treated with an early invasive approach (within 48 hours from symptom onset), and they were more likely to present with typical chest pain and had a higher prevalence of previous chest pain, lower prevalence of Killip class 3, and lower GRACE risk scores compared with those treated after 48 hours. Additionally, patients treated early had lower rates of most comorbidities but higher LVEF.

The guidelines, in my mind, should say if you have high-risk criteria you should go right away, and if you don't have high risk criteria, you should go as early as possible. Sorin Brener

All-cause mortality at 3 years (the primary outcome) was significantly reduced in the early-invasive group compared with those treated after 48 hours (7.3% vs 13.4%; adjusted HR 0.76; 95% CI 0.64-0.91). Mortality findings were similar in all subgroup analyses. Interestingly, patients who used EMS had an even lower mortality risk (HR 0.31; 95% CI 0.19-0.52) compared with those who did not (HR 0.54; 95% CI 0.46-0.95; P for interaction = 0.008). Also, patients without CKD were less likely to die at 3 years (HR 0.56; 95% CI 0.44-0.72) than those with CKD (HR 0.70; 95% CI 0.55-0.88; P for interaction = 0.027).

Additionally, the secondary composite endpoint of all-cause mortality, recurrent MI, or hospitalization for HF at 3 years was less likely in the early intervention group (12.2% vs 19.6%; adjusted HR 0.84; 95% CI 0.73-0.96).

“The present study provides a glimpse of the next randomized trial regarding optimal timing for patients with NSTEMI,” Jeong and Ahn said. “Considering total ischemic time based on symptoms rather than hospitalization time is thought to represent a new milestone in myocardial infarction treatment.”

‘Logistic Issues’

In an editorial accompanying the study, Jean-Philippe Collet, MD, PhD (Groupe Hospitalier Pitié-Salpêtrière, Paris, France), and Sripal Bangalore, MD (New York University Grossman School of Medicine, NY), pick up on this idea, proposing a new paradigm for NSTEMI research based on total ischemic time.

“If you take the STEMI analogy, it is the same concept of trying to minimize their ischemic duration, if possible,” Bangalore told TCTMD. “So would that standard apply to NSTEMI is the question. I think the ischemic time will capture the patient delay and potentially is more myocardium centric than looking at admission-to-invasive coronary angiography time.”

Performing this kind of randomization will be a bit tricky given that the exact start of symptoms for NSTEMI patients is difficult to know, he acknowledged. While the definition of early invasive has “shifted” over time, if a new study’s cut point was a conservative 48 hours or so, that would make a trial easier to conduct since most patients present to the hospital well before that time, Bangalore said.

Brener added that he would like to see future studies in this space enroll a higher-risk population and also incorporate the day of the week when patients were admitted.

Ultimately, in the United States, NSTEMI practice “seems to be driven more by logistic issues . . . more than anything else,” he added. “So, I think that is going to be a key player in when these patients go to cath.”