Early Invasive Strategy in NSTEMI Patients Improves Survival

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In patients with non-ST-segment elevation myocardial infarction (NSTEMI), routine use of a strategy involving angiography and, when necessary, revascularization can reduce both short- and long-term mortality compared with medical therapy alone, according to a registry study published in the September 2012 issue of JACC: Cardiovascular Interventions. Moreover, the benefit comes without increased bleeding.

Investigators led by Etienne Puymirat, MD, of Hôpital Européen Georges Pompidou (Paris, France), looked at 1,645 NSTEMI patients enrolled in FAST-MI (French Registry of Acute Coronary Syndrome) who presented within 48 hours of symptom onset over a 1-month period in 2005. Of this cohort, 1,316 (80%) underwent an invasive strategy consisting of early angiography and, if warranted, revascularization, while 329 (20%) were managed medically. The 2 groups differed in many respects; notably, the conservatively managed group was older and had higher GRACE risk scores and creatinine levels as well as lower LVEF.

For the invasive group, the average time from admission to angiography was 2.35 ± 2.96 days, with 75% of patients undergoing the procedure within 3 days. Subsequently, 71% of these patients received revascularization, typically PCI.  

Short- and Long-term Mortality Reduced

In-hospital mortality and blood transfusion were less common among the invasively managed patients, while bleeding risk was similar between the groups (table 1).

Table 1. In-Hospital Complications


Invasive Strategy

(n = 1,316)

Conservative Strategy

(n = 329)

P Value




< 0.001

Major Bleeding




Minor Bleeding




Any Blood Transfusion




At 3 years, adjusted risks of all-cause death, cardiovascular death, MI, and MACE (death, nonfatal MI, or stroke) or revascularization also were lower in the invasive group (table 2).

 Table 2.  Risk at 3 Years: Invasive vs. Conservative Strategy


Adjusted HR

95% CI

P Value

All-Cause Mortality



< 0.001

Cardiovascular Mortality



< 0.001

Nonfatal MI



< 0.001

MACE or Revascularization



< 0.001

Within the invasive strategy group, patients who underwent revascularization were more likely to survive to 3 years than those who did not (86% vs. 77%; HR 1.52; 95% CI 1.15-2.01), but the difference did not persist after multivariate adjustment.

To specifically evaluate the long-term impact of the invasive strategy, 3-year outcomes were analyzed only for patients who survived the index stay, taking into account in-hospital complications and medications prescribed at discharge. In this multivariate model, the invasive strategy was associated lower likelihoods of 3-year mortality (HR 0.56; 95% CI 0.43-0.72) and MACE or revascularization (HR 0.71; 95% CI 0.58-0.89).

The invasive strategy also was associated with reduced mortality regardless of age, sex, medical therapy, or GRACE risk score, although there was an interaction between lower GRACE score (≤ 108) and greater relative risk reduction (P < 0.001).  

In an attempt to overcome the differences in baseline characteristics between the invasively and conservatively managed groups, the investigators analyzed 181 propensity score-matched pairs of patients. The analysis confirmed the superiority of the invasive strategy for 3-year survival (HR 0.54; 95% CI 0.40-0.74; P < 0.001).

No Longer Just an MI Benefit

According to the authors, several randomized trials and meta-analyses have consistently shown a reduction in the combined endpoint of mortality and MI in patients treated with an invasive strategy, but the difference was typically driven by excess MIs in the conservatively managed group. In contrast, in the current study the invasive advantage arose from increased mortality in the conservatively managed arm.

In addition, although several subgroup analyses from previous trials have suggested a greater treatment benefit in high-risk than low-risk patients, the current data suggest that the benefit applies to both categories and may even have larger relative benefit in low-risk patients, Dr. Puymirat and colleagues write.

In an accompanying editorial, Robbert J. de Winter, MD, PhD, and Jan G. P. Tijssen, PhD, of the University of Amsterdam (Amsterdam, The Netherlands), write that the study has several strengths. For example, it included all-comers from a “real-life clinical environment,” and was based on a prospective registry with 97% follow-up at 3 years.

“Early angiography is safe and practical in most patients,” the editorialists conclude. “Yet, perhaps it is time for a new, large, randomized clinical trial for intermediate-risk [NSTEMI] patients . . . using high-sensitive troponin measurements and risk stratification tools, the latest interventional modalities, and optimized pharmacological standards of care.”

Clinicians Recognize Sicker Patients—and Triage Them to Medical Therapy

In an interview with TCTMD, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), observed that many of the conservatively managed patients probably needed revascularization but were not evaluated for it because their comorbidities would make angiography riskier.

For example, conservatively managed patients were 3 times more likely to have chronic renal failure and were on average 12 years older than those in the invasive strategy group, Dr. Brener noted. “[The age disparity] is huge and probably accounts for almost all of the difference in mortality,” he commented. “But to me, the critical point is that the patients with the lowest GRACE scores went to the cath lab and those with the highest scores didn’t. That tells you that there’s cherry-picking going on here.”

Dr. Brener emphasized that adjustment could not fully erase the effects of these baseline differences.

“What this [management pattern] really shows,” he commented, “is that practitioners are very good at [identifying] people who would not benefit from [catheterization] either because they are too sick or the risk of the procedure is too high. And that number has remained fairly constant—about 20% to 25% in various registries.”

“This is a nice registry,” Dr. Brener said, “but [the issue of how to manage NSTEMI patients] cannot be addressed in this kind of dataset because the groups are simply not comparable.”

Dr. Brener said that both ischemic and bleeding risk should be assessed in each patient. “But I think it’s even more important to keep in mind what the benefit of an invasive strategy is, because if somebody has a very limited lifespan, you may want to consider that,” he added.

Overall, the main determinant of how NSTEMI patients are managed is where they present, Dr. Brener said. At hospitals without a cath lab, patients are unlikely to be transferred to a PCI center, while at hospitals with a cath lab, the majority go to the lab. In the latter setting, practitioners tend to give more weight to the immediate risk of complications from catheterization rather than to any long-term benefits, he noted. The paradoxical result is that higher-risk patients are less likely to undergo angiography.

Moreover, Dr. Brener stressed, datasets cannot capture the nuance of clinical decision making. “It’s called the ‘smell test’ You just look at the patient and know that this is not somebody you take to the cath lab,” he said.


1. Puymirat E, Taldir G, Aissaoui N, et al. Use of invasive strategy in non-ST-segment elevation myocardial infarction is a major determinant of improved long-term survival: FAST-MI (French Registry of Acute Coronary Syndrome). J Am Coll Cardiol Intv. 2012;5:893-902.

2. De Winter RJ, Tijssen JGP. Non-ST-segment elevation myocardial infarction: Revascularization for everyone? J Am Coll Cardiol. 2012;5:903-905.


  • The FAST-MI registry is supported by grants from Pfizer and Servier.
  • Drs. Puymirat, de Winter, Tijssen, and Brener report no relevant conflicts of interest.