The role of fractional flow reserve in managing STEMI patients with multivessel disease

L to R: Etienne Puymirat, Thomas Engstrom, and Colin Berry

Recent studies have indicated that complete revascularisation in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease is associated with better outcomes than that of culprit-vessel only revascularisation.1,2 Routine use of adjunctive fractional flow reserve (FFR), in combination with the angiogram, for the non-culprit lesion has the potential to increase conformity in decision making in this setting.3 Colin Berry, Thomas Engstrøm, and Étienne Puymirat explore the data for FFR in STEMI patients with multivessel disease.

Visual assessment of the coronary angiogram is subjective and associated with heterogeneous, and potentially suboptimal, revascularisation decisions.3,4 FFR-guided assessment can stratify those coronary lesions that are flow-limiting for PCI, and avoid unnecessary PCI in lesions that are non-flow limiting.4 A clinical strategy based on routine adjunctive FFR to guide decision-making has the potential to facilitate complete functional revascularisation, reduce PCI-related complications, and so optimise the PCI procedure overall.

The DANAMI-3-PRIMULTI trial was an open-label, randomised controlled trial at two university hospitals in Denmark.5 Patients presenting with STEMI who had one or more clinically significant coronary stenosis in addition to the lesion in the infarct-related artery were included. After successful PCI of the infarct-related artery, 627 patients were randomised 1:1 to either no further invasive treatment or complete FFR-guided revascularisation before discharge. The primary endpoint was a composite of all-cause mortality, non-fatal myocardial infarction, and ischaemia-driven revascularisation of lesions in non-infarct-related arteries and the median follow-up was 27 months (range 12–44 months). The primary endpoint was reduced by 44% in the FFR-guided complete revascularisation group, with an absolute reduction of 9%. The benefit of complete FFR-guided revascularisation during the initial hospitalisation was driven by significantly fewer repeat revascularisations (40% however urgent), because all-cause mortality and non-fatal re-infarction did not differ between groups.

Ongoing trials

In the Compare-Acute (Comparison between FFR guided revascularixation versus conventional strategy in acute STEMI patients with multivessel coronary artery disease) trial,6 the primary hypothesis is that FFR-guided complete PCI of all flow-limiting stenoses (FFR≤0.80) in the non-infarct related artery performed within the same procedure as the primary PCI or within the same hospitalisation will improve clinical outcomes compared to an expectant, staged approach with the decision for revascularisation informed by documented ischaemia or clinical judgment, in line with practice guidelines. The sample size is 885 participants and the trial is expected to complete in November 2016.

The FULL REVASC (Primary PCI for STEMI or high-risk NSTEMI residual non-culprit disease) trial will compare index admission FFR-guided PCI to non-culprit lesions Initial conservative management of non-culprit lesions. The primary outcome is all-cause mortality and non-fatal myocardial infarction and follow-up period will be at least one year.

The FLOWER-MI (Flow evaluation to guide revascularisation in multivessel STEMI) is a randomised trial whose main objective is to determine whether, in STEMI patients with multivessel amenable to PCI, the use of FFR in addition to angiography will improve cardiovascular outcomes, compared with the current practice of angiography-guided PCI, by improving the appropriateness of revascularisation. The secondary objectives are to assess the safety and the cost-effectiveness of the FFR-guided strategy compared to the angiography-guided strategy. The primary outcome is the composite of all-cause death, non-fatal myocardial infarction, or repeat revascularisation at one-year. The sample size is 1,170 patients and 40 centres in France are anticipated to participate. The trial is expected to start in October 2016.

Timing of complete preventive PCI

The current and intended clinical trials that we are aware of do not fully address the question of when revascularisation of non-culprit vessels in STEMI patients with multivessel disease should be performed. Theoretically, from a temporal perspective, immediate preventive PCI, as was implemented in PRAMI (Randomised trial of preventive angioplasty in myocardial infarction), should confer the most effective protection against recurrent adverse cardiac events. However, perhaps in-patient complete revascularisation would confer sufficient benefit, as compared to PCI immediately, or staged post-discharge. Only a clinical trial in which the timing of preventive PCI is allocated at random can definitively answer this question.

We anticipate that within the next five to six years, the current trials will provide a substantial body of evidence to clarify the optimal management approach(es) for patients with acute STEMI and multivessel disease. The open question is, however, will these trials have sufficient power to answer the question as to whether or not complete revascularisation improves “hard” clinical endpoints and patient well-being overall, and changes in the practice guidelines.7–9


  1. Wald et al. N Engl J Med 2013; 369(12): 1115–23.
  2. Gershlick et al. J Am Coll Cardiol 2015; 65(10): 963–72.
  3. Carrick et al. American Journal of Cardiology 2013; 111(1): 45–50
  4. Layland et al. Eur Heart J 2015; 36(2): 100–11.
  5. Engstrøm et al. Lancet 2015; 386(9994): 665–71.
  6. Smits et al.
  7. Windecker et al. Eur Heart J. 2014; 35(37): 2541–619.
  8. Steg et al. Eur Heart J 2012; 33(20): 2569–619.
  9. Levine et al. J Am Coll Cardiol 2016. Epub

Colin Berry is at BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK; Thomas Engstrøm is at the Department of Cardiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark); and Étienne Puymirat is at the Department of Cardiology, European Hospital of Georges Pompidou, Assistance Publique des Hôpitaux de Paris, Paris, France

Conflicts of interest:

CB—The University of Glasgow holds institutional research and consultancy agreements with St Jude Medical

TE—consultancy agreement with St Jude Medical

EP—consultancy agreement with St Jude Medical.