ACC.21 Interventional Focus: FLOWER-MI and HOST-EXAM

FLOWER-MI (Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction)

Teaching Points
This study1 investigated whether the use of fractional flow reserve (FFR) in complete revascularization results in a better clinical outcome than the use of angiography in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease. The study reports that for patients with STEMI undergoing complete revascularization, an FFR-guided strategy did not have a significant benefit over an angiography-guided strategy with respect to the risk of death, myocardial infarction (MI), or urgent revascularization at 1 year. Although there was no significant benefit of the FFR-guided strategy, the confidence intervals for the primary outcome are quite wide and compatible with either a 22% relative benefit or a 123% relative harm associated with the FFR-guided strategy and may not allow conclusive interpretation.

A total of 1,171 patients with STEMI and multivessel disease was enrolled and underwent randomization (590 to the FFR-guided group and 581 to the angiography-guided group). During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio 1.32; 95% confidence interval, 0.78-2.23; p = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and 10 (1.7%) in the angiography-guided group. Nonfatal MI occurred in 18 (3.1%) in the FFR-guided group and 10 (1.7%) in the angiography-guided group, and unplanned hospitalization leading to urgent revascularization occurred in 15 (2.6%) and 11 (1.9%), respectively.

Operators will likely view this as showing no value to adding FFR to the assessment of non-culprit lesions in the setting of STEMI management. Current practice and guidelines encourage percutaneous coronary intervention (PCI) of non-culprit lesions at the time of initial culprit PCI if feasible to avoid any added risks of a second procedure. In the FLOWER-MI trial, despite encouraging investigators to perform non-culprit lesions at the index procedure, this occurred in only 4% of procedures, which may have added a risk to the outcomes due to second procedures affecting the results. However, some controversy persists regarding the lack of FFR reliability in non-culprit lesions at the time of a STEMI given potential vaso-reactive changes in the acute setting. In contrast, such changes are not present in stable patients where data support the value.

Another potential factor playing a role in the results is the concept that the inflammatory state in acute STEMI may involve non-culprit lesions regardless of the functional severity. Thus, stenting of lesions negative by FFR but abnormal by visual assessment may be important for reasons beyond lesion flow due to acute plague disruption. It is conceivable that intravascular imaging might be a more appropriate tool in these patients, but this is only a hypothesis until there are additional trials. Therefore, the FLOWER-MI trial is not practice changing.

HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases—Extended Antiplatelet Monotherapy)

Teaching Point
This study compared the efficacy and safety of aspirin versus clopidogrel monotherapy during the chronic maintenance period after PCI with a drug-eluting stent. The study reports that clopidogrel monotherapy, compared with aspirin monotherapy, significantly reduced the risk of the composite of all-cause death, non-fatal MI, stroke, readmission due to acute coronary syndrome, and Bleeding Academic Research Consortium bleeding type 3 or greater. Overall, in patients requiring indefinite antiplatelet monotherapy after PCI, clopidogrel monotherapy was superior to aspirin monotherapy in preventing future adverse clinical events. The open-label design of the study has a potential for bias in outcome reporting and ascertainment, and these results should ideally be validated in a double-blinded, randomized controlled trial.

A total of 5,530 patients was enrolled; 5,438 (98.3%) patients were randomly assigned to either the clopidogrel group (2,710 [49.8%]) or to the aspirin group (2,728 [50.2%]). Ascertainment of the primary endpoint was completed in 5,338 (98.2%) patients. During 24-month follow-up, the primary outcome occurred in 152 (5.7%) patients in the clopidogrel group and 207 (7.7%) in the aspirin group (hazard ratio 0.73; 95% confidence interval, 0.59-0.90; p = 0.0035).

The vast majority of practitioners default to single antiplatelet therapy with aspirin after cessation of dual antiplatelet therapy following PCI. It is a quite natural question to consider whether thienopyridines might be a more efficacious single agent. Prior studies such as the CAPRIE (Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events) trial examined this question in a patient population with known vascular disease and found a slight superiority of clopidogrel over aspirin regarding ischemic endpoints with a similar safety profile.2 The HOST-EXAM trial specifically addresses the post-PCI population and found a reduction in a composite endpoint of both ischemic and bleeding events. Individual endpoints were interesting in that both the combined thrombotic endpoint and any bleeding were reduced significantly.

Such data will likely give practitioners impetus to consider switching to thienopyridines as single therapy in selected patients post-PCI when dual antiplatelet therapy is stopped. However, the trial has limitations, including its restriction to an east Asian population and its small size. In addition, a lingering question of variability of clopidogrel resistance persists. Nevertheless, the totality of data points to the emergence of a possible major shift in practice. As usual, larger studies are called for before a definitive recommendation can be made.


  1. Puymirat E, Cayla G, Simon T, et al. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med 2021;May 16:[Epub ahead of print].
  2. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-39.

Clinical Topics: Acute Coronary Syndromes, Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Stable Ischemic Heart Disease, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Aortic Surgery, Cardiac Surgery and SIHD, Interventions and ACS, Interventions and Coronary Artery Disease, Interventions and Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging, Chronic Angina

Keywords: ACC21, ACC Annual Scientific Session, Acute Coronary Syndrome, Angiography, Anterior Wall Myocardial Infarction, Coronary Artery Disease, Fractional Flow Reserve, Myocardial, Myocardial Infarction, Myocardial Revascularization, Percutaneous Coronary Intervention, ST Elevation Myocardial Infarction, Stents, Drug-Eluting Stents, Aspirin, Angina, Stable, Angina, Unstable, Hemorrhage, Myocardial Ischemia, Platelet Aggregation Inhibitors, Stroke, Thrombosis

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