FAME 3 Trial - Cardionerds Twitter Journal Club

CardioNerds Journal Club is a monthly forum for CardioNerds to discuss and breakdown recent publications on twitter and are produced with a corresponding infographic and detailed blog post. For more information, check out the CardioNerds Journal Club Page. This Journal Club focuses on the FAME 3 Trial.

Table of contents for the FAME 3 Trial summary:

Visual abstract
Summary
References
Credits
Twitter Archive

FAME-3 CardsJC Visual Abstract-CardioNerds

January 13, 2022

Fractional Flow Reserve–Guided PCI as Compared with Coronary Bypass Surgery

The FAME 3 Trial

William F. Fearon, M.D., Frederik M. Zimmermann, M.D., Bernard De Bruyne, M.D., Ph.D., Zsolt Piroth, M.D., Ph.D., Albert H.M. van Straten, M.D., Ph.D., Laszlo Szekely, M.D., Giedrius Davidavičius, M.D., Ph.D., Gintaras Kalinauskas, M.D., Ph.D., Samer Mansour, M.D., Rajesh Kharbanda, Ph.D., Nikolaos Östlund-Papadogeorgos, M.D., Adel Aminian, M.D., et al., for the FAME 3 Investigators^*

https://www.nejm.org/doi/full/10.1056/NEJMoa2112299

Heart disease is the leading cause of death among men and women of all races and ethnicities in the USA.¹
The estimated annual incidence of myocardial infarction is 605,000 new and 200,000 recurrent events. Approximately 21% of these cases occur as asymptomatic “silent” events.
Prompt coronary revascularization in the form of either percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) reduces mortality and improves functional status in patients presenting with acute myocardial infarction.^2-5
Revascularization strategy (PCI vs CABG) has been compared in patients with multivessel coronary artery disease (MV-CAD).
- The SYNTAX study enrolled 1800 patients with severe multivessel disease or left main CAD in a 1:1 ratio using bare-metal stents and first-generation drug-eluting stents vs. CABG and revealed a higher rate of major adverse cardiac or cerebrovascular events in the PCI vs. CABG arms at 12 months. (17.8%, vs. 12.4% for CABG; P=0.002).⁶
- Similarly, the BEST trial enrolled 880 patients with multivessel disease in a 1:1 fashion with everolimus-eluting drug-eluting stents vs. CABG and revealed higher rates of major adverse cardiovascular events in the PCI arm compared to CABG at 2-year follow up.⁷
- In 5-year follow up of the SYNTAX and BEST trials, among patients with multivessel CAD involving the proximal left anterior descending coronary artery, PCI (versus CABG) was associated with a greater composite outcome of all-cause death, MI, or stroke (HR, 1.43 [95% CI, 1.05–1.95]; P=0.026), cardiovascular death (HR, 2.17 [95% CI, 1.24–3.81]; P=0.007), and major adverse cardiovascular and cerebrovascular events (HR, 1.71 [95% CI, 1.33–2.19]; P<0.001).⁸
- The FREEDOM trial enrolled 1900 patients with diabetes and multivessel disease in a 1:1 fashion comparing drug (sirolimus and paclitaxel) eluting stents vs. CABG and revealed CABG was superior to PCI at 2-year follow up.

Importantly, functional assessment of coronary artery disease was not included in the above trials. Also notable is that second-generation stents (except BEST trial), and their potential for improved early and late outcomes, have not been compared with CABG in prior trials.
The FAME 1 Trial compared angiography-guided PCI to FFR-guided PCI in patients with stable multivessel disease and found that the use of FFR significantly reduced the composite endpoint of death, non-fatal myocardial infarction and repeat revascularization at one year.⁹
The FAME-2 Trial revealed improved outcomes in patients who underwent FFR-guided PCI with optimal medical therapy (OMT) compared to OMT alone.¹⁰

Inclusion and Exclusion Criteria:

Intervention

Randomized controlled trial.
Patients randomized to CABG received state-of-the-art therapy at the discretion of the local surgeon with a strong emphasis on arterial revascularization. FFR assessment of lesions to help guide bypass was not mandated, but if performed at the time of the diagnostic angiogram, the information could be used by the surgeon.
Patients undergoing PCI had FFR measured with a St. Jude Medical coronary pressure wire across all lesions. If the FFR was ≤0.80, then PCI was performed with the Medtronic Resolute Integrity drug-eluting stent (DES) as per the usual routine. If the FFR was >0.80, then PCI will be deferred. Intravascular imaging was performed as deemed necessary by the treating physicians.

Outcomes

Primary Endpoints

Death, MI, stroke, and any repeat revascularization (MACE) were evaluated at 1 year from the last patient randomized, where subjects contributed data from the time of enrollment until the occurrence of MACE or one-year follow-up, whichever occurs first. Subjects who died or were lost to follow up before this time were censored at their last recorded activity.

Other Secondary Endpoints

Comparison of proportion of patients in each arm with MACE at one year, including

patients lost to follow-up from each arm
MACE rate at each time point besides one year
Rate of each individual component of MACE at each time point
Rate of death, MI, and stroke at each time point
Rate of death and MI at each time point
Rate of cardiac death alone and in combination with other endpoints
Rate of death, MI, stroke, and all repeat revascularizations at each time point
Stent thrombosis (ARC definition) and graft occlusion at each time point
Bleeding complication
Significant arrhythmia
Development of acute renal failure
Length of hospital stay

Participant Characteristics:

1500 participants (757 underwent PCI, 743 underwent CABG)
Mean age 65 years, 82% male, 29% had diabetes, 39% presented with acute coronary syndrome, and 13% had undergone previous PCI.
Intravascular imaging was used in 11.7% of cases in the PCI arm.

Outcomes

The composite primary endpoint was 10.6% in the FFR-guided PCI group and 6.9% in the CABG group (HR:1.5 ; 95% CI:1.1-2.2; p:0.35)
Secondary composite endpoint of death, myocardial infarction or stroke remained similar in both groups.
Procedural complications of major bleeding, acute kidney injury, arrhythmia, and rehospitalization within 30-days were higher in CABG arm.
The mean length of stay was longer in the CABG arm.

FAME 3 Trial Conclusions

FFR-guided PCI did not meet the criteria for non-inferiority compared to CABG surgery in reducing major adverse cardiovascular and cerebrovascular events.

Limitations & Considerations

Shorter duration (1 year) follow-up of the enrolled patients.
FFR was not measured routinely in the CABG arm.
Intravascular imaging was used only 12% in the PCI arm, and regular use of intravascular imaging has shown to decrease the future need for repeat revascularization.
Women and persons of color were underrepresented in the study.