What About All the Recent "Negative" FFR Trials?

During the past 30 years, fractional flow reserve (FFR) has moved from animal models to class IA recommendations in guidelines. However, the FLOWER-MI, RIPCORD-2, FUTURE, and FAME 3 trials in 2021 were "negative"-has FFR exceeded its expiration date? We critically examine these randomized trials in order to draw insights not just about FFR but also about study design and interpretation. Are all randomized trials created equal? No, rather we must focus on discordant decisions between angiography and FFR and highlight clinical endpoints that can be improved by percutaneous coronary intervention instead of medical therapy.