For many patients, the first symptom of heart disease is acute MI, or even sudden death.
Changes in lifestyle and optimal medical treatment (OMT) are vital to the prevention of serious events, but we cannot help wondering whether preventive stenting might do it.
Intravascular ultrasound (IVUS), optical coherence tomography (OCT), NIRS near-infrared spectroscopy (NIRS) and computed tomography (CT) have proven useful to identify vulnerable plaque associated to sudden events.
Could these images stratify risk enough for us to be able to choose patients that could benefit from preventive stenting?
Lesions that turn out to be ischemic when assessed with fractional flow reserve (FFR) have revascularization indication. The question is what to do with FFR negative lesions that might be vulnerable.
There is no question that FFR negative lesions usually respond very well to OMT alone. For example, in the FAME trial, only 1 in 513 FFR negative lesions resulted in MI at 2-year followup. Combining the risk of cardiovascular death and MI, this could reach 1% in one year, in a worse-case scenario.
On the other hand, stenting (despite device, drug, and technique evolution) is not 100% harmless, both at short and long term.
Trials on modern drug eluting stents have shown MI annual rates between 2 and 3.5%; this in addition to 2% clinically driven repeat revascularization, vs 1% of medical treatment of FFR negative lesions, makes imaging necessary to make preventive stenting work.
Virtual histology with IVUS was used in the PROSPECT study, which is one of the most impressive analysis in the history of atherosclerosis. After a 3-year followup, they found a number of IVUS parameters could predict events, even though these were revascularizations or rehospitalizations. Hard events rate, such as death or MI, continued to be fairly low.
OCT studies have observed patients with 4 simultaneous characteristics defined as risky that only make 3.6% of the population. Among these “super high risk” patients who present the four factors at the same time, only 18.9% presented events after one year.
3 ongoing randomized studies were assessing FFR negative stenting, but they started enrolling patients with bioresorbable scaffolds that are now discontinued. They had to switch to DES, stop the treatment branch, or continue as an observational non-randomized cohort. Only as such might these studies be able to answer the question.
A longer followup does not seem to answer the question either. Studies like FAME or DEFER were not conclusive after 15 years. We should also consider that risk characteristics of plaque also evolve over time and therefore we can expect OMT to make these risk characteristics disappear.
In conclusion, preventive stenting of FFR negative vulnerable lesions might eventually have an absolute benefit so small that the number of patients necessary to show it would be preposterous.
FFR provides quick, clear and easily reproduced data, enough for us to go without any other resource (be it IVUS, OCT, NIRS, etc.) when its negative.
Original Title: Stenting “Vulnerable” But Fractional Flow Reserve–Negative Lesions Potential Statistical Limitations of Ongoing and Future Trials.
Reference: Frederik M. Zimmermann et al. JACC Cardiovasc Interv. 2021 Feb 22;14(4):461-467. https://doi.org/10.1016/j.jcin.2020.05.036.