A randomized controlled trial of a physiology‐guided percutaneous coronary intervention optimization strategy: Rationale and design of the TARGET FFR study

Abstract

Post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) ≥0.90 confers an improved cardiac prognosis. There are currently limited data available to determine how often it is possible to improve an angiographically acceptable but physiologically suboptimal result. A physiology-guided optimization strategy can achieve a clinically meaningful increase in the proportion of patients achieving a final post-PCI FFR ≥0.90 compared to standard care. Following angiographically successful PCI procedures, 260 patients will be randomized (1:1) to receive either a physiologyguided incremental optimization strategy (intervention group) or blinded post-PCI coronary physiology measurements (control group). Patients undergoing successful, standard-of-care PCI for either stable angina or non-ST-segment-elevation myocardial infarction who meet the study's inclusion and exclusion criteria will be eligible for randomization. The primary endpoint is defined as the proportion of patients with a final post-PCI FFR result ≥0.90. Secondary endpoints include change from baseline in Seattle Angina Questionnaire and EQ-5D-5L scores at 3 months and the rate of target vessel failure and its components (cardiac death, myocardial infarction, stent thrombosis, unplanned rehospitalization with target vessel revascularization) at 3 months and 1 year. 260 individual patients were successfully randomized between March 2018 and November 2019. Key baseline demographics of the study population are reported within. TARGET FFR is an investigator-initiated, prospective, single-center, randomized controlled trial of an FFR-guided PCI optimization strategy. The study has completed recruitment and is now in clinical follow-up. It is anticipated that primary results will be presented in Autumn 2020. ClinicalTrials.gov Identifier: NCT03259815. [Correction added on Apr 3 2020, after first online publication: Clinical Trials identifier added.]Abbreviations: CFR, coronary flow reserve; dPR, diastolic pressure ratio; FFR, fractional flow reserve; HTG, hyperemic tran-stent gradient; IC, intracoronary; iFR, instantaneous wave-free ratio; IMR, index of microcirculatory resistance; ISR, in-stent restenosis; IVUS, intravascular ultrasound; MACE, major adverse cardiovascular events; NSTEMI, non-ST segment elevation myocardial infarction; OCT, optical coherence tomography; PCI, percutaneous coronary intervention; Pd/Pa, distal coronary pressure/aortic pressure; PIOS, physiologically guided incremental optimization strategy; RFR, resting full-cycle ratio; SAQ, Seattle Angina Questionnaire; STEMI, ST-segment elevation myocardial infarction; TT hyp , mean hyperemic transit time; TT rest , mean resting transit time.

Post-stenting fractional flow reserve vs coronary angiography for optimization of percutaneous coronary intervention (TARGET-FFR)

“…The study rationale and design have been described previously. 27 The study is registered on ClinicalTrials.gov (Identifier: NCT03259815).…”

“…Using a thermodilution technique, coronary flow reserve (CFR—the ratio of resting to hyperaemic coronary flow) and the index of microcirculatory resistance (IMR—the product of mean hyperaemic distal coronary pressure and mean hyperaemic transit time) were calculated as previously described. 27 Fractional flow reserve was measured during stable hyperaemia with the sensor positioned as far distally in the vessel as practical. Finally, a hyperaemic pressure wire pullback assessment was performed and the sensor returned to the tip of the guide catheter to assess for pressure drift.…”

Angina After Percutaneous Coronary Intervention: Patient and Procedural Predictors

“…The rationale, study design, and primary outcome of the TARGET-FFR controlled trial have been published previously. 12 , 13 In brief, 260 patients undergoing standard-of-care PCI for either chronic or medically stabilized acute coronary syndromes provided informed consent to be randomized 1:1 to a control group or the experimental physiology-guided incremental optimization strategy. All patients completed questionnaires on anginal symptoms (Seattle Angina Questionnaire [SAQ-7]) and health status (European quality of life–5 dimension–5 level [EQ-5D-5L]) at baseline and were contacted to repeat this assessment 3 months after their procedure.…”

Optimal Prognostication of Patients with Coronary Stenoses in the Pre- and Post-PCI setting: Comments on TARGET FFR and DEFINE-FLOW Trials Presented at TCT Connect 2020

“…In the sample size calculation, a substantial difference between intention-to-treat and as-treated because of the absence of a target for additional optimisation measures was already expected in 60% of patients, which was even surpassed in the actual trial (69%). [ 23 ] In addition, the investigators aimed to detect a 20% difference between groups regarding the primary endpoint. [ 23 ] With regards to the p-value of 0.099 of the primary analysis, one can conclude that: the initially assumed effect of the intervention (PIOS) on final FFR was overestimated; and the study was underpowered considering the low rate of actual PIOS interventions performed.…”

“…[ 23 ] In addition, the investigators aimed to detect a 20% difference between groups regarding the primary endpoint. [ 23 ] With regards to the p-value of 0.099 of the primary analysis, one can conclude that: the initially assumed effect of the intervention (PIOS) on final FFR was overestimated; and the study was underpowered considering the low rate of actual PIOS interventions performed.…”