Abstract 4147941: Impact of a fractional flow reserve-guided invasive versus conservative management strategy on outcomes in the ISCHEMIA trial

Introduction: Fractional flow reserve (FFR) is an invasive, lesion-specific surrogate for myocardial ischemia. However, the impact of an FFR-guided invasive strategy on outcomes in chronic coronary disease (CCD) when compared to a conservative strategy is unclear. Purpose: To compare the outcomes of patients with CCD enrolled in the ISCHEMIA trial randomized to the invasive (INV) arm who underwent FFR during initial angiography with those randomized to a conservative (CON) strategy with optimal medical therapy alone. Methods: The ISCHEMIA data set was obtained from the NHLBI. Patients randomized to the INV arm who underwent FFR at initial angiography were compared to those who were treated with a CON strategy using optimal medical therapy. Unadjusted cumulative event probabilities were estimated using the Kaplan-Meier method. The co-primary endpoints of interest were cardiovascular death (CV) death and myocardial infarction (MI). Secondary outcomes included all-cause mortality and health status as determined by the Seattle Angina Questionnaire (SAQ) angina frequency (AF), quality of life (QoL) and summary scores (SS). Results: Of the 5,179 patients with CCD and at least moderate ischemia on stress testing, 2,322 were randomized to the CON strategy and 2,475 were randomized to the INV strategy. Of these, 428 underwent angiography with FFR (INV-FFR). CON patients were younger than INV-FFR patients (64.3 [9.6] years vs. 65.5 [8.7] years, P=0.013). The incidence of hypertension, diabetes, smoking, BMI, or prior MI did not differ between groups. SAQ AF, QoL, and SS scores did not differ between groups at baseline. CON patients had more vessels with greater than 70% stenosis (1.49 [0.9] vs. 1.24 [1.0], P<0.001). Of CON patients, 87% had moderate or severe ischemia vs 83% of INV-FFR patients (P=0.009). The SAQ AF, QoL, and SS scores did not differ between groups at 1, 3 or 5 years. After 5 years of follow-up, there was no difference in freedom from CV death (94% vs 97%, P=0.11) or all-cause mortality (92% vs 93%, P=0.44) in CON compared to INV-FFR groups. However, 5-year freedom from MI was lower in CON patients (87.0% vs 92%, P=0.039). Conclusion: Despite selecting for patients with less extensive coronary disease and less severe ischemia, an FFR-guided INV approach did not result in reductions in CV or all-cause mortality at 5 years or improvements in health status at 1, 3 or 5 years. However, INV-FFR was associated with a reduction in MI at 5 years.