Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Quality of Life After Fractional Flow Reserve-Guided PCI Compared With Coronary Bypass Surgery.

BACKGROUND: Previous studies have shown that quality of life improves after coronary revascularization more so after coronary artery bypass grafting (CABG) than after percutaneous coronary intervention (PCI). This study aimed to evaluate the effect of fractional flow reserve guidance and current generation, zotarolimus drug-eluting stents on quality of life after PCI compared with CABG. METHODS: The FAME 3 trial (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation) is a multicenter, international trial including 1500 patients with 3-vessel coronary artery disease who were randomly assigned to either CABG or fractional flow reserve-guided PCI. Quality of life was measured using the European Quality of Life-5 Dimensions (EQ-5D) questionnaire at baseline and 1 and 12 months. The Canadian Cardiovascular Class angina grade and working status were assessed at the same time points and at 6 months. The primary objective was to compare EQ-5D summary index at 12 months. Secondary end points included angina grade and work status. RESULTS: The EQ-5D summary index at 12 months did not differ between the PCI and CABG groups (difference, 0.001 [95% CI, -0.016 to 0.017]; P=0.946). The trajectory of EQ-5D during the 12 months differed (P<0.001) between PCI and CABG: at 1 month, EQ-5D was 0.063 (95% CI, 0.047 to 0.079) higher in the PCI group. A similar trajectory was found for the EQ (EuroQol) visual analogue scale. The proportion of patients with Canadian Cardiovascular Class 2 or greater angina at 12 months was 6.2% versus 3.1% (odds ratio, 2.5 [95% CI, 0.96-6.8]), respectively, in the PCI group compared with the CABG group. A greater percentage of younger patients (<65 years old) were working at 12 months in the PCI group compared with the CABG group (68% versus 57%; odds ratio, 3.9 [95% CI, 1.7-8.8]). CONCLUSIONS: In the FAME 3 trial, quality of life after fractional flow reserve-guided PCI with current generation drug-eluting stents compared with CABG was similar at 1 year. The rate of significant angina was low in both groups and not significantly different. The trajectory of improvement in quality of life was significantly better after PCI, as was working status in those <65 years old. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery.

BACKGROUND: Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking. METHODS: In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed. RESULTS: A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group. CONCLUSIONS: In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.).

Effects of exenatide on microvascular reactivity in patients with type 2 diabetes and coronary artery disease: A randomized controlled study.

OBJECTIVE: We studied the effect of the GLP-1RA exenatide on skin microvascular function in patients with T2DM and CAD. METHODS: Thirty-five patients with T2DM, CAD, and HbA1C 42-86 mmol/mol were randomized to treatment with exenatide or conventional non-GLP-1-based therapy for 12 weeks. Skin microvascular function was examined in the forearm by LDF and iontophoretic application of acetyl choline and SNP, and by PORH at baseline and after 12 weeks. Blood samples for fasting plasma glucose, HbA1C, and lipid profile were collected. RESULTS: At 12 weeks, patients on exenatide showed reductions in HbA1C (from 63.5 ± 13 to 60.7 ± 14 mmol/mol, p = .065), body weight (from 92.6 ± 16 to 89 ± 16 kg, p < .001), and systolic blood pressure (from 141 ± 13 to 134 ± 16 mm Hg, p < .05) as compared to the conventionally treated group. There were no significant changes in skin microvascular function between or within the two groups at follow-up. CONCLUSIONS: Three months' daily treatment with the GLP-1RA exenatide in T2DM patients with CAD showed no significant effects on skin microvascular function or blood glucose control, while this study confirms a reduction in body weight and blood pressure by exenatide, as compared to conventional antidiabetic drug treatment.

Blood haemoglobin, renal insufficiency, fractional flow reserve and plasma NT-proBNP is associated with index of microcirculatory resistance in chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMVD) is associated with adverse cardiovascular outcome. We aimed to determine the prevalence of CMVD and factors related to index of microcirculatory resistance (IMR) in consecutive patients with chronic coronary syndrome (CCS) undergoing elective coronary angiography. METHODS AND RESULTS: Non-interventional physicians enrolled 274 patients with CCS before angiography, to minimize selection bias by PCI-operators. Fractional flow reserve (FFR) and IMR were measured in the LAD. Subjects with extensively diseased LAD, no measures due to technical reasons or violation of protocol were excluded from the analysis (n = 54). The proportion of patients with IMR corrected for collateral flow (IMRcorr) >25 units was 25% (95% confidence interval [CI] 19%-31%) in all 220 patients. In subjects with FFR ≤0.80 in the LAD the proportion of IMRcorr > 25 units was 21% (95% CI 13%-30%) as compared to subjects with FFR >0.80, 29% (95% CI 21%-36%), p = .268. Haemoglobin (p < .005; r2 = 0.084), FFR in the LAD (p = .001; r2 = 0.049), creatinine clearance (p = .001; r2 = 0.049; inversely), and NT-proBNP (p = .038; r2 = 0.021) were independently associated with IMRcorr in multivariate linear regression analysis. CONCLUSIONS: We report that IMRcorr is associated with renal dysfunction, NT-proBNP, FFR in the LAD and, for the first time, blood haemoglobin. One in four of patients referred for coronary angiography due to CCS have CMVD defined as IMRcorr > 25 in the LAD.

Changes in Index of Microcirculatory Resistance during PCI in the Left Anterior Descending Coronary Artery in Relation to Total Length of Implanted Stents.

AIM: To investigate the relationship between stent length and changes in microvascular resistance during PCI in stable coronary artery disease (CAD). METHODS AND RESULTS: We measured fractional flow reserve (FFR), index of microcirculatory resistance (IMR), and coronary flow reserve (CFR) before and after stenting in 42 consecutive subjects with stable coronary artery undergoing PCI with stent in the LAD. Patients that had very long stent length (38-78 mm) had lower FFR before stenting than patients that had long (23-37 mm) and moderate (12-22 mm) stent length (0.59 (±0.16), 0.70 (±0.12), and 0.75 (±0.07); p=0.002). FFR improved after stenting and more so in subjects with very long stent length compared to long and moderate stent length (0.27 (s.d ± 16), 0.15 (s.d ± 0.12), and 0.12 (s.d ± 0.07); p for interaction = 0.013). Corrected IMR (IMRcorr) increased after stenting in subjects who had very long stent length, whereas IMRcorr was lower after stenting in subjects who had long or moderate stent length (4.6 (s.d. ± 10.7), -1.4 (s.d. ± 9,9), and -4.2 (s.d. ± 7.8); p for interaction = 0.009). CONCLUSIONS: Changes in IMR during PCI in the LAD in stable CAD seem to be related to total length of stents implanted, possibly influencing post-PCI FFR. Larger studies are needed to confirm the relationship.

Outcome and selection of revascularization strategy in left main coronary artery stenosis.

OBJECTIVES: To investigate clinical outcome in unselected real-life patients with unprotected left main coronary artery (ULMCA) stenosis and determine factors associated with selection of revascularization strategy. DESIGN: Consecutive patients with ULMCA stenosis at our institution in 2009-2013 (n = 308) were retrospectively analyzed with propensity score adjusted Cox proportional hazards models for outcome. Baseline characteristics in relation to selection of revascularization strategy were analyzed with multivariate logistic regression. RESULTS: Patients that underwent PCI (n = 94) had a higher risk of major adverse cardiac and cerebrovascular events (MACCE; adjusted HR 2.13 [95% CI 1.08-4.19]) than patients that had CABG surgery but there was no difference in the combination of death and MI (adjusted HR 1.17 [95% CI 0.50-2.75]). Later year of index angiography, age, Euroscore II and angiographer favoring PCI was associated with PCI as revascularization strategy. Higher SYNTAX score, higher systolic blood pressure and angiographer favoring CABG was associated with CABG. CONCLUSIONS: In consecutive patients with ULMCA stenosis PCI is associated with higher MACCE rates than CABG but there is no difference in death and MI. Later year of index angiography, higher age, lower systolic blood pressure, higher predicted per-procedural surgical risk, less complex coronary anatomy and angiographer favoring PCI increased the probability of revascularization with PCI instead of CABG.

Severely impaired microvascular reactivity in diabetic patients with an acute coronary syndrome.

BACKGROUND: Microvascular function is impaired in patients with stable coronary artery disease. The aim was to study microvascular function in patients with diabetes and acute coronary syndrome (ACS). METHODS: Microvascular function was evaluated in 83 patients by laser Doppler fluxmetry (LDF) [PU; perfusion unit, median (interquartile range)] measuring resting LDF and peak LDF following a six min heating of the skin to 44 °C at the foot, respectively. All patients with ACS and without previously known diabetes underwent oral glucose tolerance test. Thirty-nine patients with type 2 diabetes mellitus free from coronary artery disease served as controls. RESULTS: Peak LDF was significantly (P = 0.03) lower in patients with ACS and diabetes (n = 22; 72 (52)) and diabetes without coronary artery disease (n = 39; 69 (51)) as compared to patients with ACS without diabetes (n = 46; 97 (60)), and patients without ACS (n = 15; 140 (121)), respectively. Patients with ACS (n = 68) had significantly (P = 0.04) lower peak LDF (92 (49)) as compared to patients without ACS (n = 15) (140 (121)). CONCLUSION: Microvascular reactivity is severely impaired in patients with diabetes and ACS. Diabetes has a major influence on microvascular function in patients with coronary artery disease.