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Fractional Flow Reserve–Guided Deferred Versus Complete Revascularization in Patients With Diabetes Mellitus

      To assess the safety and efficacy of deferred versus complete revascularization using a fractional flow reserve (FFR)–guided strategy in patients with diabetes mellitus (DM), we analyzed all DM patients who underwent FFR-guided revascularization from January 1, 2010, to December 12, 2013. Patients were divided into 2 groups: those with ≥1 remaining FFR-negative (>0.80) medically treated lesions [FFR(−)MT] and those with only FFR-positive lesions (≤0.80) who underwent complete revascularization [FFR(+)CR] and were followed until July 1, 2015. The primary end point was the incidence of major adverse cardiovascular events (MACE), a composite of death, myocardial infarction (MI), target lesion (FFR assessed) revascularization, and rehospitalization for acute coronary syndrome. A total of 294 patients, 205 (69.7%) versus 89 (30.3%) in FFR(−)MT and FFR(+)CR, respectively, were analyzed. At a mean follow-up of 32.6 ± 18.1 months, FFR(−)MT was associated with higher MACE rate 44.0% versus 26.6% (log-rank p = 0.02, Cox regression–adjusted hazard ratio [HR] 2.01, 95% confidence interval [CI] 1.21 to 3.33, p <0.01), and driven by both safety and efficacy end points: death/MI (HR 2.02, 95% CI 1.06 to 3.86, p = 0.03), rehospitalization for acute coronary syndrome (HR 2.06, 95% CI 1.03 to 4.10, p = 0.04), and target lesion revascularization (HR 3.38, 95% CI 1.19 to 9.64, p = 0.02). Previous MI was a strong effect modifier within the FFR(−)MT group (HR 1.98, 95% CI 1.26 to 3.13, p <0.01), whereas this was not the case in the FFR(+)CR group (HR 0.66, 95% CI 0.27 to 1.62, p = 0.37). Significant interaction for MACE was present between FFR groups and previous MI (p = 0.03). In conclusion, in patients with DM, particularly those with previous MI, deferred revascularization is associated with poor medium-term outcomes. Combining FFR with imaging techniques may be required to guide our treatment strategy in these patients with high-risk, fast-progressing atherosclerosis.
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      References

        • Windecker S.
        • Kolh P.
        • Alfonso F.
        • Collet J.P.
        • Cremer J.
        • Falk V.
        • Filippatos G.
        • Hamm C.
        • Head S.J.
        • Juni P.
        • Kappetein A.P.
        • Kastrati A.
        • Knuuti J.
        • Landmesser U.
        • Laufer G.
        • Neumann F.J.
        • Richter D.J.
        • Schauerte P.
        • Sousa Uva M.
        • Stefanini G.G.
        • Taggart D.P.
        • Torracca L.
        • Valgimigli M.
        • Wijns W.
        • Witkowski A.
        • Authors/Task Force Members
        2014 ESC/EACTS guidelines on myocardial revascularization: the Task Force on myocardial revascularization of the European Society of Cardiology (ESC) and the European association for Cardio-Thoracic Surgery (EACTS). Developed with the special contribution of the European Association of Percutaneous Cardiovascular Interventions (EAPCI).
        Eur Heart J. 2014; 35: 2541-2619
        • Bech G.J.W.
        • De Bruyne B.
        • Pijls N.H.J.
        • de Muinck E.D.
        • Hoorntje J.C.A.
        • Escaned J.
        • Stella P.R.
        • Boersma E.
        • Bartunek J.
        • Koolen J.J.
        • Wijns W.
        Fractional flow reserve to determine the appropriateness of angioplasty in moderate coronary stenosis—a randomized trial.
        Circulation. 2001; 103: 2928-2934
        • Tonino P.A.
        • De Bruyne B.
        • Pijls N.H.
        • Siebert U.
        • Ikeno F.
        • van't Veer M.
        • Klauss V.
        • Manoharan G.
        • Engstrom T.
        • Oldroyd K.G.
        • Ver Lee P.N.
        • MacCarthy P.A.
        • Fearon W.F.
        • FAME Study Investigators
        Fractional flow reserve versus angiography for guiding percutaneous coronary intervention.
        N Engl J Med. 2009; 360: 213-224
        • De Bruyne B.
        • Pijls N.H.
        • Kalesan B.
        • Barbato E.
        • Tonino P.A.
        • Piroth Z.
        • Jagic N.
        • Mobius-Winkler S.
        • Rioufol G.
        • Witt N.
        • Kala P.
        • MacCarthy P.
        • Engstrom T.
        • Oldroyd K.G.
        • Mavromatis K.
        • Manoharan G.
        • Verlee P.
        • Frobert O.
        • Curzen N.
        • Johnson J.B.
        • Juni P.
        • Fearon W.F.
        • FAME II Study Investigators
        Fractional flow reserve-guided PCI versus medical therapy in stable coronary disease.
        N Engl J Med. 2012; 367: 991-1001
        • Hambraeus K.
        • Jensevik K.
        • Lagerqvist B.
        • Lindahl B.
        • Carlsson R.
        • Farzaneh-Far R.
        • Kellerth T.
        • Omerovic E.
        • Stone G.
        • Varenhorst C.
        • James S.
        Long-term outcome of incomplete revascularization after percutaneous coronary intervention in SCAAR (Swedish Coronary Angiography and Angioplasty Registry).
        JACC Cardiovasc Interv. 2016; 9: 207-215
        • Goraya T.Y.
        • Leibson C.L.
        • Palumbo P.J.
        • Weston S.A.
        • Killian J.M.
        • Pfeifer E.A.
        • Jacobsen S.J.
        • Frye R.L.
        • Roger V.L.
        Coronary atherosclerosis in diabetes Mellitus a population-based autopsy study.
        J Am Coll Cardiol. 2002; 40: 946-953
        • Nicholls S.J.
        • Tuzcu E.M.
        • Kalidindi S.
        • Wolski K.
        • Moon K.W.
        • Sipahi I.
        • Schoenhagen P.
        • Nissen S.E.
        Effect of diabetes on progression of coronary atherosclerosis and arterial remodeling: a pooled analysis of 5 intravascular ultrasound trials.
        J Am Coll Cardiol. 2008; 52: 255-262
        • Sianos G.
        • Morel M.
        • Kappetein A.P.
        • Morice M.C.
        • Colombo A.
        • Dawkins K.
        • van den Brand M.
        • Van Dyck N.
        • Russell M.E.
        • Mohr F.W.
        • Serruys P.W.
        The SYNTAX score: an angiographic tool grading the complexity of coronary artery disease.
        EuroIntervention. 2005; 1: 219-227
        • Pijls N.H.
        • van Schaardenburgh P.
        • Manoharan G.
        • Boersma E.
        • Bech J.W.
        • van't Veer M.
        • Bar F.
        • Hoorntje J.
        • Koolen J.
        • Wijns W.
        • de Bruyne B.
        Percutaneous coronary intervention of functionally nonsignificant stenosis: 5-year follow-up of the DEFER Study.
        J Am Coll Cardiol. 2007; 49: 2105-2111
        • Jimenez-Quevedo P.
        • Sabate M.
        • Angiolillo D.
        • Alfonso F.
        • Hernandez-Antolin R.
        • Banuelos C.
        • Bernardo E.
        • Ramirez C.
        • Moreno R.
        • Fernandez C.
        • Escaned J.
        • Macaya C.
        LDL-cholesterol predicts negative coronary artery remodelling in diabetic patients: an intravascular ultrasound study.
        Eur Heart J. 2005; 26: 2307-2312
        • Stone G.W.
        • Maehara A.
        • Lansky A.J.
        • de Bruyne B.
        • Cristea E.
        • Mintz G.S.
        • Mehran R.
        • McPherson J.
        • Farhat N.
        • Marso S.P.
        • Parise H.
        • Templin B.
        • White R.
        • Zhang Z.
        • Serruys P.W.
        • PROSPECT Investigators
        A prospective natural-history study of coronary atherosclerosis.
        N Engl J Med. 2011; 364: 226-235
        • Marso S.P.
        • Mercado N.
        • Maehara A.
        • Weisz G.
        • Mintz G.S.
        • McPherson J.
        • Schiele F.
        • Dudek D.
        • Fahy M.
        • Xu K.
        • Lansky A.
        • Templin B.
        • Zhang Z.
        • de Bruyne B.
        • Serruys P.W.
        • Stone G.W.
        Plaque composition and clinical outcomes in acute coronary syndrome patients with metabolic syndrome or diabetes.
        JACC Cardiovasc Imaging. 2012; 5: S42-S52
        • Sabate M.
        • Jimenez-Quevedo P.
        • Angiolillo D.J.
        • Gomez-Hospital J.A.
        • Alfonso F.
        • Hernandez-Antolin R.
        • Goicolea J.
        • Banuelos C.
        • Escaned J.
        • Moreno R.
        • Fernandez C.
        • Fernandez-Aviles F.
        • Macaya C.
        • DIABETES Investigators
        Randomized comparison of sirolimus-eluting stent versus standard stent for percutaneous coronary revascularization in diabetic patients: the diabetes and sirolimus-eluting stent (DIABETES) trial.
        Circulation. 2005; 112: 2175-2183
        • Farkouh M.E.
        • Domanski M.
        • Sleeper L.A.
        • Siami F.S.
        • Dangas G.
        • Mack M.
        • Yang M.
        • Cohen D.J.
        • Rosenberg Y.
        • Solomon S.D.
        • Desai A.S.
        • Gersh B.J.
        • Magnuson E.A.
        • Lansky A.
        • Boineau R.
        • Weinberger J.
        • Ramanathan K.
        • Sousa J.E.
        • Rankin J.
        • Bhargava B.
        • Buse J.
        • Hueb W.
        • Smith C.R.
        • Muratov V.
        • Bansilal S.
        • King III, S.
        • Bertrand M.
        • Fuster V.
        • FREEDOM Trial Investigators
        Strategies for multivessel revascularization in patients with diabetes.
        N Engl J Med. 2012; 367: 2375-2384
        • Serruys P.W.
        • Morice M.C.
        • Kappetein A.P.
        • Colombo A.
        • Holmes D.R.
        • Mack M.J.
        • Stahle E.
        • Feldman T.E.
        • van den Brand M.
        • Bass E.J.
        • Van Dyck N.
        • Leadley K.
        • Dawkins K.D.
        • Mohr F.W.
        • SYNTAX Investigators
        Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease.
        N Engl J Med. 2009; 360: 961-972
        • Rosner G.F.
        • Kirtane A.J.
        • Genereux P.
        • Lansky A.J.
        • Cristea E.
        • Gersh B.J.
        • Weisz G.
        • Parise H.
        • Fahy M.
        • Mehran R.
        • Stone G.W.
        Impact of the presence and extent of incomplete angiographic revascularization after percutaneous coronary intervention in acute coronary syndromes: the Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial.
        Circulation. 2012; 125: 2613-2620
        • Masrani Mehta S.
        • Depta J.P.
        • Novak E.
        • Patel J.S.
        • Patel Y.
        • Raymer D.
        • Facey G.
        • Zajarias A.
        • Lasala J.M.
        • Singh J.
        • Bach R.G.
        • Kurz H.I.
        Association of lower fractional flow reserve values with higher risk of adverse cardiac events for lesions deferred revascularization among patients with acute coronary syndrome.
        J Am Heart Assoc. 2015; 4: e002172
        • Kato K.
        • Yonetsu T.
        • Kim S.J.
        • Xing L.
        • Lee H.
        • McNulty I.
        • Yeh R.W.
        • Sakhuja R.
        • Zhang S.
        • Uemura S.
        • Yu B.
        • Mizuno K.
        • Jang I.K.
        Comparison of nonculprit coronary plaque characteristics between patients with and without diabetes: a 3-vessel optical coherence tomography study.
        JACC Cardiovasc Interv. 2012; 5: 1150-1158
        • Kedhi E.
        • Kennedy M.W.
        • Maehara A.
        • Lansky A.J.
        • McAndrew T.C.
        • Marso S.P.
        • De Bruyne B.
        • Serruys P.W.
        • Stone G.W.
        Impact of TCFA on unanticipated ischemic events in medically treated diabetes Mellitus. Insights from the PROSPECT study.
        JACC Cardiovasc Imaging. 2016; ([E-pub ahead of print])https://doi.org/10.1016/j.jcmg.2015.12.023
        • Bezerra H.G.
        • Costa M.A.
        • Guagliumi G.
        • Rollins A.M.
        • Simon D.I.
        Intracoronary optical coherence tomography: a comprehensive review clinical and research applications.
        JACC Cardiovasc Interv. 2009; 2: 1035-1046
        • Jang I.K.
        Near infrared spectroscopy: another toy or indispensible diagnostic tool?.
        Circ Cardiovasc Interv. 2012; 5: 10-11
        • Erlinge D.
        • Stone G.W.
        A multicentre prospective natural history study using multimodality imaging in patients with acute coronary syndromes—PROSPECT II (Natural History Study), combined with a randomized, controlled, intervention study—PROSPECT ABSORB (Randomized Trial).
        (Available at:) (Accessed on June 30, 2016. ClinicalTrials.gov Identifier: NCT02171065)
        • Kedhi E.
        Combined Optical Coherence Tomography Morphologic and Fractional Flow Reserve Hemodynamic Assessment of Non-culprit Lesions to Better Predict Adverse Event Outcomes in Diabetes Mellitus Patients COMBINE (OCT-ffr) Prospective Register.
        (Available at:) (Accessed on June 30, 2016. Netherlands Trial Register: NTR5376)
        • Kataoka Y.
        • Yasuda S.
        • Miyamoto Y.
        • Sase K.
        • Kosuge M.
        • Kimura K.
        • Yoshimasa Y.
        • Miyazaki S.
        • DIANA Study Investigators
        Clinical predictors of atheroma progression despite optimal glycemic control in early-stage diabetic patients with coronary artery disease: insight from the DIANA study.
        J Atheroscler Thromb. 2014; 21: 509-518
        • Nissen S.E.
        • Nicholls S.J.
        • Sipahi I.
        • Libby P.
        • Raichlen J.S.
        • Ballantyne C.M.
        • Davignon J.
        • Erbel R.
        • Fruchart J.C.
        • Tardif J.C.
        • Schoenhagen P.
        • Crowe T.
        • Cain V.
        • Wolski K.
        • Goormastic M.
        • Tuzcu E.M.
        • for the ASTEROID Investigators
        Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the asteroid trial.
        JAMA. 2006; 295: 1556-1565
        • Lindsey J.B.
        • House J.A.
        • Kennedy K.F.
        • Marso S.P.
        Diabetes duration is associated with increased thin-cap fibroatheroma detected by intravascular ultrasound with virtual histology.
        Circ Cardiovasc Interv. 2009; 2: 543-548