OBJECTIVES: INCORPORATE trial was designed to evaluate whether default coronary-angiography (CA) and ischemia-targeted revascularization is superior compared to a conservative approach for patients with treated critical limb ischemia (CLI). Registered at clinicaltrials.gov (NCT03712644) on October 19, 2018. BACKGROUND: Severe peripheral artery disease is associated with increased cardiovascular risk and poor outcomes. METHODS: INCORPORATE was an open-label, prospective 1:1 randomized multicentric trial that recruited patients who had undergone successful CLI treatment. Patients were randomized to either a conservative or invasive approach regarding potential coronary artery disease (CAD). The conservative group received optimal medical therapy alone, while the invasive group had routine CA and fractional flow reserve-guided revascularization. The primary endpoint was myocardial infarction (MI) and 12-month mortality. RESULTS: Due to COVID-19 pandemic burdens, recruitment was halted prematurely. One hundred eighty-five patients were enrolled. Baseline cardiac symptoms were scarce with 92% being asymptomatic. Eighty-nine patients were randomized to the invasive approach of whom 73 underwent CA. Thirty-four percent had functional single-vessel disease, 26% had functional multi-vessel disease, and 90% achieved complete revascularization. Conservative and invasive groups had similar incidences of death and MI at 1 year (11% vs 10%; hazard ratio 1.21 [0.49-2.98]). Major adverse cardiac and cerebrovascular events (MACCE) trended for hazard in the Conservative group (20 vs 10%; hazard ratio 1.94 [0.90-4.19]). In the per-protocol analysis, the primary endpoint remained insignificantly different (11% vs 7%; hazard ratio 2.01 [0.72-5.57]), but the conservative approach had a higher MACCE risk (20% vs 7%; hazard ratio 2.88 [1.24-6.68]). CONCLUSION: This trial found no significant difference in the primary endpoint but observed a trend of higher MACCE in the conservative arm.

2 Dept of Cardiology Medical College Jagiellonian University Krakow Poland

Department of Advanced Biomedical Sciences University of Naples Federico 2 Naples Italy

Department of Cardiology Faculty of Medicine Doctoral School of Clinical Medicine University of Szeged Szeged Hungary

Department of Cardiology University Heart Center Graz Medical University Graz Graz Austria

Department of Cardiology University of Zagreb School of Medicine Sestre Milosrdnice University Hospital Center Zagreb Croatia

Department of Clinical and Molecular Medicine Sapienza University of Rome Rome Italy

Department of Invasive Cardiology Centre of Postgraduate Medical Education Warsaw Poland

Department of Medicine and Surgery Research Unit of Cardiovascular Science Università Campus Bio Medico Di Roma and Fondazione Policlinico Universitario Campus Bio Medico Rome Italy

Division of Angiology Department of Internal Medicine Medical University Graz Graz Austria

E Meshalkin National Medical Research Center of the Ministry of Health of the Russian Federation Novosibirsk Russia

National Medical Institute of the Internal Affairs and Administration Ministry Warsaw Poland

Royal Cornwall Hospitals NHS Trust Truro UK

University Hospital Brno and Medical Faculty of Masaryk University Brno Czech Republic

Clin Res Cardiol. 2025 May;114(5):679. doi: 10.1007/s00392-024-02501-7. PubMed

Zobrazit více v PubMed

Teraa M, Conte MS, Moll FL, Verhaar MC (2016) Critical limb ischemia: current trends and future directions. J Am Heart Assoc 5. 10.1161/JAHA.115.002938 PubMed PMC

Adam DJ, Beard JD, Cleveland T et al (2005) Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet 366:1925–1934. 10.1016/S0140-6736(05)67704-5 PubMed

Bradbury AW, Adam DJ, Bell J et al (2010) Bypass versus angioplasty in severe ischaemia of the leg (BASIL) trial: an intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy. J Vasc Surg 51:5S-17S. 10.1016/j.jvs.2010.01.073 PubMed

Farooq V, Serruys PW, Bourantas C et al (2012) Incidence and multivariable correlates of long-term mortality in patients treated with surgical or percutaneous revascularization in the synergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX) trial. Eur Heart J 33:3105–3113. 10.1093/eurheartj/ehs367 PubMed

Farooq V, van Klaveren D, Steyerberg EW et al (2013) Anatomical and clinical characteristics to guide decision making between coronary artery bypass surgery and percutaneous coronary intervention for individual patients: development and validation of SYNTAX score II. Lancet 381:639–650. 10.1016/S0140-6736(13)60108-7 PubMed

Toth G, Hamilos M, Pyxaras S et al (2014) Evolving concepts of angiogram: fractional flow reserve discordances in 4000 coronary stenoses. Eur Heart J 35:2831–2838. 10.1093/eurheartj/ehu094 PubMed

Lee MS, Rha S-W, Han SK et al (2015) Clinical outcomes of patients with critical limb ischemia who undergo routine coronary angiography and subsequent percutaneous coronary intervention. J Invasive Cardiol 27:213–217 PubMed

Neumann F-J, Sousa-Uva M, Ahlsson A et al (2019) 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 40:87–165. 10.1093/eurheartj/ehy394 PubMed

Mielniczuk LM, Toth GG, Xie JX et al (2017) Can functional testing for ischemia and viability guide revascularization? JACC Cardiovasc Imaging 10:354–364. 10.1016/j.jcmg.2016.12.011 PubMed

Toth G, Brodmann M, Barbato E et al (2019) Rational and design of the INtentional COronary revascularization versus conservative therapy in patients undergOing successful peripheRAl arTEry revascularization due to critical limb ischemia trial (INCORPORATE trial). Am Heart J 214:107–112. 10.1016/j.ahj.2019.05.005 PubMed

Hardman R, Jazaeri O, Yi J et al (2014) Overview of classification systems in peripheral artery disease. Semin Intervent Radiol 31:378–388. 10.1055/s-0034-1393976 PubMed PMC

Perera D, Clayton T, O’Kane PD et al (2022) Percutaneous revascularization for ischemic left ventricular dysfunction. N Engl J Med. 10.1056/NEJMoa2206606 PubMed

Al-Lamee R, Thompson D, Dehbi H-M et al (2018) Percutaneous coronary intervention in stable angina (ORBITA): a double-blind, randomised controlled trial. The Lancet 391:31–40. 10.1016/S0140-6736(17)32714-9 PubMed

Maron DJ, Hochman JS, Reynolds HR et al (2020) Initial invasive or conservative strategy for stable coronary disease. N Engl J Med 382:1395–1407. 10.1056/NEJMoa1915922 PubMed PMC

Xaplanteris P, Fournier S, Pijls NHJ et al (2018) Five-year outcomes with PCI guided by fractional flow reserve. N Engl J Med 379:250–259. 10.1056/NEJMoa1803538 PubMed

Zimmermann FM, Omerovic E, Fournier S et al (2019) Fractional flow reserve-guided percutaneous coronary intervention vs. medical therapy for patients with stable coronary lesions: meta-analysis of individual patient data. Eur Heart J 40:180–186. 10.1093/eurheartj/ehy812 PubMed PMC

Dagenais GR, Lu J, Faxon DP et al (2013) Prognostic impact of the presence and absence of angina on mortality and cardiovascular outcomes in patients with type 2 diabetes and stable coronary artery disease. J Am Coll Cardiol 61:702–711. 10.1016/j.jacc.2012.11.036 PubMed PMC

Poredoš P, Jug B (2007) The prevalence of peripheral arterial disease in high risk subjects and coronary or cerebrovascular patients. Angiology 58:309–315. 10.1177/0003319707302494 PubMed

Hiatt WR, Goldstone J, Smith SC et al (2008) Atherosclerotic peripheral vascular disease symposium II. Circulation 118:2826–2829. 10.1161/CIRCULATIONAHA.108.191171 PubMed

Murabito JM, Evans JC, Nieto K et al (2002) Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. Am Heart J 143:961–965. 10.1067/mhj.2002.122871 PubMed

Criqui MH, Langer RD, Fronek A et al (1992) Mortality over a period of 10 years in patients with peripheral arterial disease. N Engl J Med 326:381–386. 10.1056/NEJM199202063260605 PubMed

McKenna M, Wolfson S, Kuller L (1991) The ratio of ankle and arm arterial pressure as an independent predictor of mortality. Atherosclerosis 87:119–128. 10.1016/0021-9150(91)90014-T PubMed

Knuuti J, Ballo H, Juarez-Orozco LE et al (2018) The performance of non-invasive tests to rule-in and rule-out significant coronary artery stenosis in patients with stable angina: a meta-analysis focused on post-test disease probability. Eur Heart J 39:3322–3330. 10.1093/eurheartj/ehy267 PubMed

Andreini D, Collet C, Leipsic J et al (2022) Pre-procedural planning of coronary revascularization by cardiac computed tomography: an expert consensus document of the Society of Cardiovascular Computed Tomography. EuroIntervention 18:e872–e887. 10.4244/EIJ-E-22-00036 PubMed PMC

McFalls EO, Ward HB, Moritz TE et al (2004) Coronary-artery revascularization before elective major vascular surgery. N Engl J Med 351:2795–2804. 10.1056/NEJMoa041905 PubMed

Zobrazit více v PubMed

ClinicalTrials.gov
NCT03712644