Myocardial protective effect of intracoronary administration of nicorandil and alprostadil via targeted perfusion microcatheter in patients undergoing elective percutaneous coronary intervention: A randomized controlled trial

Weifeng Zhang, Jinjie Dai, Xiaowen Zheng, Ke Xu, Xiaoxiao Yang, Lan Shen, Xiaolei Wang, Ziyong Hao, Xingbiao Qiu, Lisheng Jiang, Hongyu Shi, Linghong Shen, Ben He, Weifeng Zhang, Jinjie Dai, Xiaowen Zheng, Ke Xu, Xiaoxiao Yang, Lan Shen, Xiaolei Wang, Ziyong Hao, Xingbiao Qiu, Lisheng Jiang, Hongyu Shi, Linghong Shen, Ben He

Abstract

Background: The aim of the study was to evaluate the efficacy of nicorandil and alprostadil on myocardial protection in patients undergoing elective percutaneous coronary intervention (PCI).

Methods: In this prospective, single-blinded, randomized controlled study, 90 consecutive patients scheduled for elective PCI for de novo coronary lesions were assigned to the nicorandil, alprostadil, and nitroglycerin groups in a 1:1:1 ratio. Drugs were administered intracoronary via a targeted perfusion microcatheter. The primary endpoint was the thrombolysis in myocardial infarction (TIMI) myocardial perfusion frame count (TMPFC). Additionally, the corrected TIMI frame count (cTFC), TIMI myocardial perfusion grade (TMPG), and incidence of periprocedural myocardial injury (PMI) were assessed.

Results: Both nicorandil and alprostadil were significantly effective in reducing TMPFC (114.6 ± 33.7 vs 93.4 ± 30.9, P = .016; 114.3 ± 34.3 vs 94.7 ± 33.3, P = .029, respectively). Similar findings were observed in the improvement of cTFC (20.3 ± 10.5 vs 13.5 ± 5.0, P = .003; 20.2 ± 7.4 vs 15.2 ± 5.2, P = .003, respectively) and percentage of TMPG 3 (100% vs 82.8%, P = .052; 83.3% vs 96.7%, P = .196, respectively); whereas, nitroglycerin produced a limited effect on TMPFC (114.4 ± 30.9 vs 112.1 ± 31.9, P = .739), cTFC (19.4 ± 7.2 vs 19.3 ± 7.2, P = .936), and percentage of TMPG 3 (86.7% vs 86.7%, P = 1.000). No significant difference was found in the incidence of PMI (16.7% vs 16.0% vs 27.6%, P = .537), though it was comparatively lower in the nicorandil and alprostadil groups. Furthermore, the intracoronary administration of nicorandil and alprostadil had a mild effect on blood pressure and heart rate.

Conclusions: The intracoronary administration of nicorandil and alprostadil via a targeted perfusion microcatheter was more effective in improving myocardial perfusion in patients undergoing elective PCI than nitroglycerin.

Trial registration: ClinicalTrials.gov NCT03252665.

Conflict of interest statement

The authors report no conflicts of interest.

Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.

Figures

Figure 1
Figure 1
The time course of TMPFC for myocardial perfusion in a patient after successful revascularization of the left anterior descending artery. The opacification of the myocardium occurred at the 17th frame. This frame was thus taken as the first frame of TMPFC (F1). The last frame of TMPFC was the 66th frame, where the contrast was washed out (F2). TMPFC was therefore (F2 − F1) × 2 = (66−17) × 2 = 98 frames, which indicates the myocardial perfusion time for this artery. TMPFC, thrombolysis in myocardial infarction myocardial perfusion frame count.
Figure 2
Figure 2
The time course of TMPFC for myocardial perfusion in a patient after successful revascularization of the right coronary artery. The opacification of the myocardium occurred at the 19th frame. This frame was thus taken as the first frame of TMPFC (F1). The last frame of TMPFC was the 70th frame, where the contrast was washed out (F2). TMPFC was therefore (F2−F1) × 2 = (70−19) × 2 = 102 frames, which indicates the myocardial perfusion time for this artery. TMPFC, thrombolysis in myocardial infarction myocardial perfusion frame count.
Figure 3
Figure 3
Efficacy of nicorandil, alprostadil, and nitroglycerin in ameliorating myocardial perfusion. (A) to (C): TMPFC, cTFC, and TMPG in the nicorandil group; (D) to (F): TMPFC, cTFC, and TMPG in the alprostadil group; (G) to (I): TMPFC, cTFC, and TMPG in the nitroglycerin group. TMPFC, thrombolysis in myocardial infarction myocardial perfusion frame count; cTFC, corrected thrombolysis in myocardial infarction frame count; TMPG, thrombolysis in myocardial infarction myocardial perfusion grade. ∗P < .05; ∗∗P < .01.

References

    1. Task Force M, Montalescot G, Sechtem U, et al. . 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34:2949–3003.
    1. Fihn SD, Blankenship JC, Alexander KP, et al. . 2014ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2014;130:1749–67.
    1. Prasad A, Herrmann J. Myocardial infarction due to percutaneous coronary intervention. N Engl J Med 2011;364:453–64.
    1. Babu GG, Walker JM, Yellon DM, et al. . Peri-procedural myocardial injury during percutaneous coronary intervention: an important target for cardioprotection. Eur Heart J 2011;32:23–31.
    1. Fan Y, Jiang Y, Fu X, et al. . Effects of liposomal prostaglandin E1 on periprocedural myocardial injury in patients with unstable angina undergoing an elective percutaneous coronary intervention. Coron Artery Dis 2015;26:671–7.
    1. Ota S, Nishikawa H, Takeuchi M, et al. . Impact of nicorandil to prevent reperfusion injury in patients with acute myocardial infarction: Sigmart Multicenter Angioplasty Revascularization Trial (SMART). Circ J 2006;70:1099–104.
    1. Lee HC, An SG, Choi JH, et al. . Effect of intra-coronary nicorandil administration prior to reperfusion in acute ST segment elevation myocardial infarction. Circ J 2008;72:1425–9.
    1. Kawai Y, Hisamatsu K, Matsubara H, et al. . Intravenous administration of nicorandil immediately before percutaneous coronary intervention can prevent slow coronary flow phenomenon. Eur Heart J 2009;30:765–72.
    1. Qi Q, Niu J, Chen T, et al. . Intracoronary nicorandil and the prevention of the no-reflow phenomenon during primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction. Med Sci Monit 2018;24:2767–76.
    1. Sheng X, Ding S, Ge H, et al. . Intracoronary infusion of alprostadil and nitroglycerin with targeted perfusion microcatheter in STEMI patients with coronary slow flow phenomenon. Int J Cardiol 2018;265:06–11.
    1. Dehmer GJ, Blankenship JC, Cilingiroglu M, et al. . SCAI/ACC/AHA expert consensus document: 2014 update on percutaneous coronary intervention without on-site surgical backup. Circulation 2014;129:2610–26.
    1. Jang HJ, Koo BK, Lee HS, et al. . Safety and efficacy of a novel hyperaemic agent, intracoronary nicorandil, for invasive physiological assessments in the cardiac catheterization laboratory. Eur Heart J 2013;34:2055–62.
    1. Ding S, Pu J, Qiao ZQ, et al. . TIMI myocardial perfusion frame count: a new method to assess myocardial perfusion and its predictive value for short-term prognosis. Catheter Cardiovasc Interv 2010;75:722–32.
    1. Ge H, Ding S, An D, et al. . Frame counting improves the assessment of post-reperfusion microvascular patency by TIMI myocardial perfusion grade: evidence from cardiac magnetic resonance imaging. Int J Cardiol 2016;203:360–6.
    1. Gibson CM, Cannon CP, Daley WL, et al. . TIMI frame count: a quantitative method of assessing coronary artery flow. Circulation 1996;93:879–88.
    1. Thygesen K, Alpert JS, Jaffe AS, et al. . Fourth Universal Definition of Myocardial Infarction (2018). J Am Coll Cardiol 2018;72:2231–64.
    1. Su Q, Li L, Liu Y. Short-term effect of verapamil on coronary no-reflow associated with percutaneous coronary intervention in patients with acute coronary syndrome: a systematic review and meta-analysis of randomized controlled trials. Clin Cardiol 2013;36:E11–16.
    1. Huang D, Qian J, Ge L, et al. . REstoration of COronary flow in patients with no-reflow after primary coronary interVEntion of acute myocaRdial infarction (RECOVER). Am Heart J 2012;164:394–401.
    1. Niu X, Zhang J, Bai M, et al. . Effect of intracoronary agents on the no-reflow phenomenon during primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction: a network meta-analysis. BMC Cardiovasc Disord 2018;18:03.
    1. Huang RI, Patel P, Walinsky P, et al. . Efficacy of intracoronary nicardipine in the treatment of no-reflow during percutaneous coronary intervention. Catheter Cardiovasc Interv 2006;68:671–6.
    1. Mehta HH, Morris M, Fischman DL, et al. . The spontaneous coronary slow-flow phenomenon: reversal by intracoronary nicardipine. J Invasive Cardiol 2019;31:42–5.
    1. Akai K, Wang Y, Sato K, et al. . Vasodilatory effect of nicorandil on coronary arterial microvessels: its dependency on vessel size and the involvement of the ATP-sensitive potassium channels. J Cardiovasc Pharmacol 1995;26:541–7.
    1. Group IS. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet 2002;359:1269–75.
    1. Shen J, He B, Wang B. Effects of lipo-prostaglandin E1 on pulmonary hemodynamics and clinical outcomes in patients with pulmonary arterial hypertension. Chest 2005;128:714–9.
    1. Wheatley RM, Dockery SP, Kurz MA, et al. . Interactions of nitroglycerin and sulfhydryl-donating compounds in coronary microvessels. Am J Physiol 1994;266(1 Pt 2):H291–297.
    1. Piana RN, Paik GY, Moscucci M, et al. . Incidence and treatment of ’no-reflow’ after percutaneous coronary intervention. Circulation 1994;89:2514–8.
    1. Fugit MD, Rubal BJ, Donovan DJ. Effects of intracoronary nicardipine, diltiazem and verapamil on coronary blood flow. J Invasive Cardiol 2000;12:80–5.
    1. Gibson CM, Cannon CP, Murphy SA, et al. . Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs. Circulation 2000;101:125–30.
    1. Gibson CM, Cannon CP, Murphy SA, et al. . Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction. Circulation 2002;105:1909–13.
    1. Gibson CM, Pride YB, Buros JL, et al. . Association of impaired thrombolysis in myocardial infarction myocardial perfusion grade with ventricular tachycardia and ventricular fibrillation following fibrinolytic therapy for ST-segment elevation myocardial infarction. J Am Coll Cardiol 2008;51:546–51.
    1. Bethke A, Shanmuganathan L, Andersen GO, et al. . Microvascular perfusion in infarcted and remote myocardium after successful primary PCI: angiographic and CMR findings. Eur Radiol 2019;29:941–50.
    1. Zeitouni M, Silvain J, Guedeney P, et al. . Periprocedural myocardial infarction and injury in elective coronary stenting. Eur Heart J 2018;39:1100–9.
    1. Idris H, Lo S, Shugman IM, et al. . Varying definitions for periprocedural myocardial infarction alter event rates and prognostic implications. J Am Heart Assoc 2014;3:e001086.
    1. Kim SJ, Kim W, Woo JS, et al. . Effect of myocardial protection of intracoronary adenosine and nicorandil injection in patients undergoing non-urgent percutaneous coronary intervention: a randomized controlled trial. Int J Cardiol 2012;158:88–92.
    1. Hwang J, Lee HC, Kim BW, et al. . Effect on periprocedural myocardial infarction of intra-coronary nicorandil prior to percutaneous coronary intervention in stable and unstable angina. J Cardiol 2013;62:77–81.
    1. Pang Z, Zhao W, Yao Z. Cardioprotective effects of nicorandil on coronary heart disease patients undergoing elective percutaneous coronary intervention. Med Sci Monit 2017;23:2924–30.
    1. Ye Z, Su Q, Li L. The clinical effect of nicorandil on perioperative myocardial protection in patients undergoing elective PCI: a systematic review and meta-analysis. Sci Rep 2017;7:45117.
    1. Zhu H, Xu X, Fang X, et al. . Effects of mitochondrial ATP-sensitive potassium channel activation (nicorandil) in patients with angina pectoris undergoing elective percutaneous coronary interventions: a meta-analysis of randomized controlled trials. Medicine (Baltimore) 2019;98:e14165.
    1. Menees DS, Peterson ED, Wang Y, et al. . Door-to-balloon time and mortality among patients undergoing primary PCI. N Engl J Med 2013;369:901–9.
    1. Niccoli G, Scalone G, Lerman A, et al. . Coronary microvascular obstruction in acute myocardial infarction. Eur Heart J 2016;37:1024–33.
    1. Niccoli G, Burzotta F, Galiuto L, et al. . Myocardial no-reflow in humans. J Am Coll Cardiol 2009;54:281–92.
    1. de Waha S, Patel MR, Granger CB, et al. . Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: an individual patient data pooled analysis from seven randomized trials. Eur Heart J 2017;38:3502–10.
    1. Niccoli G, Montone RA, Ibanez B, et al. . Optimized treatment of ST-elevation myocardial infarction. Circ Res 2019;125:245–58.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe