Efficacy of Verapamil Injection into the Saphenous Vein Graft Before Percutaneous Coronary Intervention in Preventing Slow-Flow and No-Reflow

Document Type : Original Article


1 Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

2 Rajaie Cardiovascular, Medical, and Research Center, Iran University of Medical Sciences, Tehran, IR Iran.

3 San Joaquin General Hospital, CA, USA.


Background: Degenerative plaques in the saphenous vein graft (SVG) are prone to embolization during percutaneous coronary intervention (PCI), resulting in the slow-flow or no-reflow phenomenon and unfavorable PCI outcomes.
Methods: This prospective cohort study was conducted on 63 patients who underwent PCI on the SVG divided into 2 groups. The case group (n=32) received 200 μg of verapamil injection into the SVG before PCI, and the control group (n=31) did not receive verapamil. The primary endpoints comprised slow-flow or no-reflow, the thrombolysis in myocardial infarction (TIMI) flow grade, the TIMI frame count, and the TIMI myocardial perfusion grade after PCI. The secondary endpoints consisted of unstable angina and major adverse cardiac events, defined as a composite of total death, ST-segment or non–ST-segment elevation myocardial infarction, cerebrovascular accident, hospitalization due to heart failure, and revascularization (PCI and coronary artery bypass grafting) during hospitalization and a 3-month follow-up.
Results: The patients who received verapamil injection, compared with the control group, had significantly low rates of slow-flow and no-reflow (4.8% vs 17.5%; P=0.01) and favorable TIMI frame counts (46% vs 12%; P<0.01), TIMI flow grades (31.7% vs 14.3%; P=0.015), and TIMI myocardial perfusion grades (34.9% vs 9.5%; P=0.001). There were no differences in the secondary outcomes during both hospital stay and the 3-month follow-up.
Conclusions: Our study demonstrated that verapamil injection into the SVG before PCI significantly decreased the rate of postprocedural slow-flow and no-reflow and conferred favorable TIMI flow grades, TIMI frame counts, and TIMI myocardial perfusion grades. (Iranian Heart Journal 2021; 22(2): 101-109)


  1. Michael S Lee, Seung-Jung Park, David E Kandzari, Ajay J Kirtane, William F Fearon, Emmanouil S Brilakis, et al. Saphenous Vein Graft Intervention, JACC: cardiovascular intervention, 2011;4: 8.
  1. Fitzgibbon GM, Kafka HP, Leach AJ, Keon WJ, Hooper GD, Burton JR. Coronary bypass graft fate and patient outcome: angiographic follow-up of 5,065 grafts related to survival and reoperation in 1,388 patients during 25 years. J Am CollCardiol 1996; 28:616-26.
  2. Jessica Forcillo, MD-MSc, and Louis P. Perrault, MD, PhD. Prevention of Venous Graft Disease After Coronary Artery Bypass Grafting: Is Ex Vivo Statin Exposure an Answer? , Canadian Journal of Cardiology 28 (2012) 623-25.
  3. Fremes SE, Levinton C, Naylor CD, Chen E, Christakis GT, Goldman BS. Optimal antithrombotic therapy following aortocoronary bypass: a meta-analysis. Eur J CardiothoracSurg 1993; 7:169-80.
  4. M K Hong, R Mehran, G Dangas, G S Mintz, A J Lansky, A D Pichard, et al. Creatine kinase-MB enzyme elevation following successful saphenous vein graft intervention is associated with late mortality. Circulation. 1999; 100(24):2400-5.
  5. R M Califf, A E Abdelmeguid, R E Kuntz, J J Popma, C J Davidson, E A Cohen, et al. Myonecrosis after revascularization procedures. J Am CollCardiol. 1998; 31(2):241-51.
  6. R A Kloner, R E Rude, N Carlson, P R Maroko, L W DeBoer, E Braunwald. Ultrastructural evidence of microvascular damage and myocardial cell injury after coronary artery occlusion: which comes first? Circulation. 1980; 62(5):945-52.
  7. Van Gaal WJ, Banning AP. Percutaneous coronary intervention and the no-reflow phenomenon. Expert Rev CardiovascTher. 2007:5(4); 715-31.
  8. Vindhya Hindnavis, MD, Sung-Hae Cho, MD, Sheldon Goldberg, MD, Saphenous Vein Graft Intervention: A Review. 2012; 20:3.
  9. Chi-Hang Lee, Adrian Low, Bee-Choo Tai, Melissa Co, Mark Y Chan, Jimmy Lim, et al. Pretreatment with intracoronary adenosine reduces the incidence of myonecrosis after non-urgent percutaneous coronary intervention: a prospective randomized study. Eur Heart J. 2007; 28(1):19-25.
  10. Desmet WJ, Dens J, Coussement P, Van de Werf F. Does adenosine prevent myocardial micronecrosis following percutaneous coronary intervention? The ADELINE pilot trial. ADEnosineLImit myocardial Necrosis. Heart. 2002; 88(3):293-5.
  11. J A Watts, E M Hawes, S H Jenkins, T C Williams Effects of nisoldipine on the no-reflow phenomenon in globally ischemic rat hearts. J Cardiovasc Pharmacol. 1990:16(3):487-94.
  12. B Villari, G Ambrosio, P Golino, M Ragni, A Focaccio, I Tritto, et al. The effects of calcium channel antagonist treatment and oxygen radical scavenging on infarct size and the no-reflow phenomenon in reperfused hearts. Am Heart J. 1993; 125(1):11-23.
  13. Y Taniyama, H Ito, K Iwakura, T Masuyama, M Hori, S Takiuchi, N Nishikawa, et al. Beneficial effect of intracoronary verapamil on microvascular and myocardial salvage in patients with acute myocardial infarction. J Am Coll Cardiol. 1997:30(5):1193-9.
  14. Fugit MD, Rubal BJ, Donovan DJ. Effects of intracoronary nicardipine, diltiazem and verapamil on coronary blood flow. J Invasive Cardiol. 2000:12(2):80-5.
  15. K Vijayalakshmi, V J Whittaker, B Kunadian, J Graham, R A Wright, J A Hall, et al. Prospective, randomized, controlled trial to study the effect of intracoronary injection of verapamil and adenosine on coronary blood flow during percutaneous coronary intervention in patients with acute coronary syndromes. Heart. 2006:92(9):1278-84.
  16. Andrew D Michaels, Mark Appleby, Matthew H Otten, Kent Dauterman, Thomas A Ports, Tony M Chou, C Michael Gibson. Pretreatment with intragraft verapamil prior to percutaneous coronary intervention of saphenous vein graft lesions: results of the randomized, controlled vasodilator prevention on no-reflow (VAPOR) trial. J Invasive Cardiol. 2002; 14(6):299-302.
  17. B M Kaplan, K H Benzuly, J W Kinn, T R Bowers, F V Tilli, C L Grines, et al. Treatment of no-reflow in degenerate saphenous vein graft interventions: comparison of intracoronary verapamil and nitroglycerin. Cathet Cardiovasc Diagn. 1996; 39(2):113-8.
  18. R N Piana, G Y Paik, M Moscucci, D J Cohen, C M Gibson, AD Kugelmass, et al. Incidence and treatment of “no re-flow” after percutaneous coronary intervention. Circulation. 1994; 89(6):2514-8.
  19. Sharma S, Lardizabal JA, Singh S, Sandhu R, Bhambi BK. Intra-Graft Abciximab and Verapamil Combined with Direct Stenting is a Safe and Effective Strategy to Prevent Slow-flow and No-Reflow Phenomenon in Saphenous Vein Graft Lesions not Associated with Thrombus, Recent Patents on Cardiovascular Drug Discovery, 2012; 7:152-9.
  20. Abu Arab T, Rafik R, El Etriby A, Efficacy and Safety of Local Intracoronary Drug Delivery in Treatment of No-Reflow Phenomenon: A Pilot Study. J IntervCardiol. 2016 Oct; 29(5):496-504.
  21. Jalinus F, Mooney JA, Mooney MR. Pretreatment with intracoronary diltiazem reduces non-Q wave myocardial infarction following directional atherectomy. J InvasCardiol 1997; 9:270-3.
  22. Saito K, Nonogi H, Goto Y, Itoh A, Daikoku S, Miyazaki S, Haze K. Antiischemic effect of intracoronary diltiazem on myocardial ischemia during PTCA. Heart Vessels. 1996; 11(2):92-9.