A comparison of the effects of ticagrelor and clopidogrel on development of no-reflow phenomenon after percutaneous coronary intervention in patients with acute myocardial infarction

Öz

Aim: No-reflow phenomenon (NRP) is one of the significant factors affecting reperfusion. This study aimed to compare effects of preloading ticagrelor versus clopidogrel on development of NRP in patients with acute myocardial infarction (AMI), who underwent percutaneous coronary intervention (PCI). Method: Our retrospective single-center study included 200 patients, who underwent PCI due to AMI. Patients were classified as the patients preloaded with clopidogrel and ticagrelor based on the antiplatelet regimen administered before PCI. NRP criteria were determined according to the TIMI grade flow or ST-segment resolution after the procedure. The effect of ticagrelor and clopidogrel on NRP and the significance of the difference in specified parameters between patients with no-reflow and normal flow were evaluated. Results: There was no difference between patients with no-reflow and normal flow in terms of baseline characteristics. Number of patients with ST-elevation myocardial infarction was higher in patients preloaded with ticagrelor (p= 0.013). Age, aspartate aminotransferase (AST) and C-reactive protein (CRP) levels, CK-MB peaks, diabetes mellitus (DM) rate, mean length of stent, number of implanted stents, and number of patients with low left ventricular ejection fraction were significantly higher in patients with no-reflow. NRP development rate was significantly lower in patients preloaded with ticagrelor (19%, p= 0.001). This was independent of other independent variables including age, DM, AST, and CRP levels, number of implanted stents, and type of myocardial infarction (Odds value= 0.228, 95% confidence interval= 0.102-0.512, p<0.001). Conclusion: Ticagrelor was found to be superior to clopidogrel in preventing no-reflow.

Anahtar Kelimeler

• Ticagrelor
• clopidogrel
• no-reflow

Akut miyokard infarktüslü hastalarda perkütan koroner girişim sonrası no-reflow fenomeni gelişimi üzerine klopidogrel ile tikagrelorun etkisinin karşılaştırılması

Öz

Amaç: No-reflow fenomeni (NRF) miyokard reperfüzyonunu etkileyen en önemli faktörlerdendir. Bu çalışmada perkütan koroner girişim (PKG) uygulanan akut miyokard infarktüs(AMİ) lü hastalarda önyüklemede kullanılan tikagrelorun ve klopidogrele karşı NRF gelişimi üzerine olan etkisini araştırdık. Yöntem: Tek merkezli ve retrospektif çalışmamıza AMİ tanısıyla, PKG uygulanmış 200 hasta alındı. PKG öncesi verilen antiplatelet rejimine göre hastalar klopidogrel veya tikagrelor yüklenen hastalar olarak ayrıldı. NRF tanımlamada TIMI akım sınıflaması veya işlem sonrası ST segment rezolüsyonundan yararlanıldı. No-reflow gelişenler ve normal akım sağlananlar arasında belirtilen parametrelerdeki farkın anlamlılığı ve tikagrelorla klopidogrelin NRF üzerine olan etkisi değerlendirildi. Bulgular: No-reflow gelişenler ve normal akım sağlananlar arasında bazal karakteristik özellikler açısından fark yoktu. Tikagrelor yüklenen hasta grubunda ST elevasyonlu miyokard infaktüslü hasta sayısı daha yüksekti (p=0.013). No-reflow gelişen grupta yaş, aspartat aminotransferaz (AST), C-reaktif protein (CRP), pik CK-MB seviyeleri, diyabetes mellitus (DM) oranı, stent uzunluğu, stent sayısı, ve düşük ejeksiyon fraksiyonlu hasta sayısı anlamlı olarak yüksek bulundu. Tikagrelor yüklenen hastalarda NRF gelişme oranı anlamlı olarak düşüktü( %19 p=0.001). Bu düşüklük yaş, DM, AST ve CRP seviyeleri, yerleştirilmiş stent sayısı ve miyokard infarktüsü tipini de kapsayan diğer bağımsız değişkenlerden bağımsızdı (Odds değeri = 0.228, %95 güven aralığı = 0.102-0.512, p<0.001). Sonuç: Tikagrelorun no- reflow gelişimini önlemede klopidogrele üstün olduğu görüldü.

Anahtar Kelimeler

• Tikagrelor
• Klopidogrel
• No-reflow

Kaynakça

1. Tosun N, Erkoç Y, Buzgan T. ve ark. Türkiye kalp ve damar hastalıklarını önleme ve kontrol programı. TC Sağlık Bakanlığı, Temel Sağlık Hizmetleri Genel Müdürlüğü, Ankara, Yayın no: 812, 2010.
2. Safian RD. No-reflow. In: Safian RD, Freed M., editors. The Manual of Interventional Cardiology. 3rd ed. Royal Oak, Mich. : Physicians' Press; 2001. p.413-9.
3. Kondo M, Nakano A, Saito D, Shimono Y. Assessment of “microvascular no-reflow phenomenon” using technetium-99m macroaggregated albumin scintigraphy in patients with acute myocardial infarction. J Am Coll Cardiol 1998; 32: 898-903.
4. Galiuto L. Optimal therapeutic strategies in the setting of post-infarct no reflow: the need for a pathogenic classification. Heart. 2004; 90: 123-5.
5. Levine GN, Kern MJ, Berger PB, et al. Managment of patients undergoing percutaneous coronary revascularization. Ann Intern Med. 2003;139:123-36
6. Steinhubl SR, Berger PB, Tift Mann J, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;228:2411-20.
7. Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST- segment elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA. 2005;294:1224-32.
8. Cannon CP, Husted S, Harrington RA, et al. Safety, tolerability, and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, compared with clopidogrel, in patients with non-ST-segment elevation acute coronary syndrome: primary results of the DISPERSE-2 trial. J Am Coll Cardiol. 2007 Nov 6;50(19):1844-51.

9. Husted S, Emanuelsson H, Heptinstall S, Sandset PM, Wickens M, Peters G. Pharmacodynamics, pharmacokinetics, and safety of the oral reversible P2Y12 antagonist AZD6140 with aspirin in patients with atherosclerosis: a double-blind comparison to clopidogrel with aspirin. Eur Heart J. 2006 May;27(9):1038-47.
10. Storey RF, Husted S, Harrington RA, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol. 2007 Nov 6;50(19):1852-6.
11. Sorajja P, Gersh BJ, Costantini C, et al. Combined prognostic utility of ST-segment recovery and myocardial blush after primary percutaneous coronary intervention in acute myocardial infarction. Eur Heart J. 2005;26:667-674.
12. Piana RN, Paik GY, Moscucci M, et al. Incidence and treatment of 'no-reflow' after percutaneous coronary intervention. Circulation. 1994; 89: 2514-8.
13. Santoro GM, Valenti R, Buonamici P, et al. Relation between ST-segment changes and myocardial perfusion evaluated by myocardial contrast echocardiography in patients with acute myocardial infarction treated by direct angioplasty. Am J Cardiol. 1998;82:932–37.
14. Schofer J, Montz R, Mathey D. Scintigraphic evidence of the no-reflow phenomenon in human beings after coronary thrombolysis. J Am Coll Cardiol. 1985;5:593–98.
15. Iwakura K, Ito H, Takiuchi S, et al. Alternation in the coronary blood flow velocity pattern in patients with no reflow and reperfused acute myocardial infarction. Circulation. 1996;94:1269–75.
16. Kenner MD, Zajac EJ, Kondos GT, et al. Ability of the no-reflow phenomenon during an acute myocardial infarction to predict left ventricular dysfunction at one-month follow-up. Am J Cardiol. 1995; 76: 861-868.
17. Santoro GM, Valenti R, Buonamici P, et al. Relation between ST-segment changes and myocardial perfusion evaluated by myocardial contrast echocardiography in patients with acute myocardial infarction treated with direct angioplasty. Am J Cardiol. 1998; 82: 932-7.
18. Prasad S. Current Approach to Slow Flow and No Reflow. Cardiac Interventıons Today. 2008: 43-50.
19. Roe MT, Ohman EM, Maas AC, et al. Shifting the open artery hypothesis downstream: the quest for optimal reperfusion. J Am Coll Cardiol. 2001;37:9-18.
20. Wallentin L, Becker RC, Budaj A, et al Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009 Sep 10;361(11):1045-57.
21. Wittfeldt A, Emanuelsson H, Brandrup-Wognsen G, et al. Ticagrelor enhances adenosine-induced coronary vasodilatory responses in humans. J Am Coll Cardiol. 2013 Feb 19;61(7):723-7.
22. Singh M, Mathew V, Garratt KN, et al. Effect of age on the outcome of angioplasty for acute myocardial infarction among patients treated at the Mayo Clinic. Am J Med. 2000; 108: 187 – 192
23. Oduncu V, Tanalp AC, Erkol A, et al. Impact of Chronic Pre-Treatment of Statins on the Level of Systemic Inflammation and Myocardial Perfusion in Patients Undergoing Primary Angioplasty. Am J Cardiol. 2011;107: 179–185.
24. Stranders I, Diamant M, Gelder R, et al. Admission blood glucose level as risk indicator of death after myocardial infarction in patients with and without diabetes mellitus. Arch Intern Med. 2004;164:982–8.
25. Engler RL, Dahlgren MD, Morris DD, Peterson M A, Schmid-Schönbein G W. Role of leukocytes in response to acute myocardial ischemia and reflow in dogs. Am J Physiol. 1986;251:H314–23.
26. Libby P. Current concepts of the pathogenesis of the acute coronary syndromes. Circulation. 2001;104:365-72.
27. Walter DH, Fichtlscherer S, Sellwig M, Auch-Schwelk W, Schächinger V, Zeiher A M. Preprocedural C-reactive protein levels and cardiovascular events after coronary stent implantation. J Am Coll Cardiol. 2001;37:839-46.
28. Jesel L, Morel O, Ohlmann P, et al. Role of pre-infarction angina and inflammatory status in the extent of microvascular obstruction detected by MRI in myocardial infarction patients treated by PCI. Inter J Card. 2007;121:139-47.
29. Reffelmann T, Hale SL, Li G, Kloner RA. Relationship between no-reflow and infarct size as influenced by the duration of ischemia and reperfusion. Am J Physiol Heart Circ Physiol. 2002;282:H766–72.