Emergency. 2017; 5 (1): e32 OR I G I N A L RE S E A RC H Early vs Late Coronary Angiography and Intervention Fol- lowing Thrombolytic Therapy; a Cohort Study Bahareh Feizi1, Shahram Taghdisi1, Jalil Etemadi2∗ Amir Hossein Feizi1, Setareh Asgarzadeh3, Sepideh Kamal1 1. Clinical Research Development Center, Bouali Hospital, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran. 2. Cardiology Department, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. 3. Clinical Research Development Center, Amir-almomenin Hospital, Islamic Azad University, Tehran Medical Sciences Branch, Tehran, Iran. Received: November 2016; Accepted: December 2016; Published online: 11 January 2017 Abstract: Introduction: The precise time of using percutaneous coronary intervention (PCI) after fibrinolytic therapy for maximum efficiency and minimum side effects is still undetermined. Therefore, the present study was designed to compare the outcome of myocardial infarction (MI) patients who underwent surgical intervention (angiogra- phy and PCI) within 48 hours of thrombolytic therapy or after that. Methods: The present study is a prospective cohort study aiming to compare the occurrence of no-reflow phenomenon, unstable angina, bleeding during intervention, and one month major adverse cardiac outcomes (recurrent MI, need for repeating surgical inter- vention, and mortality) between MI patents undergoing surgical intervention within the first 48 hours of or after 48 hours of thrombolytic therapy. Results: 90 patients with the mean age of 54.97 ± 10.54 were studied (86.67% male). 50 (56%) patients underwent surgical intervention within 48 hours and 40 (44%) after that. The 2 groups were not significantly different regarding baseline characteristics. No-reflow phenomenon in the < 48 hours group was about twice the > 48 hours group (OR = 0.35; 95% confidence interval: 0.14 – 0.92; p = 0.03), other outcomes were not significantly different. No case of mortality was seen in the 1 month follow up. Conclusion: Based on the results of the present study, it seems that no-reflow phenomenon rate is significantly lower in pa- tients undergoing surgical intervention after 48 hours of fibrinolytic therapy. The difference between the two groups regarding prevalence of major adverse cardiac outcomes was not statistically significant. Keywords: Angiography; thrombolytic therapy; percutaneous coronary intervention; myocardial infarction; postoperative complications © Copyright (2017) Shahid Beheshti University of Medical Sciences Cite this article as: Feizi B, Taghdisi Sh, Etemadi J, Feizi A, Asgarzadeh S, Kamal S. Early vs Late Coronary Angiography and Intervention Following Thrombolytic Therapy; a Cohort Study. Emergency. 2017; 5(1): e32. 1. Introduction C oronary artery disease (CAD) and its associated side effects are the most common cause of mortality and disability all over the world and its cost burden is the highest among health care costs (1, 2). Currently, each year 900 thousand people are affected with acute myocardial in- farction (MI) in the United States, which brings about 225 thousand deaths(3). In the past, open-heart surgery was the major treatment for CAD (4). Yet, in recent years, coronary artery angioplasty through the skin has been proposed as an ∗Corresponding Author: Jalil Etemadi; Cardiology Department, Imam Hos- sein Hospital, Shahid Madani Avenue, Imam Hossein Square, Tehran, Iran. Tel: 09143231444 Email: jalil_md73@yahoo.com efficient treatment for ST elevation MI (STEMI)(5). Unfortu- nately, many STEMI patients either visit hospitals where per- cutaneous coronary intervention (PCI) is not available, or are not referred to PCI centers in the time range suggested by guidelines (6). In these cases, alternative treatment is using fibrinolytic agents such as tissue plasminogen activator and streptokinase. Although according to the most recent guide- lines of American Heart Association (AHA), angiography and PCI should be done within 3 to 24 hours of fibrinolytic ther- apy, evidence presented in it are derived from level B and C articles, which partially affects its reliability (6). Initial studies have questioned effectiveness of PCI and early angiography after fibrinolytic therapy (7, 8). Yet, the power of the studies carried out in this regard are not high enough to confirm the effectiveness of this treatment (5, 9-11). Consequently, the precise time of using PCI after fibrinolytic therapy for max- This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com B. Feizi et al. 2 imum efficiency and minimum side effects is still undeter- mined. Therefore, the present study was designed to com- pare the outcome of MI patients who underwent surgical in- tervention (angiography and PCI) within 48 hours of throm- bolytic therapy or after that. 2. Methods 2.1. Study design and setting The present study is a prospective cohort study aiming to compare the outcome of MI patients who underwent surgical intervention (angiography and PCI) either within the first 48 hours of or after 48 hours of undergoing thrombolytic ther- apy. The researchers adhered to the principles of Helsinki Declaration throughout the study and the protocol of the study was approved by the Ethical committee of Islamic Azad University, Medical Sciences Branch. 2.2. Participants Patients visiting the emergency department (ED) of Bouali Hospital, Tehran, Iran, who were diagnosed with STEMI, were evaluated. Patients over 18 years old, suffering from STEMI, whose symptoms had initiated less than 12 hours ago, and had successful thrombolytic therapy were included. In contrast, those with underlying illnesses such as cancer, chronic hepatic and renal failure (creatinine > 250 mmol/l); pregnant women; drug and alcohol addicts; and those pro- hibited from using fibrinolytic therapy were excluded. After reaching diagnosis in ED, patients were sent to coronary care unit (CCU), where they underwent thrombolytic therapy and were scheduled for surgical intervention, based on patient condition and preference of in charge cardiologist. Without any interferences from the researches, the participants were followed for 1 month regarding major adverse cardiac out- comes. 1-month follow-up was done by phone calls or in- person. After the follow-up period, patients were divided into 2 groups of < 48 hours and > 48 hours based on time inter- val between thrombolytic therapy and surgical interventions, and the surgical side effects and one month adverse cardiac outcomes were compared between the 2 groups. The time interval between initiation of fibrinolytic therapy and inter- vention was 3 to 48 hours in <48 hours group. 2.3. Outcome Patients were followed regarding no-reflow phenomenon, unstable angina, and bleeding during intervention, as well as one month major adverse cardiac outcomes including re- current STEMI or non-ST elevation MI (NSTEMI), need for repeating surgical intervention, and mortality. 2.4. Definitions -Recurrent NSTEMI: presence of a Q wave in 2 or more adja- cent electrocardiogram leads accompanied by a rise in crea- tine kinase MB or troponin concentration to above the nor- mal range and more than 50% of the previous measure 18 hours after surgical intervention. - Recurrent STEMI: relapse of ischemia symptoms while rest- ing, accompanied by ST elevation of at least 0.1 millivolt in at least 2 adjacent electrocardiogram leads for more than 30 minutes during the first 18 hours after surgical intervention. - Unstable angina: chest pain while resting, with or without changes in electrocardiogram (ECG) and pain class (based on the classification of Canadian Cardiovascular Society), or presence of dangerous arrhythmias such as atrial tachycar- dia and atrial fibrillation. - No-reflow phenomenon: inadequate muscle perfusion without angiographic evidence of obstruction in a myocar- dial vessel (12). Severity of hemorrhage during intervention was determined based on GUST (Global Use of Strategies to Open coronary arteries) severity scale (13). 2.5. Statistical Analysis Data were analyzed using SPSS version 20.0. Qualitative data were presented as frequency and percentage and quantita- tive ones as mean ± standard deviation. Student t-test was used for comparing means and chi-square or Fisher’s exact tests for comparing categorical variables. In all analyzes p < 0.05 was considered as significance level. 3. Results 90 patients with the mean age of 54.97 ± 10.54 were evalu- ated (86.67% male). 50 (56%) patients underwent surgical intervention within 48 hours and 40 (44%) after that. Table 1 compares the baseline characteristics of patients in the 2 groups. The 2 groups were not significantly different regard- ing baseline characteristics. Table 2 compares the frequency of outcomes in the groups, which showed a significant differ- ence only regarding no-reflow phenomenon. This outcome in the < 48 hours group was about twice the > 48 hours group (p = 0.03). The odds ratio for occurrence of no-reflow phe- nomenon in patients who underwent surgical intervention after 48 hours of fibrinolytic therapy was significantly lower (OR = 0.35; 95% confidence interval: 0.14 – 0.92; p = 0.03). 4. Discussion The findings of this study showed that the frequency of ad- verse outcomes between MI patients undergoing surgical in- tervention (angiography and PCI) within the first 48 hours and after 48 hours of receiving thrombolytic agents was not significantly different except for no-reflow phenomenon. In This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com 3 Emergency. 2017; 5 (1): e32 Table 1: Baseline characteristics in the studied groups Variable First 48 hours (%) After 48 hours (%) P Total (n=50) Total (n=40) Age (year) 55.5 ± 12.1 54.3 ± 10.9 0.63 Sex (Male) 43 (86.0) 35 (87.5) 0.84 Medical history of Diabetes mellitus 17 (34.0) 14 (35.0) 0.92 Hypertension 22 (44.0) 14 (35.0) 0.39 Hyperlipidemia 20 (40.0) 14 (35.0) 0.63 Cardiovascular accident 7 (14.0) 5 (12.5) 0.84 Myocardial infarction 13 (26.0) 7 (17.5) 0.34 Smoking 25 (50.0) 24 (60.0) 0.4 ∗ Data are presented as mean Âś standard deviation or number and percentage. Table 2: Comparison of patient outcomes in the 2 groups Complications First 48 hours (%) After 48 hours (%) P Bleeding during intervention 1 (2) 0 (0.0) 0.56 No-Reflow phenomenon 22 (44) 9 (22.5) 0.03 One month adverse cardiac outcomes Recurrent Myocardial infarction 1 (2) 0 (0.0) 0.56 Repeating revascularization 0 (0.0) 0 (0.0) — Mortality 0 (0.0) 0 (0.0) — other words, the odds of no-reflow phenomenon was signif- icantly lower in patients who underwent surgical interven- tion after 48 hours. Although the difference between other studied outcomes was not statistically significant, both cases of major adverse cardiac outcomes were seen in < 48 hours group. No mortality was seen in the 1-month follow-up. In the years before using stent, early PCI has not been efficient and has been associated with side effects such as hemor- rhage, mortality, and coronary artery re-occlusion (14, 15). However, using stents has significantly decreased post-PCI coronary artery re-occlusion incidence (16, 17). This has en- couraged doing PCI immediately after fibrinolytic therapy (6, 18-20). As a result, the most recent guideline of AHA has expressed that STEMI patients should undergo PCI as soon as possible. In cases that the patient has undergone fibri- nolytic therapy, the ideal time for doing PCI is within the first 24 hours, yet it should not be done in the first 2 – 3 hours (6). In a trial, Armstrong et al. have expressed that early PCI and angiography show better outcomes and fewer side ef- fects compared to late PCI (21). Cantor et al. also believed that early PCI is an efficient therapy with few side effects and the smaller the time interval between fibrinolytic therapy and PCI, the better the results (14). In contrast, the findings of the present study showed that PCI and angiography in the first 48 hours have more side effects compared to the sec- ond 48 hours. In line with this study, Collet et al. in their meta-analysis showed that patients who undergo early PCI show more side effects compared to those who undergo in- tervention after 24 or 48 hours (9). However, a study by Ed- mond et al. showed that there is no difference between vari- ous time intervals of PCI after fibrinolytic therapy, and results and side effects are similar (22). A review article by Capo- danno et al. revealed that pharmaco-invasive therapy is ef- fective in STEMI treatment and its time does not make a dif- ference in the outcome of treatment or side effects (23). Vant Hof et al. did not detect a significant difference between early and after 48 hours PCI (24). As can be seen, there is signifi- cant difference between study results, which might be due to differences in study design (cohort, clinical trial, or cross- sectional), type of MI, type of thrombolytic used (streptoki- nase or t-PA), and not paying attention to outcomes such as no-reflow phenomenon. This variation in findings also re- veals the need for further studies in this field. 5. Limitation The power of the present study was low for comparing mor- tality rate and other side effects, except for no-reflow phe- nomenon between the two groups. 1-month follow-up done in the present study only evaluates the short-term adverse outcomes, while long-term follow-ups may enable more ac- curate assessment. Long-term follow-up and designing fur- ther interventional studies is suggested. This open-access article distributed under the terms of the Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0). Downloaded from: www.jemerg.com B. Feizi et al. 4 6. Conclusion Based on the results of the present study, it seems that no- reflow phenomenon rate is significantly lower in patients un- dergoing surgical intervention after 48 hours of fibrinolytic therapy. 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