The present study is the first to compare clinical characteristics among STEMI patients from the Middle East treated with three commonly used thrombolytic agents. The main findings from this study are: STEMI patients from the Middle East are predominantly male, young and are thrombolysed with streptokinase and reteplase in equal numbers; nearly one-fifth of eligible STEMI patient did not receive any reperfusion therapy; there was inappropriately long symptom-onset to hospital presentation time as well as door-to-needle time; use of newer thrombolytic agents in high risk patients was appropriate; and newer thrombolytic agents were associated with significant reduction in mortality at both 1-month and 1-year compared to the older agent, streptokinase.
In this registry, among 2,465 STEMI patients who presented to the hospital within 12 hours of symptoms onset, the majority were male and young. Nearly 66% of the total STEMI patients received thrombolysis, indicating that thrombolysis is the major form of reperfusion strategy in the Middle East countries. However, nearly 23% of the patients with STEMI who present within 12 hours and are candidates for TT according to current guidelines, did in fact receive no such therapy. This is not different from the situation in other countries, since this reperfusion therapy shortfall is already known from multinational registries in Europe and other countries, and remains an issue.[13
The overall median symptom-onset to hospital presentation was 165 minutes, which is inappropriately- long compared to 89 minutes and 120 minutes in Emergency Medical Services (EMS)-transported and self-transported patients, respectively, in the NCDR registry.[15
] One of the main possible reason for this long delay is underutilization of EMS services in the Middle Eastern countries (only 17% vs. 60% in NCDR registry).[16
] Increased delay times to restoration of coronary flow are associated with increased infarction size, increased risk of subsequent congestive heart failure, and higher mortality.[17
] Furthermore, those patients who presented late were more likely to be treated with streptokinase than with either reteplase or tenecteplase (190 vs. 137 vs. 170 minutes, respectively). This is in contrast to guideline recommendations which advocate fibrin-specific newer thrombolytic agent for patients presenting more than 4 hours after the onset of symptoms. This is attributed to the drug's fibrin specificity leading to better dissolution of older coronary clots.[1
] The overall median door-to-needle time in this study was 38 minutes which is longer compared to 29 and 30 minutes seen in the NCDR and GRACE registry, respectively.[15
] The predominant cause for this delay observed in this registry was the administration of TT by the cardiology service unit and in CCU/ICU rather than in the ER room by the ER physicians thus leading to a delay in transport and subsequent administration of TT. The guideline recommended optimal door-to-needle time of <30 minutes was achieved in only 34% of the patients, which is low compared to 45%, 64% and 67% in the GRACE, Euro Heart Survey ACS-III and the UK MINAP registry, respectively.[17
Out of the cohort that was thrombolysed; equal numbers of patients were treated with reteplase and streptokinase, even though guidelines recommend newer thrombolytic agents such as reteplase and tenecteplase which have the potential advantages of prolonged half-life (less re-occlusion rates), increased fibrin specificity (more potent and lower non-cerebral bleeding risk) and increased resistance to inhibition by plasminogen activators as well as increased 90-minute coronary patency rates (60-75% vs. 50% with streptokinase) and TIMI (Thrombolysis in Myocardial Infarction) grade 3 flow ( 60% vs. 32% with streptokinase).[1
] The majority of patients in the higher GRACE risk score were treated with newer thrombolytic agents. This is in accordance with the guideline recommendations. One other observation from our data relates to the increased use of evidence based secondary prevention drug therapies in patients treated with newer TT when compared to streptokinase.
Apart from the GUSTO-I trial[8
] that demonstrated the superiority of alteplase over streptokinase, no other trial has demonstrated a reduced mortality with one thrombolytic agent in comparison with another.[9
] In two large meta-analysis comparing the efficacy of thrombolytics in acute myocardial infarction, Dundar et al
] and Giraldz et al
] reported that there was no significant differences in 30-35 days mortality among these three thrombolytic agents. In this registry, on univariate analysis, the use of newer thrombolytic agents was associated with significantly lower mortalities at both 1-month and 1-year. The mortality benefits of the newer thrombolytic agents in this registry may be related to more use of other evidence based medications with newer thrombolytic agents as demonstrated in this study as well as in CLARITY-TIMI-28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myocardial Infarction)[26
] and COMMIT (Clopidogrel and Metoprolol in Myocardial Infarction Trial)[27
] trials. This study has clinical implications. The mortality benefit seen from newer thrombolytic agents suggests that there should be a change in the pattern of use of thrombolytic agents in the Middle East countries. The use of streptokinase needs to be discouraged. The cost consideration does not seem to be a factor in this population as treatment in the Middle Eastern countries is provided freely to their citizens.
As with any registry study, confounding or unknown variables could have influenced the results especially with the fact that multivariable techniques were not employed due to low study power. Furthermore, losses to follow-up at both, 1-month and 1-year, could have biased the results either way. Although Gulf RACE included a broad representation of hospital types, there is a probability that some of the participating centres may not be fully representative of their countries with respect to STEMI management. However, registry data does provide crucial complementary evidence and hence the results are more likely to reflect clinical practice.