![]() The primary endpoint of the trial occurred at 30 days in 7.4% versus 10.5% of patients in the invasive versus conservative arms, respectively, p=0.009. ![]() This point is easily elucidated by careful review of clinical outcome data at the two time points of the trial: at 30 days and 6 months. Third, strikingly, all the differences in adverse outcomes occurred in the early few weeks following randomisation. Finally, stents were used in no more than 83% and 86% of procedures in the invasive and conservative arms, respectively. Given the fact that PCI was performed in 41% and 24% of patients in the invasive versus conservative arms, respectively, this would yield a differential in the use of tirofiban of 38.5% versus 14.2% (nearly 2.7-fold more frequent) of patients in the invasive versus the conservative arms, respectively. And, most importantly, whereas tirofiban was administered during 94% of percutaneous coronary intervention (PCI) procedures in the invasive-strategy group, this crucial drug was administered during only 59% of procedures in the conservative-strategy group. Additionally, only 52% of patients received lipid-lowering agents. Furthermore, patients did not receive low-molecular-weight heparins, with already proven reduction of major adverse cardiac events as compared with unfractionated heparin in the setting of non-ST-elevation ACS, 3 not to mention the fact that unfractionated heparin was given in the trial without weight adjustment. Patients did not receive platelet receptor P2Y12 inhibitors, one of the cornerstones of the standard antithrombotic therapy in patients presenting with ACS (class I, level of evidence A, according to the 2011 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation MI), 2 leave aside the degree of risk and the intended management strategy. Second, adjunctive pharmacological interventions were far diverse from what constitutes current real-life clinical practice, and what is recommended by the most updated guidelines alike. Moreover, clinical outcome was slightly better in the conservative arm in the subset of patients with low TIMI risk score. Ongoing with this was the observation that the primary endpoint at 6 months was similar between the two arms in patients with prior aspirin use, in those without ST-segment changes, and in those without elevation of cardiac markers. One can wonder whether such low-risk patients with unstable angina were eligible for the early invasive strategy. In a randomised controlled trial, patients must be equally eligible for both arms of the trial. ![]() Overall, patients with low TIMI risk score constituted 25% of the population. 1 At 6-month follow-up, the primary endpoint (a composite of death, non-fatal MI and rehospitalisation for ACS) occurred less frequently with the invasive, as compared with the conservative strategy (p=0.025), and so was the composite of death or non-fatal MI (p0.05 mV) of ST-segment depression (62%), nor with elevation of cardiac markers (61% had creatine kinase MB ≤5 ng/ml, 59% had troponin T ≤0.1 ng/ml). The TACTICS TIMI 18 trial randomly assigned a little over 2200 patients with unstable angina, or non-ST-elevation acute myocardial infarction (MI), to either an early invasive strategy based on routine catheterisation within 48 h, and revascularisation as appropriate, or a conservative strategy in which catheterisation was performed only if the patient had objective evidence of recurrent ischaemia or an abnormal stress test. To underscore this viewpoint, let us review evidence from one of the landmark randomised controlled trials published a little more than a decade ago, that rigorously contributed to the standard-of-care approach in the management of patients presenting with non-ST-elevation acute coronary syndrome (ACS). Overextending the conclusions of a clinical trial beyond the specific population ultimately enrolled, and the context of pharmacological interventions eventually rendered, would be a grave prejudice. A randomised controlled trial should be interpreted exclusively within the background of the population actually enrolled, and the therapeutic regimens received. Making good sense of this notion is never more relevant than in the realm of randomised controlled trials when comparing two alternative therapeutic strategies. This may explain why we can never get too close to it, because it is like the mirage that recedes each time we approach it. One important fact to keep in mind about science is that it never stands still, but is constantly changing. Making science appealing is quite a challenging task and the scientific research industry is among the most sophisticated and promising. ![]()
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