A SPIRIN IS A CORNERSTONE OF therapy for patients undergoing coronary intervention. Its use is considered a standard of care before the procedure and lifelong following revascularization. Adding to aspirin a short course (2-4 weeks) of an adenosine diphosphate (ADP) P2Y 12 receptor antagonist (ticlopidine or clopidogrel) leads to even greater protection from thrombotic complications following a percutaneous coronary intervention (PCI) with a stent. 1-4 However, the optimal timing for the initiation of clopidogrel and aspirin, as well as their duration of treatment following a PCI procedure, remains unknown.The results of multiple observational and nonrandomized studies suggest that treating patients with an ADP receptor antagonist prior to a planned PCI may provide additional, incremental benefit beyond that provided by aspirin, and even beyond that of glycoprotein (Gp) IIb/IIIa antagonists. [5][6][7] Despite the consistency of this observation, patient or procedural characteristics may have biased the results in

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Inclacumab appears to reduce myocardial damage after PCI in patients with non-ST-segment elevation myocardial infarction. (A Study of RO4905417 in Patients With Non ST-Elevation Myocardial Infarction [Non-STEMI] Undergoing Percutaneous Coronary Intervention; NCT01327183).

BackgroundThe Effects of the P‐Selectin Antagonist Inclacumab on Myocardial Damage After Percutaneous Coronary Intervention for Non‐ST‐Segment Elevation Myocardial Infarction (SELECT‐ACS) trial suggested beneficial effects of inclacumab, a monoclonal antibody directed against P‐selectin, on periprocedural myocardial damage. This study evaluated the effect of inclacumab on myocardial damage according to varying time intervals between study drug infusion and percutaneous coronary intervention (PCI).Methods and ResultsPatients (n=544) enrolled in the SELECT‐ACS trial and randomized to receive 1 infusion of placebo or inclacumab (5 or 20 mg/kg, administered between 1 and 24 hours before PCI) were divided according to the time interval between study drug infusion and PCI. The primary end point was the change in troponin I from baseline at 16 and 24 hours after PCI. In patients receiving inclacumab 20 mg/kg with a short (less than median) time interval between infusion and PCI, placebo‐adjusted geometric mean percent changes in troponin I, creatine kinase–myocardial band, and peak troponin I at 24 hours were −45.6% (P=0.005), −30.7% (P=0.01), and −37.3% (P=0.02), respectively. No significant changes were observed in patients with a long (greater than median) time interval between infusion and PCI. Placebo‐adjusted geometric mean percent changes in troponin I and creatine kinase–myocardial band were −43.5% (P=0.02) and −26.0% (P=0.07), respectively, when inclacumab 20 mg/kg was administered between 1 and 3 hours before PCI, whereas the drug had no effect with longer intervals.ConclusionsInclacumab 20 mg/kg significantly reduces myocardial damage after PCI in patients with non–ST‐segment elevation myocardial infarction, and benefits are larger when the infusion is administered <3 hours before PCI.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01327183.

To enable early detection of DIN and to ensure patients' safety through appropriate risk minimization and mitigation strategies, future research should focus on identification and validation of novel predictive biomarkers of kidney injury and development of DIN-specific classification and staging system. This could help in reducing the current high rate of attrition during drug development, and reduce marketing and post-marketing withdrawals of nephrotoxic drugs.