Cangrelor, Tirofiban, and Chewed or Standard Prasugrel Regimens in Patients With ST-Segment–Elevation Myocardial Infarction

Abstract

Background: Standard administration of newer oral P2Y 12 inhibitors, including prasugrel or ticagrelor, provides suboptimal early inhibition of platelet aggregation (IPA) in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). We sought to investigate the effects of cangrelor, tirofiban and prasugrel, administered as chewed or integral loading dose, on IPA in patients undergoing primary PCI. Methods: The FABOLUS-FASTER is an investigator-initiated, multicenter, open-label, randomized study. A total of 122 P2Y 12 -naïve STEMI patients were randomly allocated (1:1:1) to cangrelor (n=40), tirofiban (n=40), both administered as bolus and 2h infusion followed by 60 mg of prasugrel, or 60 mg loading dose of prasugrel (n=42). The latter group underwent an immediate 1:1 sub-randomization to chewed (n=21), or integral (n=21) tablets administration. The trial was powered to test 3 hypotheses (non-inferiority of cangrelor compared with tirofiban using a non-inferiority margin of 9%, superiority of both tirofiban and cangrelor compared with chewed prasugrel and superiority of chewed prasugrel as compared with integral prasugrel; each with alpha of 0.016) for the primary endpoint that was 30-minute IPA at light transmittance aggregometry (LTA) in response to 20 μmol/L adenosine diphosphate (ADP). Results: At 30 min, cangrelor did not satisfy non-inferiority compared with tirofiban, which yielded superior IPA over cangrelor (IPA: 95.0±8.9 vs. 34.1±22.5; P<0.001); cangrelor or tirofiban were both superior to chewed prasugrel (IPA: 10.5±11.0, P<0.001 for both comparisons), which did not provide higher IPA over integral prasugrel (6.3±11.4; P=0.47), despite yielding higher prasugrel's active metabolite concentration (ng/ml; 62.3±82.6 vs 17.1±43.5; P=0.016). Conclusions: Cangrelor provided inferior IPA compared with tirofiban; both treatments yielded greater IPA compared with chewed prasugrel which led to higher active metabolite concentration but not greater IPA compared with integral prasugrel. Clinical Trial Registration: clinicaltrials.gov NCT02978040, and EudraCT 2017-001065-24

Clinical features of patients with acute coronary syndrome during the COVID-19 pandemic

“…The identification of the mechanisms leading to the reduction in admissions for AMI is beyond the scope of the present work. Nevertheless, recent reports suggested that the decreased number of ACS patients was due to the fear of exposure to COVID-19 affected subjects at hospital admission or a true reduction in the incidence of ACS as the potential result of low physical stress during the social containment [ 6 , 12 , 13 ].…”

Analysis of the Financial Impact of Using Cangrelor on the Safety and Efficacy Outcomes in Patients Undergoing Percutaneous Coronary Intervention in Whom Oral Therapy with P2Y12 Inhibitors is Not Feasible or Desirable, in Spain

“…Taking into account the frame of the present analysis, meaning early PCI (<2 h) 4 , 5 under clinical conditions in which the adjuvant antiplatelet treatment with oral P2Y 12 inhibitors may not be feasible or desirable, it should also be considered that the antiplatelet effect of crushed ticagrelor 37 and chewed prasugrel 38 were also investigated as potential alternatives to improve their oral bioavailability. Although the results showed that time to maximum plasma concentration was shorter in the crushed ticagrelor group versus the integral tablets group, the median time of 2 h vs 4 h, respectively, still represents the delayed onset of the ticagrelor antiplatelet effect.…”

“… 37 In line with these results, the recently published FABOLUS FASTER pharmacodynamic study compared the antiplatelet effect of chewed prasugrel vs a loading dose of integral prasugrel tablet and demonstrated that chewed prasugrel led to higher active metabolite concentration but not to a greater platelet aggregation inhibition. 38 The results of these pharmacodynamic studies emphasize that even the faster oral P2Y 12 alternatives may still not be desirable. In this context, cangrelor represents an affordable iv alternative for immediate P2Y 12 inhibition.…”

Pre-Hospital Antiplatelet Therapy for STEMI Patients Undergoing Primary Percutaneous Coronary Intervention: What We Know and What Lies Ahead

“…In STEMI patients, randomized data demonstrated that cangrelor may be used as an adjunct to ticagrelor and provides faster and stronger periprocedural platelet inhibition compared with ticagrelor alone (85,86). However in the recent FABOLUS-FASTER trial, tirofiban demonstrated superior efficacy than cangrelor on inhibition of platelet aggregation in patients undergoing primary PCI, suggesting that GPI might be preferable to cangrelor to minimize the risk of acute ischemic complications (87). Further studies powered for clinical endpoints are needed.…”