Search

Background Aspirin forms a cornerstone of management in patients with established cardiovascular disease (CVD). Despite proven efficacy, variability of aspirin response has long been recognised, with early studies suggesting rates of high on treatment platelet reactivity (HTPR) as ranging between 5 and 45%. Whether aspirin responsiveness relates to long-term prognosis in patients with CVD is unknown. Methods A prospective, single-centre analysis of 224 troponin positive non-ST elevation myocardial infarction (NSTEMI) patients undergoing coronary angiography. Aspirin-naive patients were loaded with 300 mg aspirin and maintained on 75 mg daily. Blood samples were obtained at the time of angiography and the VerifyNow Aspirin assay utilised to determine aspirin effect. The primary end point was all-cause mortality at 10 years. Results Time from aspirin loading (or admission on aspirin) to angiography was 4.9 ± 2.7 days. Platelet aggregation results, expressed as aspirin reaction units (ARU) were divided into tertiles: T1 (ARU 363–405) (n = 76), T2 (ARU 406–436) (n = 76), T3 (ARU 437–596) (n = 72). Higher ARU values were associated with increased mortality (log rank, p = 0.009), with those in the T3 having a 3-fold higher rate of events than those in the T1 (HR 3.03 [95% CI 1.33–6.99], p = 0.009) over a 10-year follow up. Conclusion Our study demonstrates that aspirin responsiveness is directly related to 10-year survival and may identify patients who may benefit from additional antithrombotic therapy. Further, ARU values less than the previously defined cut off 550 are associated with reduced survival at 10 years.

Background/Introduction Aspirin, the most commonly prescribed anti-platelet agent, forms a cornerstone of management in patients with established cardiovascular disease. Despite proven efficacy, variability of aspirin response has long been recognised, with early studies suggesting rates of high on treatment platelet reactivity (HPR) as high as 5–45%. True “aspirin resistance”, when defined by strict platelet function testing is present in approximately 2–5% and is associated with poorer outcomes at 1–2 years in ACS patients. We sought to investigate whether the impact of VerifyNow determined response to aspirin, even at levels previously thought to indicate adequate aspirin response, was prognostically important in terms of all-cause mortality at 10 years. Methods A prospective single centre analysis of 224 consecutive troponin positive NSTEMI patients undergoing coronary angiography. All aspirin naive patients were loaded with 300 mg aspirin and maintained on 75 mg daily. Those admitted on aspirin continued on 75 mg daily. Citrated blood samples were obtained at the time of coronary angiography and the VerifyNow Aspirin assay was utilised to determine aspirin reaction units (ARU). The primary end point of our study was an assessment of survival at 10 years, expressed as all-cause mortality. Long term survival data were obtained using Office of National Statistics data. Results Baseline characteristics and cardiovascular risk factors are described in table 1. The mean time between the administration of an aspirin loading dose (or admission on aspirin) to angiography was 4.9 ± 2.7 days. Platelet aggregation results, expressed as VN ARU were divided into tertiles: T1 (ARU 363 - 405) (n = 76), T2 (ARU 406 - 436) (n = 76), T3 (ARU 437 - 596) (n = 72). Figure 1, demonstrates that all-cause mortality is significantly different between groups, (log-rank, P=0.009), with higher ARU values being associated with increased mortality. A co-regression analysis indicates that, ex-smoker status (HR = 3.60, 95%CI [1.47 – 8.85] p = 0.005), in addition to HPR on presentation (HR = 3.13, 95%CI [1.38 – 7.10] p = 0.006), were statistically significant predictors of mortality at 10 years. Conclusion Our study demonstrates that ARU values less than the previously defined cut off 550 are associated with reduced survival at 10 years. There are currently a number of pharmacological strategies aimed at reducing the considerable ongoing ischaemic risk in patients admitted with NSTEMI, including prolonged dual antiplatelet therapy, prolonged monotherapy with a P2Y12 inhibitor or low dose rivaroxaban. In order to improve long-term prognosis, NSTEMI patients with suboptimal, but not strict HPR to aspirin, might benefit from alternative and/or adjunctive antithrombotic treatment options. We suggest that this hypothesis warrants further study. Conflict of Interest None

Introduction Mechanical coronary reperfusion with primary percutaneous coronary intervention (PPCI) and concomitant oral dual antiplatelet therapy, is the preferred strategy in patients presenting with ST elevation myocardial infarction (STEMI). Currently, guidelines regarding the choice of oral P2Y12 inhibitor are conflicting. We sought to determine the impact of clopidogrel, prasugrel and ticagrelor in a real-world STEMI population on the incidence of in-hospital, 30 day and 1 year mortality, in addition to their effects on the incidence of in-hospital major bleeding episodes. Methods A retrospective observational analysis of 2200 STEMI patients managed by PPCI between November 2011 and November 2015 was undertaken. During this period our clinical protocol changed sequentially from prescribing clopidogrel to prasugrel to ticagrelor for patients undergoing PPCI. All data were collected and verified by review of the patient clinical records. Mortality data were obtained via the Office of National Statistics. Bleeding information was taken from the clinical records and review of haematology database. Statistical analysis was two fold: standard multi-logistic regression and a second propensity score (PS) based analysis. Results The study population n=2200 (24% female) were treated with either clopidogrel (n=570), prasugrel (n=1058) or ticagrelor (n=592). Refer to table 1 for baseline characteristics. Figures 1 and 2 demonstrate that ticagrelor treated patients had improved in-hospital (PS, p=0.001), 30 day (PS, p Conclusion This is the first clinical analysis of the three major oral P2Y12 inhibitors in STEMI patients treated with PPCI. There appear to be advantages associated with the use of ticagrelor when compared to prasugrel, in terms of mortality at all time points, and when compared to clopidogrel at 1 year.

Introduction Ticagrelor, an orally administered, direct acting, reversible P2Y12 receptor inhibitor, provides faster onset and greater levels of platelet inhibition when compared to clopidogrel. Current data indicates a reduced antiplatelet effect in STEMI. We sought to determine the early pharmacokinetic (PK) and pharmacodynamic (PD) effect of ticagrelor loading doses administered to patients undergoing PCI for STEMI and NSTEMI. Methods This is a single centre non-randomised study. P2Y12 naive patients presenting with STEMI or NSTEMI were considered for inclusion. All patients gave informed consent. Enrolled patients were administered a loading dose of aspirin 300 mg and ticagrelor 180 mg prior to PCI. Blood was sampled at 20 min, coronary balloon time, 1 hour and 4 hours after loading. PD results are expressed as P2Y12 reaction units (PRU) and were assessed using VerifyNow. A PRU>208 indicates a sub-optimal antiplatelet response. PK properties were assessed by measuring plasma concentration of ticagrelor parent compound (T-PC) and active metabolite (T-AM) using liquid chromatography in tandem with mass spectrometry. The lower limits of quantification of T-PC and its active metabolite, AR-C124910XX (T-AM) are 1 ng/ml and 2.5 ng/ml respectively. PRU and plasma concentrations over time were tested between the two groups using 2-way ANOVA. p Results 30 patients (15 STEMI/15 NSTEMI) were recruited. Baseline characteristics are described in Table 1. PD analysis In STEMI patients high residual platelet reactivity is seen at 20 min following administration of ticagrelor 180 mg (256±13.1), an attenuated effect is also observed at 4 hours. However, in our NSTEMI patients, a marked and rapid antiplatelet effect is seen at all time points (figure 1). PK analysis Low plasma concentrations of T-PC are observed in STEMI vs NSTEMI patients; (9.0±4.1) vs (22.8±10.3), p=0.225 and this trend continues until 4 hours. A similar trend is noted for T-AM concentrations (figure 2). Conclusion Ticagrelor, in STEMI does not provide adequate P2Y12 inhibition at the point of reperfusion. In contrast platelet inhibition is significantly more rapid in patients with NSTEMI. Although a directly acting P2Y12 inhibitor that can exert an antiplatelet effect independent of metabolic biotransformation, ticagrelor is still reliant upon absorption via the gastrointestinal (GI) tract. The sub-therapeutic PRU and plasma concentrations of both T-PC and T-AM indicate that GI absorption is an important determinant of the onset of action and clinical efficacy of ticagrelor during the acute phase of a STEMI. GI absorption may be further impaired by co-administration of morphine. Modification of formulation e.g administration of chewed/orodispersible tablets or an intravenous agent (cangrelor) could help to overcome delayed GI absorption and provide adequate levels of platelet inhibition during the acute phase of presentation in STEMI patients.

Background Oral P2Y12 inhibitors have a delayed onset of action in ST-segment elevation myocardial infarction (STEMI) patients. We describe the first randomised controlled trial comparing Cangrelor with Ticagrelor in the context of primary percutaneous coronary intervention (PPCI). Methods 100 subjects with first acute STEMI were randomised on arrival to Ticagrelor (180 mg then 90 mg bd) or Cangrelor (bolus then infusion). Cangrelor treated subjects received Ticagrelor 30 min prior to infusion end. All patients received Aspirin 300 mg. Platelet P2Y12 inhibition was assessed using VerifyNow at first coronary balloon inflation, 4 and 24 hours post drug initiation. Coronary microcirculation was assessed after PPCI by calculating the index of microvascular resistance (IMR). ST-segment resolution at 90 min was measured and the corrected TIMI frame count, flow grade and myocardial perfusion grade were calculated. Peak Troponin level at 24 hours and infarct size at 12 weeks were measured by cardiac magnetic resonance imaging (CMRI) (ClinicalTrials.gov NCT02733341). Results P2Y12 inhibition was markedly greater in the Cangrelor group (PRU 145.2 vs 248.3 p Conclusion Early, more potent P2Y12 inhibition with Cangrelor does not translate into improved measures of microcirculatory function or infarct size.

A 62-year-old man presented with an anterior ST elevation myocardial infarction and underwent primary percutaneous coronary intervention to an occluded diagonal artery. Following stenting, a type III distal guidewire-induced coronary perforation of the diagonal branch was recognized with extravasation of contrast into the pericardial space. Prolonged balloon inflations proximal to the site of the perforation were unsuccessful. Subcutaneous fat was therefore harvested from the patients upper thigh under local anesthetic and embolized through an Export catheter into the distal diagonal vessel, resulting in the immediate cessation of leak through the site of perforation. We discuss the technical aspects of this technique as well as alternative methods of distal embolization and the potential complications that must be considered.

Although uncommon, guidewire entrapment and/or fracture is a serious complication of PCI. It may occur when a coronary guidewire is ‘jailed’, or by looping or snagging of a wire during PCI. In this chapter, several techniques are described that can be used to try to salvage trapped or fractured wires. The use of further wires and balloons is described; snare devices and stents may also be effective and are discussed in detail.

A 62-year-old man presented with an anterior ST elevation myocardial infarction and underwent primary percutaneous coronary intervention to an occluded diagonal artery. Following stenting, a type III distal guidewire-induced coronary perforation of the diagonal branch was recognized with extravasation of contrast into the pericardial space. Prolonged balloon inflations proximal to the site of the perforation were unsuccessful. Subcutaneous fat was therefore harvested from the patients upper thigh under local anesthetic and embolized through an Export catheter into the distal diagonal vessel, resulting in the immediate cessation of leak through the site of perforation. We discuss the technical aspects of this technique as well as alternative methods of distal embolization and the potential complications that must be considered.

Introduction Oral P2Y12 inhibitors have proven clinical efficacy in a variety of cardiological settings. The degree and time course of platelet inhibition using common P2Y12 inhibitors during the acute phase of a myocardial infarction is an under explored area. We aimed to determine the effect of clopidogrel, prasugrel and ticagrelor in the first four hours following loading in patients admitted with STEMI undergoing primary percutaneous coronary intervention (PPCI). Methods A single centre non-randomised study in patients presenting with STEMI. All patients gave informed consent. Enrolled patients were administered a loading dose of aspirin 300mg and then either clopidogrel 600mg, prasugrel 60mg or ticagrelor 180mg prior to percutaneous coronary intervention. Platelet reactivity was measured using a Verify Now assay at 20 minutes post loading, first balloon inflation, 1 and 4 hours post loading. Results are expressed a P2Y12 reaction units (PRU). PRU ≥ 208 indicates poor antiplatelet response. The effect of the three drugs over time were assessed using 2 way ANOVA. P Results A total of 43 STEMI patients were recruited to the study. Refer to Table 1 for baseline characteristics. PRU results for the 3 drugs at 20 minutes, balloon time, 60 minutes and 240 minutes were determined. Mean dose to balloon time was 26.8 + 12.7. At balloon time, 20 minutes and 60 minutes none of the agents achieved a PRU Conclusion Clopidogrel in the context of STEMI does not provide adequate platelet inhibition as evidenced by PRU > 208 at all data collection time points, Both prasugrel and ticagrelor are superior to clopidogrel resulting in a significant reduction in the degree of platelet reactivity. Although Prasugrel and ticagrelor are comparable in terms of inhibition of platelet activity at 20 minutes, balloon inflation, 1 hour and 4 hours, they still do not achieve the desired levels of platelet inhibition necessary during PPCI as demonstrated by PRU > 208. It is possible that fast acting intravenous antiplatelet agents may have a role to play in achieving adequate platelet inhibition in the context of PPCI.

Introduction Current pharmacodynamic (PD) data suggest reduced antiplatelet effect in ST-Elevation myocardial infarction (STEMI) of prasugrel and ticagrelor. We sought to investigate the early PD effect of prasugrel and ticagrelor administered in two patient groups: those admitted with STEMI and a cohort admitted with NSTEMI/unstable angina (UA). Methods P2Y12 inhibitor naive patients presenting with STEMI or NSTEMI/UA were assessed for inclusion. All patients provided informed consent. All received aspirin (300mg) and loading dose of either prasugrel (60mg) or ticagrelor (180mg) in a non-randomised fashion. Platelet reactivity was measured using VerifyNow assay at 20 min, 1 and 4 h post loading. Results are expressed a P2Y12 reaction units (PRU). PRU≥208 indicates a sub optimal antiplatelet response. PRU over time was tested between groups using 2 way ANOVA, P Results A total of 58 patients were enrolled (30 STEMI, and 28 NSTEMI/UA Table 1). Results are shown in Fig 1. In the STEMI patients there was little effect of either agent at 20 min post loading (prasugrel PRU 247 + 48.8, ticagrelor PRU 256 + 50.8) with a limited effect at 1 h and persisting attenuated results at 4 h. In the NSTEMI group however there was a marked and rapid antiplatelet effect of both agents at all time points. Over time there was a significant difference between the effect of both prasugrel ( P Conclusion Prasugrel and ticagrelor in the context of STEMI do not provide adequate P2Y12 inhibition at reperfusion and the first hour post loading when compared to patients with NSTEMI/UA.

Intra-aortic balloon pumps (IABP) are commonly used in the setting of an acute myocardial infarction that is complicated by cardiogenic shock or mechanical complications such as a ventricular septal defect or papillary muscle rupture. IABP has also been shown to be useful in patients with refractory and hemodynamically unstable ventricular arrhythmias and refractory post-myocardial infarction angina. We report a case in which IABP was used in a patient with dilated cardiomyopathy and normal coronary arteries, who presented with persistent, recurrent and refractory ventricular tachycardia. His ventricular tachycardia settled immediately with the use of IABP therapy. He subsequently had an implantable defibrillator. The use of IABP is associated with favorable changes in the left ventricular wall tension and reduction in afterload, which could reduce the excitability of the myocardium, thus making it less prone to arrhythmias. The use of IABP is relatively safe and should be considered in patients with refractory ventricular arrhythmias, even if it is not associated with ischemia.

Factor Xa inhibitors, a new class of oral anticoagulants, have been evaluated in the phase II ATLAS ACS-TIMI 46 and APPRAISE trials. Addition of these agents to standard therapy has tended to reduce the incidence of adverse cardiovascular events at the expense of a dose-dependent increase in the risk of bleeding complications.

Percutaneous occlusion techniques of secundum type atrial septal defects have recently become the treatment of choice, delivering excellent results and being associated with a low rate of early and late complications. The investigators report an unusually delayed presentation of acute right heart failure due to Amplatzer septal device embolisation into the main pulmonary artery, 2 years after implantation.