Prolonged enoxaparin therapy compared with standard-of-care antithrombotic therapy in opiate-treated patients undergoing primary percutaneous coronary intervention.

A novel enoxaparin regimen consisting of intra-arterial bolus (0.75 mg/kg) followed by intravenous infusion (0.75 mg/kg/6 hours) has been developed as a possible solution to the delayed absorption of oral P2Y12 inhibitors in opiate-treated ST-elevation myocardial infarction (STEMI) patients undergoing primary angioplasty. We aimed to study the feasibility of this regimen as an alternative to standard-of-care treatment (SOC) with unfractionated heparin ± glycoprotein IIb/IIIa antagonist (GPI). One hundred opiate-treated patients presenting with STEMI and accepted for primary angioplasty were randomized (1:1) to either enoxaparin or SOC. Fifty patients were allocated enoxaparin (median age 61, 40% females) and 49 allocated SOC (median age 62, 22% females). One developed stroke before angiography and was withdrawn. One SOC patient had a gastrointestinal bleed resulting in 1 g drop in hemoglobin and early cessation of GPI infusion. Two enoxaparin patients had transient minor bleeding: one transient gingival bleed and one episode of coffee ground vomit with no hemoglobin drop or hemodynamic instability. Two SOC and no enoxaparin group patients had acute stent thrombosis. These preliminary data support further study of this novel 6-hour enoxaparin regimen in opiate-treated PPCI patients.

Study of Two Dose Regimens of Ticagrelor Compared With Clopidogrel in Patients Undergoing Percutaneous Coronary Intervention for Stable Coronary Artery Disease.

BACKGROUND: Ticagrelor has superior efficacy to clopidogrel in the management of acute coronary syndromes but has not been assessed in patients undergoing percutaneous coronary intervention for stable coronary artery disease. We compared the pharmacodynamic effects of ticagrelor and clopidogrel in this stable population. METHODS: One hundred eighty aspirin-treated stable coronary artery disease patients, who were planned to undergo elective percutaneous coronary intervention in a single center, were randomized 1:1:1 to either a standard clopidogrel regimen or 1 of 2 regimens of ticagrelor, either 90 mg (T90) or 60 mg twice daily (T60), both with a 180 mg loading dose. Cellular adenosine uptake was assessed, at the time of the procedure and pre- and postdose at 1 month, by adding adenosine 1 µmol/L to aliquots of anticoagulated whole blood and mixing with a stop solution at 0, 15, 30, and 60 seconds, then measuring residual plasma adenosine concentration by high-performance liquid chromatography. Systemic plasma adenosine concentration and platelet reactivity were assessed at the same timepoints. High-sensitivity troponin T was measured pre- and 18 to 24 hours postpercutaneous coronary intervention. RESULTS: One hundred seventy-four patients underwent an invasive procedure, of whom 162 received percutaneous coronary intervention (mean age 65 years, 18% female, 21% with diabetes mellitus). No effect on in vitro adenosine uptake was seen postdose at 1 month for either ticagrelor dose compared with clopidogrel (residual adenosine at 15 seconds, mean±SD: clopidogrel 0.274±0.101 µmol/L; T90 0.278±0.134 µmol/L; T60 0.288±0.149 µmol/L; P=0.37). Similarly, no effect of ticagrelor on in vitro adenosine uptake was seen at other timepoints, nor was plasma adenosine concentration affected (all P>0.1). Both maintenance doses of ticagrelor achieved more potent and consistent platelet inhibition than clopidogrel (VerifyNow P2Y12 reaction units, 1 month, mean±SD: predose, T60: 62±47, T90: 40±38, clopidogrel 181±44; postdose, T60: 34±30, T90: 24±21, clopidogrel 159±57; all P<0.0001 for ticagrelor versus clopidogrel). High platelet reactivity was markedly less with both T60 and T90 compared with clopidogrel (VerifyNow P2Y12 reaction units>208, 1 month postdose: 0%, 0%, and 21%, respectively). Median (interquartile range) high-sensitivity troponin T increased 16.9 (6.5-46.9) ng/L for clopidogrel, 22.4 (5.5-53.8) ng/L for T60, and 17.7 (8.1-43.5) ng/L for T90 (P=0.95). There was a trend toward less dyspnea with T60 versus T90 (7.1% versus 19.0%; P=0.09). CONCLUSIONS: Maintenance therapy with T60 or T90 had no detectable effect on cellular adenosine uptake at 1 month, nor was there any effect on systemic plasma adenosine levels. Both regimens of ticagrelor achieved greater and more consistent platelet inhibition than clopidogrel but did not appear to affect troponin release after percutaneous coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02327624.

Duration of triple antithrombotic therapy and clinical outcomes after percutaneous coronary intervention in atrial fibrillation.

BACKGROUND: Triple antithrombotic therapy (TAT) with aspirin, a P2Y12 inhibitor, and oral anticoagulation in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) raises concerns about increased bleeding. Regimens incorporating more potent P2Y12 inhibitors over clopidogrel have not been investigated adequately. RESEARCH DESIGN AND METHODS: A retrospective observational study was performed on 387 patients with AF receiving TAT for 1 month (n = 236) or ≤1 week (n = 151) after PCI. Major and clinically relevant non-major bleeding and major adverse cardiac and cerebrovascular events (MACCE) were assessed up to 30 days post-procedure. RESULTS: Bleeding was less frequent with ≤1 week versus 1 month of TAT (3.3 vs 9.3%; p = 0.025) while MACCE were similar (4.6 vs 4.7%; p = 0.998). No differences in bleeding or MACCE were observed between ticagrelor/prasugrel and clopidogrel regimens. For patients receiving ≤1 week of TAT, no excess of MACCE was seen in the subgroup given no further aspirin post-PCI compared with those given aspirin for up to 1 week (3.6 vs 5.2%). CONCLUSIONS: TAT post-PCI for ≤1 week was associated with less bleeding despite greater use of ticagrelor/prasugrel but similar MACCE versus 1-month TAT. These findings support further studies on safety and efficacy of dual therapy with ticagrelor/prasugrel immediately after PCI.

The use of ticagrelor in a patient at increased risk of stent thrombosis resistant to multiple thienopyridines.

Ticagrelor has been shown to be superior to clopidogrel in patients presenting with acute myocardial infarction who undergo early invasive treatment. We discuss a hitherto unreported use of ticagrelor in the management of a patient resistant to multiple thienopyridines at high risk of stent thrombosis.

The Impact of Virtual Fractional Flow Reserve and Virtual Coronary Intervention on Treatment Decisions in the Cardiac Catheter Laboratory.

BACKGROUND: Using fractional flow reserve (FFR) to guide percutaneous coronary intervention for patients with coronary artery disease (CAD) improves clinical decision making but remains underused. Virtual FFR (vFFR), computed from angiographic images, permits physiologic assessment without a pressure wire and can be extended to virtual coronary intervention (VCI) to facilitate treatment planning. This study investigated the effect of adding vFFR and VCI to angiography in patient assessment and management. METHODS: Two cardiologists independently reviewed clinical data and angiograms of 50 patients undergoing invasive management of coronary syndromes, and their management plans were recorded. The vFFRs were computed and disclosed, and the cardiologists submitted revised plans. Then, using VCI, the physiologic results of various interventional strategies were shown and further revision was invited. RESULTS: Disclosure of vFFR led to a change in strategy in 27%. VCI led to a change in stent size in 48%. Disclosure of vFFR and VCI resulted in an increase in operator confidence in their decision. Twelve cases were reviewed by 6 additional cardiologists. There was limited agreement in the management plans between cardiologists based on either angiography (kappa = 0.31) or vFFR (kappa = 0.39). CONCLUSIONS: vFFR has the potential to alter decision making, and VCI can guide stent sizing. However, variability in management strategy remains considerable between operators, even when presented with the same anatomic and physiologic data.

Disseminated intravascular coagulation, meningococcal infection, and ischemic changes affecting the lower extremities: a case study.

A middle-aged woman presented from an outside hospital with a diagnosis of Neisseria meningitidis and meningococcemia. A nonpalpable purpuric skin rash evolved into multiple wounds, with gradual necrosis of bilateral lower and upper extremities. Throughout the course of hospitalization, the patient developed ventricular tachycardia, normocytic anemia, thrombocytosis, Clostridium difficile infection, depression, and transient right eye blindness. The finding of decreased CH50 in the complement cascade was considered as the potential cause of the meningococcemia. The subsequent ischemia and necrosis of extremities were attributed to the systemic effect and trauma ensuing from N. meningitidis.

Pharmacodynamic Effects of a 6-Hour Regimen of Enoxaparin in Patients Undergoing Primary Percutaneous Coronary Intervention (PENNY PCI Study).

Delayed onset of action of oral P2Y12 inhibitors in ST-elevation myocardial infarction (STEMI) patients may increase the risk of acute stent thrombosis. Available parenteral anti-thrombotic strategies, to deal with this issue, are limited by added cost and increased risk of bleeding. We investigated the pharmacodynamic effects of a novel regimen of enoxaparin in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). Twenty patients were recruited to receive 0.75 mg/kg bolus of enoxaparin (pre-PPCI) followed by infusion of enoxaparin 0.75 mg/kg/6 h. At four time points (pre-anti-coagulation, end of PPCI, 2-3 hours into infusion and at the end of infusion), anti-Xa levels were determined using chromogenic assays, fibrin clots were assessed by turbidimetric analysis and platelet P2Y12 inhibition was determined by VerifyNow P2Y12 assay. Clinical outcomes were determined 14 hours after enoxaparin initiation. Nineteen of 20 patients completed the enoxaparin regimen; one patient, who developed no-reflow phenomenon, was switched to tirofiban after the enoxaparin bolus. All received ticagrelor 180 mg before angiography. Mean (± standard error of the mean) anti-Xa levels were sustained during enoxaparin infusion (1.17 ± 0.06 IU/mL at the end of PPCI and 1.003 ± 0.06 IU/mL at 6 hours), resulting in prolonged fibrin clot lag time and increased lysis potential. Onset of platelet P2Y12 inhibition was delayed in opiate-treated patients. No patients had thrombotic or bleeding complications. In conclusion, enoxaparin 0.75 mg/kg bolus followed by 0.75 mg/kg/6 h provides sustained anti-Xa levels in PPCI patients. This may protect from acute stent thrombosis in opiate-treated PPCI patients who frequently have delayed onset of oral P2Y12 inhibition.

Transfemoral aortic valve implantation for severe aortic stenosis in a patient with dextrocardia situs inversus.

Transcatheter aortic valve implantation (TAVR) has grown rapidly over the past 10 years. Device and delivery catheter systems have evolved to facilitate the procedure and reduce the risk of associated complications, including those related to vascular access. It is important to understand the utility of the TAVR equipment in patients with more challenging anatomy to select the most appropriate technique for this complex procedure. We report the first case, to our knowledge, of a patient with dextrocardia situs inversus and previous coronary artery bypass grafting who underwent TAVR from the femoral route using the Edwards SAPIEN XT Novaflex+ Transfemoral System (Edwards Lifesciences, Irvine, CA).

Longitudinal stent deformation: a retrospective analysis of frequency and mechanisms.

AIMS: Modern drug-eluting stents are constructed with thin struts and are easy to deliver and highly conformable. However, although innovative designs have enabled maintenance of radial strength, longitudinal strength may be lower with these stents and there have been recent reports of longitudinal stent compression of ostially deployed stents. We report the experience in our centre on longitudinal stent deformation and explore mechanisms of this complication and its frequency with various drug-eluting stent platforms. METHODS AND RESULTS: Nine cases of longitudinal stent deformation were identified over a four year period representing 0.2% of cases and affected 0.097% of stents deployed. There were several mechanisms for this complication including compression by post-dilatation balloons, guide catheter extensions and proximal embolic protection devices. The rate of stent deformation varied from 0% in several stent types to 0.86% in the case of the Promus Element stent. There was one case of late stent thrombosis attributable to longitudinal stent deformation. CONCLUSIONS: Longitudinal stent deformation can occur secondary to a variety of mechanisms and identification is important as, left untreated, it may be associated with a risk of stent thrombosis. Although seen with several different stents, in our series it was more commonly observed with the Promus Element stent.

Percutaneous intervention on anomalous circumflex coronary arteries--a single centre experience.

BACKGROUND: Anomalies of the origin and course of the circumflex artery are amongst the most common seen at coronary angiography. There is limited information regarding patient and procedural characteristics, technical feasibility and outcomes associated with percutaneous intervention (PCI) to these vessels. The aim of this study is to examine our experience with PCI to anomalous circumflex vessels and compare this to some aspects of percutaneous intervention on non-anomalous circumflex vessels. METHODS: Over a 41 month period, 20 PCI procedures on anomalous circumflex vessels were identified and 1550 PCI procedures on non-anomalous circumflex arteries. RESULTS: In 9 anomalous cases, the circumflex arose from the left coronary cusp, in 7 cases from the right coronary cusp, and in the remaining 4 cases from the proximal right coronary artery. There were no differences in demographics or pattern or severity of coronary disease between the 2 groups. A higher proportion of patients with anomalous vessels presented acutely. Screening times were longer in the anomalous group. All 20 procedures were associated with immediate procedural success. There was one peri-procedural myocardial infarction unrelated to anomalous circumflex intervention. After a median follow-up period of 7.3 months, the only major adverse cardiac event recorded in the anomalous group was an ischaemia-driven revascularisation to a non-target vessel branch. We describe techniques which can be used to improve support and facilitate successful PCI to anomalous circumflex vessels. CONCLUSION: PCI to anomalous circumflex vessels may be technically challenging, but is feasible and carries favourable short and long-term clinical outcomes. SUMMARY: This single centre observational study demonstrates that percutaneous coronary intervention to anomalous circumflex coronary arteries although technically challenging can be performed with satisfactory procedural success rates and favourable short and longer-term clinical outcomes. It describes various techniques that can be employed to optimise successful intervention.

The cost effectiveness of primary angioplasty compared to thrombolysis in the real world: one year results from West London.

AIMS: The aim of this study is to use real-world data from West London to compare the cost-effectiveness of a contemporary primary angioplasty (PPCI) service to thrombolysis which it superseded over a time horizon of one year. Previous studies have depended on randomised trials and economic modelling. METHODS AND RESULTS: Resource and outcome data were collected on 400 consecutive patients treated for ST segment elevation myocardial infarction (STEMI) at the hub and two spoke sites over three years. After the first 200 received thrombolysis, the PPCI service was introduced providing treatment for the next 200 cases. The incidence of major adverse cardiac events was significantly less in the PPCI group at 30 days (46.2% versus 7.0%, adjusted odds ratio (AOR) 12 p<0.001) and one year (57.4% versus 13.2%, AOR 8.6 p<0.001) driven by reductions in mortality and ischaemia driven revascularisations. Mean index and one year cumulative costs did not differ significantly between thrombolysis and PPCI (£7,016 versus £6,802; p=0.653 and £8442 versus £7,731; p=0.213 respectively). Initial angioplasty costs were significantly higher in the PPCI group offset by reduced hospital stay (8.5 versus 4 days; p<0.001). CONCLUSIONS: This model of PPCI delivery is associated with larger than expected benefits and is cost-neutral when compared to thrombolysis.

Percutaneous coronary intervention for revascularization of the diabetic patient.

The field of interventional cardiology has progressed rapidly in recent years with the advent of new technology and expanding role of adjunctive pharmacology. This article provides an overview of both current and historical approaches to treating coronary artery disease in the diabetic patient.