Alan Whelan

Randomized trial comparing 600- with 300-mg loading dose of clopidogrel in patients with non–ST elevation acute coronary syndrome undergoing percutaneous coronary intervention: Results of the Platelet Responsiveness to Aspirin and Clopidogrel and Troponin Increment after Coronary intervention in Acute coronary Lesions (PRACTICAL) Trial

BACKGROUND There is uncertainty about the benefit of a higher loading dose (LD) of clopidogrel in patients with non-ST elevation acute coronary syndrome (NSTEACS) undergoing early percutaneous coronary intervention (PCI). METHODS We compared the effects of a 600- versus a 300-mg LD of clopidogrel on inhibition of platelet aggregation, myonecrosis, and clinical outcomes in patients with NSTEACS undergoing an early invasive management strategy. Patients with NSTEACS (n = 256, mean age 63 years, 81.6% elevated troponin) without thienopyridine for at least 7 days were randomized to receive 600- or 300-mg LD of clopidogrel. Percutaneous coronary intervention was performed in 140 patients, with glycoprotein IIb/IIIa inhibitor use in 68.6%. Adenosine diphosphate (ADP)-induced platelet aggregation was measured by optical platelet aggregometry immediately before coronary angiography. RESULTS Post-PCI myonecrosis was defined as a next-day troponin I greater than 5 times the upper limit of reference range and greater than baseline levels. Clopidogrel 600-mg LD compared with 300-mg LD was associated with significantly reduced ADP-induced platelet aggregation (49.7% vs 55.7% with ADP 20 micromol/L) but did not reduce post-PCI myonecrosis or adverse clinical outcomes to 6 months. There was no association between preprocedural platelet aggregation and outcome. CONCLUSIONS These data confirm a modest incremental antiplatelet effect of a 600-mg clopidogrel LD compared with 300-mg LD but provide no support for a clinical benefit in patients with NSTEACS managed with an early invasive strategy including a high rate (69%) of glycoprotein IIb/IIIa inhibitor use during PCI.

Paclitaxel-eluting balloon and everolimus-eluting stent for provisional stenting of coronary bifurcations: 12-month results of the multicenter BIOLUX-I study

BACKGROUND Several studies investigated the combination of bare metal stents in the main branch and drug-eluting balloons in the side branch in bifurcation lesions, but data on the combination of drug-eluting stents and drug-eluting balloons are scarce. We aim to assess the feasibility of provisional stenting with an everolimus-eluting stent in the main branch and a paclitaxel-eluting balloon in the side branch. METHODS In this prospective, multi-center study conducted in 5 Australian sites, 35 patients with bifurcation lesions were enrolled. Angiographic and intravascular ultrasound assessments were conducted at 9 months; clinical follow-up was conducted until 12 months. RESULTS The primary endpoint, late lumen loss in the side branch measured by quantitative coronary angiography, was 0.10±0.43mm. No binary restenosis was observed. One patient died; 3 myocardial infarctions (one suspected and two in non-target vessels) and one target lesion revascularization occurred. No probable or definite stent thrombosis was observed. CONCLUSION The combination of an everolimus-eluting stent in the main branch and a paclitaxel-eluting balloon in the side branch appears to be a safe, effective and novel treatment option for bifurcation lesions.

Improving Guideline Compliance in Australia With a National Percutaneous Coronary Intervention Outcomes Registry

BACKGROUND Secondary prevention strategies after percutaneous coronary intervention (PCI) include statins and dual anti-platelet therapy, however there are significant gaps between guidelines and practice. Contemporary PCI practice requires comprehensive data collection to allow dynamic auditing and benchmarking of key performance and safety indices. Genesis HeartCare is Australias largest collaborative venture of cardiologists, practising at over 40 public and private hospitals. We hypothesised that measurement and local reporting of data would improve patient outcomes through improving compliance with guideline therapies. METHODS Real-time benchmarking via a national clinical quality and outcomes register, the Genesis Cardiovascular Outcomes Registry (GCOR-PCI). GCOR-PCI prospectively collected clinical, procedural, medication and outcomes data for 6720 consecutive patients undergoing PCI from 10 private hospitals across Australia. Key performance outcomes benchmarked against the aggregated study cohort and international standards were reported to individual sites. The main outcome measure was compliance with guideline medications (statins, anti-platelet agents). RESULTS Early data identified specific practice patterns associated with lower rates of statin therapy post-PCI, which led to changes in practice. Between the first and latest year of data collection there was significant improvement in the rates of statin therapy at discharge (92.1 vs. 94.4% p<0.03) and 12 months post-PCI (87.0 vs. 92.2% p<0.001) and of antiplatelet therapy at 12 months (90.7 vs. 94.3% p<0.001). CONCLUSIONS This large-scale collaboration provides a platform for the development of quality improvement initiatives. Establishment of this clinical quality registry improved patient care by identifying and monitoring gaps in delivery of appropriate therapies, driving key practice change.

Comparison of Safety and Efficacy of Unfractionated Heparin Versus Bivalirudin in Patients Undergoing Percutaneous Coronary Intervention

BACKGROUND Anti-platelet and anti-coagulant adjunctive therapies are associated with a clinically significant increased risk of major bleeding. We retrospectively assessed in-hospital major adverse clinical events (MACE) and major bleeding in patients undergoing percutaneous coronary intervention (PCI) who received either unfractionated heparin (UFH) or bivalirudin. METHOD Consecutive patients undergoing PCI for acute coronary syndrome (ACS) at Fremantle Hospital from August 2008 to December 2013 were identified. Patients received dual antiplatelet therapy (DAPT), with either UFH (50-100IU/kg) or bivalirudin (bolus 0.75mg/kg and infusion 1.75mg/kg/hr). Adjunctive glycoprotein IIb/IIIa (GPIIbIIIa) antagonist use was at the operators discretion. In-hospital events were identified from case notes and PCI database review. RESULTS Of 3371 patients identified, 1740 received UFH and 1631 received bivalirudin. The two groups were similar with respect to age, 62.5 SD 12.1 yrs vs. 62.8 SD 12.2 yrs, (p=0.575) female gender, 24% vs. 26% (p=0.10), current smokers, 66% vs. 70% (p=0.53), diabetes, 25% vs. 26% (p=0.62) and the use of DAPT (p=ns). Presentation with ST-segment-elevation myocardial infarction (STEMI) was significantly higher in the UFH group (28% vs. 19%, p<0.001). The use of transfemoral arterial access was similar (93% UFH vs. 92% bivalirudin) (p=0.41). More patients received GPIIb/IIIa antagonist in the UFH group (30% vs. 3%; p <0.001). There was no difference in pre-discharge acute stent thrombosis (<24hours) occurring in 1.0% with UFH vs. 0.5% with bivalirudin (p=0.20). The equipoise on the outcomes of stent thrombosis persisted after multivariate adjustment for difference in rates of STEMI. In-hospital BARC Type 1-3 major bleeding occurred in 3.7% in the UFH group vs. 2.9% in the bivalirudin group (p=0.20). CONCLUSION Unfractionated heparin compared with bivalirudin was not associated with a higher incidence of in-hospital MACE or major bleeding in a cohort with overall high rates of transfemoral access, despite significantly higher use of GPIIb/IIIa antagonists in the UFH group.