Clopidogrel, prasugrel or ticagrelor in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Guidelines recommend prasugrel or ticagrelor instead of clopidogrel in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary interventions (PCI). AIM: We sought to describe the trends in uptake of the newer agents and analyse the clinical characteristics and short-term outcomes of patients treated with clopidogrel, prasugrel or ticagrelor. METHODS: We analysed the temporal trends of antiplatelet use since the availability of prasugrel (2009-2013) in patients with ACS from the Melbourne Interventional Group registry. To assess clinical characteristics and outcomes, we included 1850 patients from 2012 to 2013, corresponding to the time all three agents were available. The primary outcome was major adverse cardiovascular events (MACE). The safety end-point was in-hospital bleeding. RESULTS: For the period of 2009-2013, the majority of patients were treated with clopidogrel (72%) compared with prasugrel (14%) or ticagrelor (14%). There was a clear trend towards ticagrelor by the end of 2013. Patients treated with clopidogrel were more likely to present with non-ST-elevation ACS, be older, and have more comorbidities. There was no difference in unadjusted 30-day mortality (0.9 vs 0.5 vs 1.0%, P = 0.76), myocardial infarction (2 vs 1 vs 2%, P = 0.52) or MACE (3 vs 3 vs 4%, P = 0.57) between the three agents. There was no difference in in-hospital bleeding (3 vs 2 vs 2%, P = 0.64). CONCLUSION: Prasugrel and ticagrelor are increasingly used in ACS patients treated with PCI, predominantly in a younger cohort with less comorbidity. Although antiplatelet therapy should still be individualised based on the thrombotic and bleeding risk, our study highlights the safety of the new P2Y12 inhibitors in contemporary Australian practice.

Pre-treatment with dual antiplatelet therapy in patients with non-ST-segment elevation acute coronary syndromes undergoing percutaneous coronary intervention.

BACKGROUND: Although dual antiplatelet therapy is the standard of care in non-ST-segment elevation acute coronary syndromes (NSTEACS), it remains unclear when a second antiplatelet agent should be initiated. We sought to assess the safety and efficacy of pre-treatment with clopidogrel in patients with NSTEACS undergoing percutaneous coronary intervention (PCI). METHODS: We analysed baseline clinical and procedural characteristics of 6817 patients with NSTEACS who underwent PCI from the Melbourne Interventional Group registry from 2005 to 2012. Patients were included in the pre-treatment group if clopidogrel was administered prior to cardiac catheterisation. We assessed 30-day mortality, myocardial infarction (MI) and major adverse cardiovascular events. The safety endpoint was in-hospital bleeding. RESULTS: Of the 6817 patients, only 2951 (43%) received pre-treatment with clopidogrel. Patients in the pre-treatment group were more likely to present with unstable angina (70.8% vs 68.2%, P = 0.02) and have a history of MI (35.6% vs 23.6%, P < 0.01) but were less likely to have PCI within 24 h of admission (17.2% vs 25.2%, P < 0.01). There was no difference between the groups in 30-day mortality (0.9% vs 1.4%, P = 0.06), MI (2.0% vs 2.2%, P = 0.52) or major adverse cardiovascular event (3.7% vs 4.2%, P = 0.25). There was no difference in bleeding complications (1.9% vs 1.9%, P = 0.94). CONCLUSIONS: Pre-treatment with dual antiplatelet therapy in NSTEACS is not routine clinical practice in Australia. Pre-treatment appears safe but is not associated with improved short-term clinical outcomes.

Trends in door-to-balloon time and outcomes following primary percutaneous coronary intervention for ST-elevation myocardial infarction: an Australian perspective.

BACKGROUND: Guidelines for patients with ST-elevation myocardial infarction include a door-to-balloon time (DTBT) of ≤90 min for primary percutaneous coronary intervention. AIM: The aim of this study was to assess temporal trends (2006-2010) in DTBT and determine if a reduction in DTBT was associated with improved clinical outcomes. METHODS: We compared annual median DTBT in 1926 STEMI patients undergoing primary percutaneous coronary intervention from the Melbourne Interventional Group registry. ST-elevation myocardial infarction presenting >12 h and rescue percutaneous coronary intervention was excluded. Major adverse cardiac events were analysed according to DTBT (dichotomised as ≤90 min vs >90 min). A multivariable analysis for predictors of mortality (including DTBT) was performed. RESULTS: Baseline demographics, clinical and procedural characteristics were similar in the STEMI cohort across the 5 years, apart from an increase in out-of-hospital cardiac arrest (3.6% in 2006 vs 9.4% in 2010, P < 0.0001) and cardiogenic shock (7.7-9.6%, P = 0.07). The median DTBT (interquartile range) was reduced from 95 (74-130) min in 2006 to 75 (51-100) min in 2010 (P < 0.01). In this period, the proportion of patients achieving a DTBT of ≤90 min increased from 45% to 67% (P < 0.01). Lower mortality and major adverse cardiac event rates were observed with DTBT ≤90 min (all P < 0.01). Multivariable analysis showed that a DTBT of ≤90 min was associated with improved clinical outcomes at 12 months (odds ratio 0.48; 95% confidence interval 0.33-0.73, P < 0.01). CONCLUSION: There has been a decline in median DTBT in the Melbourne Interventional Group registry over 5 years. DTBT of ≤90 min is associated with improved clinical outcomes at 12 months.

Prolonged antiplatelet therapy to prevent late thrombosis after intracoronary gamma-radiation in patients with in-stent restenosis: Washington Radiation for In-Stent Restenosis Trial plus 6 months of clopidogrel (WRIST PLUS).

BACKGROUND: Intracoronary gamma-radiation reduces recurrent in-stent restenosis. Late thrombosis (>30 days after radiation therapy) is identified as a serious complication. The Washington Radiation for In-Stent Restenosis Trial (WRIST) PLUS, which involved 6 months of treatment with clopidogrel and aspirin, was designed to examine the efficacy and safety of prolonged antiplatelet therapy for the prevention of late thrombosis. METHODS AND RESULTS: A total of 120 consecutive patients with diffuse in-stent restenosis in native coronary arteries and vein grafts with lesions <80 mm underwent percutaneous coronary transluminal angioplasty, laser ablation, and/or rotational atherectomy. Additional stents were placed in 34 patients (28.3%). After the intervention, a closed-end lumen catheter was introduced into the artery, a ribbon with different trains of radioactive (192)Ir seeds was positioned to cover the treated site, and a dose of 14 Gy to 2 mm was prescribed. Patients were discharged with clopidogrel and aspirin for 6 months and followed angiographically and clinically. All patients but one tolerated the clopidogrel. The late occlusion and thrombosis rates were compared with the gamma-radiation-treated (n=125) and the placebo patients (n=126) from the WRIST and LONG WRIST studies (which involved only 1 month of antiplatelet therapy). At 6 months, the group receiving prolonged antiplatelet therapy had total occlusion and late thrombosis rates of 5.8% and 2.5%, respectively; these rates were lower than those in the active gamma-radiation group and similar to those in the placebo historical control group. CONCLUSIONS: Six months of clopidogrel and aspirin and a reduction in re-stenting for patients with in-stent restenosis treated with gamma-radiation is well tolerated and associated with a reduction in the late thrombosis rate compared with a similar cohort treated with only 1 month of clopidogrel and aspirin.

Comparative efficacy of gamma-irradiation for treatment of in-stent restenosis in saphenous vein graft versus native coronary artery in-stent restenosis: An intravascular ultrasound study.

BACKGROUND: We used serial volumetric (post-irradiation and follow-up) intravascular ultrasound (IVUS) to compare the effectiveness of gamma-irradiation ((192)Ir) in saphenous vein graft (SVG) versus native coronary artery in-stent restenosis (ISR). METHODS AND RESULTS: The study population consisted of 47 patients with native coronary artery ISR from WRIST (Washington Radiation for In-Stent Restenosis Trial) and 31 patients with SVG ISR (12 from the WRIST and 19 from SVGWRIST). After irradiation and at 6-month follow-up, stent, lumen, and intimal hyperplasia (IH, stent minus lumen) areas were measured every 1 mm. ISR length was similar in the 2 groups (29+/-12 versus 29+/-14 mm, P=0.9). Post-intervention measurements of stent (280+/-154 versus 324+/-270 mm(3), P=0.4), lumen (184+/-91 versus 214+/-172 mm(3), P=0.3), and IH (96+/-77 versus 109+/-119 mm(3), P=0.5) volumes were similar in the 2 groups. The post-intervention minimum lumen cross sectional areas tended to be smaller in native artery ISR lesions (4.7+/-1.7 versus 5.4+/-1.6 mm(2), P=0.11). During follow-up, there was a slight increase in IH volume (9+/-38 mm(3)) in native artery ISR lesions and a slight decrease in IH volume in SVG ISR lesions (-9+/-32 mm(3), P=0.0463). There was also a slight decrease in minimum lumen area in the native artery ISR lesions versus a slight increase in minimum lumen area in the SVG ISR lesions (-0.8+/-1.7 versus 0.2+/-1.1, P=0.0087). As a result, the follow-up minimum lumen area in native artery lesions was smaller than in SVG ISR lesions (4.1+/-2.1 mm(2) versus 5.6+/-2.2 mm(2), P=0.0067). CONCLUSION: gamma-Irradiation with (192)Ir brachytherapy appears to be as effective in SVGs as it is in native artery ISR lesions.

The effect of intracoronary radiation for the treatment of recurrent in-stent restenosis in patients with chronic renal failure.

OBJECTIVES: This study was designed to analyze the in-hospital and six-month clinical and angiographic outcomes of patients with chronic renal failure (CRF) treated with intracoronary radiation for the prevention of recurrence of in-stent restenosis. BACKGROUND: Patients with CRF are at a higher risk than the general population for accelerated atherosclerotic cardiovascular disease and for restenosis after percutaneous coronary intervention. Previous studies have shown the effectiveness of both beta and gamma radiation in preventing recurrent restenosis in patients with in-stent restenosis. METHODS: We studied the in-hospital and six-month clinical and angiographic outcomes of 118 patients with CRF and 481 consecutive patients without CRF who were treated with intracoronary radiation for the prevention of recurrence of in-stent restenosis in native coronaries and saphenous vein grafts. RESULTS: Patients with CRF were usually older, women, hypertensive and diabetic, with multivessel disease and with reduced left ventricular function. In-hospital outcome for patients with CRF was marred by a higher incidence of death, non-Q-wave myocardial infarction and major vascular and bleeding complications. At six-month follow-up, the mortality rate was higher in patients with CRF, 7.6% compared with 1.9% in non-CRF patients (p = 0.003). Restenosis, target lesion revascularization (TLR) and target vessel revascularization (TVR) rates were similar in the two groups. In patients with CRF, radiation therapy compared to placebo reduced restenosis (53.8% vs. 22.6%, p = 0.04), TLR (71.4% vs. 15.3%, p < 0.0001) and TVR (78.6% vs. 23.7%, p = 0.0002). CONCLUSIONS: Intracoronary radiation for the prevention of recurrence of in-stent restenosis achieved similar rates of restenosis and revascularization procedures in patients with and without CRF. Despite this benefit, patients with renal dysfunction continued to have significantly higher in-hospital and six-month adverse outcomes.

Effects of 32P radioactive stents on in-stent restenosis in a double stent injury model of the porcine coronary arteries.

BACKGROUND: The major limitation of coronary stenting remains in-stent restenosis, due to the development of neointimal proliferation. Radioactive stents have demonstrated the ability to reduce this proliferation in the healthy nonatherosclerotic porcine animal model. However, inhibition of tissue proliferation in the in-stent restenotic lesion in a porcine model is not well characterized. The objective of this study was to examine the efficacy and safety of the 32P radioactive stent for the treatment of in-stent restenosis in a double stent injury model of the porcine coronaries. METHODS AND MATERIALS: Eighteen coronary arteries in 9 pigs underwent nonradioactive stent (8 mm in length) implantation. Thirty days after the initial stent implantation, a 32P radioactive stent (18 mm in length) with an activity of 0 and 18 microCi was implanted to cover the initial stent. The swine were killed 30 days after the second stent implantation. Histomorphometric analysis was performed for vessel area (VA), stent strut area (SSA), intimal area (IA), and lumen area (LA). RESULTS: Injury scores, VA, SSA, and LA were similar among the control and radiated groups. Neointimal formation was significantly reduced after placement of radioactive stents as compared to control in both the overlapped (0.93 +/- 0.12 vs. 1.31 +/- 0.51 mm(2), p < 0.05) and nonoverlapped segments (1.14 +/- 0.21 vs. 1.91 +/- 1.04 mm(2), p < 0.05). The smooth muscle cell index in the neointima was reduced. Intimal fibrin was increased in the radiated group as compared to the control (p < 0.01 respectively). CONCLUSIONS: 32P radioactive stents may be safe and effective in reducing neointimal formation leading to in-stent restenosis. Longer follow-up will be required to examine whether these positive findings can be maintained.

Impact of early percutaneous coronary intervention on short- and long-term outcomes in patients with cardiogenic shock after acute myocardial infarction.

This study assesses the impact of early percutaneous coronary intervention in patients presenting with cardiogenic shock after acute myocardial infarction. Predictors of in-hospital death include the need for intubation, cardiopulmonary resuscitation, and angiographic failure; long-term outcomes at 2 years in hospital survivors are favorable.

Reduced neuropsychological dysfunction using epiaortic echocardiography and the exclusive Y graft.

BACKGROUND: To examine the effect of screening the aorta for atheroma before aortic manipulation and use of exclusive Y graft revascularization on the incidence of neuropsychological dysfunction after coronary artery bypass. METHODS: Aortic atheroma was detected using epiaortic and transesophageal echocardiography. Atheroma avoidance was facilitated by use of the exclusive Y graft technique, which has no aortic coronary anastomoses. In the control group aortic atheroma was assessed by manual palpation, and we attempted to avoid any atheroma detected. In this group we also used aorta-coronary grafts. Transcranial Doppler imaging of the right middle cerebral artery was used to detect cerebral microemboli. Neuropsychological dysfunction was defined as a 20% or more decline in score for at least 20% of a neuropsychometric battery of ten tests for each patient. RESULTS: Late dysfunction at 57 +/- 2 days postoperatively in the control group was 38.1% and in the echo/Y group was 3.8% (p' = 0.012). Microemboli detected by transcranial Doppler imaging during periods of aortic manipulation was greater for those with late dysfunction (5.2 +/- 3.0 compared with 0.5 +/- 0.2) (p' = 0.018). No clinical strokes occurred in either group. CONCLUSIONS: The combined techniques of epiaortic screening and exclusive Y graft for coronary artery bypass operations resulted in a low incidence of late neuropsychological dysfunction.

Have we solved the problem of late thrombosis?

Late thrombosis (angiographic total occlusion associated with an acute coronary syndrome) is potentially a life-threatening complication after intracoronary radiation therapy. This review is intended to explore the pre-clinical and clinical evidence for late thrombosis, discuss the etiology, and provide guidelines for future management. Although we have gained a greater understanding of this complex entity, further research is required to curtail late thrombosis rates.

Clinical outcomes of drug-eluting stent use in patients with ST elevation myocardial infarction.

AIM: Randomised trials using drug-eluting stents (DES) in ST elevation myocardial infarction (STEMI) have shown mixed results, and excluded patients at the highest risk of adverse outcomes. We aimed to determine the real world clinical outcomes of DES and compare these with bare-metal stents (BMS) in an unrestricted observational study of patients presenting with STEMI. METHODS: 564 consecutive patients undergoing primary PCI for STEMI were prospectively enrolled in the Melbourne Interventional Group registry (August 2004 to May 2006). The choice of using DES was at the operator's discretion, yet restricted to patients considered at highest risk of restenosis [e.g. diabetes, long lesions (>20 mm) and small target vessels (<2.5 mm)]. Clinical, procedural, and 12-month outcomes of patients receiving DES were evaluated and compared to BMS. RESULTS: DES were used in 45% of patients presenting with STEMI. The rates of cardiogenic shock were similar in the DES and BMS groups (10.2 vs. 11%, p=0.71). In-hospital outcomes were not significantly different with respect to death (4.7 vs. 7.2%, p=0.23), major adverse cardiac events (MACE) (10.6 vs. 11.3%, p=0.80) or stent thrombosis (1.7 vs. 0.3%, p=0.71). At 12 months, target vessel revascularisation (TVR) in patients with DES was 10.2% vs. 7.2% in BMS (p=0.22). On propensity score adjusted multivariate analyses, the only independent predictor of 12-month MACE was presentation with cardiogenic shock (OR 2.59, 95% C.I 1.04-6.45), and the only predictor of 12-month TVR was reference vessel diameter ≤2.5 mm (OR 2.16, 95% C.I 1.06-4.33). DES use was not independently predictive of lower TVR, MACE rates or mortality. Late stent thrombosis rates were similar (DES 3.2 vs. BMS 3.8%, p=0.65). CONCLUSIONS: Drug-eluting stents are frequently used in Australia in the high-risk setting of STEMI. While target vessel revascularisation rates were moderate in this high-risk group, there was no increased mortality, reinfarction or stent thrombosis compared to bare-metal stents.

The foundation and launch of the Melbourne Interventional Group: a collaborative interventional cardiology project.

The Melbourne Interventional Group (MIG) is a voluntary collaborative venture of interventional cardiologists practicing at 12 major public and private hospitals in Victoria, designed to record data pertaining to percutaneous coronary interventions (PCI) and perform long-term follow-up. The potential advantages of collaboration involve large-scale analysis of current interventional strategies (e.g. drug-eluting stents, evaluation of new technologies and cost-effective analysis), provide a basis for multi-centred clinical trials and allow comparison of clinical outcomes with cardiac surgery. The established registry documents demographic, clinical and procedural characteristics of consecutive patients undergoing PCI and permits analysis of those characteristics at 30 days and 12 months. The registry is co-ordinated by the Centre of Clinical Research Excellence (CCRE), a research body within the Department of Epidemiology and Preventive Medicine (Monash University, Melbourne). The eventual goal of MIG is to provide a contemporary appraisal of Australian interventional cardiology practice, with opportunities to improve in-hospital and long-term outcomes of patients with coronary artery disease.

Intracoronary beta radiation: state of the art.

This state-of-the-art review is intended to explore the development of beta radiation including catheter delivered and permanent implants from its inception to current practice. Specific focus will be given to the isotopes currently available, radiation physics of beta emitters, preclinical studies, clinical trials, beta radiation delivery systems, and implications for future practice. The encouraging results from the clinical trials have established vascular brachytherapy as a standard of care for patients with in-stent restenosis. Vascular brachytherapy requires additional "fine-tuning" to achieve full optimization.

Clinical trials of vascular brachytherapy for in-stent restenosis: update.

Vascular brachytherapy has become the therapeutic strategy of choice for in-stent restenosis. Clinical trials evaluating the effectiveness and safety of this technology have enrolled nearly 4000 patients using both gamma and beta emitters. At present, ongoing controversies include optimal dosimetry, whether beta emitters are as effective as gamma and whether centering delivery systems perform better than non-centering systems. Complications of brachytherapy such as edge effect, late thrombosis and late restenosis have received increasing attention. This review provides an update of the current status of clinical trials utilizing vascular brachytherapy to prevent the recurrence of in-stent restenosis.

Optimal assessment of cervical spine trauma in critically ill patients: a prospective evaluation.

There is no uniformly accepted protocol for the radiological assessment of the cervical spine in critically ill trauma patients. The Alfred Trauma Centre receives about 40% of Victorian patients with major trauma. A protocol was developed for cervical spine evaluation, comprising three plain X-rays and a swimmer's view added when necessary to visualize C7-T1, CT and/or MRI for abnormal regions, and functional (flexion/extension) X-rays to exclude cervical spine instability due to soft tissue trauma. Functional X-rays were performed "actively" in conscious patients and "passively" in unconscious patients. One hundred consecutive patients were prospectively evaluated and 91 survived to complete data collection. Six (6.6%) had unstable cervical spine injuries--five detected with plain X-rays and one (1.1%) detected only with passive functional X-rays. Static cervical X-rays cost $93.00 per patient. Functional cervical X-rays added $42.00 per patient and were uncomplicated. Collar complications were common when collars remained on for more than 72 hours. This low detection rate is clinically important because of the enormous potential social and economic costs of missed unstable cervical spine fractures.

Analysis of clinical outcomes following in-hospital adult cardiac arrest.

AIMS: The outcome of in-hospital resuscitation following cardiac arrest depends on many factors related to the patient, the environment and the extent of resuscitation efforts. The aim of the present study was to determine predictors of successful resuscitation and survival to -hospital discharge following in-hospital cardiac arrest and to assess functional outcomes of survivors (cerebral performance scores). METHODS: Medical records of adult patients sustaining in-hospital cardiac arrest between June 2001 and January 2003 were reviewed. Successful resuscitation was defined as the return of spontaneous circulation at the completion of resuscitative efforts, irrespective of degree of inotropic/vasopressor support. Thirty demographic and clinical variables were analysed to determine predictors of successful resuscitation and in-hospital survival. RESULTS: In 105 patients with cardiac arrest, 46 patients (44%) were successfully resuscitated and 22 (21%) survived to hospital discharge. Predictors of successful resuscitation included a primary cardiac admission diagnosis, monitoring at the time of the arrest, a longer duration of resuscitation and the absence of the need for endotracheal intubation. Patients with ventricular tachycardia/fibrillation were more likely to survive to hospital discharge than those with asystolic or pulseless electrical activity (45 vs 12 vs 20%, P = 0.01). The sole independent predictor of survival to hospital discharge was the absence of the need for endotracheal intubation (odds ratio 0.14, 95% confidence interval 0.02-0.88, P < 0.01). The majority of survivors (73%) had normal cerebral performance scores. CONCLUSIONS: Identification of predictors of successful resuscitation following cardiac arrest is important for risk stratification. Ongoing appraisal of in-hospital cardiac arrests through a multicentre registry could improve clinical outcomes.

Three-year follow-up after intracoronary gamma radiation therapy for in-stent restenosis. Original WRIST. Washington Radiation for In-Stent Restenosis Trial.

BACKGROUND: The Washington Radiation for In-Stent Restenosis Trial (WRIST) is a double-blinded randomized study evaluating the effects of intracoronary radiation therapy (IRT) in patients with in-stent restenosis (ISR). METHODS: One hundred and thirty patients with ISR (100 native coronary and 30 vein grafts) underwent PTCA, laser ablation, rotational atherectomy, and/or additional stenting (36% of lesions). Patients were randomized to either Iridium-192 IRT or placebo, with a prescribed dose of 15 Gy to a 2-mm radial distance from the center of the source. RESULTS: Angiographic restenosis (27% vs. 56%, P=.002) and target vessel revascularization (TVR; 26% vs. 66%, P<.001) were dramatically reduced at 6 months in IRT patients. Between 6 and 36 months, IRT compared to placebo patients had more target lesion revascularization (TLR; IRT=17% vs. placebo=2%, P=.002) and TVR (IRT=17% vs. placebo=3%, P=.009). At 3 years, the major adverse cardiac event (MACE) rate was significantly reduced with IRT (39% vs. 65%, P=.003). CONCLUSIONS: In WRIST, patients with ISR treated with IRT using 192Ir had a marked reduction in the need for repeat target lesion and vessel revascularization at 6 months, with the clinical benefit maintained at 3 years.