D A Jones

The safety and efficacy of intracoronary nitrite infusion during acute myocardial infarction (NITRITE-AMI): study protocol of a randomised controlled trial

Introduction Acute myocardial infarction (AMI) is a major cause of death and disability in the UK and worldwide. Presently, timely and effective reperfusion with primary percutaneous coronary intervention (PPCI) remains the most effective treatment strategy for limiting infarct size, preserving left ventricular ejection fraction (LVEF) and improving clinical outcomes. However, the process of reperfusion can itself induce cardiomyocyte death, known as myocardial reperfusion injury, for which there is currently no effective therapy. Extensive preclinical evidence exists to suggest that sodium nitrite (as a source of endogenous nitric oxide) is an effective therapeutic strategy for preventing myocardial reperfusion injury. The purpose of NITRITE-AMI is to test whether sodium nitrite reduces reperfusion injury and subsequent infarct size in patients undergoing PPCI for MI. Methods and design NITRITE-AMI is a double-blind, randomised, single-centre, placebo-controlled trial to determine whether intracoronary nitrite injection reduces infarct size in patients with myocardial infarction undergoing primary angioplasty. The study will enrol 80 patients presenting with ST-elevation myocardial infarction. Patients will be randomised to receive either a bolus of intracoronary sodium nitrite or placebo (sodium chloride) at the time of PPCI. The primary outcome is infarct size assessed by creatine kinase area under the curve (AUC) over 48u2005h. Secondary endpoints include troponin T AUC and infarct size, LV dimensions and myocardial salvage index assessed by cardiac MR (CMR), markers of platelet reactivity and inflammation, the safety and tolerability of intracoronary nitrite, and 1u2005year major adverse cardiac events. Ethics and dissemination The study is approved by the local ethics committee (NRES Committee London West London: 11/LO/1500) and by the Medicines and Healthcare Products Regulatory Agency (MHRA) (EudraCT nr. 2010-022460-12). The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer-reviewed journals. Trial registration United Kingdom Clinical Research Network (Study ID 12117), http://clinicaltrials.gov (NCT01584453) and Current Controlled Trials (ISRCTN:38736987).

Case fatality rates for South Asian and Caucasian patients show no difference 2.5 years after percutaneous coronary intervention

Objective To compare short and medium-term prognosis in South Asian and Caucasian patients undergoing percutaneous coronary intervention (PCI) to determine if there are ethnic differences in case death rates. Design Retrospective cohort study. Setting A cardiology referral centre in east London. Patients 9771 patients who underwent PCI from October 2003 to December 2007 of whom 7966 (81.5%) were Caucasian and 1805 (18.5%) were South Asian. Main outcome measures In-hospital major adverse cardiac events (MACE; death, myocardial infarction, stroke and target vessel revascularisation), subsequent revascularisation rates (PCI and coronary artery bypass grafting; CABG) and all-cause mortality during a median follow-up of 2.5u2005years (range 1.5–3.6u2005years). Results South Asian patients were younger than Caucasian patients (59.69±0.27 vs 64.69±0.13u2005years, p<0.0001), and more burdened by cardiovascular risk factors, particularly type II diabetes mellitus (45.9%±1.2% vs 15.7%±0.4%, p<0.0001). The in-hospital rates of MACE were similar for South Asians and Caucasians (3.5% vs 2.8%, p=0.40). South Asians had higher rates of clinically driven PCI for restenosis and subsequent CABG, although Kaplan–Meier estimates of all-cause mortality showed no significant differences; this was regardless of whether PCI was performed post-acute coronary syndrome or as an elective procedure. The adjusted hazard of death for South Asians compared with Caucasians was 1.00 (95% CI 0.81 to 1.23). Conclusion In this large PCI cohort, the in-hospital and longer-term mortality of South Asians appeared no worse than that of Caucasians. South Asians had higher rates of restenosis and CABG during follow-up. Data suggest that the excess coronary mortality for South Asians compared with Caucasians is not explained by differences in case-fatality rates.

Radial primary percutaneous coronary intervention is independently associated with decreased long-term mortality in high-risk ST-elevation myocardial infarction patients.

AIMnTo compare long-term clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PPCI) using radial and femoral arterial access.nnnMETHODS AND RESULTSnThe present study was an observational cohort study of patients with STEMI treated consecutively with PPCI between 2004 and 2011 at a single centre. The primary end point was all-cause mortality at a median follow-up of 3 years.Among 2727 patients, 1600 (58.7%) underwent PPCI via the femoral route. The femoral group was older (64.7 vs. 61.7 years; Pu200a<u200a0.0001), and had higher rates of diabetes (18.6% vs. 16.0%; Pu200a<u200a0.0001), previous PCI (11.2 vs. 7.8%; Pu200a=u200a0.004), previous myocardial infarction (15.3 vs. 8.3%; Pu200a<u200a0.0001) and cardiogenic shock (9.8 vs. 1.3%; Pu200a<u200a0.0001). Bleeding complications were more frequent in the femoral group (4.7 vs. 1.2%; Pu200a<u200a0.0001). The 5-year death rate was significantly higher in the femoral group than in the radial group (10.4 vs. 3.0%; Pu200a<u200a0.0001). After adjustment for confounding variables, bleeding complications [heart rate 2.07 (95% confidence interval 1.05-4.08)] and femoral access [heart rate 1.60 (95% confidence interval 1.02-2.53)] were independent predictors of all-cause mortality. After stratification using the propensity score, excess long-term mortality in patients treated via the femoral approach was predominantly in patients with a high baseline risk of death.nnnCONCLUSIONnPatients undergoing PPCI via the femoral route are at a higher risk of adverse short-term and long-term outcomes than patients undergoing PPCI via the radial route. Patients with a high baseline risk may benefit most from radial access, and future outcome studies should focus on the most at-risk patients.

Glycoprotein IIb/IIIa inhibitors use and outcome after percutaneous coronary intervention for non-ST elevation myocardial infarction.

Aims. We investigate the effect of glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors on long-term outcomes following percutaneous coronary intervention (PCI) after non-ST elevation myocardial infarction (NSTEMI). Meta-analyses indicate that these agents are associated with improved short-term outcomes. However, many trials were undertaken before the routine use of P2Y12 inhibitors. Recent studies yield conflicting results and registry data have suggested that GP IIb/IIIa inhibitors may cause more bleeding than what trials indicate. Methods and Results. This retrospective observational study involves 3047 patients receiving dual-antiplatelet therapy who underwent PCI for NSTEMI. Primary outcome was all-cause mortality. Major adverse cardiac events (MACE) were a secondary outcome. Mean follow-up was 4.6 years. Patients treated with GP IIb/IIIa inhibitors were younger with fewer comorbidities. Although the unadjusted Kaplan-Meier analysis suggested that GP IIb/IIIa inhibitor use was associated with improved outcomes, multivariate analysis (including propensity scoring) showed no benefit for either survival (P = 0.136) or MACE (P = 0.614). GP IIb/IIIa inhibitor use was associated with an increased risk of major bleeding (P = 0.021). Conclusion. Although GP IIb/IIIa inhibitor use appeared to improve outcomes after PCI for NSTEMI, patients who received GP IIb/IIIa inhibitors tended to be at lower risk. After multivariate adjustment we observed no improvement in MACE or survival and an increased risk of major bleeding.

16 Acute stent thrombosis resulting in ST elevation myocardial infarction (STEMI) is associated with worse clinical outcomes than STEMI due to native coronary thrombosis

Background Stent thrombosis (ST) is a recognised cause of ST Elevation Myocardial infarction (STEMI) in patients with previous percutaneous coronary interventions (PCI). The incidence is increasing and to date outcomes are not well characterised, though there is a suggestion that there is a worse clinical outcome. We therefore sought to compare STEMI caused by ST vs de novo coronary thrombosis to evaluate procedural risk and clinical outcome. Methods Clinical information was analysed from a prospective database on 2421 patients who underwent Primary PCI following STEMI between October 2003 and May 2010 at a London centre. Information was entered at the time of procedure, diagnosis of stent thrombosis made at the time by primary operator and outcome assessed by all-cause mortality information provided by the Office of National Statistics via the BCIS CCAD national audit. Results Stent thrombosis (ST) accounted for 7.4% (180/2421) of all STEMIs with a frequency that has increased over time (5.4% in 2005 to 9.8% 2009). ST occurred early (0–30u2005days) in 36% (65/180), late (30u2005days–1u2005year) in 22% (40/180) and very late (>1u2005year) in 42% (75/180) of pts. Drug-eluting stents (DES) accounted for 48% of ST overall and 70% over the past 3u2005years. Proposed mechanisms included premature discontinuation of anti-platelets (11%), under-deployment of previous stent insertion (22%) and underlying prothrombotic conditions (eg, SLE) (6%). Pts with ST compared to native artery occlusion had higher rates of previous MI (53.9% vs 11%, p<0.0001) and incidence of multi-vessel disease (59.8% vs 51.7%, p=0.04 There was no difference in age, diabetes or cardiogenic shock. See Abstract 16 table 1. Infarct size based on peak enzyme markers was similar (2.5 vs 2.2, p=0.45). In patients with ST, angiographic success (postprocedural Thrombolysis In Myocardial Infarction grade III flow) was worse than in patients with de novo STEMI (87.2% vs 93.7%, p=0.02). Pts with STEMI due to ST had higher in-hospital MACE (11% vs 3%, p=0.0001), MACE at 30u2005days (19% vs 6%, p<0.0001), this persisted up to 3u2005years (41% vs 12%, p<0.0001). See Abstract 16 figure 1. MACE was driven by higher rates of MI (7% vs 2%, p<0.0001), TVR (14% vs 3%, p<0.0001) and death (18% vs 6%, p=0.0001). After adjusting for comorbidities, stent thrombosis was an independent predictor of long-term adverse outcome (OR=2.1, 95% CI=1.3 to 2.8, p<0.001).Abstract 16 Table 1 AST (n=180) No AST (n=2241) Significance (p value) Age 63.9±18 62.9±4 0.406 Multi-vessel disease 101 (59.76%) 1011 (51.74%) 0.045 Previous MI 96 (53.93%) 246 (10.96%) <0.0001 Previous CABG 9 (5.06%) 60 (2.67%) 0.020 Diabetes mellitus 46 (25.84%) 407 (18.14%) 0.061 Hypertension 101 (56.74%) 975 (43.45%) 0.002 Hypercholesterolaemia 108 (60.67%) 768 (34.30%) <0.0001 Cardiogenic shock 108 (60.67%) 768 (34.30%) <0.0001Abstract 16 Figure 1 Conclusion Primary PCI for treatment of ST is less effective, and these patients are at increased risk for in-hospital and long-term mortality compared with patients undergoing primary PCI due to de novo STEMI.

19 Treatment of multivessel coronary artery disease in primary PCI for ST elevation myocardial infarction: culprit only revascularisation is associated with higher mace rates

Background Multi-vessel disease occurs in 40%–65% of patients undergoing Primary PCI for STEMI and is associated with adverse prognosis. Contemporary guidelines recommend treating the infarct related artery alone (culprit) during the urgent procedure. There is limited data comparing outcomes of complete with infarct-related artery (IRA)-only revascularisation in primary PCI for STEMI with few studies including the option of later date elective procedures for the other lesions (staged revascularisation). We therefore sought to clarify the outcome of patients with multi-vessel disease undergoing primary PCI dependent on management strategy. Methods Clinical information was analysed from a prospective data base on 2131 STEMI patients who underwent Primary PCI between January 2004 and May 2010 at a London centre. Patients with previous CABG were excluded. Information was entered at the time of procedure and outcome assessed by all-cause mortality information provided by the Office of National Statistics via the BCIS/CCAD national audit. Patients were split into three different treatment groups: culprit vessel angioplasty-only (COR group); staged revascularisation (SR group) and simultaneous treatment of non-IRA (CR group). The primary end point used was major adverse cardiac events (MACE), defined as death, myocardial infarction (MI), stroke and target vessel revascularisation (TVR). Results There were 963 (45%) consecutive patients with STEMI and multivessel CAD undergoing primary angioplasty. There were similar baseline characteristics between the 3 groups, aside from cardiogenic shock, which was significantly higher in the complete revascularisation group. See Abstract 19 table 1. At 30-days of follow-up, 23/263 (9%) patients in the CR group experienced at least one major adverse cardiac event (MACE), 1 (1%) in the SR group and 35 (5%) in the COR group, p=0.01. This trend continued up to 1-year of follow-up with the lowest rates of events in the SR group. However after 3u2005years MACE rates are significantly increased in the COR group (24%) but were similar in the CR (18%) and SR (17%) groups. See Abstract figure 1. MACE rates were driven mainly by death in the CR with high rates of TVR in the COR and SR groups. See Abstract figure 2.Abstract 19 Table 1 COR N=638 SR N=100 CR N=263 Significance Age 64.77 61.46 64.32 0.144 Gender (female) 156 (23.7%) 13 (13.0%) 74 (27.9%) 0.0114 Ethnicity (Caucasian) 441 (67.0%) 79 (79.0%) 185 (69.8%) 0.0511 Previous MI 109 (16.6%) 11 (11.0%) 36 (13.6%) 0.2414 Previous CABG 15 (2.3%) 2 (2.0%) 3 (1.1%) 0.5231 Previous PCI 83 (12.6%) 5 (5.0%) 23 (8.7%) 0.031 Diabetes Mellitus 129 (19.6%) 16 (16.0%) 55 (20.8%) 0.5932 Hypertension 312 (48.1%) 40 (40.0%) 91 (41.2%) 0.1205 Hypercholestrolaemia 269 (41.5%) 37 (37.0%) 92 (41.6%) 0.7751 GPIIb/IIIa Inhibitor 572 (87.7%) 93 (93.0%) 231 (89.5%) 0.1724 Cardiogenic Shock 29 (4.7%) 2 (2.0%) 31 (12.26%) p<0.0001Abstract 19 Figure 1 Comparison of MACE between multivessel disease.Abstract 19 Figure 2 Breakdown of MACE at 5u2005years. Conclusions Culprit vessel-only angioplasty was associated with the highest rate of long-term MACE compared with multivessel treatment. Patients scheduled for staged revascularisation experienced a similar rate of MACE to patients undergoing complete simultaneous treatment of non-IRA.

Eptifibatide is associated with significant cost savings and similar clinical outcomes to abciximab when used during primary percutaneous coronary intervention for ST-elevation myocardial infarction: An observational cohort study of 3863 patients.

Introduction Glycoprotein IIb/IIIa inhibitors are recommended by guidelines in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. There are few studies directly comparing these agents. The aim of this study was to assess whether eptifibatide is a safe and cost-effective alternative to abciximab in the treatment of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Methods This was an observational cohort study of 3863 patients who received a GPIIb/IIIa inhibitor whilst undergoing primary percutaneous coronary intervention from 2007 to 2014. Patients who did not receive a GPIIb/IIIa inhibitor were excluded. Time to first major adverse cardiac event defined as death, non-fatal myocardial infarction, stroke or target vessel revascularization, and total hospital costs were compared between the groups. Results In all, 1741 patients received abciximab with 2122 receiving eptifibatide. Patients who received eptifibatide had higher rates of previous MI/percutaneous coronary intervention and were more likely to undergo a procedure from the radial route. Unadjusted Kaplan–Meier analysis revealed no significant difference in the 1-year event rates between patients given eptifibatide versus abciximab (pu2009=u20090.201). Age-adjusted Cox analysis demonstrated no difference in 1-year outcome between abciximab and eptifibatide (hazard ratio: 0.83; 95% confidence interval: 0.73–1.39), which persisted after multivariate adjustment (hazard ratio: 0.92; 95% confidence interval: 0.79–1.56) including the incorporation of a propensity score (hazard ratio: 0.88; 95% confidence interval: 0.71–1.44). Eptifbatide was associated with significant cost savings being 87% cheaper overall compared to abciximab (on average £650 cheaper per patient and saving approximately £950,000). Conclusion This observational data suggest that eptifibatide is associated with similar outcomes and significant cost savings compared to abciximab when used in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention.

Almanac 2012: Cell therapy in cardiovascular disease. The national society journals present selected research that has driven recent advances in clinical cardiology

The rapid translation from bench to bedside that has been seen in the application of regenerative medicine to cardiology has led to exciting new advances in our understanding of some of the fundamental mechanisms related to human biology. The first generation of cells used in phase I-II trials (mainly bone marrow

Clinical utilisation of adenosine stress CMR and its influence on patient management in a tertiary cardiac centre

Methods A retrospective cohort of 2139 patients who had undergone both adenosine stress CMR (2008-2011) and a coronary angiographic procedure (2006 to 2011) was identified. 142 patients with a diagnosis of cardiomyopathy and 98 patients with previous CABG were excluded. 1899 patients comprised the study group with the latest date of followup being 31.8.2012. Data was extracted from each patient’s hospital health record and analysed using STATA version 8.0. This study was undertaken as part of clinical service evaluation.

065 OUT OF HOURS PRIMARY PCI IS NOT ASSOCIATED WITH INCREASED ADVERSE OUTCOMES COMPARED TO IN-HOUR PROCEDURES

Background Primary percutaneous coronary intervention (PPCI) is the treatment of choice for ST-segment elevation myocardial infarction (STEMI) provided PPCI is performed in a timely manner. There is conflicting data regarding the outcomes of patients treated in-hours versus out of-hours, we sought to determine whether in-hospital and long-term outcomes are different among in-hours versus out of hours PPCI patients. Table 1 In hours Out of hours (n=1299) (n=2048) p Value Gender (Male) 74.2% 77.1% 0.051 Age (years) 64.02±14.2 63.16±14.3 0.126 Hypertension 39.2% 38.3% 0.344 Diabetes mellitus 17.3% 17.7% 0.424 Hypercholestrolaemia 30.9% 29.7% 0.253 Smoking history 55.6% 58.0% 0.116 Previous MI 13.2% 11.8% 0.156 Previous CABG 2.6% 2.6% 0.539 Previous PCI 9.9% 9.6% 0.449 Cardiogenic shock 5.3% 6.4% 0.113 Ethnicity (Caucasian) 66.6% 64.4% 0.226 LVEF 43.70±7.5 43.69±7.5 0.985 CRF (eGFR <60) 18.5% 17.9% 0.227 Methods This was an observational study of 3347 STEMI patients treated with PPCI between 2004 and 2012 at a single centre with follow-up for a median of 3.3u2005years (IQR range 1.2–4.6u2005years). The primary end-point was long-term major adverse cardiac events (MACE) with all cause mortality a secondary endpoint. Of these, 1299 patients (38.8%) underwent PPCI during a weekday between 08:00 and 18:00 (routine-hours group) and 2048 (61.2%) underwent PPCI on a weekday between 18:00 and 08:00 or a weekend (out-of-hours group). Results There were no differences in baseline characteristics between the two groups with comparable door to balloon times (IHs 67.8u2005min vs OOHs 69.6u2005min, p=0.709) and procedural success (table 1). In hospital mortality rates were comparable between the two groups (IHs 3.6% vs OFHs 3.2%) with timing of presentation not predictive of outcome (HR 1.25 (95% CI 0.74 to 2.11). Over the follow-up period there were no significant differences in rates of mortality (IHs 7.4% vs OFHs 7.2%, p=0.44) or MACE (IHs 15.4% vs OFHs 14.1%, p=0.28) (figure 1) between the two groups. After adjustment for confounding variables using multivariate analysis, timing of presentation was not an independent predictor of mortality (HR 1.04 95% CI 0.78 to 1.39). Figure 1 Conclusions This large registry study demonstrates that in a large volume, well-staffed centre, PPCI outside routine-working hours is safe with no difference in outcome compared with PPCI during routine-working hours.