James Cotton

Randomized Trial of Simple Versus Complex Drug-Eluting Stenting for Bifurcation Lesions The British Bifurcation Coronary Study: Old, New, and Evolving Strategies

Background The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. Methods and Results Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64 10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations ( 50% narrowing in both vessels). In the simplegroup (n 250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n 250), 89% of culotte (n 75) and 72% of crush (n 169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P 0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P 0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P 0.002), respectively. Procedure duration and x-ray dose favored the simple approach. Conclusions When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases.Background— The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. Methods and Results— Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64±10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations (>50% narrowing in both vessels). In the simple group (n=250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n=250), 89% of culotte (n=75) and 72% of crush (n=169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P=0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P=0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P=0.002), respectively. Procedure duration and x-ray dose favored the simple approach. Conclusions— When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00351260.

Randomised study comparing complex versus simple drug-eluting stent strategies for coronary bifurcations

Background The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. Methods and Results Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64 10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations ( 50% narrowing in both vessels). In the simplegroup (n 250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n 250), 89% of culotte (n 75) and 72% of crush (n 169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P 0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P 0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P 0.002), respectively. Procedure duration and x-ray dose favored the simple approach. Conclusions When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases.Background— The optimal strategy for treating coronary bifurcation lesions remains a subject of debate. With bare-metal stents, single-stent approaches appear to be superior to systematic 2-stent strategies. Drug-eluting stents, however, have low rates of restenosis and might offer improved outcomes with complex stenting techniques. Methods and Results— Patients with significant coronary bifurcation lesions were randomized to either a simple or complex stenting strategy with drug-eluting stents. In the simple strategy, the main vessel was stented, followed by optional kissing balloon dilatation/T-stent. In the complex strategy, both vessels were systematically stented (culotte or crush techniques) with mandatory kissing balloon dilatation. Five hundred patients 64±10 years old were randomized; 77% were male. Eighty-two percent of lesions were true bifurcations (>50% narrowing in both vessels). In the simple group (n=250), 66 patients (26%) had kissing balloons in addition to main-vessel stenting, and 7 (3%) had T stenting. In the complex group (n=250), 89% of culotte (n=75) and 72% of crush (n=169) cases were completed successfully with final kissing balloon inflations. The primary end point (a composite at 9 months of death, myocardial infarction, and target-vessel failure) occurred in 8.0% of the simple group versus 15.2% of the complex group (hazard ratio 2.02, 95% confidence interval 1.17 to 3.47, P=0.009). Myocardial infarction occurred in 3.6% versus 11.2%, respectively (P=0.001), and in-hospital major adverse cardiovascular events occurred in 2.0% versus 8.0% (P=0.002), respectively. Procedure duration and x-ray dose favored the simple approach. Conclusions— When coronary bifurcation lesions are treated, a systematic 2-stent technique results in higher rates of in-hospital and 9-month major adverse cardiovascular events. This difference is largely driven by periprocedural myocardial infarction. Procedure duration is longer, and x-ray dose is higher. The provisional technique should remain the preferred strategy in the majority of cases. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT 00351260.

A Prospective Randomized Trial of Everolimus-Eluting Stents Versus Bare-Metal Stents in Octogenarians: The XIMA Trial (Xience or Vision Stents for the Management of Angina in the Elderly)

OBJECTIVESnThe aim of this study was to determine whether drug-eluting stents (DES) are superior to bare-metal stents (BMS) in octogenarian patients with angina.nnnBACKGROUNDnPatients ≥80 years of age frequently have complex coronary disease warranting DES but have a higher risk of bleeding from prolonged dual antiplatelet therapy.nnnMETHODSnThis multicenter randomized trial was conducted in 22 centers in the United Kingdom and Spain. Patients ≥80 years of age underwent stent placement for angina. The primary endpoint was a 1-year composite of death, myocardial infarction, cerebrovascular accident, target vessel revascularization, or major hemorrhage.nnnRESULTSnIn total, 800 patients (83.5 ± 3.2 years of age) were randomized to BMS (n = 401) or DES (n = 399) for treatment of stable angina (32%) or acute coronary syndrome (68%). Procedural success did not differ between groups (97.7% for BMS vs. 95.4% for DES; p = 0.07). Thirty-eight percent of patients had ≥2-vessel percutaneous coronary intervention, and 66% underwent complete revascularization. Patients who received BMS had shorter stent implants (24.0 ± 13.4 mm vs. 26.6 ± 14.3 mm; p = 0.01). Rates of dual antiplatelet therapy at 1 year were 32.2% for patients in the BMS group and 94.0% for patients in the DES group. The primary endpoint occurred in 18.7% of patients in the BMS group versus 14.3% of patients in the DES group (p = 0.09). There was no difference in death (7.2% vs. 8.5%; p = 0.50), major hemorrhage (1.7% vs. 2.3%; p = 0.61), or cerebrovascular accident (1.2% vs. 1.5%; p = 0.77). Myocardial infarction (8.7% vs. 4.3%; p = 0.01) and target vessel revascularization (7.0% vs. 2.0%; p = 0.001) occurred more often in patients in the BMS group.nnnCONCLUSIONSnBMS and DES offer good clinical outcomes in this age group. DES were associated with a lower incidence of myocardial infarction and target vessel revascularization without increased incidence of major hemorrhage. (Xience or Vision Stent-Management of Angina in the Elderly [XIMA]; ISRCTN92243650).

Contemporary clinical outcomes of patients treated with or without rotational coronary atherectomy - An analysis of the UK central cardiac audit database

INTRODUCTIONnRotational atherectomy (RA) is widely used for treating calcified coronary lesions. Clinical data however remain limited.nnnMETHODSnWe assessed outcome and survival among patients undergoing percutaneous coronary intervention (PCI) with or without RA in the UK between September 2007 and March 2011.nnnRESULTSnData from 221,669 percutaneous coronary intervention (PCI) procedures were analysed; 2152 patients (0.97%) underwent RA (RA+); the remainder underwent conventional PCI (RA-). RA+ patients were older (71.7±9.6 vs. 64.1±12.8 year; p<0.001), and had a higher incidence of diabetes (26.4% vs. 18.0%; p<0.001), hypertension, (61.9% vs. 49.4%; p<0.001), peripheral vascular disease (9.9% vs. 4.2%, p<0.001), cerebrovascular disease (5.5% vs. 3.4%, p<0.001), renal impairment (3.4% vs. 1.5%, p<0.001) and poor left ventricular function (11.4% vs. 4.3%,p<0.001). Procedural success was lower among RA+ patients (90.3% vs 94.6%; p<0.001) and procedural complications were more frequent (9.7% vs 5.4%; p<0.001). After 2.4±1.2 years follow-up, unadjusted Cox proportional hazard modeling demonstrated poorer survival for RA+ patients (HR 2.21, 95%CI 1.97-2.49; p<0.0001). This disadvantage remained after adjustment for adverse variables (HR 1.26, 95%CI 1.11-1.44; p=0.0004) and following propensity analysis. There was evidence however of improved survival for RA+ patients with left main stem disease (HR 0.52, 95%CI 0.35-0.75, p<0.0001), and peripheral vascular disease (HR 0.65, 95%CI 0.43-0.98, p<0.0005).nnnCONCLUSIONSnRotational atherectomy was undertaken in patients with higher pre-procedural risk. Medium term survival was worse among patients undergoing rotational atherectomy, and this survival disadvantage remained after correction for available adverse factors. Rotational atherectomy however remains clinically useful for patients with calcified coronary lesions.

Anemia in cardiac surgery: next target for mortality and morbidity improvement?:

Objective To assess the effects of preoperative anemia on outcomes of cardiac surgery and to explore the trend in mortality over an 8-year period. Methods During the study period (2005–2012), all 1170 patients undergoing elective or urgent cardiac surgery and classed as anemic were included. A matched group of non-anemic 1170 patients was used as a control group. Postoperative outcomes were compared between the 2 groups. The association between preoperative anemia and postoperative outcomes was analyzed using a logistic regression model. Results Compared with patients without anemia, the need for airway support (15% vs. 12%, pu2009=u20090.05), renal replacement therapy (13% vs. 8%, pu2009<u20090.01) and the rate of in-hospital surgical site infection (9% vs. 7%, pu2009=u20090.05) were higher in the anemic group. Anemia was associated with greater need for renal replacement therapy (odds ratiou2009=u20091.76, confidence interval: 1.21–2.37, pu2009=u20090.002) and prolonged (> 7 days) hospital stay (odds ratiou2009=u20091.21, confidence interval: 0.97–1.51, pu2009=u20090.08). The blood transfusion rate (54% vs. 33%, pu2009<u20090.01) and hospital mortality (5.6% vs. 3.5%, pu2009=u20090.02) were higher in the anemic group. Over the 8-year period, there was a significant improvement in mortality in the non-anemic group (from 6.5% to 1.6%) but less so in the anemic group (from 6.7% to 4.7%). Conclusion Anemia impacts significantly on morbidity and mortality after cardiac surgery, with less improvement over time compared to patients without anemia. Preoperative correction of anemia, when feasible, could potentially help to improve cardiac surgery outcomes.

Pharmacokinetics and pharmacodynamics of oral P2Y12 inhibitors during the acute phase of a myocardial infarction: A systematic review

BACKGROUNDnThe immediate administration of oral antiplatelet therapy in the form of aspirin plus a P2Y12 inhibitor is the universally recognised standard of care for patients who present with acute myocardial infarction. Despite strong recommendations for their use, there are a paucity of data describing their onset of action and clinical efficacy during the short time frames from confirmation of diagnosis to reperfusion with primary percutaneous coronary intervention.nnnOBJECTIVESnTo complete a systematic review evaluating the currently available evidence regarding the pharmacokinetic and pharmacodynamic activity of orally administered clopidogrel, prasugrel and ticagrelor during the acute phase of a myocardial infarction in relation to mechanical reperfusion with primary percutaneous coronary angioplasty.nnnMETHODSnWe searched PubMed and EMBASE databases up to January 2016 using the terms outlined in our search strategy.nnnRESULTSnTwelve papers were included in our final analysis; seven relating to pharmacodynamic studies, one to a pharmacokinetic study and four to pharmacokinetic/pharmacodynamic studies.nnnCONCLUSIONnOur results indicate that despite the administration of oral P2Y12 inhibitors including newer more potent agents that should allow for greater and more consistent levels of platelet inhibition, the physiological state of ST segment elevation MI (STEMI) and the co-administration of opioid based analgesia are associated with a reduction in the degree of platelet inhibition achieved following their administration.

Bleeding associated with the management of acute coronary syndromes

### Learning objectivesnnRupture or erosion of a coronary artery atheroma exposes flowing blood to the prothrombotic contents of the plaque, resulting in platelet activation and subsequent thrombus formation. If this process results in reduced coronary blood flow, the patient may present with an acute coronary syndrome (ACS). Total thrombotic occlusion generally results in ST-segment elevation myocardial infarction (STEMI), whereas incomplete occlusion (or extensive collateralisation) is more likely to present as non-STEMI or unstable angina without evidence of myonecrosis (collectively non-ST-segment elevation ACS (NSTE-ACS)). Revascularisation, most commonly with percutaneous coronary intervention (PCI) is standard of care in ACS, as it restores myocardial perfusion by addressing both the thrombotic obstruction and the underlying coronary stenosis. However, adjunctive pharmacological treatment after revascularisation, or in patients managed conservatively, may be of equal importance in influencing prognosis.1–3nnContemporary adjunctive antithrombotic therapy in ACS includes potent antiplatelet and anticoagulant agents, each of which carries the risk of bleeding. The frequency and implications of haemorrhagic complications must be factored into the risk-benefit analysis for each patient since PCI is increasingly performed in complex subgroups such as those with renal dysfunction, underlying anaemia and the elderly, cohorts with inherently increased bleeding risk.4 ,5 Furthermore, although the absolute bleeding risk will vary according to individual patient characteristics, the overall relative bleeding risk increases with the number, potency and duration of agents co-administered. For example, those patients with ACS, already taking chronic oral anticoagulation (OAC) for stroke protection in atrial fibrillation, are then treated with dual antiplatelet therapy (DAPT) (so-called ‘triple therapy’).6 ,7nnThere is extensive evidence in the published literature that demonstrates major bleeding to …

Intravenous iron does not effectively correct preoperative anaemia in cardiac surgery: a pilot randomized controlled trial

OBJECTIVESnPreoperative anaemia is a strong predictor of blood transfusion requirements and must be assessed for appropriate optimization before elective surgery. Iron therapy is a transfusion-sparing approach effective for increasing haemoglobin concentrations. However, its role in elective cardiac surgery and the optimal route of administration remain unknown. This single-centre, non-blinded, randomized, controlled trial compared the effectiveness of intravenous ferric carboxymaltose therapy with oral iron for anaemic patients undergoing elective cardiac surgery.nnnMETHODSnFifty anaemic patients scheduled for elective cardiac surgery were randomized to receive either oral or intravenous iron therapy 3-8u2009weeks preoperatively. Changes in haemoglobin concentration were measured. Blood transfusion and postoperative outcome data were collected.nnnRESULTSnPreoperative median increases in haemoglobin were 1.0u2009g/l (interquartile range -3.25 to 7.25 g/l) and 3.0u2009g/l (interquartile range -1.25 to 6.25 g/l) for patients receiving intravenous and oral iron, respectively (Pu2009=u20090.42). The median first 12-h blood loss was significantly higher in the intravenous group (655u2009ml; interquartile range 162-1540u2009ml) compared to the oral group (313u2009ml; interquartile range 150-1750u2009ml; Pu2009<u20090.007). Median increments in serum ferritin were superior for the intravenous group (median difference 313u2009µg/l; interquartile range 228-496) compared to the oral group (median difference 5.5u2009µg/l; interquartile range -1.4 to 19.4; Pu2009<u20090.001).nnnCONCLUSIONSnIncreases in ferritin after intravenous iron administration were significantly greater than those after oral iron administration. There was no significant difference in haemoglobin increments between groups. Despite significantly higher intraoperative blood loss in the group receiving intravenous iron, blood transfusion requirements for both groups were not statistically different.nnnCLINICAL TRIAL REGISTRATIONnISRCTN22158788.

Association of comorbid burden with clinical outcomes after transcatheter aortic valve implantation

Objectives To investigate the association of the CharlsonComorbidity Index (CCI) with clinical outcomes after transcatheter aortic valve implantation (TAVI). Background Patients undergoing TAVI have high comorbid burden; however, there is limited evidence of its impact on clinical outcomes. Methods Data from 1887 patients from the UK, Canada, Spain, Switzerland and Italy were collected between 2007 and 2016. The association of CCI with 30-day mortality, Valve Academic Research Consortium-2 (VARC-2) composite early safety, long-term survival and length of stay (LoS) was calculated using logistic regression and Cox proportional hazard models, as a whole cohort and at a country level, through a two-stage individual participant data (IPD) random effect meta-analysis. Results Most (60%) of patients had a CCI ≥3. A weak correlation was found between the total CCI and four different preoperative risks scores (ρ=0.16u2009to 0.29), and approximately 50% of patients classed as low risk from four risk prediction models still presented with a CCI ≥3. Per-unit increases in total CCI were not associated with increased odds of 30-day mortality (OR 1.09, 95%u2009CI 0.96 to 1.24) or VARC-2 early safety (OR 1.04, 95%u2009CI 0.96 to 1.14) but were associated with increased hazard of long-term mortality (HR 1.10, 95%u2009CI 1.05 to 1.16). The two-stage IPD meta-analysis indicated that CCI was not associated with LoS (HR 0.97, 95%u2009CI 0.93 to 1.02). Conclusion In this multicentre international study, patients undergoing TAVI had significant comorbid burden. We found a weak correlation between the CCI and well-established preoperative risks scores. The CCI had a moderate association with long-term mortality up to 5u2009years post-TAVI.

109 Marked Differences in the Pharmacodynamics of Modern P2Y12 Inhibitors in Patients Undergoing Treatment for ST Segment Elevation MI (STEMI) and Non ST Segment Elevation MI (NSTEMI)

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 naïve 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 < 0.05 was considered significant. Results A total of 58 patients were enrolled (30 STEMI, and 28 NSTEMI/UA Table 1).Abstract 109 Table 1 Baseline characteristics Characteristic STEMI (N=30) NSTEMI (N=28) P-value Age (yrs) 59.94 ± 12.68 61.61 ± 11 0.595 Female 7 3 0.301 Diabetes Mellitus 6 12 0.089 Hypertension 14 13 1 Current Smoker 7 4 0.508 Ex-Smoker 12 11 1 Hyperlipidaemia 8 16 0.032 Familial History of CAD 17 15 1 CAD = Coronary Artery Disease 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 < 0.001) and ticagrelor ( P < 0.001) in STEMI patients vs NSTEMI patients. There was no significant difference in the effect of ticagrelor vs prasugrel over time in either STEMI or NSTEMI/UA.Abstract 109 Figure 1 The degree of inhibition of platelet reactivity (expressed as PRU) over time following the administration of prasugrel (A) and ticagrelor (B) in STEMI and NSTEMI patients. PRU = P2Y12 reactivity units 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.