Bivalirudin Versus Heparin During PCI in NSTEMI: Individual Patient Data Meta-Analysis of Large Randomized Trials.

BACKGROUND: The benefit:risk profile of bivalirudin versus heparin anticoagulation in patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) is uncertain. Study-level meta-analyses lack granularity to provide conclusive answers. We sought to compare the outcomes of bivalirudin and heparin in patients with non-ST-segment-elevation myocardial infarction undergoing PCI. METHODS: We performed an individual patient data meta-analysis of patients with non-ST-segment-elevation myocardial infarction in all 5 trials that randomized ≥1000 patients with any myocardial infarction undergoing PCI to bivalirudin versus heparin (MATRIX [Minimizing Adverse Hemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox], VALIDATE-SWEDEHEART [Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry Trial], ISAR-REACT 4 [Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 4], ACUITY [Acute Catheterization and Urgent Intervention Triage Strategy], and BRIGHT [Bivalirudin in Acute Myocardial Infarction vs Heparin and GPI Plus Heparin Trial]). The primary effectiveness and safety end points were 30-day all-cause mortality and serious bleeding. RESULTS: A total of 12 155 patients were randomized: 6040 to bivalirudin (52.3% with a post-PCI bivalirudin infusion), and 6115 to heparin (53.2% with planned glycoprotein IIb/IIIa inhibitor use). Thirty-day mortality was not significantly different between bivalirudin and heparin (1.2% versus 1.1%; adjusted odds ratio, 1.24 [95% CI, 0.86-1.79]; P=0.25). Cardiac mortality, reinfarction, and stent thrombosis rates were also not significantly different. Bivalirudin reduced serious bleeding (both access site-related and non-access site-related) compared with heparin (3.3% versus 5.5%; adjusted odds ratio, 0.59; 95% CI, 0.48-0.72; P<0.0001). Outcomes were consistent regardless of use of a post-PCI bivalirudin infusion or routine lycoprotein IIb/IIIa inhibitor use with heparin and during 1-year follow-up. CONCLUSIONS: In patients with non-ST-segment-elevation myocardial infarction undergoing PCI, procedural anticoagulation with bivalirudin and heparin did not result in significantly different rates of mortality or ischemic events, including stent thrombosis and reinfarction. Bivalirudin reduced serious bleeding compared with heparin arising both from the access site and nonaccess sites.

Post-infarction ventricular septal defect: percutaneous or surgical management in the UK national registry.

AIMS: Post-infarction ventricular septal defect (PIVSD) is a mechanical complication of acute myocardial infarction (AMI) with a poor prognosis. Surgical repair is the mainstay of treatment, although percutaneous closure is increasingly undertaken. METHODS AND RESUTS: Patients treated with surgical or percutaneous repair of PIVSD (2010-2021) were identified at 16 UK centres. Case note review was undertaken. The primary outcome was long-term mortality. Patient groups were allocated based upon initial management (percutaneous or surgical). Three-hundred sixty-two patients received 416 procedures (131 percutaneous, 231 surgery). 16.1% of percutaneous patients subsequently had surgery. 7.8% of surgical patients subsequently had percutaneous treatment. Times from AMI to treatment were similar [percutaneous 9 (6-14) vs. surgical 9 (4-22) days, P = 0.18]. Surgical patients were more likely to have cardiogenic shock (62.8% vs. 51.9%, P = 0.044). Percutaneous patients were substantially older [72 (64-77) vs. 67 (61-73) years, P < 0.001] and more likely to be discussed in a heart team setting. There was no difference in long-term mortality between patients (61.1% vs. 53.7%, P = 0.17). In-hospital mortality was lower in the surgical group (55.0% vs. 44.2%, P = 0.048) with no difference in mortality after hospital discharge (P = 0.65). Cardiogenic shock [adjusted hazard ratio (aHR) 1.97 (95% confidence interval 1.37-2.84), P < 0.001), percutaneous approach [aHR 1.44 (1.01-2.05), P = 0.042], and number of vessels with coronary artery disease [aHR 1.22 (1.01-1.47), P = 0.043] were independently associated with long-term mortality. CONCLUSION: Surgical and percutaneous repair are viable options for management of PIVSD. There was no difference in post-discharge long-term mortality between patients, although in-hospital mortality was lower for surgery.

Impact of established cardiovascular disease on outcomes in the randomized global leaders trial.

OBJECTIVE: To investigate the impact of different anti-platelet strategies on outcomes after percutaneous coronary intervention (PCI) in patients with established cardiovascular disease (CVD). METHODS: GLOBAL LEADERS was a randomized, superiority, all-comers trial comparing one-month dual anti-platelet therapy (DAPT) with ticagrelor and aspirin followed by 23-month ticagrelor monotherapy (experimental treatment) with standard 12-month DAPT followed by 12-month aspirin monotherapy (reference treatment) in patients treated with a biolimus A9-eluting stent. Established CVD was defined as ≥1 prior myocardial infarction, PCI, coronary artery bypass operation, stroke, or established peripheral vascular disease. The primary endpoint was a composite of all-cause death or new Q-wave MI at 2-years. The secondary safety endpoint was BARC 3 or 5 bleeding. Exploratory secondary endpoints were the patient-orientated composite endpoint and net adverse clinical events. RESULTS: Among the 15,761 patients in this cohort were 6,693 patients (42.5%) with established CVD. Compared to those without established CVD, these patients had significantly higher rates of the primary (5.1 vs. 3.3%, HR1.59[1.36-1.86], p < .001) and secondary composite endpoints with no significant differences in bleeding. There was a nonsignificant reduction in the primary endpoint in patients with established CVD receiving the experimental treatment (4.6 vs. 5.6%, HR0.82[0.66-1.02], p = .07). When comparing patients without CVD to those with one or three territories of CVD, the hazard ratio for the primary endpoint increased in unadjusted and adjusted models. CONCLUSIONS: The poorer outcomes in patients with established CVD are not mitigated by prolonged monotherapy with a potent P2Y12 inhibitor suggesting a greater need to focus on modifiable risk factors.

A comparison of hospital episode statistics and traditional methods to identify outcomes in a randomized trial; a sub-study of HEAT-PPCI.

BACKGROUND: This study aims to compare information from hospital episode statistics (HES) and traditional direct patient contact to identify readmission and clinical events in the follow-up of a randomized controlled trial (RCT). METHODS: The study followed 1812 patients for 28 days using direct contact (DC). In addition, we obtained HES for this period. We examined medical records for all suspected readmissions and determined confirmed events by adjudication. We compared the ability of the individual DC and HES methods to determine readmission and the occurrence of trial-specific events, confirmed at adjudication. RESULTS: In the ascertainment of readmission, compared to DC, HES demonstrated a trend towards better sensitivity (identifying 153/166 = 92.2% versus 144/166 = 86.7%; difference = 5.4%, 95% CI: 0.1-11.5%) and better specificity (1492/1492 = 100% versus 1426/1492 = 95.5%; difference = 4.4%, 95% CI: 4.2-5.6%).An examination of HES coding does not identify rates for specific events that match those from adjudication, with limitations in both sensitivity and specificity. CONCLUSION: HES is effective in the ascertainment of readmission and is a useful tool in follow-up. Information from HES provides a reflection of a patient's course and associated cost, as perceived by the healthcare system. Future studies could modify outcome definitions to reflect episode coding.

Radial versus femoral vascular access in ST-elevation myocardial infarction: Are the results of femoral operators unfairly represented in observational research?

BACKGROUND: Recent randomized controlled trials comparing femoral and radial access in primary percutaneous coronary intervention (PPCI) have shown conflicting results regarding the incidence of major adverse cardiovascular events (MACE) and major bleeding. METHODS: Using data from the HEAT-PPCI trial, we compared the primary efficacy (all-cause mortality, stroke, new myocardial infarction or unplanned repeat revascularization) and safety (major bleeding BARC 3-5) outcomes at 28 days, by final access site used (radial or femoral) and by default operator type. We then assessed outcomes in femoral cases performed by both operator types. RESULTS: Radial access (RA) was associated with fewer MACE (91/1472 = 6.2% vs. 36/332 = 10.8% P = .003) and major bleeding events (38/1472 = 2.6% vs 22/332 = 6.6% P = .001) when compared to femoral access (FA). When analyzing outcomes by default operator type, there was a similar incidence of MACE (111/1575 = 7% vs 16/229 = 7% P = .97) and major bleeding events (49/1575 = 3.1% vs 11/229 = 4.8% P = .18). In cases where FA was performed by default radial operators, there was a higher rate of MACE (22/122 = 18% vs 14/210 = 6.7% P = .003) and major bleeding events (11/122 = 9% vs 11/210 = 5.2% P < .001), potentially explained by a higher risk profile in these cases. CONCLUSION: Default femoral operators achieved comparable outcomes when compared to default radial operators. The less favorable outcomes observed in FA cases may result from its selective use by radial operators in high risk cases.

Effect of the REG1 anticoagulation system versus bivalirudin on outcomes after percutaneous coronary intervention (REGULATE-PCI): a randomised clinical trial.

BACKGROUND: REG1 is a novel anticoagulation system consisting of pegnivacogin, an RNA aptamer inhibitor of coagulation factor IXa, and anivamersen, a complementary sequence reversal oligonucleotide. We tested the hypothesis that near complete inhibition of factor IXa with pegnivacogin during percutaneous coronary intervention, followed by partial reversal with anivamersen, would reduce ischaemic events compared with bivalirudin, without increasing bleeding. METHODS: We did a randomised, open-label, active-controlled, multicentre, superiority trial to compare REG1 with bivalirudin at 225 hospitals in North America and Europe. We planned to randomly allocate 13,200 patients undergoing percutaneous coronary intervention in a 1:1 ratio to either REG1 (pegnivacogin 1 mg/kg bolus [>99% factor IXa inhibition] followed by 80% reversal with anivamersen after percutaneous coronary intervention) or bivalirudin. Exclusion criteria included ST segment elevation myocardial infarction within 48 h. The primary efficacy endpoint was the composite of all-cause death, myocardial infarction, stroke, and unplanned target lesion revascularisation by day 3 after randomisation. The principal safety endpoint was major bleeding. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, identifier NCT01848106. The trial was terminated early after enrolment of 3232 patients due to severe allergic reactions. FINDINGS: 1616 patients were allocated REG1 and 1616 were assigned bivalirudin, of whom 1605 and 1601 patients, respectively, received the assigned treatment. Severe allergic reactions were reported in ten (1%) of 1605 patients receiving REG1 versus one (<1%) of 1601 patients treated with bivalirudin. The composite primary endpoint did not differ between groups, with 108 (7%) of 1616 patients assigned REG1 and 103 (6%) of 1616 allocated bivalirudin reporting a primary endpoint event (odds ratio [OR] 1·05, 95% CI 0·80-1·39; p=0·72). Major bleeding was similar between treatment groups (seven [<1%] of 1605 receiving REG1 vs two [<1%] of 1601 treated with bivalirudin; OR 3·49, 95% CI 0·73-16·82; p=0·10), but major or minor bleeding was increased with REG1 (104 [6%] vs 65 [4%]; 1·64, 1·19-2·25; p=0·002). INTERPRETATION: The reversible factor IXa inhibitor REG1, as currently formulated, is associated with severe allergic reactions. Although statistical power was limited because of early termination, there was no evidence that REG1 reduced ischaemic events or bleeding compared with bivalirudin. FUNDING: Regado Biosciences Inc.

Bivalirudin, glycoprotein inhibitor, and heparin use and association with outcomes of primary percutaneous coronary intervention in the United Kingdom.

AIMS: The HORIZONS trial reported a survival advantage for bivalirudin over heparin-with-glycoprotein inhibitors (GPIs) in primary PCI for ST elevation myocardial infarction. This drove an international shift in clinical practice. Subsequent studies have produced divergent findings on mortality benefits with bivalirudin. We investigated this issue in a larger population than studied in any of these trials, using the United Kingdom national PCI registry. METHODS AND RESULTS: 61 136 primary PCI procedures were performed between January 2008 and January 2012. Demographic and procedural data were obtained from the registry. Mortality information was obtained through the UK Office of National Statistics. Multivariable logistic regression and propensity analysis modelling were utilized to study the association of different anti-thrombotic strategies with outcomes. Unadjusted data demonstrated near-identical survival curves for bivalirudin and heparin-plus-GPI groups. Significantly higher early and late mortality was found in patients treated with heparin alone ( ITALIC! P < 0.0001) but this group had a markedly higher baseline risk. After propensity matching, the bivalirudin vs. heparin-plus-GPI groups still demonstrated very similar adjusted mortality (odds ratio 1.00 at 30 days, and 0.96 at 1 year). Patients treated with heparin alone continued to show higher mortality after adjustment, although effect size was considerably diminished (odds ratio vs. other groups 1.17-1.24 at 30 days). CONCLUSIONS: Analysis of recent UK data showed no significant difference in short- or medium-term mortality between ST elevation myocardial infarction patients treated with bivalirudin vs. heparin-plus-GPI at primary PCI.

Feasibility of cardiovascular magnetic resonance derived coronary wave intensity analysis.

BACKGROUND: Wave intensity analysis (WIA) of the coronary arteries allows description of the predominant mechanisms influencing coronary flow over the cardiac cycle. The data are traditionally derived from pressure and velocity changes measured invasively in the coronary artery. Cardiovascular magnetic resonance (CMR) allows measurement of coronary velocities using phase velocity mapping and derivation of central aortic pressure from aortic distension. We assessed the feasibility of WIA of the coronary arteries using CMR and compared this to invasive data. METHODS: CMR scans were undertaken in a serial cohort of patients who had undergone invasive WIA. Velocity maps were acquired in the proximal left anterior descending and proximal right coronary artery using a retrospectively-gated breath-hold spiral phase velocity mapping sequence with high temporal resolution (19 ms). A breath-hold segmented gradient echo sequence was used to acquire through-plane cross sectional area changes in the proximal ascending aorta which were used as a surrogate of an aortic pressure waveform after calibration with brachial blood pressure measured with a sphygmomanometer. CMR-derived aortic pressures and CMR-measured velocities were used to derive wave intensity. The CMR-derived wave intensities were compared to invasive data in 12 coronary arteries (8 left, 4 right). Waves were presented as absolute values and as a % of total wave intensity. Intra-study reproducibility of invasive and non-invasive WIA was assessed using Bland-Altman analysis and the intraclass correlation coefficient (ICC). RESULTS: The combination of the CMR-derived pressure and velocity data produced the expected pattern of forward and backward compression and expansion waves. The intra-study reproducibility of the CMR derived wave intensities as a % of the total wave intensity (mean ± standard deviation of differences) was 0.0 ± 6.8%, ICC = 0.91. Intra-study reproducibility for the corresponding invasive data was 0.0 ± 4.4%, ICC = 0.96. The invasive and CMR studies showed reasonable correlation (r = 0.73) with a mean difference of 0.0 ± 11.5%. CONCLUSION: This proof of concept study demonstrated that CMR may be used to perform coronary WIA non-invasively with reasonable reproducibility compared to invasive WIA. The technique potentially allows WIA to be performed in a wider range of patients and pathologies than those who can be studied invasively.

Unfractionated heparin versus bivalirudin in primary percutaneous coronary intervention (HEAT-PPCI): an open-label, single centre, randomised controlled trial.

BACKGROUND: Bivalirudin, with selective use of glycoprotein (GP) IIb/IIIa inhibitor agents, is an accepted standard of care in primary percutaneous coronary intervention (PPCI). We aimed to compare antithrombotic therapy with bivalirudin or unfractionated heparin during this procedure. METHODS: In our open-label, randomised controlled trial, we enrolled consecutive adults scheduled for angiography in the context of a PPCI presentation at Liverpool Heart and Chest Hospital (Liverpool, UK) with a strategy of delayed consent. Before angiography, we randomly allocated patients (1:1; stratified by age [<75 years vs ≥75 years] and presence of cardiogenic shock [yes vs no]) to heparin (70 U/kg) or bivalirudin (bolus 0·75 mg/kg; infusion 1·75 mg/kg per h). Patients were followed up for 28 days. The primary efficacy outcome was a composite of all-cause mortality, cerebrovascular accident, reinfarction, or unplanned target lesion revascularisation. The primary safety outcome was incidence of major bleeding (type 3-5 as per Bleeding Academic Research Consortium definitions). This study is registered with ClinicalTrials.gov, number NCT01519518. FINDINGS: Between Feb 7, 2012, and Nov 20, 2013, 1829 of 1917 patients undergoing emergency angiography at our centre (representing 97% of trial-naive presentations) were randomly allocated treatment, with 1812 included in the final analyses. 751 (83%) of 905 patients in the bivalirudin group and 740 (82%) of 907 patients in the heparin group had a percutaneous coronary intervention. The rate of GP IIb/IIIa inhibitor use was much the same between groups (122 patients [13%] in the bivalirudin group and 140 patients [15%] in the heparin group). The primary efficacy outcome occurred in 79 (8·7%) of 905 patients in the bivalirudin group and 52 (5·7%) of 907 patients in the heparin group (absolute risk difference 3·0%; relative risk [RR] 1·52, 95% CI 1·09-2·13, p=0·01). The primary safety outcome occurred in 32 (3·5%) of 905 patients in the bivalirudin group and 28 (3·1%) of 907 patients in the heparin group (0·4%; 1·15, 0·70-1·89, p=0·59). INTERPRETATION: Compared with bivalirudin, heparin reduces the incidence of major adverse ischaemic events in the setting of PPCI, with no increase in bleeding complications. Systematic use of heparin rather than bivalirudin would reduce drug costs substantially. FUNDING: Liverpool Heart and Chest Hospital, UK National Institute of Health Research, The Medicines Company, AstraZeneca, The Bentley Drivers Club (UK).

Validation of high temporal resolution spiral phase velocity mapping of temporal patterns of left and right coronary artery blood flow against Doppler guidewire.

BACKGROUND: Temporal patterns of coronary blood flow velocity can provide important information on disease state and are currently assessed invasively using a Doppler guidewire. A non-invasive alternative would be beneficial as it would allow study of a wider patient population and serial scanning. METHODS: A retrospectively-gated breath-hold spiral phase velocity mapping sequence (TR 19 ms) was developed at 3 Tesla. Velocity maps were acquired in 8 proximal right and 15 proximal left coronary arteries of 18 subjects who had previously had a Doppler guidewire study at the time of coronary angiography. Cardiovascular magnetic resonance (CMR) velocity-time curves were processed semi-automatically and compared with corresponding invasive Doppler data. RESULTS: When corrected for differences in heart rate between the two studies, CMR mean velocity through the cardiac cycle, peak systolic velocity (PSV) and peak diastolic velocity (PDV) were approximately 40 % of the peak Doppler values with a moderate - good linear relationship between the two techniques (R(2): 0.57, 0.64 and 0.79 respectively). CMR values of PDV/PSV showed a strong linear relationship with Doppler values with a slope close to unity (0.89 and 0.90 for right and left arteries respectively). In individual vessels, plots of CMR velocities at all cardiac phases against corresponding Doppler velocities showed a consistent linear relationship between the two with high R(2) values (mean +/-SD: 0.79 +/-.13). CONCLUSIONS: High temporal resolution breath-hold spiral phase velocity mapping underestimates absolute values of coronary flow velocity but allows accurate assessment of the temporal patterns of blood flow.

Long-term mortality data from the balloon pump-assisted coronary intervention study (BCIS-1): a randomized, controlled trial of elective balloon counterpulsation during high-risk percutaneous coronary intervention.

BACKGROUND: There is conflicting evidence on the utility of elective intra-aortic balloon pump (IABP) use during high-risk percutaneous coronary intervention (PCI). Observational series have indicated a reduction in major in-hospital adverse events, although randomized trial evidence does not support this. A recent study has suggested a mortality benefit trend early after PCI, but there are currently no long-term outcome data from randomized trials in this setting. METHODS AND RESULTS: Three hundred one patients with left ventricular impairment (ejection fraction <30%) and severe coronary disease (BCIS-1 jeopardy score ≥8; maximum possible score=12) were randomized to receive PCI with elective IABP support (n=151) or without planned IABP support (n=150). Long-term all-cause mortality was assessed by tracking the databases held at the Office of National Statistics (in England and Wales) and the General Register Office (in Scotland). The groups were balanced in terms of baseline characteristics (left ventricular ejection fraction, 23.6%; BCIS-1 jeopardy score, 10.4) and the amount and type of revascularization performed. Mortality data were available for the entire cohort at a median of 51 months (interquartile range, 41-58) from randomization. All-cause mortality at follow-up was 33% in the overall cohort, with significantly fewer deaths occurring in the elective IABP group (n=42) than in the group that underwent PCI without planned IABP support (n=58) (hazard ratio, 0.66; 95% confidence interval, 0.44-0.98; P=0.039). CONCLUSIONS: In patients with severe ischemic cardiomyopathy treated with PCI, all-cause mortality was 33% at a median of 51 months. Elective IABP use during PCI was associated with a 34% relative reduction in all-cause mortality compared with unsupported PCI. CLINICAL TRIAL REGISTRATION: URL: http://www.isrctn.org. Unique identifier: ISRCTN40553718; and http://www.clinicaltrials.gov. Unique identifier: NCT00910481.

Percutaneous Left Ventricular Unloading During High-Risk Coronary Intervention: Rationale and Design of the CHIP-BCIS3 Randomized Controlled Trial.

INTRODUCTION: Percutaneous coronary intervention for complex coronary disease is associated with a high risk of cardiogenic shock. This can cause harm and limit the quality of revascularization achieved, especially when left ventricular function is impaired at the outset. Elective percutaneous left ventricular unloading is increasingly used to mitigate adverse events in patients undergoing high-risk percutaneous coronary intervention, but this strategy has fiscal and clinical costs and is not supported by robust evidence. METHODS: CHIP-BCIS3 (Controlled Trial of High-Risk Coronary Intervention With Percutaneous Left Ventricular Unloading) is a prospective, multicenter, open-label randomized controlled trial that aims to determine whether a strategy of elective percutaneous left ventricular unloading is superior to standard care (no planned mechanical circulatory support) in patients undergoing nonemergent high-risk percutaneous coronary intervention. Patients are eligible for recruitment if they have severe left ventricular systolic dysfunction, extensive coronary artery disease, and are due to undergo complex percutaneous coronary intervention (to the left main stem with calcium modification or to a chronic total occlusion with a retrograde approach). Cardiogenic shock and acute ST-segment-elevation myocardial infarction are exclusions. The primary outcome is a hierarchical composite of all-cause death, stroke, spontaneous myocardial infarction, cardiovascular hospitalization, and periprocedural myocardial infarction, analyzed using the win ratio. Secondary outcomes include completeness of revascularization, major bleeding, vascular complications, health economic analyses, and health-related quality of life. A sample size of 250 patients will have in excess of 80% power to detect a hazard ratio of 0.62 at a minimum of 12 months, assuming 150 patients experience an event across all follow-up. CONCLUSIONS: To date, 169 patients have been recruited from 21 National Health Service hospitals in the United Kingdom, with recruitment expected to complete in 2024. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05003817.

Challenges in Primary PCI: How to Treat a Large Intracoronary Thrombus With TIMI 3 Flow?

This case highlights 2 important issues: the immediate management of large intracoronary thrombus in the ST-segment elevation myocardial infarction setting with TIMI 3 flow, and the risks/benefits associated with sealing a plaque in an unobstructed artery by stenting. Potent antithrombotic therapy with a view to subsequent intracoronary imaging to define etiology and plaque morphology appears to be a reasonable initial strategy in this specific population. Furthermore, for patients with acute coronary syndromes diagnosed with plaque erosion by optical coherence tomography and residual diameter stenosis <70%, deferred stenting appears a viable option.

Twelve-month mortality from the "How Effective are Antithrombotic Therapies in Primary Percutaneous Coronary Intervention (HEAT-PPCI) Trial".

BACKGROUND: There is ongoing uncertainty regarding the safety and efficacy of unfractionated heparin and bivalirudin when used for systemic anticoagulation in patients undergoing primary percutaneous coronary intervention (PPCI). This paper reports 12-month mortality from the HEAT-PPCI randomised trial. METHODS: In this open-label, randomised controlled trial (RCT) we enrolled consecutive adults with suspected ST-elevation myocardial infarction (STEMI). Patients were randomised to heparin (bolus 70 U/kg) or bivalirudin (bolus 0.75 mg/kg followed by an infusion 1.75 mg/kg/h for the duration of the procedure). We report the pre-specified secondary outcome of all-cause mortality at 12 months. Mortality was classified as cardiovascular or not, blinded to treatment allocation. Deaths in the first 28 days were classified by formal event adjudication and later events classified from death certificates. RESULTS: Mortality status at 12 months was obtained for 1805/1812 = 99.6% of participants. Overall mortality was 160/1812 = 8.9%. There were more deaths in those randomised to bivalirudin (95/902 = 10.5% vs 65/903 = 7.2%; HR 1.48; 95% CI 1.08 to 2.03; p = 0.015). Most deaths were classified as cardiovascular (71/902 = 7.9% in the bivalirudin group and 53/904 = 5.9% in the heparin group). The difference between the rates of cardiovascular deaths in each treatment group did not reach statistical significance: HR 1.35; 95% CI 0.95 to 1.93; p = 0.095. CONCLUSIONS: At 12 months, treatment with bivalirudin, rather than heparin, was associated with a higher rate of all-cause mortality. Cardiovascular mortality was higher with bivalirudin although this difference was not statistically significant.

Coronary perforation complicating percutaneous coronary intervention in patients presenting with an acute coronary syndrome: An analysis of 1013 perforation cases from the British Cardiovascular Intervention Society database.

BACKGROUND: The evidence base for coronary perforation occurring during percutaneous coronary intervention in patients presenting with an acute coronary syndrome (ACS-PCI) is limited and the specific role of acute pharmacology in its clinical presentation unclear. METHODS AND RESULTS: Using the BCIS PCI database, data were analysed on all ACS-PCI procedures performed in England and Wales between 2007 and 2014. Multiple regressions were used to identify predictors of coronary perforation and its association with outcomes. Propensity score matching was used to evaluate the association between differing P2Y12 inhibitors or glycoprotein inhibitors (GPI) and CP. During 270,329 ACS-PCI procedures, 1013 coronary perforations were recorded (0.37%) with a stable annual incidence. In multiple regression analysis, covariates associated with increased frequency of coronary perforation included age, female gender, CTO intervention, number and length of stents used, and rotational atherectomy use, whilst differing P2Y12 inhibitors were not predictive. Using propensity score matching, use of a GPI was independently associated with tamponade (OR 1.50, [1.08-2.06], p = 0.014). The adjusted odds ratios for all clinical outcomes were adversely affected by coronary perforation. CONCLUSIONS: Coronary perforation is an infrequent event during ACS-PCI but is closely associated with adverse clinical outcomes. GPI use was associated with higher rates of tamponade.

Association between post-percutaneous coronary intervention bivalirudin infusion and net adverse clinical events: a post hoc analysis of the GLOBAL LEADERS study.

AIMS: The efficacy and safety of continued bivalirudin infusion after percutaneous coronary intervention (PCI) remains uncertain. We sought to investigate the association between post-PCI bivalirudin infusion and the risk of net adverse clinical events (NACE) at 30 days. METHODS AND RESULTS: In the GLOBAL LEADERS study, all patients who received bivalirudin during PCI were categorized according to the use of bivalirudin infusion after the procedure. The primary endpoint of the present analysis was NACE [a composite of all-cause death, any stroke, any myocardial infarction, all revascularization, and bleeding assessed according to the Bleeding Academic Research Consortium (BARC) criteria Type 3 or 5] at 30 days. The key safety endpoint was BARC Type 3 or 5 bleeding and definite stent thrombosis. Of 15 968 patients, 13 870 underwent PCI with the use of bivalirudin. In total, 7148 patients received continued bivalirudin infusion after procedure, while 6722 patients received standard care. After propensity score covariate adjustment, the risk of NACE did not significantly differ between two treatments after PCI [continued bivalirudin infusion vs. no bivalirudin infusion: 3.2% vs. 3.1%, adjusted hazard ratio (aHR) 1.35, 95% confidence interval (CI) 0.99-1.84, P = 0.06] nor the BARC Type 3 or 5 bleeding (0.7% vs. 0.7%, aHR 0.89, 95% CI 0.44-1.79; P = 0.743) and definite stent thrombosis (0.5% vs. 0.3%, aHR 1.71, 95% CI 0.77-3.81, P = 0.189). However, continued bivalirudin infusion was associated with an increased risk of NACE and definite stent thrombosis in ST-elevation myocardial infarction (STEMI) patients. CONCLUSION: In an all-comers population undergoing PCI, there was no significant difference in the risk of NACE at 30 days between continued bivalirudin infusion vs. no bivalirudin infusion after procedure but continued bivalirudin infusion was associated with a higher risk of NACE in STEMI patients when compared with no infusion.

Individual Patient Data Pooled Analysis of Randomized Trials of Bivalirudin versus Heparin in Acute Myocardial Infarction: Rationale and Methodology.

BACKGROUND: Individual randomized controlled trials (RCTs) of periprocedural anticoagulation with bivalirudin versus heparin during percutaneous coronary intervention (PCI) have reported conflicting results. Study-level meta-analyses lack granularity to adjust for confounders, explore heterogeneity, or identify subgroups that may particularly benefit or be harmed. OBJECTIVE: To overcome these limitations, we sought to develop an individual patient-data pooled database of RCTs comparing bivalirudin versus heparin. METHODS: We conducted a systematic review to identify RCTs in which ≥1,000 patients with acute myocardial infarction (AMI) undergoing PCI were randomized to bivalirudin versus heparin. RESULTS: From 738 identified studies, 8 RCTs met the prespecified criteria. The principal investigators of each study agreed to provide patient-level data. The data were pooled and checked for accuracy against trial publications, with discrepancies addressed by consulting with the trialists. Consensus-based definitions were created to resolve differing antithrombotic, procedural, and outcome definitions. The project required 3.5 years to complete, and the final database includes 27,409 patients (13,346 randomized to bivalirudin and 14,063 randomized to heparin). CONCLUSION: We have created a large individual patient database of bivalirudin versus heparin RCTs in patients with AMI undergoing PCI. This endeavor may help identify the optimal periprocedural anticoagulation regimen for patient groups with different relative risks of adverse ischemic versus bleeding events, including those with ST-segment and non-ST-segment elevation MI, radial versus femoral access, use of a prolonged bivalirudin infusion or glycoprotein inhibitors, and others. Adherence to standardized techniques and rigorous validation processes should increase confidence in the accuracy and robustness of the results.