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.

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.

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.

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.

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.

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.

Clinical Implication of Quantitative Flow Ratio After Percutaneous Coronary Intervention for 3-Vessel Disease.

OBJECTIVES: The aim of this study was to investigate the impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) on clinical outcomes in patients with de novo 3-vessel disease (3VD) treated with contemporary PCI. BACKGROUND: The clinical impact of post-PCI QFR in patients treated with state-of-the-art PCI for de novo 3VD is undetermined. METHODS: All vessels treated in the SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) II trial were retrospectively screened and analyzed for post-PCI QFR. The primary endpoint of this substudy was vessel-oriented composite endpoint (VOCE) at 2 years, defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction, and target vessel revascularization. The receiver-operating characteristic curve was used to calculate the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE. All the analyzable vessels were stratified on the basis of the optimal cutoff value. RESULTS: A total of 968 vessels treated with PCI were screened. Post-PCI QFR was analyzable in 771 (79.6%) vessels. A total of 52 (6.7%) VOCEs occurred at 2 years. The mean value of post-PCI QFR was 0.91 ± 0.07. The diagnostic performance of post-PCI QFR to predict 2-year VOCE was moderate (area under the curve: 0.702; 95% confidence interval: 0.633 to 0.772), with the optimal cutoff value of post-PCI QFR for predicting 2-year VOCE 0.91 (sensitivity 0.652, specificity 0.635). The incidence of 2-year VOCE in the vessels with post-PCI QFR <0.91 (n = 284) was significantly higher compared with vessels with post-PCI QFR ≥0.91 (n = 487) (12.0% vs. 3.7%; hazard ratio: 3.37; 95% confidence interval: 1.91 to 5.97; p < 0.001). CONCLUSIONS: A higher post-PCI QFR value is associated with improved vessel-related clinical outcomes in state-of-the art PCI practice for de novo 3VD. Achieving a post-PCI QFR value ≥0.91 in all treated vessels should be a target when treating de novo 3VD. These findings require confirmation in future prospective trials.

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.

A randomised controlled trial to compare two coronary pressure wires using simultaneous measurements in human coronary arteries: the COMET trial.

AIMS: We aimed to examine the relative performance of the new COMET wire from Boston Scientific (BS), and the established technology from St. Jude/Abbott Vascular (SJ). METHODS AND RESULTS: We compared simultaneous readings from pairs of wires. Patients were randomised to one of three groups: BS/BS, SJ/SJ, or SJ/BS. The last group was sub-randomised to specify the type of wire that would be passed first. After pressure equalisation at the guide catheter, we recorded paired observations in sequence: (a) distal to proximal pressure ratio at baseline, (b) FFR at maximum hyperaemia, and (c) pressure on withdrawal into the guide catheter to quantify "drift". We randomised 106 patients, yielding 288 sets of paired recordings (BS/BS=90; SJ/SJ=90; SJ/BS=108). Drift was recorded from 208 vessels (BS=105; SJ=103). All wires were successfully advanced to their desired positions in the coronary vasculature. The mean (±SD) differences for the randomised pairs were similar: BS/BS=0.0016 (0.023); SJ/SJ=0.002 (0.03); SJ/BS=0.0013 (0.028). The primary outcome tested the hypothesis that the absolute magnitude of the difference (irrespective of sign) observed in the SJ/BS pairing would be similar to that in the SJ/SJ group. The median (IQR) values were SJ/BS=0.015 (0.01-0.03); SJ/SJ=0.01 (0.00-0.03); p=0.61. The drift, expressed as the median (IQR) difference in Pd/Pa from 1.0 (irrespective of sign), was similar: BS=0.02 (0.01-0.05); SJ=0.02 (0.01-0.04); p=0.14. CONCLUSIONS: We found no significant difference between these wires in terms of safety and performance.

Comparison of the antiplatelet and antithrombotic effects of bivalirudin versus unfractionated heparin: A platelet substudy of the HEAT PPCI trial.

In randomised trials, bivalirudin has been associated with higher rates of acute stent thrombosis (AST) compared to unfractionated heparin (UFH), without mechanistic explanation. Furthermore, data are discrepant regards the antiplatelet effects of bivalirudin. This prespecified study, part of a larger HEAT-PPCI Platelet Substudy, aimed to compare the antiplatelet and antithrombotic effects of bivalirudin and UFH using short thrombelastography (s-TEG), an ex vivo whole blood platelet function assay. In HEAT-PPCI, patients were randomised to receive UFH or bivalirudin before angiography. Assay with s-TEG was performed in 184 patients (10.2%) at end of procedure (EOP) and repeated at 24 h. In addition to adenosine diphosphate- (ADP) and arachidonic acid- (AA) mediated platelet aggregation, thrombin-mediated clotting (TMC) was assessed using kaolin with and without heparinase. There were no significant differences between UFH and bivalirudin in ADP- and AA-mediated platelet aggregation at EOP or 24 h. Whilst UFH obliterated TMC at EOP, bivalirudin prolonged R time (19.7 min [15.9-25.4] vs. 8.4 min [7.5-10]; P < 0.0001), K time (2.4 min [1.9-3.4] vs. 2.2 min [1.8-2.7]; P = 0.007) and significantly increased maximum clot strength (MA 62.7 mm [58.7-67.4] vs. 58.6 [55-63]; P = 0.0005), compared to control. In conclusion, there were no significant differences in the antiplatelet effects of UFH and bivalirudin. However, whilst UFH obliterated TMC, bivalirudin prolonged clot initiation but potentiated maximum clot strength. As AST is likely multifactorial in aetiology, in patients treated with bivalirudin, increased clot strength may contribute to this hazard in some individuals and this observation warrants further investigation.

Design and Rationale of the RIPCORD 2 Trial (Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain?): A Randomized Controlled Trial to Compare Routine Pressure Wire Assessment With Conventional Angiography in the Management of Patients With Coronary Artery Disease.

BACKGROUND: Investigation of anginal chest pain has traditionally involved either assessment of the coronary anatomy by angiography or noninvasive testing for reversible ischemia. Invasive pressure wire assessment at the time of angiography offers information on both anatomy and physiology. Fractional flow reserve-guided percutaneous coronary intervention is associated with lower resource utilization and improved clinical outcome compared with angiographic guidance alone. However, the value of routine fractional flow reserve of all major coronary vessels at the time of diagnostic angiography has not been established in a randomized trial despite persuasive observational data. A change in practice to routine fractional flow reserve assessment of all major vessels during diagnostic angiography would require evidence not just of clinical benefit but also of cost effectiveness. This randomized trial aims to test that strategy. METHODS AND RESULTS: RIPCORD 2 (Does Routine Pressure Wire Assessment Influence Management Strategy at Coronary Angiography for Diagnosis of Chest Pain?) is an 1100 patient prospective, multicenter, randomized trial. Participants are randomized, after initial coronary angiography, and in equal proportion, to assessment and management according to (1) conventional angiography only or (2) additional routine pressure wire assessment in all epicardial vessels of sufficient size to be amenable to revascularization. The primary economic outcome measure will be a comparison of healthcare costs at 1 year. The primary quality-of-life outcome measure analysis will compare patient-reported quality-of-life scores at 1 year. Secondary outcome measures include clinical events at 1 year, management strategy (optimal medical therapy with or without revascularization), and angina status at 1 year according to Canadian Cardiovascular Society angina grade. CONCLUSIONS: The aim of the RIPCORD 2 trial is to assess whether a strategy of routine fractional flow reserve-guided assessment and management of all major coronary arteries will be associated with more effective resource utilization, improved quality of life, and better clinical outcome, compared with angiographic guidance alone. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02892903.

Comparison of the effects of P2Y12 receptor antagonists on platelet function and clinical outcomes in patients undergoing Primary PCI: A substudy of the HEAT-PPCI trial.

AIMS: The HEAT-PPCI trial compared bivalirudin and unfractionated heparin in patients undergoing primary percutaneous coronary intervention (PPCI). The aim of this study was to report pre-specified, secondary analyses comparing the effects of P2Y12 inhibiting agents on platelet reactivity and clinical events. METHODS AND RESULTS: All patients received preprocedural oral antiplatelet therapy. During the early stages of the trial, the P2Y12 inhibitor of choice was prasugrel with some use of clopidogrel. Later, routine therapy switched to ticagrelor. For cases performed during working hours, multiple electrode aggregometry (MEA) was used to assess ADP-induced platelet aggregation at the end of the index procedure. The effect of P2Y12 inhibitors on the primary efficacy (major adverse cardiac events [MACE]) and safety (major bleeding) outcomes was assessed in all patients. Multiple logistic regression was used to adjust for differences in baseline characteristics. With MEA data from 469 patients, prasugrel therapy resulted in significantly greater suppression of ADP-induced platelet aggregation at 40 U (23, 78) (median; interquartile range [IQR]) when compared against ticagrelor 75 U (41, 100.75); p<0.001 or clopidogrel 79 U (56, 96); p<0.001. In the entire study population (N=1,803), prasugrel therapy was associated with significantly fewer MACE (26/497; 5.2%) in comparison to ticagrelor (83/1,123; 7.4%) or clopidogrel (18/183; 9.8%); odds ratio (OR) 0.64, confidence interval (CI): 0.41-0.99, p=0.045. For major bleeding, there were no significant differences among the three groups - clopidogrel (3/183; 1.6%), prasugrel (13/497; 2.6%) and ticagrelor (43/1,123; 3.8%); OR 0.73, CI: 0.39-1.35, p=0.31. Patients treated with clopidogrel had more high-risk features and clopidogrel use was more common as an alternative to prasugrel. After adjustment, there were no significant differences in the rates of MACE (OR 0.70, CI: 0.41-1.21, p=0.20) or major bleeding (OR 0.80, CI: 0.41-1.60, p=0.53). CONCLUSIONS: In HEAT-PPCI, patients who received prasugrel (rather than clopidogrel or ticagrelor) had significantly greater suppression of ADP-induced platelet aggregation at the end of the procedure. After adjustment for differences in baseline characteristics, there were no significant differences in ischaemic or bleeding outcomes among the antiplatelet therapies.

Investigating the prevalence, predictors, and prognosis of suboptimal statin use early after a non-ST elevation acute coronary syndrome.

BACKGROUND: High-potency statin therapy is recommended in the secondary prevention of cardiovascular disease but discontinuation, dose reduction, statin switching, and/or nonadherence occur in practice. OBJECTIVES: To determine the prevalence and predictors of deviation from high-potency statin use early after a non-ST elevation acute coronary syndrome (NSTE-ACS) and its association with subsequent major adverse cardiovascular events (MACE) and all-cause mortality (ACM). METHODS: A total of 1005 patients from a UK-based prospective NSTE-ACS cohort study discharged on high-potency statin therapy (atorvastatin 80 mg, rosuvastatin 20 mg, or 40 mg daily) were included. At 1 month, patients were divided into constant high-potency statin users, and suboptimal users incorporating statin discontinuation, dose reduction, switching statin to a lower equivalent potency, and/or statin nonadherence. Follow-up was a median of 16 months. RESULTS: There were 156 suboptimal (∼15.5%) and 849 constant statin users. Factors associated in multivariable analysis with suboptimal statin occurrence included female sex (odds ratio 1.75, 95% confidence interval [CI] 1.14-2.68) and muscular symptoms (odds ratio 4.28, 95% CI 1.30-14.08). Suboptimal statin use was associated with increased adjusted risks of time to MACE (hazard ratio 2.10, 95% CI 1.25-3.53, P = .005) and ACM (hazard ratio 2.46, 95% CI 1.38-4.39, P = .003). Subgroup analysis confirmed that the increased MACE/ACM risks were principally attributable to statin discontinuation or nonadherence. CONCLUSIONS: Conversion to suboptimal statin use is common early after NSTE-ACS and is partly related to muscular symptoms. Statin discontinuation or non-adherence carries an adverse prognosis. Interventions that preserve and enhance statin utilization could improve post NSTE-ACS outcomes.

A risk scoring system to predict coronary stent thrombosis.

OBJECTIVE: Stent thrombosis (ST) is a potentially life-threatening complication of percutaneous coronary intervention (PCI). We aimed to develop a scoring system to predict the risk of ST following PCI. RESEARCH DESIGN AND METHODS: Odds ratios (ORs) for risk factors associated with ST were identified from a meta-analysis based on a systematic literature review, and through consensus expert opinion (Delphi-RAND method). The combined ORs were used to calculate risk scores for acute (within 24 hours), early (within 30 days) and late (31 days to 1 year) ST. Risk scores were validated against patient-level data from the TRITON-TIMI 38 study. Twenty risk factors were identified. RESULTS: The most highly predictive factor for early and late ST was "incomplete duration of dual antiplatelet therapy". Derived total risk scores ranged from 0 to 22 for acute and early ST, and from 0 to 20 for late ST. Increasing scores were associated with an increasing risk of ST when applied to trial data. Model discrimination was 0.60 (p = .0028), 0.67 (p < .0001) and 0.66 (p < .0001) for acute, early and late ST respectively, indicating good discriminatory power for predicting ST. Key limitations included a lack of published data on acute ST, resulting in a risk score for this time point being based predominantly on expert opinion, and that it was not possible to map all risk factors to variables collected in the TRITON-TIMI 38 study. CONCLUSION: Our weighted scoring system may help to stratify ST risk and individualize antiplatelet therapy in patients undergoing PCI.