Impact of the COVID-19 Pandemic on Infective Endocarditis Management and Outcomes: Analysis of a National Clinical Database.

COVID-19 has widely affected health care delivery, but its impact on the management of infective endocarditis (IE), including valve surgery, is uncertain. We compared the national trends in admissions, demographics, and outcomes of IE before and after COVID-19 onset, using a national sample of IE admissions between 2016 and 2022 from the Vizient Clinical Database. The pre-COVID-19 and post-COVID-19 time periods were separated by the start of the second quarter of 2020, the time during which the COVID-19 pandemic was declared. For all admissions and for admissions involving valve surgery, pre-COVID-19 versus post-COVID-19 baseline characteristics and outcomes were compared using 2-sample t tests or chi-square tests. Propensity score-matched cohorts were similarly compared. Before COVID-19, there were 82,867 overall and 11,337 valve-related surgical admissions, and after COVID-19, there were 45,672 overall and 6,322 valve-related surgical admissions. In the matched analysis for all admissions, the in-hospital mortality increased from 11.4% to 12.4% after COVID-19 onset (p <0.001); in-hospital stroke (4.9% vs 6.0%, p <0.001), myocardial infarction (1.3% vs 1.4%, p = 0.03), and aspiration pneumonia (1.8% vs 2.4%, p <0.001) also increased, whereas other complications remained stable. In the matched analysis of surgical admissions, there was decreased in-hospital mortality (7.7% vs 6.7%, p = 0.03) and intensive care unit stay (8.5 ± 12.5 vs 8.0 ± 12.6 days, p = 0.04); other outcomes remained stable. In conclusion, patients admitted with IE after COVID-19 were more medically complex with worsened outcomes and mortality, whereas patients who underwent valve surgery had stable outcomes and improved mortality despite the pandemic.

Multicenter experience with valve-in-valve transcatheter aortic valve replacement compared with primary, native valve transcatheter aortic valve replacement.

BACKGROUND: Valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) offers an alternative to reoperative surgical aortic valve replacement. The short- and intermediate-term outcomes after ViV TAVR in the real world are not entirely clear. PATIENTS AND METHODS: A multicenter, retrospective analysis of a consecutive series of 121 ViV TAVR patients and 2200 patients undergoing primary native valve TAVR from 2012 to 2017 at six medical centers. The main outcome measures were in-hospital mortality, 30-day mortality, stroke, myocardial infarction, acute kidney injury, and pacemaker implantation. RESULTS: ViV patients were more likely male, younger, prior coronary artery bypass graft, "hostile chest," and urgent. 30% of the patients had Society of Thoracic Surgeons risk score <4%, 36.3% were 4%-8% and 33.8% were >8%. In both groups many patients had concomitant coronary artery disease. Median time to prosthetic failure was 9.6 years (interquartile range: 5.5-13.5 years). 82% of failed surgical valves were size 21, 23, or 25 mm. Access was 91% femoral. After ViV, 87% had none or trivial aortic regurgitation. Mean gradients were <20 mmHg in 54.6%, 20-29 mmHg in 30.6%, 30-39 mmHg in 8.3% and ≥40 mmHg in 5.87%. Median length of stay was 4 days. In-hospital mortality was 0%. 30-day mortality was 0% in ViV and 3.7% in native TAVR. There was no difference in in-hospital mortality, postprocedure myocardial infarction, stroke, or acute kidney injury. CONCLUSION: Compared to native TAVR, ViV TAVR has similar peri-procedural morbidity with relatively high postprocedure mean gradients. A multidisciplinary approach will help ensure patients receive the ideal therapy in the setting of structural bioprosthetic valve degeneration.

Cost-effectiveness analysis of a resource-intensive approach versus minimally invasive strategy for high-risk transcatheter aortic valve replacement patients.

Aortic stenosis has a high mortality rate in patients who do not receive aortic valve replacement. Previously, transcatheter aortic valve replacement (TAVR) was an intervention reserved for individuals deemed high-risk for surgery. Since that time, TAVR has increasingly been offered to lower risk patients, yet it is unclear whether TAVR will meet an acceptable cost-effectiveness threshold in this group. In this cost-effectiveness study, we employed a decision tree model with Monte Carlo probability sensitivity analysis to determine the incremental cost (in US$) per quality-adjusted life year (QALY) and life year (LY) of performing the TAVR procedure using the resource-intensive approach versus the minimally invasive strategy in high-risk surgical patients.

Propensity-Matched Comparison of Evolut-R Transcatheter Aortic Valve Implantation With Surgery in Intermediate-Risk Patients (from the SURTAVI Trial).

The SURTAVI trial demonstrated the noninferiority of transcatheter aortic valve implantation (TAVI) to surgical aortic valve replacement (SAVR) in patients with severe, symptomatic aortic stenosis at intermediate surgical risk. Most TAVI patients received an early generation device which is no longer commercially available. This analysis compares TAVI outcomes in patients that received the Evolut R valve to those of similar patients randomized to SAVR in the SURTAVI trial. The continued access study of SURTAVI (CAS) enrolled 290 patients. Of them, 252 were implanted with the 23, 26, or 29 mm Evolut R device. Propensity-score matching between this group and SURTAVI SAVR patients with annular diameter of 26 mm or less was based on 22 clinical characteristics, resulting in 197 matched pairs for analysis. The primary end point for comparison was the rate of all-cause mortality or disabling stroke at 1-year. The mean age for TAVI and SAVR patients in the propensity-score matched population was 79.1 years and STS-PROM was 4.0 ± 1.5% for TAVI and 3.9% ± 1.3% for SAVR. The rate of all-cause mortality or disabling stroke at 30-days significantly favored TAVI (0.5% vs 5.1%; p = 0.006). At 1-year TAVI was numerically favored (4.1% vs 8.2%; p = 0.082). In conclusion, compared with SAVR, TAVI using Evolut R had a favorable 30-day safety profile, significantly better hemodynamic performance, and a comparable 1-year rate of all-cause mortality or disabling stroke, suggesting this may be a preferred treatment for patients with severe, symptomatic aortic stenosis at intermediate surgical risk.

The Learning Curve for Shared Decision-making in Symptomatic Aortic Stenosis.

Importance: Shared decision-making (SDM) is widely advocated for patients with valvular heart disease yet is not integrated into the heart team model for patients with symptomatic aortic stenosis. Decision aids (DAs) have been shown to improve patient-centered outcomes and may facilitate SDM. Objective: To determine whether the repeated use of a DA by heart teams is associated with greater SDM, along with improved patient-centered outcomes and clinician attitudes about DAs. Design, Setting, and Participants: This mixed-methods study included a nonrandomized pre-post intervention and clinician interviews. It was conducted between April 30, 2015, and December 7, 2017, with quantitative analysis performed between January 12, 2017, and May 26, 2017, within 2 academic medical centers in northern New England among 35 patients with symptomatic aortic stenosis who were at high to prohibitive risk for surgery. The qualitative analysis was performed between August 6, 2018, and May 7, 2019. The Severe Aortic Stenosis Decision Aid was delivered by 6 clinicians, with patients choosing between transcatheter aortic valve replacement and medical management. Main Outcomes and Measures: Clinician SDM performance was measured using the Observer OPTION5 scale with dual-independent coding of audiotaped clinic visits. Previsit and postvisit surveys measured the patient's knowledge, satisfaction, and decisional conflict. Audiotaped clinician interviews were coded, and qualitative thematic analysis was performed. Results: Six male clinicians and 35 patients (19 of 34 women [55.9%; 1 survey was missing]; mean [SD] age, 85.8 [7.8] years) participated in the study. Shared decision-making increased stepwise with repeated use of the DA (mean [SD] Observer OPTION5 scores: usual care, 17.9 [7.6]; first use of a DA, 60.5 [30.9]; fifth use of a DA, 79.0 [8.4]; P < .001 for comparison between usual care and fifth use of DA). Multiple uses of the DA were associated with increased patient knowledge (mean difference, 18.0%; 95% CI, 1.2%-34.8%; P = .04) and satisfaction (mean difference, 6.7%; 95% CI, 2.5%-10.8%; P = .01) but not decisional conflict (mean [SD]: usual care, 96.0% [9.4%]; first use of DA, 93.8% [12.5%]; fifth use of DA, 95.0% [11.2%]; P = .60). Qualitative analysis of clinicians' interviews revealed that clinicians perceived that they used an SDM approach without DAs and that the DA was not well understood by elderly patients. There was infrequent values clarification or discussion of stroke risk. Conclusion and Relevance: In a mixed-methods pilot study, use of a DA for severe aortic stenosis by heart team clinicians was associated with improved SDM and patient-centered outcomes. However, in qualitative interviews, heart team clinicians did not perceive a significant benefit of the DA, and therefore sustained implementation is unlikely. This pilot study of SDM clarifies new research directions for heart teams.

Durability and Clinical Outcomes of Transcatheter Aortic Valve Replacement for Failed Surgical Bioprostheses.

BACKGROUND: Valve-in-valve transcatheter aortic valve replacement (TAVR) is an option when a surgical valve demonstrates deterioration and dysfunction. This study reports 3-year results following valve-in-valve with self-expanding TAVR. METHODS: The CoreValve US Expanded Use Study is a prospective, nonrandomized, single-arm study that evaluates safety and effectiveness of TAVR in extreme risk patients with symptomatic failed surgical biologic aortic valves. Study end points include all-cause mortality, need for valve reintervention, hemodynamic changes over time, and quality of life through 3 years. Patients were stratified by presence of preexisting surgical valve prosthesis-patient mismatch. RESULTS: From March 2013 to May 2015, 226 patients deemed extreme risk (STS-PROM [Society of Thoracic Surgeons Predicted Risk of Mortality] 9.0±7%) had attempted valve-in-valve TAVR. Preexisting surgical valve prosthesis-patient mismatch was present in 47.2% of the cohort. At 3 years, all-cause mortality or major stroke was 28.6%, and 93% of patients were in New York Heart Association I or II heart failure. Valve performance was maintained over 3 years with low valve reintervention rates (4.4%), an improvement in effective orifice area over time and a 2.7% rate of severe structural valve deterioration. Preexisting severe prosthesis-patient mismatch was not associated with 3-year mortality but was associated with significantly less improvement in quality of life at 3-year follow-up (P=0.01). CONCLUSIONS: Self-expanding TAVR in patients with failed surgical bioprostheses at extreme risk for surgery was associated with durable hemodynamics and excellent clinical outcomes. Preexisting surgical valve prosthesis-patient mismatch was not associated with mortality but did limit patient improvement in quality of life over 3-year follow-up. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01675440.

Recovery of Kidney Dysfunction After Transcatheter Aortic Valve Implantation (from the Northern New England Cardiovascular Disease Study Group).

Acute Kidney Recovery (AKR) is a potential benefit of transcatheter aortic valve implantation (TAVI). We determined the incidence and predictors of AKR in a multicenter prospective registry of TAVI. After excluding patients on dialysis or who died within 48 hours postprocedure, we reviewed 1,502 consecutive patients underwent TAVI in Northern New England from 2012 to 2017. Patients were categorized into 3 groups based on the change in postprocedure estimated glomerular filtration rate (eGFR): Acute Kidney Injury (AKI, decrease in eGFR >25%), AKR (increase in eGFR >25%) or no change in kidney function on discharge creatinine following TAVI. We then focused in patients with baseline chronic kidney disease (CKD defined as eGFR ≤60 ml/min; n = 755) and developed multivariate predictor models to determine the clinical and procedural variables associated with AKR. For the TAVI cohort (n = 1,502), the overall incidence of AKR was 17.8%. AKR was threefold higher in patients with eGFR ≤60 ml/min as compared to those with eGFR >60 ml/min (26.6% vs 8.9%, p < 0.001). In the CKD population, hospital complications were similar among patients with no change in renal function and AKR; patients with AKI had a higher rate of hospital mortality, pacemaker implantation, length of hospitalization, and transfusions. Using multivariable logistic regression, moderate to severe lung disease, eGFR < 50 ml/min and previous aortic valve surgery were found to be independent predictors of AKR. Patients with diabetes mellitus, baseline anemia, and Society of thoracic surgeons score >6.1 were less likely to develop AKR. In conclusion, AKR occurred in 1 of 4 of all TAVI patients with baseline CKD and was a more frequent phenomena than AKI. Patients with decreased lung function, previous aortic valve surgery and worse baseline renal function were more likely to demonstrate AKR, whereas patients with diabetes mellitus, baseline anemia, and higher Society of thoracic risk scores were less likely to see improvements in renal function after TAVI.

Mechanical Intervention for Aortic Valve Stenosis in Patients With Heart Failure and Reduced Ejection Fraction.

The risk and benefit of mechanical interventions in valvular heart disease have been primarily described among patients with normal ejection fraction. The advent of nonsurgical mechanical interventions for aortic stenosis (transcatheter aortic valve replacement) may alter the risk-benefit ratio for patients who would otherwise be at increased risk for valve surgery. This review describes the epidemiology and pathophysiology of aortic stenosis with heart failure and reduced ejection fraction and summarizes the current registry and clinical trial data applicable to this frequently encountered high-risk group. It concludes with discussion of ongoing trials, new approaches, emerging indications, and a potential clinical algorithm incorporating optimal mechanical intervention for patients with aortic stenosis and concomitant reduced ejection fraction.

1-Year Results in Patients Undergoing Transcatheter Aortic Valve Replacement With Failed Surgical Bioprostheses.

OBJECTIVES: This study evaluated the safety and effectiveness of self-expanding transcatheter aortic valve replacement (TAVR) in patients with surgical valve failure (SVF). BACKGROUND: Self-expanding TAVR is superior to medical therapy for patients with severe native aortic valve stenosis at increased surgical risk. METHODS: The CoreValve U.S. Expanded Use Study was a prospective, nonrandomized study that enrolled 233 patients with symptomatic SVF who were deemed unsuitable for reoperation. Patients were treated with self-expanding TAVR and evaluated for 30-day and 1-year outcomes after the procedure. An independent core laboratory was used to evaluate serial echocardiograms for valve hemodynamics and aortic regurgitation. RESULTS: SVF occurred through stenosis (56.4%), regurgitation (22.0%), or a combination (21.6%). A total of 227 patients underwent attempted TAVR and successful TAVR was achieved in 225 (99.1%) patients. Patients were elderly (76.7 ± 10.8 years), had a Society of Thoracic Surgeons Predicted Risk of Mortality score of 9.0 ± 6.7%, and were severely symptomatic (86.8% New York Heart Association functional class III or IV). The all-cause mortality rate was 2.2% at 30 days and 14.6% at 1 year; major stroke rate was 0.4% at 30 days and 1.8% at 1 year. Moderate aortic regurgitation occurred in 3.5% of patients at 30 days and 7.4% of patients at 1 year, with no severe aortic regurgitation. The rate of new permanent pacemaker implantation was 8.1% at 30 days and 11.0% at 1 year. The mean valve gradient was 17.0 ± 8.8 mm Hg at 30 days and 16.6 ± 8.9 mm Hg at 1 year. Factors significantly associated with higher discharge mean aortic gradients were surgical valve size, stenosis as modality of SVF, and presence of surgical valve prosthesis patient mismatch (all p < 0.001). CONCLUSIONS: Self-expanding TAVR in patients with SVF at increased risk for surgery was associated with a low 1-year mortality and major stroke rate, significantly improved aortic valve hemodynamics, and low rates of moderate and no severe residual aortic regurgitation, with improved quality of life.

Antiplatelet therapy in prevention of cardio- and venous thromboembolic events.

The contribution of platelets in the pathophysiology of low-shear thrombosis-specifically, in atrial fibrillation (AF) and venous thromboembolic events (VTE)-remains less clear than for arterial thrombosis. AF itself appears to lead to platelet activation, offering a potential target for aspirin and other antiplatelet agents. Randomized trial results suggest a small benefit of aspirin over placebo, and of dual antiplatelet therapy (aspirin plus clopidogrel) over aspirin alone, for prevention of cardioembolic events in AF. Antiplatelet therapy thus can represent an option for patients with AF who are unsuitable for therapy with warfarin or novel oral anticoagulant agents. For VTE, the rationale for antiplatelet therapy reflects the venous response to disrupted blood flow-interactions among monocytes, neutrophil extracellular traps, and platelets. Early randomized trials generally showed poorer performance of aspirin relative to heparins and danaparoid sodium in prevention of VTE. However, results from large placebo- and dalteparin-controlled randomized trials have spurred changes in the most recent practice guidelines-aspirin is now recommended after major orthopedic surgery for patients who cannot receive other antithrombotic therapies.

In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography.

OBJECTIVES: The aim of this study was to characterize the morphological features of plaque erosion and calcified nodule in patients with acute coronary syndrome (ACS) by optical coherence tomography (OCT). BACKGROUND: Plaque erosion and calcified nodule have not been systematically investigated in vivo. METHODS: A total of 126 patients with ACS who had undergone pre-intervention OCT imaging were included. The culprit lesions were classified as plaque rupture (PR), erosion (OCT-erosion), calcified nodule (OCT-CN), or with a new set of diagnostic criteria for OCT. RESULTS: The incidences of PR, OCT-erosion, and OCT-CN were 43.7%, 31.0%, and 7.9%, respectively. Patients with OCT-erosion were the youngest, compared with those with PR and OCT-CN (53.8 ± 13.1 years vs. 60.6 ± 11.5 years, 65.1 ± 5.0 years, p = 0.005). Compared with patients with PR, presentation with non-ST-segment elevation ACS was more common in patients with OCT-erosion (61.5% vs. 29.1%, p = 0.008) and OCT-CN (100% vs. 29.1%, p < 0.001). The OCT-erosion had a lower frequency of lipid plaque (43.6% vs. 100%, p < 0.001), thicker fibrous cap (169.3 ± 99.1 µm vs. 60.4 ± 16.6 µm, p < 0.001), and smaller lipid arc (202.8 ± 73.6° vs. 275.8 ± 60.4°, p < 0.001) than PR. The diameter stenosis was least severe in OCT-erosion, followed by OCT-CN and PR (55.4 ± 14.7% vs. 66.1 ± 13.5% vs. 68.8 ± 12.9%, p < 0.001). CONCLUSIONS: Optical coherence tomography is a promising modality for identifying OCT-erosion and OCT-CN in vivo. The OCT-erosion is a frequent finding in patients with ACS, especially in those with non-ST-segment elevation ACS and younger patients. The OCT-CN is the least common etiology for ACS and is more common in older patients. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538).

Antithrombotic treatment in transcatheter aortic valve implantation: insights for cerebrovascular and bleeding events.

Transcatheter aortic valve implantation (TAVI) has emerged as a therapeutic alternative for patients with symptomatic aortic stenosis at high or prohibitive surgical risk. However, patients undergoing TAVI are also at high risk for both bleeding and stroke complications, and specific mechanical aspects of the procedure itself can increase the risk of these complications. The mechanisms of periprocedural bleeding complications seem to relate mainly to vascular/access site complications (related to the use of large catheters in a very old and frail elderly population), whereas the pathophysiology of cerebrovascular events remains largely unknown. Further, although mechanical complications, especially the interaction between the valve prosthesis and the native aortic valve, may play a major role in events that occur during TAVI, post-procedural events might also be related to a prothrombotic environment or state generated by the implanted valve, the occurrence of atrial arrhythmias, and associated comorbidities. Antithrombotic therapy in the setting of TAVI has been empirically determined, and unfractionated heparin during the procedure followed by dual antiplatelet therapy with aspirin (indefinitely) and clopidogrel (1 to 6 months) is the most commonly recommended treatment. However, bleeding and cerebrovascular events are common; these may be modifiable with optimization of periprocedural and post-procedural pharmacology. Further, as the field of antiplatelet and anticoagulant therapy evolves, potential drug combinations will multiply, introducing variability in treatment. Randomized trials are the best path forward to determine the balance between the efficacy and risks of antithrombotic treatment in this high risk-population.

High dose intracoronary N-acetylcysteine in a porcine model of ST-elevation myocardial infarction.

We sought to evaluate the safety and efficacy of N-acetylcysteine (NAC) on ischemia and reperfusion in a pig model focusing on cardio-renal protection. High doses of NAC may provide protection from contrast induced nephropathy (CIN). NAC has also been demonstrated to reduce myocardial infarction size and improve left ventricular function after ischemia in both humans and animals studies. In this study we tested the safety and cardiorenal protective efficacy of intracoronary NAC delivered in the radiographic contrast agent in a pig model that simulates the catheter based reperfusion therapy of ST elevation myocardial infarctions. 27 pigs underwent 45 min of ischemia after surgical ligation of distal left descending coronary artery. With coronary reperfusion the animals received at total of 200 mL of the contrast agent Iopamidol with and without NAC to mimic radiographic contrast use during invasive reperfusion therapy. At 24 h the following endpoints were compared: LV function (MRI, echocardiography), myocardial injury (infarct size, area-at-risk, troponin, creatinine kinase) and CIN (creatinine, BUN and renal histology). The effects of NAC on platelet reactivity were also evaluated. Intracoronary administration of NAC administered in the contrast agent is safe. NAC reduces platelet reactivity and there was a trend towards a better cardiac function at 24 h. There was no significant difference in the size of the myocardial infarction. In this model of ischemia-reperfusion high dose NAC did not protect from CIN. High dose intracoronary NAC administered with the radiographic contrast is safe but does not provide significant cardio-renal protection.

Increased local cytokine production at culprit superficial femoral artery plaques.

Characterization of local inflammation at culprit superficial femoral artery (SFA) stenosis has not been studied. We hypothesized that arterial cytokine concentrations would be greater at sites of stenosis. Twenty patients with ≥50 % angiographic stenosis of the SFA had blood drawn just proximal to the lesion and from a contralateral site free of disease. A microplate immunoassay was used to determine the concentrations of 42 distinct cytokines and growth factors. Exact conditional logistic analysis was used to compare measures at the two sites with interaction terms describing clinical factors used to identify difference mediators. Interaction terms identified clinical factors that could predict cytokine levels. The concentrations of soluble CD40 ligand (sCD40L; mean 212 and 177 pg/ml, p = 0.01) and tumor necrosis factor beta (TNF-B; mean 16.6 and 15.9 pg/ml, p = 0.04) were increased immediately proximal to areas of stenosis. Factors associated with greater concentrations at sites of stenosis were bilateral ankle-brachial index ≤0.90 (p = 0.04), no statin use (p = 0.02), claudication (p = 0.03), low leukocyte count (p = 0.03), absence of limb ischemia (p = 0.04) and lack of aspirin or clopidogrel therapy (p ≤ 0.06). Greater concentrations of sCD40L and TNF-B at sites of stenosis suggest that these cytokines play a role in the pathogenesis of symptomatic SFA disease. Our results also suggest that statin, aspirin and clopidogrel therapy may attenuate localized inflammation in the SFA, though due to a small sample size and the use of multiple comparisons across groups, these findings can be viewed as hypothesis generating only. In conclusion, selected cytokines are heightened at culprit SFA lesions and inflammation may be modulated by statin and antiplatelet therapy.

Reduced immediate ischemic events with cangrelor in PCI: a pooled analysis of the CHAMPION trials using the universal definition of myocardial infarction.

BACKGROUND: There is a clinical need for an intravenous P2Y(12) inhibitor in patients with acute coronary syndromes (ACS) for patients who are unable to take oral medications or might benefit from a rapidly reversible compound. As the time from admission to percutaneous coronary intervention (PCI) shortens, establishing the benefit of novel therapies impacting ischemic events is increasingly challenging. Cangrelor, an intravenous potent rapidly acting P2Y(12) inhibitor, bolus 30 µg/Kg plus infusion of 4 µg/Kg/min, was compared to a 600-mg loading dose of clopidogrel either before or early after PCI in patients with ACS undergoing PCI in The CHAMPION (Cangrelor versus standard tHerapy to Achieve optimal Management of Platelet InhibitiON) PLATFORM and PCI studies. METHODS: As both CHAMPION studies used similar inclusion/exclusion criteria and death, myocardial infarction, or ischemia-driven revascularization (including stent thrombosis) at 48 hours as their primary end points, the studies were pooled. The clinical events committee adjudicated myocardial infarction. The universal definition was used to define myocardial infarction. RESULTS: A total of 13 049 patients were included. Cangrelor had no effect on the primary end point with the original MI definition (P = .646). With the use of the universal definition, the primary end point was decreased with cangrelor (odds ratio 0.82, 95% confidence interval 0.68-0.99, P = .037). Stent thrombosis was reduced from 0.4% to 0.2% (odds ratio 0.44, 95% confidence interval 0.22-0.87, P = .018). Thrombolysis in Myocardial Infarction major bleeding and transfusions were not increased with cangrelor. CONCLUSION: With the use of the universal definition of myocardial infarction, cangrelor was associated with a significant reduction in early ischemic events when compared with clopidogrel in patients with non-ST-elevation ACS undergoing PCI.