Universal Myocardial Infarction Research Articles

Percutaneous Coronary Intervention vs. Coronary Artery Bypass Grafting in Left Main Coronary Artery Disease: An Updated Systematic Review and Meta-Analysis.

Recently, both US and European guidelines have predominantly recommended coronary artery bypass grafting (CABG) as the preferred revascularisation method. However, emerging data have raised the possibility of percutaneous coronary intervention (PCI) being a viable and effective alternative. This meta-analysis sought to evaluate the latest insights from major clinical trials to ascertain whether PCI could be as effective as CABG in treating left main coronary artery (LMCA) disease. To achieve this, a comprehensive systematic search was conducted across databases, including Medline (via PubMed), Embase, Cochrane, and clinicaltrials.gov. The search spanned from the inception of these databases to August 20, 2022, and exclusively focused on randomized controlled trials (RCTs). Employing the random effects model, selected studies underwent rigorous analysis. The study outcomes encompassed a spectrum of factors such as all-cause mortality, major adverse cerebrovascular and cardiovascular events (MACCE), myocardial infarction (MI), stroke, and revascularisation procedures. The observation periods of interest included the 30-day mark, 1 year, 5 years, and 10 years. The analysis integrated six RCTs, revealing noteworthy patterns. In terms of all-cause mortality, PCI demonstrated non-inferiority to CABG across all observed time frames: 30 days (OR 0.6), 1 year (OR 0.77), 5 years (OR 1.41), and 10 years (OR 1.08). Analysis of MACCE outcomes favored PCI at 30 days and CABG at 5 years. The utilisation of the original five-year EXCEL (Evaluation of XIENCE versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularisation) trial definition for MI highlighted higher MI rates for PCI compared to CABG (OR 1.66, P < 0.05). Intriguingly, when the subsequently released EXCEL data, aligned with the third universal MI definition, was incorporated, the five-year data consistently leaned towards CABG. Specifically, the PCI group exhibited 7.5% MI rates in contrast to the 3.6% in the CABG cohort (OR 2.19, P < 0.001). Concerning stroke, PCI proved advantageous at 30 days and 1 yearwhile exhibiting no significant disparity at 5 and 10 years. Revascularisation procedures favoured CABG at one and five years, with comparability at the remaining time points. In summation, the outcomes of this comprehensive meta-analysis suggest that PCI could serve as a feasible alternative to CABG in the context of uncomplicated LMCA disease. It's worth noting that CABG might still hold an advantage for complex lesions.

Fibrinogen to Albumin Ratio Predicts Burden of Coronary Artery Disease in Patients with NSTEMI

Objective: Fibrinogen plasma level rises in the event of inflammatory cases. It is known that there is a powerful intercourse between fibrinogen level and plasma viscosity. Albumin plasma level dropes during the inflammatory cases. The aim of this work determine significance of fibrinogen albumin ratio (FAR) as a indicator emphases the burden of atherosclerosis.&#x0D; Method: The study included 83 patients diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI) between January and September 2015. The definition of NSTEMI was made according to “Definition of Third Universal Myocardial Infarction” guidelines published on 2013 by European Society of Cardiology. Burden of atherosclerosis was evaluated by Syntax score (SS) and Gensini Score. Patients were seperated two groups as medium-high SS (n=23) and low SS (n=60). FAR levels were compared.&#x0D; Results: FAR was 80.71 ± 30.3 in low SS group and 120 ± 49.72 in the mid-high SS group respectively (p

Biomarkers for infarct diagnosis and rapid rule-out/rule-in of acute myocardial infarction

The 4th edition of the Universal Definition of Myocardial Infarction (MI) recommends measurement of cardiac troponin (cTn)T orI for the diagnosis of MI due to their absolute cardiac tissue specificity. In this MI definition, values exceeding the 99th percentile of ahealthy reference population distinguish between detectable troponin due to physiological cell turnover as opposed to pathological myocardial injury. In clinical routine, high-sensitivity (hs) troponin assays that allow earlier diagnosis of MI and detection of myocardial injury that would have escaped detection due to the lower sensitivity of previous assay generations are increasingly used. While the 2015 European Society of Cardiology (ESC) guidelines already recommend are-testing of cTn after 3 h, if anhs-cTn assay is available, faster protocols that reassess hs-cTn after 60-120 min are increasingly performed, since these protocols allow faster patient disposition, increase discharge rates from the emergency department (ED), and are at least as safe as the standard protocol for the guidance of discharge after rule-out. However, decision cut-offs are lower than the 99th percentile and concentration change criteria depend on the individual hs-cTn assay and protocol used. The following article provides an overview of the recommendations of the 4th universal MI definition as well as the current 2015 ESC guidelines on cTn and other potential biomarker candidates for patients presenting with suspected acute coronary syndromes. Limitations and areas of controversy are discussed.

Effect of Evolocumab on Type and Size of Subsequent Myocardial Infarction

The PCSK9 inhibitor evolocumab reduced major vascular events in the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) trial, yet the types and sizes of myocardial outcomes in FOURIER have not been previously explored. To assess the types and sizes of myocardial infarction (MI) and the effect of evolocumab on MI by subtype. A prespecified analysis of a multicenter double-blind randomized clinical trial. Patients were randomized to evolocumab or placebo and followed up for a median of 2.2 years. The study included 27 564 patients with stable atherosclerotic disease receiving statin therapy. Clinical end points were evaluated by the Thrombolysis in Myocardial Infarction clinical events committee. Rates presented are 3-year Kaplan-Meier estimates. Data were collected from 2013 to 2016 and analyzed from June 2017 to December 2019. Myocardial infarction was defined based on the third universal MI definition, and further classified according to MI type (universal MI subclass, ST-segment elevation myocardial infarction [STEMI] vs non-STEMI) and by MI size (determined by peak troponin level). A total of 27 564 patients were randomized, with a mean (SD) age of 62.5 (9.0) years, and 20 795 (75%) were male. Of these, 1107 patients experienced a total of 1288 MIs. Most MIs (68%) were atherothrombotic (type 1), with 15% from myocardial oxygen supply-demand mismatch (type 2) and 15% percutaneous coronary intervention-related (type 4). Sudden death (type 3) and coronary artery bypass grafting-related (type 5) accounted for a total of 21 MIs (<2%). Evolocumab significantly reduced the risk of first MI by 27% (4.4% vs 6.3%; hazard ratio [HR], 0.73; 95% CI, 0.65-0.82; P < .001), type 1 by 32% (2.9% vs 4.5%; HR, 0.68; 95% CI, 0.59-0.79; P < .001), and type 4 by 35% (0.8% vs 1.1%; HR, 0.65; 95% CI, 0.48-0.87; P = .004), with no effect on type 2 (0.9% vs 0.8%; HR, 1.09; 95% CI, 0.82-1.45; P = .56). Most MIs (688 [59.8%]) had troponin levels greater than or equal to 10 times the upper limit of normal. The benefit was highly significant and consistent regardless of the size of MI with a 34% reduction in MIs with troponin level greater than or equal to 10 times the upper limit of normal (2.6% vs 3.7%; HR, 0.66; 95% CI, 0.56-0.77; P < .001) and a 36% reduction in the risk of STEMI (1.0% vs 1.5%; HR, 0.64; 95% CI, 0.49-0.84; P < .001). Low-density lipoprotein cholesterol lowering with evolocumab was highly effective in reducing the risk of MI. This reduction with evolocumab included benefit across multiple subtypes of MI related to plaque rupture, smaller and larger MIs, and both STEMI and non-STEMI. These data are consistent with the known benefit of low-density lipoprotein cholesterol lowering and underscore the reduction in clinically meaningful events. ClinicalTrials.gov Identifier: NCT01764633.

Impact of the Location of ST-T Abnormalities Accompanying Minor Q-Waves on the Definition of Prior Myocardial Infarction

According to the Fourth Universal Definition of myocardial infarction (MI), the likelihood of a previous MI is increased when ST-T abnormalities exist with minor Q-waves in the same leads. Therefore, we examined whether differences in location of ST-T abnormalities in relation to minor Q-waves as part of the old MI definition impact the prevalence and prognostic significance of MI. This analysis included 7,878 participants with available baseline electrocardiogram (ECG) and follow-up data from the third National Health and Nutrition Examination Survey. Two ECG MI definitions were utilized; both were based on the standards of the Minnesota Code (MC) ECG Classification, and both incorporated major Q-waves but differed in whether major ST-T abnormalities and minor Q waves, as part of the definition, were in the same lead group (Standard MC-MI) or not (Fourth Universal MI). All-cause mortality and cardiovascular disease mortality were ascertained during 14 years (median). We found no difference between baseline prevalence of Standard MC-MI (3.48%; n = 274) and Fourth Universal MI (3.27%; n = 258), p = 0.46. Also, Standard MC-MI and Fourth Universal MI were similarly associated with increased risk of all-cause mortality (hazard ratio [95% confidence interval] 1.64 [1.42 to 1.90] and 1.61 [1.38 to 1.87], respectively; p value for differences in associations = 0.86), and cardiovascular disease mortality (hazard ratio [95% confidence interval] 1.99 [1.61 to 2.48] and 1.94 [1.56 to 2.42], respectively; p value for differences in associations = 0.84). In conclusion, the location of ST-T abnormalities accompanying minor Q-waves does not impact the prevalence or prognostic significance of a prior MI which raise doubts about the clinical impact of considering the location of ST-T in relation to minor Q-waves when defining an old MI.

Diagnosis of myocardial infarction in critically ill, ventilated patients

Elevated cardiac troponin values are frequently observed in critically ill patients. These are often not due to myocardial infarction (MI) but caused by various other etiologies of myocardial injury. Understanding the etiology of any troponin elevation is of enormous importance for management and therapy. According to the fourth version of the Universal Definition of MI, myocardial injury is present if at least one troponin value is above the 99th percentile upper reference limit and considered acute, when arise and/or fall occurs. Patients with acute MI are asubgroup of patients with acute myocardial injury, who present in an ischemic clinical context. Variables defining the clinical criteria of MI include symptoms of ischemia, presumably new electrocardiographic (ECG) changes or imaging evidence of new loss of viable myocardium or regional wall motion abnormalities, or detection of an intracoronary thrombus. In critically ill or mechanically ventilated patients, the diagnosis of MI is challenging due to limitations in history taking, co-existence of comorbidities, overlapping symptoms and equivocal or unspecific ECG changes. This article presents the diagnostic criteria of the Universal MI definition, discusses subtypes of MI and focuses on various differential diagnoses. Furthermore, implications of diagnosis of MI in critically ill patients, especially regarding the use of ECG and troponin assays, are discussed.

Differentiation of Type 1 and Type 2 Myocardial Infarctions Among HIV-Infected Patients Requires Adjudication Due to Overlap in Risk Factors.

The Universal Myocardial infarction (MI) definition divides MIs into different types. Type 1 MIs (T1MI) result spontaneously from atherosclerotic plaque instability. Type 2 MIs (T2MI) are due to secondary causes of myocardial oxygen demand/supply mismatch such as occurs with sepsis. T2MI are much more common among those with HIV than in the general population. T1MI and T2MI have different mechanisms, risk factors, and potential treatments suggesting that they should be distinguished to achieve a better scientific understanding of MIs in HIV. We sought to determine whether MI type could be accurately predicted by patient characteristics without adjudication in HIV-infected individuals. We developed a statistical model to predict T2MI versus T1MI using adjudicated events from six sites utilizing demographic characteristics, traditional cardiovascular, and HIV-related risk factors. Validation was assessed in a seventh site via mean calibration, and discrimination level was assessed by the area under the curve (AUC). Of 812 MIs, 388 were T2MI. HIV-related factors including hepatitis C infection were predictive of T2MI, whereas traditional cardiovascular risk factors including total cholesterol predicted T1MI. The score predicted 69 T2MI in the validation sample resulting in poor calibration, given that 90 T2MIs were observed. The development sample AUC was 0.75 versus 0.65 in the validation sample, suggesting relatively poor discrimination. The level of discrimination to predict MI type based on patient characteristics is insufficient for individual level prediction. Adjudication is required to distinguish MI types, which is necessary to advance understanding of this important outcome among HIV populations.

Consensus or Controversy?: Evolution of Criteria for Myocardial Infarction After Percutaneous Coronary Intervention.

The definition and the clinical implications of myocardial infarction (MI) occurring in the setting of percutaneous coronary intervention have been subjects of unresolved controversy. As a result of the use of more sensitive diagnostic tools such as cardiac troponin, the expanding evidence, and the ensuing debate, the definition of procedural MI (pMI) has evolved, leading to several revisions, different proposed definitions, and lack of standardization in randomized clinical trials. In this review, we will describe the key clinical data on cardiac biomarkers, creatine kinase isoenzyme MB and cTn, in the setting of percutaneous coronary intervention and the main issues that have lead to various consensus documents with a proposed definition of pMI. We will focus on the rationale of the current "Third Universal Definition of Myocardial Infarction" and of the alternative approach proposed by the Society for Cardiovascular Angiography and Interventions. The definition of pMI is an evolving field where the Third Universal MI definition represents the best attempt to date to incorporate available evidence along with scientific and clinical judgment into criteria to ensure adequate specificity in the diagnosis and the relevant prognostic significance, while trying to maintain sensitivity. Questions on the recommended criteria and their practical implementation remain, but the Third Universal definition document represents an important milestone toward a better standardization and enhanced consensus on the pMI definition.

State-of-the-art diagnosis of myocardial infarction.

The current version of the Universal Definition of Myocardial Infarction (MI) was published in 2012. An acute myocardial infarction (AMI) is characterized by evidence of myocardial necrosis in a clinical setting of acute myocardial ischemia. Diagnostic criteria include a rise and/or fall of serially tested cardiac biomarkers (preferentially cardiac troponins) with at least one value above the 99th percentile of the upper reference limit combined with symptoms of ischemia, new changes on electrocardiogram (ECG), imaging evidence of a new loss of viable myocardium or new regional wall motion abnormalities or the identification of an intracoronary thrombus by angiography or autopsy. Compared to previous versions, the current definition of MI includes minor modifications regarding ECG criteria and subtypes of MI as well as the use of cardiac imaging and high sensitivity troponin assays. This article summarizes the Universal MI definition and includes recommendations from the current guidelines for the management of patients with acute coronary syndrome. Strategies for "early rule-in" and "rule-out" of non-ST-elevation MI with high sensitivity cardiac troponin assays, risk scores for assessment of ischemic and bleeding risk and criteria for optimal timing of angiography are presented.

Coronary angiography-related myocardial injury as detected by high-sensitivity cardiac troponin T assay.

We sought to evaluate rates and mechanisms of myocardial injury and type 4a myocardial infarction (MI) after an elective diagnostic coronary angiography (CAG) as detected by high-sensitivity cardiac troponin T (hsTnT) assay. Cardiac troponin concentrations were measured in consecutive patients before and after undergoing an elective CAG -with or without coronary intervention (PCI)- using an hsTnT assay. The study population consisted of 545 patients: 320 (58.7%) patients received only an elective CAG and another 225 patients (41.3%) received an additional PCI. Significant hsTnT increases occurred in 97 (30.3%) cases within the CAG group and in 152 (67.6%) cases within the PCI group. Rates of normal baseline hsTnT values (<99th percentile upper reference limit) were 75.9% in the CAG group and 71.6% in the PCI group. In cases with normal baseline hsTnT values, peak levels meeting criteria of MI type 4a according to the second or third version of the universal MI definition were observed in five (1.6%) and one (0.3%) cases within the CAG group, as well as in 32 (14.2%) and 22 (9.8%) cases within the PCI group, respectively. Use of the hsTnT assay may allow identification of myocardial injury during an uneventful diagnostic coronary angiography in the absence of any coronary or non-coronary interventions.

Varying definitions for periprocedural myocardial infarction alter event rates and prognostic implications.

BackgroundPeriprocedural myocardial infarction (PMI) has had several definitions in the last decade, including the Society for Cardiovascular Angiography and Interventions (SCAI) definition, that requires marked biomarker elevations congruent with surgical PMI criteria.Methods and ResultsThe aim of this study was to examine the definition‐based frequencies of PMI and whether they influenced the reported association between PMI and increased rates of late death/ myocardial infarction (MI). We studied 742 patients; 492 (66%) had normal troponin T (TnT) levels and 250 (34%) had elevated, but stable or falling, TnT levels. PMI, using the 2007 and the 2012 universal definition, occurred in 172 (23.2%) and in 99 (13.3%) patients, respectively, whereas 19 (2.6%) met the SCAI PMI definition (P<0.0001). Among patients with PMI using the 2012 definition, occlusion of a side branch ≤1 mm occurred in 48 patients (48.5%) and was the most common angiographic finding for PMI. The rates of death/MI at 2 years in patients with, compared to those without, PMI was 14.7% versus 10.1% (P=0.087) based on the 2007 definition, 16.9% versus 10.3% (P=0.059) based on the 2012 definition, and 29.4% versus 10.7% (P=0.015) based on the SCAI definition.ConclusionIn this study, PMI, according to the SCAI definition, was associated with more‐frequent late death/MI, with ≈20% of all patients, who had PMI using the 2007 universal MI definition, not having SCAI‐defined PMI. Categorizing these latter patients as SCAI‐defined no PMI did not alter the rate of death/MI among no‐PMI patients.

What Constitutes a Relevant Change in High-Sensitivity Troponin Values over Serial Measurement?

The universal definition of myocardial infarction (MI)2 requires both an increase in cardiac troponin concentrations and a rise and/or fall in values over serial measurement (1). It is noteworthy that there is no mention in the current consensus document regarding what magnitude of change in troponin values should be required to meet the definition for spontaneous MI. The conspicuous absence of criteria to define troponin concentration change in that document reflects important knowledge gaps and the lack of consensus with regard to this important component of the MI definition. The introduction of high-sensitivity troponin assays has created both challenges and opportunities with regard to the universal MI definition. A major challenge is the observation that a substantial proportion of individuals without MI have troponin concentrations persistently above the MI detection limit (2). This is in part related to the effects of age, male sex, subclinical cardiac structural abnormalities, and renal disease on troponin concentration (3), but is also influenced by poor characterization of the 99th percentile threshold, particularly for the high-sensitivity cardiac troponin T (hs-cTnT) assay. Indeed, a recent study that included data from 3 large population-based cohorts has shown that the recommended 14-ng/L threshold value for defining MI by use of the hs-cTnT assay is actually well below the actual 99th percentile value for men ≥50 years and women ≥65 years old (4). On the other hand, higher precision of the high-sensitivity troponin assays should improve characterization of troponin concentration changes over serial measurement. Indeed, it has been argued strongly that assessment of serial high-sensitivity troponin changes is the solution to the “specificity problem” with these assays (1, 5); however, little guidance is available as to what constitutes a relevant change. In the past few years, data have begun to emerge from 2 broad categories of studies …

The Fall and Rise of Cangrelor

Abstract Clinical Development Phases I‐III Regulatory, Quality, Manufacturing The antagonism of the platelet P2Y12 receptor is essential for the treatment of patients undergoing percutaneous coronary intervention (PCI). Cangrelor is an intravenous P2Y12 receptor antagonist that being both reversible and very short acting has the potential to overcome some of the limitations of currently available oral agents like clopidogrel, prasugrel, and ticagrelor. Cangrelor has been studied in a large phase III program called Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON (CHAMPION) that included three randomized controlled trials (RCTs): PCI, PLATFORM, and PHOENIX. The first two RCTs, conducted concurrently, were prematurely interrupted for futility. However, it was soon evident that unanticipated challenges in the ascertainment of PCI‐related myocardial infarction (MI) due to shorter‐than‐expected times to cardiac catheterization may have reduced the ability to detect cangrelor efficacy. While CHAMPION PCI and PLATFORM were ongoing, the universal definition of MI provided recommendations to address these challenges. Specifically, this consensus document recommended the presence of a rise and/or a fall of cardiac biomarkers to define MI. The universal MI definition enhanced by novel approaches to efficiently and accurately implement this definition was used to adjudicate MI in PHOENIX, which showed superiority of cangrelor over clopidogrel, with an effect that was mostly evident in MI. The development of cangrelor illustrates the critical importance of PCI‐related MI as end point, the challenges in its definition in patients undergoing a very early invasive management, and the role of the universal MI definition in overcoming these challenges.

Has the frequency of peri-procedural myocardial infarction reduced using third universal definition?

Background: Peri-procedural myocardial infarction (MI) in the 2012 universal definition requires, in addition to cardiac biomarker elevations, ischaemic chest pain and/or abnormal findings on ECGs or imaging. As MI, including post percutaneous coronary intervention (PCI) is an important endpoint in clinical trials and as post-PCI Troponin T (TnT) elevations are prognostic in patients with stable coronary heart disease (CHD), we determined whether the frequency of post-PCI MI was reduced, and whether it was associated with increased rates of late death/MI. Methods and results: To compare 2007 and 2012 peri-procedural MI definitions, we evaluated TnT levels within 24 hours post-PCI and assessed other criteria in747 patients undergoing PCI, for stable-CHD (18%), for non-ST elevation MI (43%) and for unstable angina (40%). The patients' mean age was 64±12years, 75% were male, 28% had diabetes and 60% had ACC/AHA class B2/C lesions. Pre-PCI TnT levels were normal ( 5xURL, 89 (18%) had levels >3xURL. Patients with elevated pre-PCI TnT levels, 88 (35%) had >20% elevation in TnT levels post-PCI. Among patients with an increase in post-PCI TnT levels to >5xURL or had increase by > 20% above elevated pre-PCI TnT levels (using third universal MI definition), the frequencies of both ischaemic chest pain and ECG changes was (only)7%. Peri-procedural MI occurred in 177 (24%) patients had using 2007 definition whereas 142 (19%) had post-PCI TnT levels either >5xURL or > 20% increased above elevated pre-PCI levels (p<0.0001). At median follow-up of 37 [IQR: 17-52] months, rates of death/MI in patients with stable-CHD were 28% and 10% in those with, and without, post-PCI TnT levels >5xURL, respectively (p=0.05), whereas these event rates in patients with ACS who did, and did not, have post-PCI TnT >5xURL or >20% above elevated pre-PCI TnT levels were 26% and 24% (p=0.58). Conclusion: The diagnosis of peri-procedural MI was less frequent when the 2012 universal definition was used compared to the 2007 definition. This has implications for clinical trial endpoint frequency and thus trial costs. Peri-procedural MI using the 2012 definition was prognostic in patients with stable-CHD.

Effect of vorapaxar on myocardial infarction in the thrombin receptor antagonist for clinical event reduction in acute coronary syndrome (TRA{middle dot}CER) trial

The TRA·CER trial compared vorapaxar, a novel platelet protease-activated receptor (PAR)-1 antagonist, with placebo in 12 944 patients with high-risk non-ST-segment elevation acute coronary syndromes (NSTE ACS). In this analysis, we explored the effect of vorapaxar on myocardial infarction (MI). A blinded, independent central endpoint adjudication committee prospectively defined and classified MI according to the universal MI definition, including peak cardiac marker value (creatine kinase-MB [CK-MB] and/or troponin). Because the trial failed to meet its primary endpoint, these analyses are considered exploratory. During a median follow-up of 502 days, 1580 MIs occurred in 1319 patients. The majority (n = 1025, 64.9%) were type 1 (spontaneous) MI, followed by type 4a [percutaneous coronary intervention (PCI)-related] MI (n = 352; 22.3%). Compared with placebo, vorapaxar reduced the hazard of a first MI of any type by 12% [hazard ratio (HR), 0.88; 95% confidence interval (CI), 0.79-0.98; P = 0.021] and the hazard of total number of MIs (first and subsequent) by 14% (HR, 0.86; 95% CI, 0.77-0.97; P = 0.014), an effect that was sustained over time. Vorapaxar reduced type 1 MI by 17% (HR, 0.83; 95% CI, 0.73-0.95; P = 0.007). Type 4a MIs were not significantly reduced by vorapaxar (HR, 0.90; 95% CI, 0.73-1.12; P = 0.35). Vorapaxar effect was consistent across MI sizes defined by peak cardiac marker elevations and across key clinical subgroups; however, in patients not treated with thienopyridine at baseline (HR, 0.65; 95% CI, 0.46-0.92) compared with patients who received thienopyridine (HR, 0.91; 95% CI, 0.81-1.02), there was a trend towards a higher effect (Pint = 0.077). The PAR-1 antagonist vorapaxar was associated with a reduction of MI, including total number of infarctions. This reduction was sustained over time and was mostly evident in type 1 MI, the most common type of MI observed.

A novel approach to systematically implement the universal definition of myocardial infarction: insights from the CHAMPION PLATFORM trial

ObjectiveTo reassess the efficacy of cangrelor efficacy using the universal definition of myocardial infarction (MI).DesignWe adopted a novel approach to systematically implement the universal definition of MI. Two physicians blinded...

Implementation of standardized assessment and reporting of myocardial infarction in contemporary randomized controlled trials: a systematic review

Myocardial infarction (MI) is a key endpoint in randomized controlled trials (RCTs), but heterogeneous definitions limit comparisons across RCTs or meta-analyses. The 2000 European Society of Cardiology/American College of Cardiology MI redefinition and the 2007 universal MI definition consensus documents made recommendations to address this issue. In cardiovascular randomized trials, we evaluated the impact of implementation of three key recommendations from these reports-troponin use to define MI; separate reporting of spontaneous and procedure-related MI; and infarct size reporting. We searched ClinicalTrials.gov and MEDLINE databases for cardiovascular RCTs with more than 500 patients in which enrolment began between September 2000 and July 2012 and that listed MI in the primary endpoint. We searched English-language publications with primary results or design papers. Of 3222 studies screened, 96 (3.0%) met our criteria. We extracted enrolment start date, number of patients and MI events, follow-up duration, and coronary revascularization rate. Data extraction quality was assessed by duplicated extractions. Of 96 RCTs, 80 had a primary results publication, comprising 608 091 patients and 43 621 endpoint MIs. Myocardial infarction represented 45.3% (95% confidence interval, 40.2-50.4) of events in the primary composite endpoint. Troponin defined MI in 57% (53/93) of trials with an MI definition available. Of these RCTs, three used troponin only if creatine kinase-MB was unavailable, six used troponin to define peri-procedural MI, seven specified the 99th percentile as the MI decision limit, and three reported spontaneous and procedure-related MI separately. None reported biomarker-based infarct size, but five reported MI as multiples of the assay upper limit of normal. Although MI is a major component of cardiovascular RCT primary endpoints, standardized MI reporting and implementation of consensus document recommendations for MI definition are limited. Developing appropriate strategies for uniform implementation is required.

Circulation Editors' Picks

<i>Circulation</i> Editors' Picks

Rationale and design of the Cangrelor versus standard therapy to acHieve optimal Management of Platelet InhibitiON PHOENIX trial

Despite robust efficacy in the reduction of ischemic events in patients who require percutaneous coronary intervention (PCI), current P2Y(12) inhibitors have limitations. In particular, they require hours to be effective, and they can only be administered orally. Cangrelor is an intravenous, potent, and reversible P2Y(12) inhibitor with fast onset and offset of action. We designed CHAMPION PHOENIX to evaluate the efficacy and safety of cangrelor in patients with atherosclerosis undergoing PCI. The CHAMPION PHOENIX is a randomized, double-blind, double-dummy, superiority trial comparing cangrelor with clopidogrel standard of care in approximately 10,900 patients who have not previously received a P2Y(12) inhibitor and who require PCI, including patients with stable angina and with acute coronary syndromes (with or without ST-segment elevation). The primary objective of the study is to demonstrate that cangrelor will reduce the incidence of the composite of death, myocardial infarction (MI), ischemia-driven revascularization, or stent thrombosis in the 48 hours after randomization compared with clopidogrel without excessive periprocedural bleeding. The key secondary objective is to demonstrate that cangrelor will reduce the incidence of stent thrombosis. Myocardial infarction will be defined according to the universal MI definition, adapting the definition of PCI-related (type 4a) MI. Bleeding will be assessed according to the thrombolysis in myocardial infarction, GUSTO, and Bleeding Academic Research Consortium (BARC) scales. The CHAMPION PHOENIX may establish the role of cangrelor in the care of patients who require PCI across the spectrum of stable and unstable coronary diseases in the setting of current treatment strategies.