5 trials that dominated Acute myocardial Infarction management in 2015
The field of cardiology, has also seen many developments in the year 2015, some of them which have changed the protocol in the management of Acute Myocardial Infarction. Here are a few of the major of the trials in the management of Acute MI 2015
TOTAL TRIAL
"Universal Thrombosection may not be the best Strategy."
MI is all about Thrombus. While treating MI the obvious thought is that removing thrombus manually at the time of PCI, will definitely improve the final outcome. TAPAS trial (2008) concluded that thrombus aspiration results in better reperfusion and clinical outcome than conventional PCI, irrespective of clinical and angiographic characteristics. And this became the guidelines of MI as a part of the recommendations.
Year 2015 brought the TOTAL trial, which said something completely opposite and challaged the guidelines themselves. In this randomised trial, A total of 10,732 patients (mean age, 61 years; 77% male) presenting with STEMI and undergoing primary PCI within 12 hours of symptom onset were randomly assigned to upfront manual thrombectomy before PCI or PCI alone.
The investigator noted that at 180 days, no difference was seen between groups for the primary composite outcome of cardiovascular death, MI, cardiogenic shock, or class IV heart failure (6.9% for thrombectomy + PCI and 7.0% for PCI alone). There were also no significant differences in any of the individual components of the primary endpoint. In subgroup analyses, there were no subgroups in which thrombectomy showed an advantage over PCI alone. However an excess of stroke within 30 days was seen in the thrombectomy arm (0.7% vs. 0.3%; Hazard ratio, 2.06; p=0.015), as were an excess of stroke or transient ischemic attack within 30 days (p=0.003) and stroke within 180 days (p=0.002).
The trial concluded that routine thromectomy compared to PCI alone without bailout thromectomy did not reduce subsequent cardiovascular outcome within 180 days and was associated with increased risk of stroke within 30 days.
The investigator noted that the increase in stroke after routine thromectomy was unexpected because stroke is a “ Very clinically relevant” endpoint as compared to repeat angina
With this result posted by TOTAL, Clinicians are waiting to see what the next guidelines have to say.
ABSORB III TRIAL
Bio-absobable stents proven only non-inferior to Xience V
Till 2015, bio-absorbable scaffolds was heavily promoted by Aboott as the next- generation stent stent for treatment of CAD. Similar to XIence V eluting everolimus and then resolving naturally into the body leaving no permanent scaffold. Three generations of innovations were done to develop a robust, useful ABSORD stent.
Obviously,due to its features of resoling by itself, this type of stent was looking to be superior than the previously used stents including XIENCE V.
To prove its superiority, over XIENCE, ABSORB III was undertaken with a lot of expectations.
ABSORB III was a large-scale, multicenter trial to determine the relative safety and effectiveness of the Absorb BVS compared to the Xience stent in patients with coronary artery disease.A total of 2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an Absorb BVS or a Xience stent.
The investigators noted that the primary endpoint of target-lesion failure (TVF; cardiac death, target-vessel MI, or ischemia-driven target lesion revascularization) at 1 year occurred in 7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7%; p=0.007 for non-inferiority and 0.16 for superiority).No differences were seen in rates of cardiac death (0.6% for Absorb and 0.1% for Xience; p=0.29), target-vessel myocardial infarction (6.0% and 4.6%, respectively; p=0.18), or ischemia-driven TLR (3.0% and 2.5%, respectively; p=0.50).Rates of angina, all revascularization, and ischemia-driven target vessel revascularization did not differ at 1 year.
However, Device thrombosis (definite or probable) was seen in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (p=0.13).
The investigators concluded that in this large study, the Absorb BVS was non-inferior to the Xience everolimus-eluting stent with respect to target lesion failure at 1 year or any of its individual components.
The trial has put into doubt the excitement of cardiologists in using self-destroying stents. Though the concept of a self-degrading stent may seem “intuitively attractive,” but this particular trial has raised concern over the numerically higher rates of TVF and all its individual components in the BVS arm, even though the trial met its predefined criteria for noninferiority.
MARTIX TRIAL
Trans-radial may be the default strategy while treating AMI
Traditionally, Femoral atery has been the default acess to perform Coronary Angiography and Percutaneous Coronary intervention. However, off lately some European countries as well as Canada began recommending trans-radial access, as it is associated with significantly less bleeding. To test this premise that reduced excess site bleeding and vascular complications actually results in better outcomes, MATRIX trial was performed.
8,404 patients with ACS (mean age, 67 years; 73% male) were enrolled from October 2011 to November 2014. Among them, 48% had ST-segment elevation myocardial infarction (STEMI), and 80% underwent PCI following coronary angiography.
Comparing in terms of MACE ( major adverse cardiovascular events ) and NACE ( net adverse clinical-event rate ), the study found that
For MACE, there was no statistically significant difference between the radial- and femoral-access arms (8.8% in the radial arm vs. 10.3% in the femoral arm; p=0.031, but missing prespecified two-sided α of 0.025 for superiority). The NACE rate was significantly reduced with the transradial approach (9.8% in the radial arm vs 11.7% in the femoral arm; p=0.009). Moreover, there was a statistically significant reduction in all-cause mortality with transradial intervention (1.6% vs. 2.2% for transfemoral; p=0.045), but no difference in cardiovascular death (1.5% and 2.1%, respectively; p=0.08). No differences were seen in stent thrombosis rates, but bleeding defined by the Academic Research Consortium (BARC) as requiring a blood transfusion/surgical intervention or fatal bleeding (BARC 3 and 5) was significantly reduced with the transradial approach (1.6% vs 2.3%; p=0.013).
The results were so staggering that it made the investigator conclude, " Our results combined with previous studies suggest that the radial approach should become the default access for patients with ACS undergoing invasive management.”
ANGIO MATRIX TRIAL
"Bivalirudin may not be superior to Heparin while treating AMI"
Bivalirudin a specific and reversible direct thrombin inhibitor ( DTI), earlier ,seemed to overcome many limitations that were seen with the indirect thrombin inhibitor, such has heparin. 7 major randomized trial of ST elevation MI undergoing PCi showed persistant positive outcomes with Bivalirudin having fewer adverse events compared to patients recivng heparin. Owing to this, Bivalirudin soon revcieved a class I recommendation in number of US and EU guidelines.
Angio matrix studied Bivalirudin versus unfractionated heparin (UFH) in patients undergoing percutaneous coronary intervention (PCI) and whether it is associated with reduction and MACE and NACE.
In this 2x2 factorial designed study, patients were first considered for the “access” program (a comparison of radial vs femoral-access PCI) and, depending on the planned revascularization strategy, included in the antithrombin component of the trial. In total, 7213 participants with ACS undergoing coronary angiography and PCI were randomized to bivalirudin with bailout GPI or to UFH with planned or bailout GPI use. Just over one quarter of patients in the UFH arm and 4.6% of patients in the bivalirudin arm received a GPI.
Overall, the antithrombotic regimen with bivalirudin failed to significantly reduce the 30-day risk of MACE or NACE when compared with patients who received UFH. Also, the rate of definite stent thrombosis was significantly higher in the bivalirudin arm (relative risk 1.71; p=0.048). however investigators did find a significant reduction in mortality and bleeding.
The investigators concluded that in this largely unselected population of ACS patients randomly assigned to radial or femoral access, the use of bivalirudin as compared to UFH with provisional GPI did not reduce the composite of death, MI, or stroke, or the composite of death, MI, stroke, and major bleeding. This finding was consistent across subgroups, including access site.
BAAC TRIAL
Diagnose AMI in one hour by high sensitivity troponin I
Acute MI Management is first about diagnosis which is early and accurate, and then about its treatement. An electrocardiogram, the traditional and most accurate diagnostic modality remains negative in large number of Acute MI. The biomarkers, like Troponin has come as a next accurate diagnosis of acute MI but takes atlas three hours to give positive reports.
To reduce the time to accurate diagnosis, a The Biomarkers in Acute Cardiovascular Care (BACC) study was done, which tested the application of high sensitivity troponin I (hsTnI) for a rapid 1-hour rule-out and rule-in compared to a standard 3-hour approach.
The researchers identified 1,045 patients presenting with acute chest pain and suggested AMI. Non-ST-segment elevation myocardial infarction (NSTEMI) was diagnosed in 184 patients by measuring troponin T (using a standard assay) on presentation and after 3 hours, combined with clinical data, imaging, ECG and clinical judgment. Patients were also assayed for hs-TnI at presentation and after 1 and 3 hours. Patients were followed for 6 months.
Comparing the results of both assays, the researchers calculated that the best TnI cut-off value to rule out AMI was 6 ng/L, much lower than the 99th percentile cut-off that is generally used (27 ng/L). The cutoff (and no clinical data) was tested in the full cohort and showed no clinically important loss of safety for ruling-out patients after 1 hour (negative predictive values of 99.7% after 1 hour and 100% after 3 hours).
The results of the study made the investigators conclude "Use of this algorithm in patients with suspected AMI allows for highly accurate and rapid rule-out as well as rule-in, enabling safe discharge or rapid treatment initiation." The investigators suggested that this new algorithm has wide applicability and is safe, although further study is needed to test the best cut-off for each troponin assay and to validate the 1-hour algorithm prospectively.
