Best of #AHA20 Interventional Trials

Condensed take-home messages from the AHA 2020 Scientific Sessions

AHA 2020 VIRTUAL EXPERIENCE - November 13-17, 2020

ARREST Trial (Published in Lancet)

Study Summary:

This is a single-centre, open-label, safety and efficacy randomized trial. It included adults aged 18–75 years with an Out of Hospital Cardiac Arrest (OHCA) and refractory ventricular fibrillation with no return of spontaneous circulation after three shocks. An automated cardiopulmonary resuscitation with a Lund University Cardiac Arrest System (LUCAS) was instituted. The estimated transfer time was 30 minutes. Patients were randomly assigned to early Extracorporeal membrane oxygenation (ECMO) or standard ACLS protocol upon hospital arrival. The primary outcome was survival to hospital discharge. The secondary outcomes were safety, survival, and functional assessment at hospital discharge, 3 months and 6 months after discharge. The analysis was on an intention-to-treat basis. Early ECMO-facilitated resuscitation for patients with OHCA and refractory ventricular fibrillation significantly improved survival to hospital discharge compared with standard ACLS treatment The 6-month survival was superior in the ECMO arm. The study was terminated early after enrolling 30 patients where the ECMO arm superiority exceeded the pre-specified monitoring boundary by the DSMB.

Critical Appraisal:

• This is a small study; however, the effect size is large enough to reconsider pathways in centres able to provide advanced ECMO support.
• The population studied included those who had optimal CPR delivered by an automated LUCAS machine and transport to an advanced facility within 30 minutes was possible. These inclusion criteria mean it is not applicable to all or any OHCA.

Alpheus Trial (Published in Lancet)

Study Summary:

The ALPHEUS study is a randomized, open-label, multicenter trial conducted in France and Czech Republic. Patients with stable coronary artery disease (CAD) were included if they had an indication for percutaneous coronary intervention (PCI) and at least one high-risk characteristic. Patients were randomly assigned to either ticagrelor (180 mg loading dose, 90 mg twice daily for 30 days) or clopidogrel (300–600 mg loading dose, 75 mg daily t for 30 days). The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction (MI) or major myocardial injury and the primary safety outcome was major bleeding within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI at 48 hours or 30 days. The primary safety outcome did not differ between the two groups, but minor bleeding events were higher in the ticagrelor arm although it did not reach statistical significance.

Critical Appraisal:

• Despite more potent platelet inhibition further suggested by the higher incidence of dyspnea and minor bleeding in the ticagrelor arm, this didn’t translate into better efficacy (lower periprocedural MI and myocardial injury) in patients with stable CAD. The measurement of platelet inhibition and cardiovascular outcomes has been inconsistent in many studies suggesting that other factors impact outcomes in CAD beyond platelet inhibition.
• The patients included in the study did have some high-risk features that included some troponin positive patients, left main and bifurcation PCIs making the results valuable in this subset as well.
• 80% of those enrolled were men and the mean age was 66 years; as such, it is difficult to make inferences specific to women or elderly populations.
• Upon considering the totality of evidence in such a population: the CREDO trial demonstrated that clopidogrel did reduce MACE at one year compared with placebo. In the SASSICAIA trial, prasugrel didn’t reduce 30-day MACE compared with clopidogrel, and Alpheus failed to demonstrate an early benefit of ticagrelor. As such, for stable CAD, clopidogrel remains the antiplatelet of choice.
• Finally, given this is a stable disease population, it is necessary to define the long-term outcomes.

RIVER Trial (Published in NEJM)

Summary:

This is a multicenter randomized trial conducted in Brazil that compared rivaroxaban (20 mg once daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation (AF) and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. 1005 patients were enrolled. In patients with AF and a bioprosthetic mitral valve, rivaroxaban was non-inferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months.

Critical Appraisal:

• The results validate current practice whereby rivaroxaban is used in bioprosthetic mitral valves and AF. The results cannot be extended to mechanical valves or those without AF.
• The mean CHADsVAsC score was 2.6 and the mean HASBLED score was 1.6. The rate of clinically relevant bleeding was not significantly different and the overall risk of major bleeding was lower in the rivaroxaban arm albeit nonsignificant.
• There were fewer strokes in the rivaroxaban arm; however, the overall number of events was low, the confidence interval was wide and the difference was not adjusted for multiplicity.
• Of note, 31% had the valve replacement 5 years prior to the study and 18% within 3 weeks. Very few were enrolled within 48 hours to 30 days making an analysis by date difficult.
• Whether the underlying pathology (eg rheumatic mitral stenosis) and whether the size of the left atrium impact outcomes also remains unknown.

ONE MONTH Trial

Summary:

This is a randomized, parallel, open label trial. The goal was to evaluate a 1-month dual antiplatelet (DAPT) regimen compared with 6-12 month of DAPT among patients undergoing elective PCI for stable or unstable CAD.  Approximately 1500 were enrolled in each arm (1-month (n = 1,507) vs 6-12 months (n = 1,513)).  After completion of the assigned DAPT duration, the monotherapy consisted of aspirin. In the 1-month DAPT group, patients received a polymer-free drug-coated stent (BioFreedom). In the 6- to 12-month DAPT group, patients received a contemporary DES (Biomatrix or Ultimaster). The duration of follow-up was 12 months. The Mean age was 67 years, females represented 31% of the total study population and diabetes in 37%. The investigators concluded that among patients undergoing PCI for stable or unstable CAD, 1 month of DAPT was noninferior to 6-12 months of DAPT.

Critical Appraisal:

• Overall, this was a very low risk population with exclusion of acute myocardial infarction and complex PCI and a very low rate of prior CABG, PCI, and chronic kidney disease in the enrolled population.
• Compared to other trials examining an abbreviated DAPT regimen in stable disease, this study used aspirin for monotherapy (In STOP DAPT clopidogrel was the antiplatelet used for monotherapy).
• When abbreviating DAPT, the most important ischemic endpoint is stent thrombosis which this study was not powered to address.
• There was signal towards benefit for 6-12 months of DAPT among those with unstable CAD and it would be interesting to obtain longer follow up to see if the results persist and the curves diverge further.
• 17% of the short DAPT arm continued DAPT beyond one month, so the ITT analysis biased towards a non-inferiority design and it is necessary to perform a per protocol analysis.
• This is not a 2:2 factorial design, so there is caution in interpreting results with respect to the type of stent technologies. Although the BioFreedom stent was used in this study, one shouldn’t confuse the study population with that of the LEADERS FREE trials. This is not a high bleeding risk population. 

RAPID CTCA Trial

Study Summary:

This is a randomized parallel study comparing early cardiac computed tomography (CT) angiography to the usual care among patients with suspected or provisional acute coronary syndrome (ACS). The total number enrolled was 1748 (CT angiography (n = 877) and usual care (n = 871)). The follow up duration was 1 year. The mean age was 62 years with 36% women and 18% diabetics. Those included had either a prior history of CAD, Troponin >99th percentile or an abnormal EKG. 23% had normal coronary arteries, 29% nonobstructive disease and 47% obstructive disease. 44% had a GRACE score <109. There was no difference in the primary outcome of all-cause death or myocardial infarction (type 1, spontaneous) or (4b, stent thrombosis) at 1 year. As for the secondary outcomes, invasive coronary angiography was lower in the CT angiography group. There was no difference in overall ACS or preventive treatments in both arms. There was a modest increase in the median length of hospitalization (2.2 days for CT angiography vs. 2.0 days for usual care) and median health care costs ($9,494 for CT angiography vs. $8,776 for usual care).

Critical Appraisal:

• Compared to other trials evaluating the role of CT in those with suspected or confirmed ACS, this study enrolled higher risk populations with positive troponins or EKG changes.
• Among patients with suspected or possible ACS, cardiac CT angiography did not reduce the incidence of death or subsequent MI. So, the use of CT angiography did not come with a penalty with respect to CVS events, but with an increased hospital costs and stay.
• This was not a blinded protocol. Only 87% of those assigned to the CT arm got the examination and the diagnostic quality was achieved in 90%. In a high-risk population that is inadequate as anatomic definition and stratification is integral to the care plan. With this number of uninterpretable studies, the widespread application of CT in centres without the appropriate expertise, protocols or facilities is not wise.
• Approximately 53% had MINOCA (MI with non-obstructive coronary arteries) using the accepted standard definitions further validating current pathways and not replacing them. Another trial, HARP study, also presented at AHA20 reported that 64% of MINOCA patients were due to MI further explaining why the prevention and treatment strategies were not impacted by the CT.

MITHRAS Trial (Published in Circulation)

Study Summary:

This is a randomized study evaluating the closure of iatrogenic atrial septal defects (iASD) following transcatheter mitral repair with a Qp:Qs >=1.3 compared to conservative treatment. Of the 240 patients enrolled 35% had such an iASD with a mean Qp:Qs >=1.5. The primary end point was 6-minute walk and the secondary endpoint was heart failure symptoms, hospitalizations or survival. The closure was performed 3 days after randomization. Follow up was for 5 months. The analysis was on an ITT basis.

Critical Appraisal:

• Closure of iASD after TMV Repair was not superior to conservative Rx with respect to the primary end point of 6-minute walk.
• In line with the primary outcome, the secondary results demonstrate no increase in heart failure (HF) symptoms, hospitalizations or survival. However, HF hospitalizations were increased in the presence of iASD irrespective of the strategy compared to those without iASD.
• It is important to recognize that iASD may be of prognostic value and not causative of worse outcomes.
• There was. A45% reduction in the Qp/Qs at 1-month noted in the conservative arm prompting one to wonder whether closure at day 3 was too early to differentiate between the 2 strategies. The overall sample size was too small and the follow-up was short. Perhaps a larger study with longer follow up would demonstrate better outcomes with closure. Once again, since the sample size is small, subanalysis according to the volumes and filling pressures is not possible.
• A few remaining questions include the appropriateness of individualized patient centred decisions and stratification by the degree of shunting.

Author

Mirvat Alasnag

@mirvatalasnag

Interventional cardiologist / Cardiologist

Jeddah, Saudi Arabia

Latest contributions

OPTION-STEMI: Immediate versus staged complete revascularisation during index admission in patients with STEMI and multivessel disease PCRonline @ ESC Congress 2025: the interventional cardiology perspective! PCI for complex bifurcation disease - LIVE Case

View full profile