Month: December 2014

FFR(CT) Is Back! And Better Than Ever!

Invasive coronary angiography is problematic – specifically, it’s invasive.  Radial artery approaches have reduced the incidence of bleeding complications, but it remains a costly and non-risk-free procedure.  In lieu of ICA, CT coronary angiography has become increasingly popular.  However, CCTA is problematic – specifically, it’s inaccurate.

A few years ago, DeFACTO was published in JAMA and covered on this blog, a study evaluating a non-invasive model of fractional flow reserve added on to CCTA in an attempt to improve accuracy at identifying true culprit lesions.  DeFACTO was negative – specifically, the per-vessel performance at predicting flow-limiting lesions compared to the traditional 50% stenosis cut-off of CCTA was nearly identical.

Two years have passed, however, and we have a new study – NXT – using the next iteration of the HeartFlow software, and, of course, performed by authors with robust conflicts-of-interest.  Now, improvements in image quality and luminal modeling – as well as refined exclusion criteria to prevent troublesome images confounding their software – have improved performance to the point where, yes, it now seems to out-perform baseline CCTA.

The catch, of course, is the CCTA criterion standard is abysmal.  Compared with the ACRIN-PA or ROMICAT studies with their pro-CCTA COI, in which CCTA is the best thing since sliced bread, these folks are unconcerned with the collateral damage of degrading CCTA.  In this study, as performed on patients with suspected CAD, of 237 vessels read as “positive” by CCTA (>50% stenosis), only 83 (35.0%) were actually judged to be flow-limiting lesions on ICA – which is to say, false positives doubled the true positives.  Likewise – in contrast to the ROMICAT and ACRIN studies purveying CCTA as a bulletproof mechanism for discharge – 17 of 247 (6.8%) patients read as negative by CCTA (<50% stenosis) actually had flow-limiting disease.

False positives more two-thirds of the time?  And then a 7% miss rate of clinically important stenosis?  Basic, anatomic CCTA as previously described – not as fantastic as you’ve been led to believe.

The HeartFlow software?  Perhaps.  Effectiveness evaluations absent pervasive COI will be necessary to truly describe its value.

“Diagnostic Performance of Noninvasive Fractional Flow Reserve Derived From Coronary Computed Tomography Angiography in Suspected Coronary Artery Disease”
http://www.ncbi.nlm.nih.gov/pubmed/24486266

4-Factor Works for Factor Xa Inhibitors

The newest study regarding the reversal of the novel oral anticoagulants also concerns the newest of their family – edoxaban, joining a market already occupied by rivaroxaban and apixiban.  Yes, it’s just another “me too” drug trying to shoehorn its way into the massive warfarin-replacement market – but, at least, this is useful evidence.

4-Factor prothrombin concentrate complexes have been established as a treatment option in the setting of hemorrhagic complications during anticoagulation with the Factor Xa inhibitors.  However, the initial studies of PCCs primarily concerned themselves with laboratory markers of reversal, and any live bleeding studies were in animals (rabbits!).  For this study, however, the authors & Daiichi Sankyo paid 110 healthy volunteers to take edoxaban, then undergo punch biopsy, and then receive either placebo or 4-factor PCC in either 10 IU/kg, 25 IU/kg, or 50 IU/kg doses.

And, pleasantly, it works – in a dose dependent fashion, even, with 50 IU/kg providing the most effective reversal.  So, this essentially confirms what we thought we knew about PCCs based on surrogate markers and animal studies.  These volunteers only suffered a minor dermatologic procedure – and are not critically ill patients with other associated coagulopathies – but it still provides reasonable insight.

How this reversal strategy will fit versus andexanet alfa, a NOAC-specific reversal agent, remains to be seen – particularly with regards to cost and pro-thrombotic adverse effects.

“Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate”
http://circ.ahajournals.org/content/early/2014/11/16/CIRCULATIONAHA.114.013445.abstract

More Futility for Mechanical CPR

A few weeks ago we reported on the use of the LUCAS-2 for crushing the thorax, resulting in significant internal injuries.  None of these injuries were judged to have contributed to any patient’s demise – but, still, concerning.  This could be more forgivable if there were other advantages, say, survival.

Unfortunately, yet again, mechanical CPR fails to demonstrate superiority.

This is the PARAMEDIC trial, from the Lancet, a cluster-randomized trial aiming to demonstrate the superiority of the LUCAS-2 device as compared to manual CPR.  Based on a deployment of 143 available LUCAS devices, these authors compared 1,652 patients randomized to attempt device deployment compared with 2,819 in a control group.  There were no important differences in the baseline characteristics of the two groups, and other measures of initial treatment were similar.  And, in the end, there was no difference between initial return of circulation, event survival, 30-day survival, 3-month survival, or 12-month survival (all dismal).

The mildly interesting aspect to this trial is that it was not directly a test of the LUCAS device – but, rather, a pragmatic trial comparing deployment with LUCAS as an option with deployment without.  Thus, 638 patients in the clusters randomized to include the LUCAS device received manual compressions.  However, on multiple causal effect analyses, no advantage was detected from cases in which the LUCAS device was used, nor was a selection bias apparent.

In the absence of efficacy data, use of mechanical devices is defended primarily on the basis of convenience – freeing up hands for other tasks.  However, this argument fails in the face of these data – as it does not appear the handsfree advantage, when available, results in improved patient outcomes.

“Mechanical versus manual chest compression for out-of-hospital cardiac arrest (PARAMEDIC): a pragmatic, cluster randomised controlled trial”
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)61941-3/fulltext