The Take Home: TCT

Last year’s Transcatheter Cardiovascular Therapeutics Scientific Symposium, held in San Francisco, attracted an all-time high attendance of nearly 12,000 attendees from more than 90 countries. With more than 1,500 submitted abstracts, the final program featured 799 abstracts — separated into 140 oral presentations and 659 posters — 115 sessions, and more than 20 late-breaking clinical trials and first-report investigations. Hot topics spanned the gamut of intervention, from potentially revolutionizing therapies, such as transcatheter aortic valve replacement and the rapid-acting P2Y12 inhibitor cangrelor, to analyses of interventional techniques, including comparisons of radial vs. femoral access approaches.

To find out which of these and other presented data were the most clinically impactful, Cardiology Today Intervention spoke with two of its Editorial Board member attendees, Anthony Bavry, MD, MPH, assistant professor of medicine at the University of Florida, and Sunil V. Rao, MD, associate professor of medicine, Duke University Medical Center, Durham, N.C., and asked them to share their thoughts.

Anthony Bavry, MD, MPH

RAPID GENE

	Anthony Bavry

One of the most important trials from TCT for me was the RAPID GENE trial, which looked at genotyping patients (n=200) for the CYP2C19 allele. Patients who carry this allele are at increased risk for adverse events; therefore, this trial tried to determine if we can identify these patients and treat them with a more potent antiplatelet agent to improve outcomes. In the RAPID GENE trial, researchers identified patients who were carriers of the allele by rapid genotyping from a buccal swab specimen and gave them prasugrel (Effient, Eli Lilly). These patients had a reduction in their platelet reactivity in contrast to patients who received standard clopidogrel (Plavix, Sanofi-Aventis) therapy. The trial was not powered to look at clinical outcomes.

This was an important trial, but I think a question going forward is whether we will need to genotype these patients or just check their platelet reactivity ahead of time. GRAVITAS, an earlier trial, looked at a strategy of higher-dose clopidogrel and was unable to show a benefit in clinical outcomes, despite reducing platelet reactivity. So, a lot of work to be done here, but the RAPID GENE study showed that rapid genotyping is feasible and can be used to tailor antiplatelet therapy.

ADAPT DES

Another trial on a similar theme was ADAPT DES. This trial set out to measure platelet reactivity by various means and determine whether high-platelet reactivity was associated with stent thrombosis. The trial looked at different measures of platelet reactivity, such as aspirin reaction units, glycoprotein IIb/IIIa platelet reactivity units and P2Y12 platelet reactivity units, and identified two cut-offs for a P2Y12 reaction unit (PRU): one was a cut-off of 208 or more and the other was a cut-off of 230 or more. Both were valid: 208 cut-off had a higher sensitivity but lower specificity for predicting stent thrombosis, while the cut-off of 230 had a lower sensitivity but a higher specificity. Both tests had a very good negative predictive value.

We still need some work to determine what the best threshold PRU level should be for predicting adverse events. Currently, that number seems to be somewhere between 208 and 230; either one would be valid. Again, we go back to the question of if we identify a patient with a high P2Y12 number, can we improve outcomes by treating them with a more potent antiplatelet agent? That has been elusive so far with the GRAVITAS trial as an example, which was unable to show an improvement in clinical outcomes despite improving platelet reactivity. So, high-platelet reactivity identifies a high-risk group, but we are still trying to determine how to reduce adverse outcomes in this group.

TRIGGER-PCI

TRIGGER-PCI looked at non-responders to clopidogrel (n=2,150) and hypothesized that prasugrel would be better in these patients. This study used a PRU cut-off of 208 by the VerifyNow assay (Accumetrics). Among patients with high platelet reactivity who received a drug-eluting stent, the primary composite outcome of cardiac death or MI was virtually the same and very low in both groups. A significant proportion of MIs that occur after PCI is due to stent thrombosis. Although this is an important event, it is fortunately uncommon, which makes it very hard to show any difference in treatment strategies.

In summary, we get a little more data with this trial, but it was too underpowered to give us any real meaningful results.

BRIDGE

BRIDGE was an interesting trial. An important problem with first-generation DES is when the need for non-cardiac surgery arises and patients are asked to stop taking aspirin and/or clopidogrel. BRIDGE looked at bridging these patients (n=210) preoperatively with cangrelor (The Medicines Company), which is an IV adenosine diphosphate receptor antagonist that has a very short half-life of approximately 5 minutes. Patients had clopidogrel stopped in anticipation of surgery, at which point cangrelor was started. Cangrelor was shown to decrease PRUs. In this study, the cut-off for PRU was less than 240, so it was shown to significantly improve the proportion of patients who had a PRU less than 240 vs. the placebo group. The trial was not powered for clinical events, but major adverse events that happened pre- and post-procedurally were similar between the groups.

Most events of stent thrombosis occur operatively or postoperatively; the pre-operative period is a relatively lower-risk period, so the operative and postoperative times are the high-risk areas that we need to focus on.

Second-generation DES appear to be less thrombogenic, so further research is required to determine if these patients carry the same perioperative risk as recipients of first-generation DES.

In summary, the concept of bridging is under study and mainly applies to patients with a first-generation DES.

Disclosure: Dr. Bavry reports no relevant financial disclosures.

Sunil V. Rao, MD

RIFLE STEACS

	Sunil V. Rao

Of the entire meeting, the one trial that spoke to me the most was RIFLE STEACS. The randomized trial was performed in Italy and included just over 1,000 patients with STEMI undergoing primary PCI who were randomly assigned to either radial or femoral access approaches. This was a tremendous effort on the part of the researchers. Not only were they able to randomize patients, but they were also able to look at the new definition of bleeding that’s been incorporated into a lot of trials now called BARC (Bleeding Academic Research Consortium), which produced some interesting results. This trial was one that caught everybody by surprise. The investigators were able to show a 4% absolute reduction in 30-day mortality with transradial primary PCI, which paralleled the almost 4% reduction in BARC bleeding. This showed that, at least in experienced hands (all investigators were experienced radial operators), the radial approach to primary PCI not only reduces bleeding but also reduces 30-day mortality as well.

PARTNER Cohorts A and B

There were also some interesting TAVR data that came out of TCT with respect to quality of life and cost-effectiveness from PARTNER cohort A. The trial involved 699 high-risk patients with severe aortic stenosis and suggested that transfemoral TAVR, but not transapical TAVR, could improve both cost and QOL when compared with surgery. The study was consistent with what we probably expected considering traditional, societal standards for cost-effectiveness with TAVR.

Additionally, the 2-year, long-term data from PARTNER cohort B were presented and look very good for TAVR. In the trial, patients treated with TAVR (n=179) had superior outcomes, including all-cause and CV mortality, when compared with standard medical therapy (n=179) at 2 years, confirming what had been observed at 1 year.

Overall, the two PARTNER trials are encouraging, and suggest to me that there doesn’t seem to be much to worry about with TAVR, particularly with respect to cost and QOL.

Disclosure: Dr. Rao is a consultant for Terumo, which makes radial equipment.