The Take Home: ACC

Issue: May/June 2012

Cardiology Today Intervention spoke with two of its board members who attended the American College of Cardiology Scientific Sessions in Chicago this past March, Jeffrey W. Moses, MD, of Columbia University Medical Center/Weill Cornell Medical Center, New York, and Matthew Price, MD, of Scripps Clinic, San Diego, and asked them to give their take on the most clinically impactful data coming from the meeting.

Jeffrey W. Moses, MD

PARTNER Cohort A


	Jeffrey W. Moses

The 2-year PARTNER cohort A data for the high-risk surgical group are reassuring, particularly because the all-cause mortality rates are virtually identical between the groups (TAVR, 33.9% vs. surgical AVR, 35%). The stroke controversy has also died down because at the end of 2 years it was almost a wash (HR=1.22; 95% CI, 0.67-2.23), as the stroke rate has narrowed considerably. The findings on paravalvular leak, which was significantly higher with TAVR (P<.001), are important in the sense that it is another avenue for improvement; if we eliminate it, which is technologically feasible, then we could probably even define a superior outcome in many groups with this technology. So these results were very encouraging.

ASCERT

The comparative effectiveness data from the National Cardiovascular Data Registry (NCDR) and Society of Thoracic Surgeons database, which was used in the ASCERT trial, are fatally flawed. In the analysis, PCI-treated patients were shown to have a higher rate of mortality during the first 4 years after treatment than those who were treated with CABG (20.8% vs. 16.4%). However, I don’t understand how they can take a dataset from the NCDR that doesn’t have the fields to identify inoperable patients and compare it with a group of operable patients. By definition that is an invalid comparison. We know that patients who are inoperable have a much higher mortality rate. There was no exclusion of such cases in this analysis, therefore the study is confounded by this very important factor, which may be responsible for the higher mortality rate in PCI patients. In this study they don’t know what’s driving the higher mortality rate or even if the difference is in cardiac mortality.

In an older population, the decision-making is simple: Sicker patients get PCI and the healthier get CABG. So how do you compensate for that when you don’t capture those factors? That’s why I think this study is a huge disservice. I believe they should suspend these analyses until they have a credible dataset.

ACRIN PA 4005

The results of the ACRIN PA 4005 trial appear very promising. Coronary CTA was able to reliably predict which patients with chest pain can safely be sent home. For example, none of the patients at low-to-intermediate risk (n=640) had an MI or died by 30 days after discharge and the 30-day event rate was less than 1%. Coronary CTA was also better than stress tests for finding patients with CAD (9% vs. 3%).

Previously, coronary CTA had a bad reputation because of the way it was brought into the market, but for screening, triaging and identifying patients at risk and not at risk it is a tremendous tool. I hope that payers will start paying more attention to it. Right now, they just slam the door on CT because of the potential for abuse, but in reality, if it is applied properly, it is tremendously valuable. Identifying coronary anatomy has tremendous value, especially when you can eliminate the prospect of significant coronary disease literally within seconds.

EINSTEIN PE and MOPETT

To me, the biggest message coming out of the meeting are the potential game-changers to the practice of pulmonary embolism treatment. In EINSTEIN PE, patients with a primary diagnosis of pulmonary embolism who were given rivaroxaban (Xarelto, Janssen Pharmaceuticals) alone had a non-inferior outcome in recurrences compared with patients treated with standard therapy (2.1% vs. 1.8%), while having better rates of bleeding (10.3% vs. 11.4%). In MOPETT, patients with moderate pulmonary embolism were either given half the standard dose of thrombolysis plus a modified regimen of anticoagulants (n=61) or anticoagulants alone (n=60). After 28 months, the thrombolysis group had a reduced rate of pulmonary hypertension and recurrent pulmonary embolism (P<.001) and earlier hospital discharge (P<.001) compared with anticoagulants alone.

These findings are exciting, particularly when one thinks about the potential for reducing costs associated with hospitalization. This can change the whole paradigm for pulmonary embolism treatment.

Disclosure: Dr. Moses was an investigator in the PARTNER trial.

Matthew Price, MD


	Matthew Price

TRA 2P-TIMI 50

TRA 2P-TIMI 50 was a critical trial that showed how challenging it has become to improve net clinical outcomes in our high-risk patients using agents with novel antiplatelet targets. In the trial, vorapaxar, when compared with placebo among stable patients with atherosclerosis treated for at least 1 year in addition to standard therapy, reduced the rate of CV death, MI and stroke (9.3% vs. 10.5%; P<.001), but increased the rate of GUSTO moderate or severe bleeding (4.2% vs. 2.5%; P<.001) and TIMI clinically significant bleeding (15.8% vs. 11.1%; P<.001).

As a result, we are still searching for that silver bullet of a drug that reduces recurrent thrombotic events without a substantial increase in bleeding. Whether there is a certain group of patients who could benefit from vorapaxar remains to be explored, but the overall results are disappointing.

INFUSE AMI

The results of the INFUSE AMI trial are provocative and interesting given that we really accepted aspiration thrombectomy as the standard of care based on a single-center randomized trial. However, in this multicenter trial that included 452 patients with anterior STEMI, 30-day results showed that aspiration thrombectomy did not reduce MI size compared with no aspiration (17% vs. 17.3%), whereas intracoronary abciximab (Reopro, Centocor) seemed to provide benefit when compared with no abciximab (15.1% vs. 17.9%). These results emphasize the need for multiple, multicenter trials, before we accept a given treatment strategy or approach as the gold standard. Often, one trial is not the answer, and in this case there appears to be a continuing role for glycoprotein IIb/IIIa inhibitors in anterior STEMI.

EINSTEIN PE

The EINSTEIN PE trial provides important data that suggest rivaroxaban is safer than enoxaparin (Lovenox, Sanofi-Aventis), and its efficacy appears to be as good as the control arm of enoxaparin transitioning to a vitamin K antagonist. It is important to note that the noninferiority margin was such that the HR could have been as high as 1.68 and still have been noninferior. Nevertheless, given the safety advantages and ease of therapy, it’s good to have this strategy in our armamentarium; however, we do need to understand that we may be sacrificing this for some efficacy, although we can’t know that for sure based on the results of this trial.

HOST-ASSURE

As a US-based physician, I don’t see the results of HOST ASSURE applying much to my practice. The long-term double-dose clopidogrel (Plavix, Sanofi-Aventis) treatment tested in the trial is currently not used in the United States routinely, especially in patients with stable angina, which encompassed about one-third of the patients enrolled in this trial. They compared this double-dose clopidogrel regimen (n=1,879) to cilostazol (Pletal, Otsuka Pharmaceuticals) plus dual antiplatelet therapy (n=1,876) following angioplasty. At 1 month, there was no difference in the composite primary endpoint, which included cardiac death, nonfatal MI, definite or probable stent thrombosis, stroke and PLATO major bleeding, between the triple antiplatelet therapy (1.2%) and double-dose clopidogrel DAPT (1.4%) approaches.

So my take home is that the event rates were very low in the overall trial and that the control arm is not a pharmacologic strategy commonly used in the United States.

ASCERT

The ASCERT findings are an important example of comparative effectiveness studies using current observational registries that are commonly applied in hospitals across the United States, in this case the CATH PCI registry for interventional cardiology and the STS database for bypass surgery. As trial investigator William Weintraub, MD, noted, given the provocative results, we have to understand the limitations of these analyses, particularly adjusting for all potential confounders and keeping in mind that the level of data integrity, ie monitoring, is not at the level we are accustomed to in randomized controlled trials. The two databases are quite different, really apples and oranges, so there are a lot of adjustments that need to be made. We need to take the results of ASCERT with a rather large grain of salt.

Disclosure: Dr. Price has received consulting fees from Boston Scientific, Janssen Pharmaceuticals, Medtronic and St. Jude Medical, consulting fees and speakers’ honoraria from Daicchi Sankyo/Eli Lilly and AztraZeneca, as well as consulting fees and research support from Accumetrics and Bristol-Myers Squibb/Sanofi-Aventis.