The Take Home: SCAI

Issue: July/August 2015

In May, interventional cardiologists at the annual Society for Cardiovascular Angiography and Interventions Scientific Sessions attended presentations featuring cutting-edge research, taped cases from around the world, case reviews, interactive workshops and more. This year’s meeting in San Diego focused on five main tracks: congenital heart disease, coronary, peripheral, quality improvement and structural. Commenting on the take-home messages from the meeting were Payam Dehghani, MD, FRCP(C), FSCAI, interventional cardiologist within the Regina Qu’Appelle Health Region and a SCAI 2015-2017 Emerging Leader Mentorship fellow; and Jeffrey M. Schussler, MD, FSCAI, interventional cardiologist at Baylor University Medical Center in Dallas.

TECHNOLOGY: THE NEW FRONTIER

Schussler: The opening lectures at SCAI 2015, given by Christian Assad-Kottner, MD, and Peter J. Fitzgerald, MD, PhD, felt more like a TED Talk than a plenary session. This set the tone for the meeting.

Dr. Assad-Kottner made the point that it is getting harder to separate our technologies in the cath lab from the technologies that we are using outside the cath lab, and the overlap of these two is becoming more apparent. “It used to be that you came to meetings to network, but no longer,” he said. You can only talk to a few (maybe a few hundred) people when you physically show up at a meeting. With social networks, you can simultaneously network with and be networked with thousands or more, instantly. Social networks, which he suggested should be called “information” networks, are priceless and allow wide dispersal of information to physicians and patients.

Jeffrey M. Schussler

New technologies such as IBM’s Watson may actually help us think better. Computer systems, filled with huge banks of knowledge, allow vast integration of diagnoses and help with diagnostic algorithms. Apple is getting into the medical field with its new focus on personalized medicine, wearable devices and software (HealthKit) that allow design of applications for individuals. There is a huge explosion of new devices such as Google Glass that allow creation of augmented reality, using both real and computer-generated imagery, which, at least in a cath lab setting, allow the presentation of virtually created imagery in your field of view. In 2 years, you may wear a pair of smart glasses (ODG, VitalMedicals) that allow you to see point-of-view streaming images, keeping angiograms in your field of view, in addition to supplemental integrated images. For instance, you can have your own personal “screen” on which data can be projected to help guide interventions, valve placement, and so on. Teaching and training others to perform procedures, and its impact on medical education, may be the most exciting area in which virtual reality may be employed. Actually experiencing what happens during a procedure from the operator’s point of view allows a level of depth of experience that simple case presentation cannot convey.

Images provided by the Society for Cardiovascular Angiography and Interventions; printed with permission.

Dr. Fitzgerald talked about disruptive technologies, such as creating new heart cells from de-differentiated epithelial cells, which may allow personalized cardiac medication, tested on an individual’s cardiac structure. Genotyping may pave the way for individualized treatment programs based on individual genetic variability. Noninvasive evaluation of a coronary tree using CT coronary angiography is now allowing anatomic as well as physiologic (using CT fractional flow reserve) evaluation before a patient even gets to the cath lab. Robotic and artificial intelligence technology, such as that used to drive cars without drivers, will move into our arena and will standardize the variability of our treatment strategies. Placement of a stent without wearing lead, without radiation and with less contrast for the patient will be available to us in the near future. Haptic force-feedback will soon be available to help with placement of transcatheter valves, and with other structural heart disease treatments.

Once again, personalized technologies (the so-called “wearables”) were introduced at the 2015 Consumer Electronics Show, allowing new personal diagnostic capabilities that will be put into the hands of consumers. For example, patients with congestive HF may be soon wearing or have implanted devices that can monitor the patient at home and prevent readmission rates, reducing deviations from expected parameters that would otherwise only be checked intermittently.

The biggest shift may be in point of care or consumer care, which will be administered (diagnostics, as well as therapeutics) in new venues that are not traditionally thought of as health care sites. There will be an “Uber-ization of medicine,” brought to the patients, rather than the patients going to it.

The current era allows very rapid-cycle changes, unheard of dispersal of information (in real-time or near real-time) and will lead to new advancements in our field. This will also be a disruptive time in medicine, in general, and cardiology specifically. It is happening — whether we like it or not — and we all need to learn about these technologies that are being brought to market and will likely have a direct impact on our patients and our practice of interventional cardiology.

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ORBIT II

Dehghani: Previous studies have shown that a high load of calcium in coronary arteries predicts an increased rate of major adverse cardiac events. The Diamondback 360 Orbital Atherectomy System (Cardiovascular Systems Inc.) is an FDA-approved device designed to tackle severe calcific lesions. Unlike rotational atherectomy, this is an orbital atherectomy device that is advertised as easier to use, simpler to set up, and treats the entire lumen in antegrade and retrograde fashion. The prospective, multicenter ORBIT II trial evaluated this device with the primary safety endpoint of MACE and primary efficacy endpoint of procedural success. This non-ACS group consisted of mostly men (64%), of whom 36% had diabetes, 15% had history of CABG and drug-eluting stents were used in 88%. The target lesion had to have fluoroscopic or IVUS evidence of severe calcium.

As presented at SCAI 2015 as a late-breaking clinical trial, results demonstrated that the device was efficacious in successfully deploying stents in 98% of cases, with a notable MACE rate of 19.4% at 2 years mainly driven by MI. Cardiac death (4.3%) and target vessel revascularization (8.1%) were modest in this patient population. Interestingly, diabetes did not increase MACE risk. The investigators projected total possible cost offset/savings of $4,913 at 1 year.

It is timely that use of the atherectomy device should be revisited, as this is the first prospective atherectomy study in more than 20 years. The taste left in the mouths of most of us from previous atherectomy studies is that atherectomy devices are difficult to use, and although they may be associated with acute gain, they are often associated with late loss. The ORBIT II trial provides a viable FDA-approved option for such lesions, but it was not designed to look at acute and chronic effects on vessel size. The main limitation of this trial is the lack of a comparator arm. Therefore, it is difficult to put in context this high 2-year MACE rate of 20%.

There is a feasible, easy-to-use device that is FDA approved and has been shown to facilitate and enable stent implantation with impressive procedural success. However, the jury is still out as to whether you are lessening your patients’ chance of coming back for revascularization or a cardiac event.

TRIALS OF PRASUGREL

Dehghani: Efficacy is established in randomized clinical trials. Effectiveness, however, is established in registry and/or nonrandomized observational data. The PROMETHEUS and TRIAGE studies, both presented as late-breaking clinical trials, were attempts to establish effectiveness of prasugrel (Effient, Daiichi Sankyo/Eli Lilly).

For the PROMETHEUS study, Usman Baber, MD, MS, and colleagues retrospectively characterized a cohort of nonrandomized ACS patients taking prasugrel and then compared their 90-day MACE rates vs. patients who were taking clopidogrel. The study was performed at eight U.S. academic medical centers. The researchers found the following: (1) only one in five patients were assigned prasugrel (total cohort = 19,914); (2) the prasugrel group was a much lower-risk group than the clopidogrel group, with less diabetes, chronic kidney disease and MI; and (3) the primary endpoint of adjusted MACE at 90 days from PCI was not significantly different between the two treatment groups.

The TRIAGE study, presented by Jaya Chandrasekhar, MBBS, was a prospective trial designed to compare outcomes in patients treated with prasugrel vs. clopidogrel at the time of PCI following determination of platelet reactivity in conjunction with clinical risks. By extension, a more important question was whether higher-risk patients assigned prasugrel would have a lower primary endpoint of MACE at 1 year. The findings presented here were notable because: (1) recruitment was terminated at 318 patients due to slow enrollment (originally designed to enroll 1,000 patients); (2) by protocol, prasugrel was assigned to only 28% of the study population; and (3) MACE at 1 year was not significantly different in the two treatment groups.

Based on these study findings, what we should not derive is that prasugrel is less effective than clopidogrel in patients with ACS. Both studies highlight similar themes. First, the PROMETHEUS study tells us that we may be scared to start patients on prasugrel in exactly the patients who require it the most. Could it be that the reported excess bleeding as consciously, and maybe subconsciously, concerned us to such a degree that we are “cherry picking” patients? Therefore, to justify its use, we come up with complex algorithmic approach, as in the TRIAGE study, as to who should be on prasugrel. Lack of recruitment of the right number of patients again highlights our attitudes about committing patients to prasugrel. As the late-breaking clinical trial session panelists Roxana Mehran, MD, Cardiology Today’s Intervention associate medical editor, and Matthew Price, MD, Cardiology Today’s Intervention editorial board member,discussed, the bigger question we should ask is why have the novel antiplatelet agents not penetrated the U.S. market? Second, it is difficult, despite complex propensity scoring systems, to derive meaningful conclusions regarding MACE rates when the two arms are so different (as in the PROMETHEUS study), or when they come up so short in meeting their sample size (as in the TRIAGE study).

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However, a silver-lining finding from both of these studies is that bleeding was not increased with prasugrel, suggesting that our fear may not be warranted. This finding is particularly notable as there was a signal, although not statistically significant, that adjusted MACE rates were favoring prasugrel from both studies. Perhaps the TRIAGE study would have demonstrated superior effectiveness in the prasugrel group if the study investigators could have completed the study. I agree that we cannot make any conclusions from studies with negative primary endpoints or inadequate power. However, the investigators should be congratulated for attempting to characterize and find the right niche for patients taking prasugrel, a medication proven to be efficacious and still looking to establish its effectiveness.

ANTIPLATELET THERAPY IN AD HOC SETTING

Dehghani: It was previously established in the PLATO trial that ticagrelor (Brilinta, AstraZeneca) is superior to clopidogrel in patients with ACS who were pretreated with a loading dose. But one question is whether we can extrapolate, as we often do in clinical practice, this finding to troponin-negative patients with an unstable pattern of chest pain. More than half of all elective PCI procedures in North America are done on an ad hoc basis immediately after angiography. As common as this scenario is, there is little evidence that ticagrelor is as good as clopidogrel for ad hoc PCI in low-risk, troponin-negative patients with ACS.

At SCAI 2015, we heard the presentation of pharmacodynamics data showing that in troponin-negative patients with unstable angina platelet reactivity as measured by VerifyNow decreases to a greater extent at 2 hours after a 180-mg loading dose of ticagrelor compared with a 600-mg loading dose of clopidogrel. Dr. Mehran and fellow investigators randomly assigned 100 patients at 15 U.S. centers to ticagrelor or clopidogrel in the ad hoc PCI scenario. The percentage of high on-treatment P2Y12 reactivity units was significantly less common in the ticagrelor group at 2 hours compared with the clopidogrel group (13% vs. 78%).

Payam Dehghani

What we need to be reminded of, however, is that although this trend was the correct way, ticagrelor did not kick in until the first 30 minutes of PCI, a period which arguably is the most important time for reducing periprocedural MI. Am I asking too much from an orally administered drug? Likely, yes. Measured in another way, however, by the end of the PCI procedure (shortly after 30 minutes), there was already statistical significant in improved platelet inhibition with ticagrelor compared with clopidogrel.

Although we now have pharmacodynamic confirmation that ticagrelor is superior to clopidogrel in troponin-negative, low-risk ACS, ad-hoc PCI patients, can we prove there is clinical superiority in this patient population? This trial was not powered to answer that question, but sets of the biologic rationale for clinical efficacy in this setting.

MILLION

Dehghani: The answer to the question of whether combining intensive LDL reduction (< 70 mg/dL) with aggressive BP reduction (< 120 mm Hg/70 mm Hg) reduces plaque volume as measured by IVUS in nonculprit plaques of Japanese patients undergoing PCI is yes — a 9% reduction, to be exact, in volume plaque after 18 to 24 months of therapy. However, this 9% reduction in plaque volume was also achieved in patients with moderate LDL reduction (< 100 mg/dL) and standard BP reduction (< 140 mm Hg/90 mm Hg). These different targets were achieved with different doses of amlodipine and atorvastatin in standard and aggressive regimens (mean, 4.9 mg vs. 6.4 mg in amlodipine arm and 6.3 mg vs. 14.1 mg in atorvastatin arm, respectively). As both standard and aggressive therapies led to similar reduction in plaque volume, the MILLION study, conducted by Masa-aki Kawashiri, MD, and colleagues did not meet its primary endpoint. It is conceivable that a larger sample size (the current sample size was only 97 patients) and a longer follow-up may have shown a difference. However, the more important question, not addressed by this study, is whether there was a change in plaque composition. The pendulum has now swung toward understanding fibrous cap thickness and amount of lipid core.

Although this trial did not meet its primary endpoint, it is still highly instructive for reminding our patients that current guideline-driven targets lead to close to 10% reduction in plaque volume.

Disclosures: Dehghani reports receiving research grants from AstraZeneca. Schussler reports no relevant financial disclosures.