Interventional News in Review: and the Winners are…
There was a lot of news in interventional cardiology in 2016, and CardioSource WorldNews Interventions (now reborn with this edition as Cardiology: Interventions) covered it all. Kudos go out to all the writers, reporters, interviewers, proofreaders, and especially all the people who actually put it all together to make it happen.
Looking back at what we covered raises the obvious question: “With all the trials, reports, stories, etc. that made interventional cardiology news in 2016, which really made a difference?” An easy answer is that each of them, even those with negative outcomes, added to our factual database. Some made big headlines; others seemed under the radar.
PARTNER and SENTINEL
PARTNER 2 put intermediate-risk patients squarely into the transcatheter aortic valve replacement (TAVR) sights, and I suspect, like in Europe, interventionalists and their patients will opt for TAVR over surgery in ever increasing numbers for ever decreasing risk groups.
Interestingly, some trials did not give us the answers we wanted, or hoped for. SENTINEL is an example. Though embolic debris was collected in an astonishingly high percentage in the cerebral protection arm of patients undergoing TAVR, clinical outcomes were surprisingly similar to “unprotected” patients. Should we disregard the use of cerebral protection for TAVR patients? I doubt that will happen. Short term there may be no difference, but it is hard to imagine that embolic debris does not wreak some havoc in the brain, and longer-term outcomes may well tell us the real story. I cannot imagine that cerebral embolic protection is useless, and wonder how we can best prove that what we guess is correct, actually is. I await the longer-term outcomes, but these may never appear as trials simply cannot effectively follow patients for decades. Hopefully calmer heads and other trials will prevail.
EXCEL and NOBLE
EXCEL and NOBLE produced more controversy, and came to slightly differing conclusions regarding PCI versus CABG for left main disease. The differences lay in the shorter-term outcomes reported in EXCEL and other possibly confounding factors between the two trials. The pros and cons of each trial have been dissected multiple times in the past months, but there is actually further news on the topic. In a meta-analysis published online in Circulation: Cardiovascular Interventions, EXCEL, NOBLE, PRECOMBAT, SYNTAX and a German randomized trial from 2011 were studied. There was no significant difference in the endpoints of all-cause mortality, myocardial infarction, or stroke between PCI and surgery. Not surprisingly, when repeat revascularization was added to the endpoints, CABG patients had fewer outcomes (odds ratio 1.85). The good news is that PCI for left main disease appears to be “not harmful,” and therefore is an option. But the PCI option carries with it an important, repetitive bit of data from almost all the left main trials – the risk of needing a repeat revascularization is greater with the PCI option. Not all patients with left main disease should automatically go to PCI and the possibility of needing “another quick stent” in the future may not be so appealing to younger patients with low CABG risk. We also know that a patent left internal mammary artery to left anterior descending artery is a great ally for patients with proximal left anterior descending disease. Will the guidelines be changed in favor of, or include, PCI? I suspect they will, but cautiously.
RESPECT and PIONEER AF-PCI
In my view, the 10-year outcomes of the RESPECT trial and the PIONEER AF-PCI trial were the real game-changers. RESPECT finally showed us that long-term outcomes after patent foramen ovale (PFO) closure are superior, even in an intention-to-treat analysis, to “standard” therapy. PFO closure will return to the catheterization lab as a useful and proven intervention. A closure device, now Food and Drug Administration approved, will return to the shelves. The mandate that neurologists and cardiologists should advise for patients being considered for PFO closure is a welcome extension to the heart team concept.
Whereas PFO closure will not be done every day, patients in atrial fibrillation (AFib) who need a PCI will be an almost daily occurrence. We have struggled for years with how to best treat patients with AFib post stent. Triple therapy using warfarin and dual antiplatelets has been tricky at best because of bleeding risk. PIONEER AF-PCI changed all that. Two anticoagulation strategies using rivaroxaban significantly reduced bleeding risk over warfarin use. In short, patients in AFib with low bleeding risk (and a higher ischemic risk after stenting, such as a left main stent) can be treated with very low-dose rivaroxaban (2.5 mg/day) plus dual antiplatelet therapy. Patients (a majority undergoing PCI) with higher risk of bleeding and low ischemic risk can have low-dose rivaroxaban (15 mg/day) plus a P2Y12 inhibitor and no aspirin. The rules have indeed changed.
GAUSS 3 and GLAGOV
That leaves two “medical” trials for interventionalists to take heed of: GAUSS 3 and GLAGOV. GAUSS 3 showed us that the PCSK9 inhibitor evolocumab can dramatically lower LDL cholesterol in statin intolerant patients – the first sign that PCSK9 inhibition might be the next giant step forward in risk reduction for atherosclerotic disease. The question is, does an LDL in the 30 to 50 mg/dl range really make a difference? GLAGOV measured coronary plaque volume with intravascular ultrasound and found that atheroma volume increased 0.05 percent in the placebo group and decreased 0.95 percent in the evolocumab group. That translates into a 5.8 mm3 reduction in atheroma volume after PCSK9 treatment. Perhaps that does not sound like much – but here are two thoughts:
First, resistance to blood flow in a coronary artery is dependent on radius, length and viscosity. The equations for resistance to blood flow have radius in the denominator, and resistance is dependent on the fourth power of the coronary radius. Even a small decrease in radius increases coronary resistance by a lot (e.g., a 50 percent reduction in radius increases resistance by 16-fold). Translating that into flow, the short version is that the equations for flow now have radius (to the fourth power) in the numerator. Flow depends directly on the fourth power of the radius. Even a small increase in coronary radius can make a big difference in coronary flow. That is why POBA (plain old balloon angioplasty) works – the plaque is split open by the balloon and the radius for blood flow is increased enough to relieve ischemia. Stents, of course, do a more thorough job because they greatly increase coronary radius at the site of previous obstruction. So… even an apparently small reduction in atheroma volume induced by PCSK9 inhibition can make a big difference in flow.
Second, what can be surmised, but not yet proven, is that plaque reduction also has physiological consequences. It is possible that PCSK9-induced plaque reduction is accompanied by enough intra-plaque physio-biochemical changes to stabilize an otherwise unstable situation. Plaque stability increases, and the chances for ischemia are reduced.
One might say that interventionalists should not worry about such things – they are outside our interests. Not really. PCSK9 inhibitors hold huge promise for the reduction of coronary atherosclerosis (and possibly atherosclerotic disease in general). I have said to many trainees that if we do our jobs correctly, we will put ourselves out of work. That is a noble goal. Not for tomorrow, perhaps, but stay tuned.
Peter C. Block, MD, FACC is a professor of medicine and cardiology at Emory University Hospital and School of Medicine in Atlanta, GA.
Keywords: ACC Publications, Cardiology Interventions, Brain, Databases, Factual, Europe, Intracranial Embolism, Pyrrolidinones, Transcatheter Aortic Valve Replacement
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