The American Journal of Managed Care® interviewed Ashish Pershad, MD, an interventional cardiologist at Banner–University Medicine Heart Institute, on findings of the PARTNER 3 low-risk randomized trial, SPYRAL-HTN OFF MED pivotal trial, and ISCHEMIA and ISCHEMIA-CKD trials. These studies are part of the 2020 American College of Cardiology / World Congress of Cardiology Virtual Experience.
The American Journal of Managed Care® (AJMC® ) interviewed Ashish Pershad, MD, an interventional cardiologist at Banner University Medicine Heart Institute, on 2 late breaking clinical trials titled, “Two-year Clinical And Echocardiographic Outcomes From The Partner 3 Low-risk Randomized Trial,” and “Catheter-based Renal Denervation In The Absence Of Antihypertensive Medications: Primary Results From The Spyral Htn-off Med Pivotal Trial,” as well as a featured clinical study titled, “Clinical And Quality Of Life Outcomes With Invasive Versus Conservative Strategy In Patients With Stable Ischemic Heart Disease Across The Spectrum Of Baseline Kidney Function: Insights From The ISCHEMIA And ISCHEMIA-CKD Trials.”
The trial findings were released through the American College of Cardiology (ACC) and World Congress of Cardiology (WCC) Annual Meeting—ACC.20/WCC Virtual Experience.
AJMC®: When treating patients with stable ischemic heart disease (SIHD), can you discuss what factors are considered when deciding whether to take either a conservative (CON) or invasive (INV) management approach?
Pershad: I think the fundamental precept that we need to understand in SIHD is that any interventional approach whether it be with surgery or with angioplasty and stenting, it does not prolong life in the vast majority of patients, except in a very small subset; but what it does do is it tremendously improves a patient's quality of life.
So, to circle back patients with the most symptoms, either angina or dyspnea combined with moderate to severe ischemia on some sort of functional test, would be the ones that would derive the most benefit from angioplasty and stenting or bypass versus conservative therapy with drugs.
AJMC®: Results examining data from the ISCHEMIA and ISCHEMIA-CKD trials indicated that there was no difference in INV vs CON for the primary or major secondary outcomes, however a significant and durable benefit was exhibited for INV in improving angina related quality-of-life (QOL). What should cardiologists and patients take away from these findings and do you see further research being warranted to compare these management approaches?
Pershad: Yeah, for me, the bigger takeaway from ISCHEMIA-CKD was that patients with CKD 3, 4, and 5—in other words, patients with kidney dysfunction have an incredibly high 3-year rate of death and MI [myocardial infarction]–almost approaches 40% of patients while on dialysis. That is a dramatic finding. We kind of suspected that, but this is really 1 of the first trials that has included a substantial number of patients with significant renal impairment. So that to me is eye opening.
The other thing was that there isn't any heterogeneity of effect in patients across the spectrum—in other words, this is in line with the original ISCHEMIA group in terms of the QOL benefit that's derived across this entire spectrum. However, we do know that QOL effect is attenuated to some degree in patients who have minor symptoms and advanced CKD because they have so many other medical issues that come to the forefront where their QOL impairment just from the angina doesn't seem to impact them as negatively as it would if they did not have CKD.
The other big story of the study is that you have a penalty to pay for an invasive strategy that's not insignificant—the procedural MI rates, stroke rates, and even massive bleeding risk, but that is only partially offset by a third reduction or 32% less likelihood of having a spontaneous MI over 3 years. So, those to me are the big takeaways from the ISCHEMIA-CKD study.
AJMC®: In the PARTNER 3 study, transcatheter aortic valve replacement (TAVR) proved equivalent to surgery at 2 years among low surgical risk aortic stenosis patients, which reduced the initial optimism that TAVR may have proved more beneficial based on 1-year data. What does this finding mean for physicians who are counseling patients on the risk and benefit of both options?
Pershad: I think the decision making for patients who are younger or low risk patients with aortic stenosis needs to be individualized, and this personalization has to take into account the projected life expectancy of the patient. So, for example, if you have a patient that met PARTNER 3 inclusion and was say over the age of 65, had a tricuspid aortic valve, had no adverse features on the CT scan—he clearly even in the context of equivalency between surgery and TAVR can and probably will choose TAVR over surgery, but what we need to be cautious about is the off-label use of TAVR in low risk patients.
By that I mean, patients who are, for example, under the age of 65, patients who have bicuspid valve, patients to have complex underlying coronary disease, patients who have accompanying aortic pathology, patients on the CT scan who have some severe adverse features that would make TAVR not suitable—for example, LVOT calcification or low lying coronary ostia. All of those things need to be factored into the decision. For that decision to be a good decision. you need a well functioning heart team so that the patients are offered the optimal choice, not just for that instance, but for the life expectancy of that patient.
AJMC®: As researchers continue to look at the efficacy of TAVR and open heart valve replacement surgery over the next decade, what key findings will you be monitoring when deciding what is the optimal therapy choice?
Pershad: I think that the biggest thing that people will look at is durability of both surgical and transcatheter valves, and structural heart deterioration of the valve situation, because I think this has not been systematically evaluated in this way for surgical heart valves. So, information obtained over 10 years for studies like the PARTNER 3 low risk study and the EVOLUT-R low risk study will allow us to determine what the true durability of these valves are, and assess the impact of potential disruptive technology on the surgical side, like anticalcification treatment with some newer available technologies like Resilia, etc, which potentially and theoretically seem to benefit the valve durability by a decade, which then completely changes the treatment paradigm for these patients, because we need to think about what we do over a 30-year period or a 20-year period over a patient's lifespan if he's 65, as opposed to the here now.
The other things we were looking at are pacemaker rates, which obviously still continue to be higher than they are with surgery, and this business of mild paravalvular leak, which we also need to continue to monitor because we don't know the true impact of that over a decade or more when these patients are followed because there's clearly no sub benefit of surgery over TAVR in terms of presence or absence of paravalvular leak.
AJMC®: Can you discuss the significance of the SPYRAL-HTN OFF MED pivotal trial findings? What would renal denervation add to the current standards of treatment for hypertension?
Pershad: I think this is a big deal—this is a very significant study, because I think that patients don't like to take medicine, hypertension is a chronic lifelong condition, and any dent or impact you make in treating hypertension better than we do now, will subsequently pay off in heart failure and stroke rates over a decade later. So, I think if you can prove, which we can't based on the information we have yet, that this type of intervention can be sustained and does significantly drop the blood pressure consistently over that 4 millimeter range in systolic blood pressure or ambulatory blood pressure monitoring and 10 millimeter range of office systolic blood pressure as shown in the study–that I think it would serve as a very useful adjunct to medications because patients will need less medicine for this problem.
AJMC®: Do you see more non-drug treatments being implemented to assist chronic diseases such as hypertension?
Pershad: Yeah, I think it's happening in hypertension, heart failure—all these things there's a big unmet need and a big gap, because we could prescribe medicines to patients until they’re blue in the face, but if patients are not compliant or taking the medications regularly, and it's really hard to take a medicine twice a day for an entire life and be compliant with that more than 90% of the time, because life gets in the way. Sometimes having a non-pharmacological approach to treat a chronic medical condition like hypertension, I think is therefore always going to be attractive.