The Cancer Patient Needing PCI Poses Conundrums for Care
Randomized trials are sorely lacking and bleeding remains a concern, but new data reassure on stent safety in cancer.
More and more people with cancer also have an indication for PCI, posing a dilemma for cardiologists uncertain of revascularization’s risks and benefits in this group. In recent months, however, a flurry of new research has shed light on these questions, providing some reassurance that stents do not pose additional risks but also reminding clinicians that bleeding is a significant concern, especially with certain cancer types.
Cancer patients have typically been excluded from PCI studies, particularly patients undergoing active cancer treatments or requiring surgery. As a result, the risk-benefit trade-offs with PCI and the need for protracted dual antiplatelet therapy (DAPT) are considerations that interventionalists grapple with on a daily basis. In 2016, the Society for Cardiovascular Angiography and Interventions (SCAI) in collaboration with several other national groups published an expert consensus document that includes advice on interventional procedures in patients with concomitant cancer and CVD. But research has been slow to fill the voids identified in that document.
“There's not a huge amount of data out there,” said Mamas Mamas, BMBCh, DPhil (Keele University, Stoke-on-Trent, England), who led a recent analysis published in the European Heart Journal. “In the past people have looked at the cohorts who have a diagnosis of cancer and have not thought about the fact that these patients may have very different outcomes depending on the type of cancer or the stage of cancer. We know that patients with cancer have adverse outcomes [following ACS], but there's not really a huge amount of information as to how to treat these patients.”
“Cancer patients are a very specific population and they require, by definition, a very individualized approach,” agreed Lorenz Räber, MD, PhD (Bern University Hospital, Switzerland), senior author on a paper published last month in JACC: CardioOncology. “They are completely understudied—I’m not aware of a single randomized controlled trial that has actually investigated all these questions, despite the relatively high frequency of these patients.”
There is a growing cancer population and there is a growing population of cancer survivors, and they are all coming into each and every one of our clinics. Bonnie Ky
The lack of data coupled with a burgeoning population of cancer survivors and the fast pace of drug development in oncology—such that new cardiac side effects are regularly coming to light—all help explain the exploding interest in cardio-oncology research and specialized care. But even clinicians with no interest in dedicated training or research in this field need answers, noted Bonnie Ky, MD (Hospital of the University of Pennsylvania, Philadelphia), editor of JACC: CardioOncology. The quarterly, open-access journal published its first issue online in September 2019.
“Cardio-oncology is applicable to everyone,” Ky told TCTMD. “There is a growing cancer population and there is a growing population of cancer survivors, and they are all coming into each and every one of our clinics. So, although physicians may not be clinically specializing in the field, everyone needs to know something about it.”
A Growing Problem
Recent numbers hammer home the fact that CVD is, in many cases, the number one killer of cancer patients. According to a report published in the December 2019 issue of EHJ, of the more than 3.2 million cancer patients included in the United States Surveillance, Epidemiology, and End Results (SEER) database over a 40-year period, fully one in 10 died of cardiovascular disease. The analysis, led by Kathleen Sturgeon, MD (Penn State College of Medicine, Hershey, PA), also notes that the risk of CVD was higher for certain cancers than others. Among patients with breast, prostate, endometrial, and thyroid cancer in SEER, half died from cardiovascular disease. By contrast, the most aggressive cancers—including lung, brain, stomach, gallbladder, among others—were more likely to be the cause of death for patients with these diseases.
At the heart of the matter, many people have preconceived ideas—myself included before this study—about how these patients will do. Mamas Mamas
As more cancer patients survive longer, the rate of cardiovascular deaths will continue to increase, the authors point out. “We hope these findings will increase awareness in patients, primary care physicians, oncologists, and cardiologists as to the risk of cardiovascular disease among cancer patients and the need for earlier, more aggressive, and better-coordinated cardiovascular care,” Sturgeon said in a press statement.
Just how aggressive to be is a question many cardiologists struggle with on a daily basis and was in part the motivation behind two additional papers published last month.
In Räber et al’s paper, which reviewed 1-year outcomes among all consecutive patients undergoing PCI in the Bern PCI Registry between 2009 and 2017, one in 10 patients had an established diagnosis of cancer and 13% of this subset were undergoing active cancer treatment at the time of their PCI. After matching patients with and without a cancer diagnosis, Räber and colleagues, with lead author Yasushi Ueki, MD (Bern University Hospital), found no difference in a composite endpoint of device-related events, and no differences in stent thrombosis, myocardial infarction, or target lesion revascularization. However, overall deaths, cardiac death, and BARC 2 to 5 bleeding each were higher in cancer patients. Of note, those risks differed according to the time since cancer diagnosis. In patients with a recent cancer diagnosis (1 year or less), the risks of cardiac death and bleeding were significantly increased, whereas no significantly increased risk was seen for either endpoint for patients whose diagnosis was 1-5 years or more than 5 years prior.
The second study by Mamas and colleagues, led by Aditya Bharadwaj, MD (Loma Linda University, CA), Jessica Potts, PhD (Keele University), and Mohamed O. Mohamed, MD (Keele University), looked at in-hospital outcomes among more than 6.5 million acute MI patients included in the United States National Inpatient Sample (NIS) between 2004 and 2014. During this time, 186,605 patients presenting with acute MI had current cancer, while 409,697 had a history of cancer. Diagnosis of STEMI or NSTEMI, additional comorbidities, as well as the different cancer diagnoses were inferred from ICD-9-CM codes in the NIS database.
Among the cancer patients, just 21% underwent PCI, as compared with 44% of patients without the disease. Cancer patients as a whole had higher rates of in-hospital mortality and major adverse cardiovascular and cerebrovascular events (MACCE). Medically managed patients, however, had higher in-hospital mortality across the four major cancer types (prostate, breast, colon, and lung) as compared with patients managed invasively. Of note, outcomes varied considerably according to the type of cancer and whether patients had metastatic disease. For example, lung cancer patients had the highest rates of in-hospital mortality, MACCE, and stroke, while colon cancer patients had more bleeding. Across the board, metastatic cancer was associated with worse in-hospital outcomes.
At least in this retrospective analysis, said Mamas, “the prognosis of patients with cancer who have a PCI is much, much better than those that are medically managed. And whilst there probably is a degree of selection bias, this points to the fact that we should be managing these patients more invasively because what we're showing here is that patients are less likely to get invasive management and those that do, do better.”
To TCTMD, both Mamas and Räber acknowledged that the low rates of intervention in cancer patients speak partly to the uncertainty cardiologists feel about the risks of cardiovascular interventions and their relative importance, particularly alongside a current cancer diagnosis.
“I think there is a bit of a kid-glove approach,” Mamas said, noting that it was his own misgivings about intervening in a patient with breast cancer and ACS that motivated him to delve deeper.
“We all know that patients with cancer have cardiovascular risk factors that portend worse outcomes. They are much more likely to have anemia, they are much more likely to have thrombocytopenia, they have a greater propensity to bleed, etc,” he explained, adding, “But at the heart of the matter, many people have preconceived ideas—myself included before this study—about how these patients will do. And even though our interventional practice has advanced, we can use radial, we can use regimes with shorter DAPT durations and better platforms and more intravascular imaging tools to reduce the risk of stent thrombosis, I think as interventional cardiologists we really have perhaps a mistaken view about what the prognosis is for these patients, particularly in the short term, and hence why we’re seeing more conservative strategies.”
Räber, too, said his own uncertainty was a key reason for analyzing patients in the Bern registry, saying that most physicians, himself among them, have been acting on “gut feelings” given the lack of data. But while prospective trials are badly needed, gut feelings are not necessarily a bad thing, he continued. These cases “always need an individualized decision: a gut feeling means that you consult your experience as an MD.”
Jay Giri, MD (University of Pennsylvania, Philadelphia), who co-authored an editorial accompanying Räber et al’s paper titled “The pros and cons of PCI in patients with cancer,” says that given the many unknowns, the recent research will have an impact on his practice.
“When I see a cancer patient with ACS or acute MI, which is certainly a clinical scenario we run into, I’ll be more inclined to take that patient for a diagnostic angiogram and more inclined to treat them as I would treat a patient without cancer from the standpoint of stent performance,” Giri told TCTMD. “The approach is always ‘first do no harm,’ and now I know I'm not harming them with a stent in this complex medical situation that we're in.”
The approach is always ‘first do no harm,’ and now I know I'm not harming them with a stent in this complex medical situation that we're in. Jay Giri
But of course, Giri continued, “there is a price to pay,” a point made clear by both the EHJ and JACC: CardioOncology papers. “The real specific risk to [patients] in this scenario does not appear to be stent thrombosis or ischemic complications: the real risk is bleeding. That comes out loud and clear,” Giri said.
Given the higher risk of bleeding, all of the physicians who spoke with TCTMD emphasized the need to tailor dual antiplatelet regimens. “I’m somewhat less concerned about ischemic complications, so I would not be hesitant to treat the patient with acute myocardial infarction and cancer,” said Räber. “But I would consider tailoring DAPT intensity and duration in cancer patients because of the excess in bleeding. Those patients may benefit from shorter and less intensive DAPT and downgrading from a potent to a less potent P2Y12 inhibitor potentially makes sense.” Moreover, platelet function or genetic tests may have particular value in this setting, he added.
For patients who also have an indication for an anticoagulant—not an uncommon occurrence in cancer patients—it might be especially prudent to consider avoiding triple therapy in these patients and instead “sticking with a DOAC plus a single antiplatelet,” Giri suggested.
Individualized Care and Physician Assumptions
Ky, too, stressed the importance of individualizing patient care, taking into account not only clinical criteria and emerging knowledge but also patient preferences. Cardiologists may feel daunted by the vagaries of cancer care and the uncertainties around patient prognosis, she advised, but in addition to educating themselves using emerging data and guidance, they shouldn’t assume that a patient doesn’t want to “deal” with treating their cardiovascular disease aggressively.
“I've had some patients for whom it is overload,” Ky said. “They have cancer, they’re going under treatment, and then now what? They have this, too?” She continued: “I try to be sensitive to not overwhelming patients because if I was in their position, I’d feel pretty darn overwhelmed with everything that was going on.”
But assuming that a patient might feel overwhelmed is not the appropriate approach, she stressed. Some patients after surviving cancer “want to know everything they can about their health” and keep on top of it. Knowing how to tease apart which patients want to be aggressive about their cardiovascular care versus those who feel the dual diagnosis is too much, all at once, means listening to patients.
Last fall, the American College of Cardiology convened a forum inviting 20 patients with cancer and cardiovascular disease to answer questions and engage in discussion about their concerns and priorities. The outcomes were not necessarily as expected, Ky said. Patients provided a wide range of responses, with some wanting intensive management of their cardiovascular disease and others less so. The upcoming (third) issue of JACC: CardioOncology, she noted, will include a first-person perspective by someone who survived cancer only to now be facing a diagnosis of cardiovascular disease.
Räber hypothesized that most cancer patients are only being sent for cath and PCI if there’s a strong indication such as acute MI or severe uncontrolled angina that drastically limits quality of life. The latter, he pointed out, is a very important consideration for patients after they “reenter normal life” following an intensive cancer regimen.
Improvements in cancer care are a key reason why cardiovascular trials that include cancer patients will become more common, Räber predicted. “I think the growth of the subspecialty of cardio-oncology, together with the new journal [and] educational efforts at congresses—these will all help to raise awareness and by this increasing awareness there will be more trials.”
Given the already substantial burden posed by cancer treatments as well as doctor and hospital visits, Räber said he believes that any trials looking specifically at the question of PCI outcomes in cancer patients will need to be pragmatic by design and “not with extended follow-up. Patients want to avoid more contact than what they are already required to have.”
Ky listed numerous trials already underway, some supported by National Institutes of Health, that should provide answers on specific questions in the years to come. But even with new answers, she cautioned, individualized care will always need to account for patient prognosis, the type of care the person received, and the type and grade of cancer.
This applies not only to PCI but to other interventional procedures as well. Ky recently had a 91-year-old patient with metastatic renal cell cancer who’d been treated with an antiangiogenic tyrosine kinase inhibitor, which can cause or exacerbate hypertension and heart failure; this particular patient was taking medications for both.
“One day he was admitted to hospital with shortness of breath and heart failure. He had a known history of aortic stenosis, but it had progressed and was now severe, and we struggled with the decision of TAVR versus no TAVR and how to balance that with his heart medications and his cancer medications, because they had these toxicities that could exacerbate his heart failure,” Ky said. “In the end we decided to manage him medically, and we decided not to TAVR him because his metastatic lesions were growing larger in size.”
Situations like this “give everyone some pause,” she added. It’s always a case-by-case decision, never easy, and doctors “always wonder” afterward whether they made the right call.
Mamas and colleagues currently have research in progress trying to look at life expectancy following a cancer diagnosis and what the excess mortality risk might be from an acute MI perspective with or without intervention. For the PCI setting, he stressed the importance of teasing out the balance between ischemic and bleeding complications for different cancers.
“I think a lot of the practice today is driven by ignorance, because there hasn’t been granular data in the past,” said Mamas. “Analyses have looked at all cancers together and not thought about the fact that prostate cancer is very different from lung cancer with metastases. People have been treating cancer patients as if one size fits all, which I think is wrong.”
Sturgeon KM, Deng L, Bluethmann SM, et al. A population-based study of cardiovascular disease mortality risk in US cancer patients. Eur Heart J. 2019;40:3889-3897.
Bharadwaj A, Potts J, Mohamed MO, et al. Acute myocardial infarction treatments and outcomes in 6.5 million patients with a current or historical diagnosis of cancer in the USA. Eur Heart J. 2019;Epub ahead of print.
Ueki Y, Vögeli B, Karagiannis A, et al. Ischemia and bleeding in cancer patients undergoing percutaneous coronary intervention. J Am Coll Cardiol CardioOnc. 2019;1:145-155.
Giri J, Nathan AS. The pros and cons of percutaneous coronary intervention in patients with cancer. J Am Coll Cardiol CardioOnc. 2019;1:156-158.
- Mamas and co-authors report having no relevant conflicts of interest.
- Räber reports research grants to his institution from Abbott Vascular, Biotronik, Boston Scientific, HeartFlow, Sanofi, and Regeneron; and speaker fees from Abbott, Amgen, AstraZeneca, Bayer, CSL Behring, Occlutech, and Sanofi.
- Ky reports consulting fees from Bristol-Myers Squibb.
- Sturgeon reports having no relevant conflicts of interest.
- Giri reports having served on advisory boards for AstraZeneca and Phillips Medical and research support to his institution from St. Jude Medical and Recor Medical for serving as site principal investigator of trials evaluating TAVR and renal denervation.