Welcome Data Show Two Sides of PCI in Patients With Cancer

Patrice Wendling

December 31, 2019

Despite concerns about hypercoagulability in patients with cancer, they did not have more ischemic events after percutaneous coronary intervention (PCI) with newer generation drug-eluting stents, new research shows.

In a propensity-score matched cohort, there was no significant difference in the primary ischemic endpoint ― a device-oriented composite of cardiac death, target vessel myocardial infarction (MI), and target lesion revascularization ― between PCI patients with and those without cancer at 1 year (11.5% vs 10.2%; P = .181).

Rates of stroke were also similar between the two groups (2.1% vs 1.3%; P = .097).

On the other hand, patients with cancer had higher rates of bleeding and cardiac death, particularly in the first year after cancer diagnosis.

"There is a higher bleeding risk and this needs to be addressed but, yes, we can treat cancer patients," senior author Lorenz Räber, MD, PhD, Bern University Hospital, Switzerland, told theheart.org | Medscape Cardiology. "We should not be reluctant to accept them for PCI in case of acute coronary syndromes or in case of stable CAD with uncontrollable angina. This is the message."

A growing number of patients with cancer are undergoing PCI. However, previous studies have shown inconsistent results because of small cohorts, lack of detailed information on cancer characteristics, and a limited number of endpoints to estimate ischemic and bleeding risk, he noted.

"This is a single-center investigation, and it's purely observational, but I think the key benefit is the high granularity of the data," Räber said. "We know everything about cancer type, duration of treatment, et cetera."

The investigators studied 13,647 consecutive patients prospectively enrolled in the Bern PCI Registry between 2009 and 2017. Of these, 1368 had an established diagnosis of cancer. The four most common cancers were prostate (21.5%), gastrointestinal tract (13.7%), hematopoietic (12.9%), and breast (12.6%).

At index PCI, 179 patients were being actively treated for cancer, and 121 had metastatic cancer. Surgery was performed in 70.1% of patients; chemotherapy, hormone therapy, or biologic therapy was administerd in 38.5%; and radiotherapy was used in 33.4%.

After propensity score–matching, there were 1343 pairs in the study, which was published online December 17 in JACC: CardioOncology.

Excess Risk

In matched analyses, patients with cancer had higher 1-year event rates of the following:

  • BARC 2 to 5 bleeding: 8.0% vs 6.0%; P = .005

  • all-cause death: 12.6% vs 6.8%; P < .001

  • cardiac death: 6.8% vs 4.5%; P = .004

  • unclear death: 2.7% vs 1.5%; P = .015

  • noncardiovascular death: 5.2% vs 1.7%; P < .001

The increased risk for cardiac death and BARC 2 to 5 in cancer patients was still observed after considering noncardiac death and all-cause death, respectively, as a competing risk.

In multivariable Cox regression, cancer diagnosis within 1 year was an independent predictor for both cardiac death (adjusted hazard ratio [HR], 1.92; 95% confidence interval [CI], 1.10 – 3.36) and BARC 2 to 5 (adjusted HR, 1.75; 95% CI, 1.03 – 2.98).

Possible explanations for the excess risk in cardiac death are that anticancer treatments are typically ongoing in the first year and can lead to surgery, interruption of dual antiplatelet therapy (DAPT), or endothelial damage, cardiovascular toxicity, and cardiac events, Räber suggested.

"Of course, post-PCI bleeding is known to be associated with increased mortality to a much greater degree than post-discharge myocardial infarction. So that could be another risk factor," he said.

Patients with cancer also had a higher risk for unclear death, "and whether it is cardiac or not, by definition, you categorize those as cardiac death."

Although cancer in the previous 12 months is acknowledged as a major criterion for high bleeding risk during PCI in a recent international consensus document, current guideline-endorsed bleeding risk scores do not include cancer, Räber noted.

The C-statistic of the PRECISE-DAPT score was numerically lower among cancer patients than those without cancer in the overall cohort and the propensity matched cohort, despite the higher incidence of bleeding among patients with cancer.

Notably, the adjusted risk for BARC 2 to 5 bleeding and cardiac death was also slightly higher in patients diagnosed with cancer at least 5 years earlier (HR, 1.41 and 1.71, respectively; P = .014). This is not as easy to explain but may be related to the long-term effects of radiation, "because it usually takes 10 to 15 years before long-term cardiac damage of radiation comes into play," Räber hypothesized.

Still, the overall excess risk in cardiac death is consistent with a recent population-based study in which cancer patients had on average 2 to 6 times higher CVD mortality risk than the general population, he said.

The investigators note that the lack of ischemic event risk may be partly attributable to a lack of power, but Räber also pointed out that most newer-generation drug-eluting stents, used in nearly 90% of all patients, have a low thrombogenic potential and that more than 90% of patients received DAPT at discharge.

"The next step is to focus on the excess in bleeding, and we need dedicated trials for that," he said. "The question is, can we shorten DAPT duration, particularly in cancer patients, without increasing the risk of ischemia?"

Time to Focus on Cancer Patients

Given that 10% of PCI patients have cancer, "I think it’s high time now to start focusing on these patients, which are no longer a minority," Räber said. "That's important to note and why I'm grateful this new journal has been brought up, because it raises our awareness."

Commenting to theheart.org | Medscape Cardiology, Jay Giri, MD, MPH, Hospital of the University of Pennsylvania, Philadelphia, said, "First of all, we should be studying these patient more aggressively. But also maybe our hangups about ischemic events are a little bit overblown and the bleeding is really the issue in these patients and that's what's really going to tip the scale into them having bad outcomes."

In a linked editorial, Giri and Ashwin S. Nathan, MD, MSHP, also with the Hospital of the University of Pennsylvania, write that although stents may perform well in patients with cancer, it is "paramount to identify strategies to modify bleeding risk in this high-risk population."

They suggest reducing the use of potent P2Y12 inhibitors (prasugrel or ticagrelor) in favor of clopidogrel and minimizing the use of triple antithrombotic therapy. In the study, patients with cancer were less likely to be receiving potent P2Y12 inhibitors at discharge (30.6% vs 41.6%), although triple therapy was more frequent (12.3% vs 8.2%; both P < .001).

Data have emerged that the combination of just one antiplatelet, usually clopidogrel, with a direct oral anticoagulant (DOAC) dramatically reduces bleeding compared to triple antithrombotic therapy, Giri said.

"Although cancer patients were not adequately represented in the studies, with all these signals of increased bleeding in cancer patients, it makes me think we should be thinking more carefully about utilization of that type of dual strategy as opposed to the triple antithrombotic therapy, which seems to be used a little more frequently in them," he said.

Research in patients with cancer is also needed on DAPT duration post PCI, with recent trials such as EVOLVE Short DAPT and TWILIGHT providing support for cutting back on DAPT duration and intensity.

Asked how short a DAPT he'd use, Giri replied, "In a nonacute coronary syndrome patient, a stable angina patient, I think I'd tend to be in that 3-month [range] in this population, based on what I'm seeing. But I probably wouldn't criticize somebody who did drop it all the way to 1 month."

Patients with cancer may also represent an attractive population to tailor antiplatelet therapy using genotyping for clopidogrel resistance, Giri said. A recent trial showed the safety of deescalating antiplatelet therapy in a broad group of patients with ST-segment elevation when normal clopidogrel metabolism was confirmed with CYP2C19 genotyping.

"From the standpoint of how I look at this for my practice and will it change how I view some of these patients, it says two things to me," Giri said. "It says that if there's an acute coronary syndrome going on, I think that it's rational to approach these patients from a similar way from a stent perspective that we do other patients. We should treat their acute coronary syndromes with catheterization and/or PCI, when necessary, and in some selected patients who have very significant life-limiting angina, it may be appropriate to also utilize that type of strategy.

"But on the back end, let's also think very carefully about limiting bleeding risk through our careful and judicious prescription and selection of antithrombotic therapies," he added, "and maybe not think that the balance in these patients is one that favors longer and more intensive antithrombotic regimens because it doesn't look like that’s what the data is showing us."

Räber has received 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. Coauthor disclosures are listed in the original article. Giri has served on advisory boards for AstraZeneca and Phillips Medical; and received research support to his institution from St. Jude Medical, and Recor Medical for serving as site principal investigator of trials evaluating transcatheter aortic valve replacement and renal denervation. Nathan has disclosed no relevant financial relationships.

J Am Coll Cardiol CardioOnc. Published online December 17, 2019. Full text, Editorial

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