5/17/2021 PCI: Risks and Outcomes in Patients With Cancer - American College of Cardiology

PCI: Risks and Outcomes in Patients With

Cancer
May 24, 2019   |  Wendy Bottinor, MD, FACC; Nirmanmoh Bhatia, MBBS, FACC

Expert Analysis

Case Vignette

A 54-year-old woman with recently diagnosed triple negative breast cancer is

undergoing neoadjuvant therapy with doxorubicin, cyclophosphamide, and
paclitaxel. She develops acute chest pain during her third infusion of paclitaxel.
Her electrocardiogram is notable for 2 mm ST-segment elevations in leads V1-V6.
She is taken emergently for cardiac catheterization, and an acute occlusion of the
proximal left anterior descending artery is revealed. Intravascular ultrasound-
guided percutaneous coronary intervention (PCI) is performed, and an everolimus-
eluting stent is deployed in the proximal left anterior descending artery. She is
treated with aspirin, ticagrelor, and heparin initially, followed by aspirin 81 mg
daily and ticagrelor 90 twice daily for 6 weeks. She subsequently undergoes
successful tumor resection without any complications.

Introduction

The complex relationship between cancer and cardiovascular disease is

increasingly being recognized. Reasons for the link between cancer and
cardiovascular disease include the shared risk factors, such as obesity, diabetes,
hypertension, hyperlipidemia, tobacco use, diet, physical activity, and older age.1
The toxicities of cancer treatment also contribute to this relationship. Several
chemotherapeutic agents have been associated with acute coronary syndromes
(ACS), including antimetabolites (5-fluorouracil, capecitabine, gemcitabine), anti-
microtubule
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tumor antibiotics
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(bortezomib, carfilzomib), vascular endothelial OK growth factor inhibitors
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5/17/2021 PCI: Risks and Outcomes in Patients With Cancer - American College of Cardiology

(bevacizumab, ramucirumab, aflibercept, sunitinib, sorafenib, pazopanib, axitinib,

regorafenib), immunomodulatory drugs (lenalidomide), and BCR-ABL tyrosine
kinase inhibitors (nilotinib, ponatinib) (Table 1).2-6 For some of these agents
(cisplatin, ponatinib, nilotinib, and radiation therapy), the risk for coronary disease
persists even after cessation of therapy.2,7 Cancer generates a pro-inflammatory
and pro-thrombotic milieu. Tumor biology influences this, and advanced-stage
cancers as well as gastric, pancreatic, lung, bladder, testicular, gynecologic, and
lymphomatous cancers are considered to have higher prothrombotic potential.3,8

Table 1: Cancer Therapies Associated With ACS and Potential Mechanisms of

Toxicity2,4-6

Despite the overlap between cancer and cardiovascular disease, data regarding
PCI in patients with cancer are limited. Patients with cancer are generally excluded
from PCI clinical trials and national registries. Available data, however, do indicate
worse outcomes with PCI in patients with cancer compared with those without
cancer.9 What follows is a discussion about the outcomes and risks of PCI in
patients with cancer and potential considerations unique to this patient
population.
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Outcomes of PCI in Patients With Cancer and Cancer Survivors
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5/17/2021 PCI: Risks and Outcomes in Patients With Cancer - American College of Cardiology

As the number of patients with cancer and cancer survivors increases, so does the
frequency of PCI performed in these populations9,10 due to the high prevalence of
cardiovascular disease in this subgroup.11 These patients tend to be older and
have more co-morbidities than non-cancer populations, which may adversely
affect PCI outcomes.9,10 Some shared risk factors between cancer and
cardiovascular disease such as smoking history and diabetes mellitus may also
impact post-PCI outcomes.12,13

In patients who present with ST-segment elevation myocardial infarction, those

with cancer are noted to have worse outcomes in comparison to those without
cancer. This has been partly attributed to the lower utilization of PCI in patients
with cancer.14 However, among patients with cancer who receive PCI, the
incidence of cardiac death is higher at 1 year.15 The lower use of drug-eluting
stents (DES) and glycoprotein IIb/IIIa inhibitors in patients with cancer may
contribute to this outcome. In addition, there is a higher incidence of
cardiovascular comorbidities among patients with cancer.15 A cancer diagnosis
within the 6 months preceding a ST-segment elevation myocardial infarction is
also a risk factor primarily due to higher rates of anemia and cardiogenic shock.15

Type of cancer may also play a critical role. In a recent study comparing outcomes
in the four most common cancers (prostate, breast, colon, and lung), a current
diagnosis of lung cancer was associated with a twofold risk of in-hospital mortality
and any in-hospital complication.9 Colon and prostate cancer were associated with
increased bleeding with PCI but a similar mortality risk to patients without cancer.
Interestingly, a diagnosis of breast cancer was not associated with increased in-
hospital mortality or complications.9 Not surprisingly, patients with metastatic
cancer who undergo PCI have a higher in-hospital mortality and bleeding risk.9

In cancer survivors, rates of mortality and non-fatal myocardial infarction are

higher during long-term follow-up after PCI when compared with patients without
cancer.16 However, because malignancies are heterogenous in terms of their
natural history, prognosis, and adverse systemic effects, their impact on PCI
outcomes are not identical. As such, recent data stratified by cancer type indicated
worse outcomes for survivors of lung cancer but not other common
malignancies. 9 This suggests that each patient with cancer may need a different
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5/17/2021 PCI: Risks and Outcomes in Patients With Cancer - American College of Cardiology

In patients with cancer, the balance of coagulability can be challenging. Cancer

cells can influence the expression of hemostatic proteins, inflammatory cytokines,
proangiogenic factors, procoagulant microparticles, and adhesion molecules,
causing hypercoagulability.8 It is thought that a cyclic relationship exists in which
cancer cells promote thrombosis and clotting proteins support cancer growth.8
Patients with cancer are up to 7 times more likely to experience venous
thromboembolism (VTE), and this is a leading cause of death.17 VTE is most
common in cancers of the brain, pancreas, stomach, liver, lungs, and kidneys and
lymphomas and myeloma.8 In addition, clinical factors such as anemia,
leukocytosis, and thrombocytosis also play a role. Several risk assessment models
have been developed to predict the risk of VTE in patients with cancer.8

Cancer can also lead to an increased risk for bleeding. Bleeding occurs in
approximately 10% of patients with solid tumors and is even more frequent in
patients with hematologic malignancies.8 Gastric cancer, thrombocytopenia, and
high body mass index are identified risk factors for malignancy-related bleeding.18

Interventional Approach in Patients With Cancer and Cancer Survivors

In general, all patients with a current or prior history of cancer should be treated
as a high-risk group while undergoing PCI. It is essential to minimize the adverse
impact of PCI in patients with ongoing cancer therapy, especially when both
malignancy and cancer therapy may predispose the patient to bleeding and
coagulation abnormalities. Minimizing access site complications by using radial or
ulnar artery access instead to femoral artery access is important to reduce
bleeding complications.19 When femoral artery access must be used, safe
practices such as using ultrasound and fluoroscopy to guide access should always
be in place.19

Low platelet count should not preclude PCI in situations of ACS, and a platelet
count of 40,000-50,000/mL may be sufficient to safely perform most interventional
procedures in the absence of associated coagulation abnormalities. In the setting
of extremely low platelet counts (20,000/mL or less), platelet transfusion may be
considered in consultation with the hematologist or oncologist. Withholding
aspirin in thrombocytopenic patients with cancer and ACS has resulted in poorer
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5/17/2021 PCI: Risks and Outcomes in Patients With Cancer - American College of Cardiology

Another consideration is the impact of cancer and cancer therapy on

endothelialization and the risk for stent thrombosis. Circulating endothelial cells
and endothelial progenitor cells may be decreased due to malignancy and cancer
therapy.20 Nevertheless, a recent large study suggested superior outcomes in
patients with cancer who had a DES placed compared with those with a bare-
metal stent (BMS) placed.9 This could represent selection bias, but modern DES
have demonstrated excellent outcomes with relatively short (1-3 months)
durations of dual antiplatelet therapy (DAPT), and certain DES platforms have
shown outcomes superior to BMS with a similar duration of DAPT.21 Whenever
possible, these new-generation DES should be used instead of BMS.

Optimizing PCI is extremely important in this patient population, particularly given

the increased likelihood that shorter duration of DAPT may be required. One
important strategy is liberal utilization of intracoronary imaging to avoid stent
under-sizing and malapposition and residual untreated complications such as
edge dissections, all of which may lead to worse outcomes, especially with shorter
duration of DAPT.19 Recent data suggest that routine use of intracoronary imaging
leads to superior outcomes, which is paramount when shorter durations of DAPT
are required.22 When possible, bifurcation and overlapping stents should be
avoided to reduce the risk of stent thrombosis.19

The overlap between cancer and cardiovascular disease is significant. As

treatments and survival for both diseases continue to improve, the prevalence of
patients with both conditions continues to increase. Further data regarding best
practices in this patient population are needed. In addition, collaboration between
multidisciplinary oncology and cardiology teams is essential to determine the best
approach to minimize periprocedural adverse events in patients with cancer and
cancer survivors undergoing PCI.

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References

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Cardiovascular Disease and Cancer. Circulation 2016;133:1104-14.
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The Old and the New--An Evolving Avenue. Circulation 2016;133:1272-89.
3. Tuzovic M, Herrmann J, Iliescu C, Marmagkiolis K, Ziaeian B, Yang EH. Arterial
Thrombosis in Patients with Cancer. Curr Treat Options Cardiovasc Med
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13. Zhang YJ, Iqbal J, van Klaveren D, et al. Smoking is associated with adverse
clinical outcomes in patients undergoing revascularization with PCI or CABG:
the SYNTAX trial at 5-year follow-up. J Am Coll Cardiol 2015;65:1107-15.
14. Pothineni NV, Shah NN, Rochlani Y, et al. Temporal trends and outcomes of
acute myocardial infarction in patients with cancer. Ann Transl Med 2017;5:482.
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infarction in patients with cancer treated with primary percutaneous coronary
intervention. Am J Cardiol 2013;112:1867-72.
16. Landes U, Kornowski R, Bental T, Assali A, et al. Long-term outcomes after
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Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management,

Cardio-Oncology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Heart
Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and
Intervention, Noninvasive Imaging, Prevention, Pulmonary Hypertension and
This siteThromboembolism,
Venous uses cookies to improveVascular your experience.
Medicine, Atherosclerotic Disease
By continuing to use our site, you agree
(CAD/PAD), Anticoagulation Management to our Cookie Policy, Privacy
and Policy and Terms
ACS, of Service.
Anticoagulation
Management and Venothromboembolism, OK Acute Heart Failure, Interventions

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5/17/2021 PCI: Risks and Outcomes in Patients With Cancer - American College of Cardiology

and ACS, Interventions and Coronary Artery Disease, Interventions and

Imaging, Interventions and Vascular Medicine, Angiography, Nuclear Imaging,
Diet, Exercise, Hypertension, Smoking

Keywords: Coronary Angiography, Acute Coronary Syndrome, Adenosine, Alkylating Agents,

Anemia, Antimetabolites, Arteries, Body Mass Index, Aspirin, Breast Neoplasms,
Cardiovascular Diseases, Chest Pain, Comorbidity, Cause of Death, Coronary Artery Disease,
Cyclophosphamide, Cytokines, Colon, Cardiac Catheterization, Diabetes Mellitus, Doxorubicin,
Drug-Eluting Stents, Diet, Electrocardiography, Exercise, Factor VIII, Femoral Artery,
Hematologic Neoplasms, Heparin, Hemorrhage, Hospital Mortality, Follow-Up Studies,
Fluoroscopy, Hypertension, Hyperlipidemias, Leukocytosis, Hemostatics, Lymphoma, Liver,
Lung Neoplasms, Neoplasms, Obesity, Myocardial Infarction, Neoadjuvant Therapy, Paclitaxel,
Percutaneous Coronary Intervention, Platelet Count, Platelet Glycoprotein GPIIb-IIIa Complex,
Platelet Transfusion, Prevalence, Prostatic Neoplasms, Prognosis, Proteasome Inhibitors,
Referral and Consultation, Referral and Consultation, Risk Assessment, Selection Bias, Risk
Factors, Shock, Cardiogenic, Stents, Smoking, Stomach Neoplasms, Thrombocytopenia,
Thrombocytosis, Thrombosis, Thrombophilia, Tobacco Use, Ulnar Artery, Vascular Endothelial
Growth Factors, Venous Thromboembolism, Cardiotoxicity, Cardiotoxins

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