Coronary Intervention
Cancer and Coronary Heart Disease ― To Bleed or Not to Bleed, That Is the Question ―
2021 Volume 85 Issue 6 Pages 847-849
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2021 Volume 85 Issue 6 Pages 847-849
Cancer promotes hypercoagulability, which causes both venous and arterial thrombosis.1–3 Primary conditions associated with cancer pathobiology result in the abnormal production of coagulant factors and a cytokine storm that cause vascular endothelial injury.4 In addition, immobility or a sedentary lifestyle in patients with advanced cancer is known to be a secondary cause of cancer-associated thrombosis.5
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Furthermore, cancer patients are more vulnerable to bleeding because of comorbid hematological disorders or erosive lesions due to tumor cell invasion,5–7 in addition to the effects of anticancer drugs.8 Thus, more careful control of antithrombosis therapy is required for patients with ischemic heart disease and cancer because of the risk of thrombosis.
The study of Kanenawa et al9 is the first to report on clinical outcomes after percutaneous coronary intervention (PCI) in Japanese patients with cancer. It is important to note that one of the unique characteristics of the Japanese cancer population is that, with the exception of sex-specific malignancies, the most frequent type of cancer is gastrointestinal cancer,10 which is also a major cause of clinically relevant non-major bleeding (CRMN) in the cancer population.1,6 For example, many guidelines for cancer-associated thrombosis provide specific warnings regarding bleeding complications following the administration of direct oral anticoagulants (DOACs).1 More importantly, patients in the study of Kanenawa et al underwent cancer screening prior to the first PCI.9 Surprisingly, following screening, 2.2% of 1,303 patients were positive for cancer; a possible reason for this is the overlap of risk factors between cancer and atherosclerotic disease, such as aging, smoking, and diabetes,9 presumably associated with clonal hematopoiesis.11 Cancer screening in PCI patients is a challenge in terms of reducing medical expenses and the tasks required for cardiology care; however, as cardiologists, we are supposed to provide well-rounded patient care to make the lives of our patients better, and we may tend to lose sight of this during our too-busy days as practicing cardiologists.
Consistent with the trend in cancer statistics,10 with the exception of sex-specific malignancies, Kanenawa et al found that the major type of lesion in patients prior to PCI was gastrointestinal cancer, which was also the leading cause of new-onset cancer during the 1-year follow-up period after PCI.9 Notably, a recent paper regarding cancer incidence among 6,571,034 patients undergoing PCI procedures in the US (>60% of whom were Caucasian) found that current and previous cancer rates were 1.8% and 5.8%, respectively, and that the 4 most common cancers were prostate, breast, colon, and lung cancer.12 This highlights a point of concern and a major limitation of the study of Kanenawa et al. The procedures for cancer screening used by Kanenawa et al only focused on cancer in the upper and lower gastrointestinal tract: stool occult blood and upper and lower endoscopy.9 Therefore, there is a significant bias in the higher incidence of gastrointestinal cancers; more precisely, the cancer incidence in that paper was specific for those gastrointestinal cancers in the elective PCI patient population.
As expected, patients with cancer requiring ongoing therapy more often experienced major bleeding than those with recently diagnosed cancer (16.7% vs. 3.4%).9 During the 1-year follow-up period, 25 patients (2.0%) were diagnosed with cancer, 48.0% of whom experienced bleeding events that led to a cancer diagnosis.9 Kanenawa et al aimed to predict the risk of bleeding complications using the criteria of the Academic Research Consortium for high bleeding risk (ARC-HBR8) compared with other bleeding risk scores namely, Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT),13 Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS),14 and Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto).8 Interestingly, the ARC-HBR was found to be useful in predicting >1-year major bleeding risk than the other bleeding risk scores in both patients with (7.9% vs. 0.0%) and without (7.1% vs. 2.5%) cancer.9 As mentioned by Kanenawa et al,9 the ARC-HBR criteria8 and CREDO-Kyoto score15 include active cancer in their criteria, and patients with a high bleeding risk (HBR) were more prevalent among those with cancer, whereas active cancer is excluded as a risk factor in the PRECISE-DAPT13 and PARIS bleeding scores.14 Components of each score are summarized in Figure 1. The ARC-HBR criteria have been proposed to standardize the definition of HBR,8 but there are several major criteria that are not common in the Japanese population, such as liver cirrhosis with portal hypertension, a history of spontaneous major bleeding etc. In 2020, the JCS Working Committee published a more useful version of the ARC-HBR, which included frailty and sarcopenia, presumably considering the real-world situation in Japan as the most super-aged society.7 Based on the JCS-2020 version of HBR and components of the ARC-HBR, factors conferring considerable bleeding risks are shown in Figure 2. Support for the factors shown in Figure 2 will come from the accumulation of clinical evidence using the JCS-2020 HBR criteria in the future.
Comparison of high bleeding risk (HBR) criteria among the Academic Research Consortium for High Bleeding Risk (ARC-HBR), Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto), Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT), and the Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients (PARIS) scores. AF, atrial fibrillation; BARC, Bleeding Academic Research Consortium; bAVM, brain arteriovenous malformation; BMI, body mass index; CKD, chronic kidney disease; CrCl, creatinine clearance; DAPT, dual antiplatelet therapy; eGFR, estimated glomerular filtration rate; GUSTO, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) bleeding scale; ICH, intracranial hemorrhage; MI, myocardial infarction; N, no; N/A, not applicable; NSAIDs, non-steroidal anti-inflammatory drugs; PCI, percutaneous coronary intervention; PVD, peripheral vascular disease; TIMI, Thrombolysis in Myocardial Infarction; Y, yes.
Traffic signal for assessment of high bleeding risk (HBR). This illustration was created by minor modification of JCS 2020 guidelines regarding HBR and the Academic Research Consortium for High Bleeding Risk (ARC-HBR). bAVM, brain arteriovenous malformation; CKD, chronic kidney disease; CNS, central nervous system; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease; Hb, hemoglobin; HD, hemodialysis; HF, heart failure; ICH, intracranial hemorrhage; MI, myocardial infarction; NSAIDs, non-steroidal anti-inflammatory drugs; OAC, oral anticoagulant; PHx, past medical history; Plt, platelets; PVD, peripheral vascular disease.
In summary, the study of Kanenawa et al has shed light on 3 essential points for cardiologists:
(1) malignancy is not rare complication of ischemic heart disease
(2) major bleeding risk should be monitored in patients with ischemic heart disease or undergoing PCI (with the ARC-HBR criteria being a useful tool)
(3) make the lives of patients better.
