The key findings of our study are as follows: (i) Non-active cancer patients, based on our definition, have significantly lower bleeding rates than active cancer patients. (ii) Bleeding after PCI could occur during both the DAPT and SAPT periods. (iii) The majority of bleeding sites involved the gastrointestinal tract.
In our definition of non-active cancer, patients scheduled for radical surgery within 3 months were included in addition to patients who had already received interventions. In the real-world clinical setting, CAD is often diagnosed during preoperative examination for cancer surgery; at this time point, cardiologists and oncologists make difficult decisions regarding when to perform PCI. It has been reported that historically, cancer patients experienced fewer in-hospital bleeding events than current cancer patients with prostate, colon, and lung cancer [15]. As cancer patients are known to have a higher bleeding risk, a better stratification of risk for cancer patients is needed. As indicated in the European Society of Cardiology guidelines [16], the recommended DAPT duration after PCI for stable CAD in high bleeding risk patients is 3 months. Thus, we defined “PCI <3 months before planned radical surgery” as non-active cancer patients for further stratification of bleeding risk. Nonetheless, active cancer is sometimes difficult to define. However, whether the patients are eligible for or have already had radical surgery could be an easy and clear indicator of risk stratification. Therefore, we chose the criteria for “active” and “non-active” cancer of the present study accordingly.
One of the major differences in the baseline characteristics of the 2 groups was the prevalence of ACS. In the present study, the prevalence of ACS was higher in the active cancer group than in the non-active cancer group. This finding was reasonable because ACS should be treated with primary PCI even in active cancer patients; more non-active cancer patients underwent PCI for stable CAD because of their relatively better prognosis.
Impact of Activeness of Cancer on Bleeding Event Rates in Patients After PCI
Several studies have reported bleeding risks after PCI largely in ischemic heart disease patients without cancer. The 1-year outcomes of bleeding of BARC types 2 and 3 were observed in 3.6% and 1.8% of patients, respectively [17]. Another study reported the bleeding risk for 3 months of DAPT (ticagrelor and aspirin), followed by randomized assignment to the ticagrelor plus placebo group or continuation of DAPT group. The risk of BARC type 3 or 5 bleeding at 1 year was reported to be 1.0% for the placebo group and 2.0% for the DAPT group [18]. Furthermore, in the AFIRE study, bleeding risk was the safety endpoint of rivaroxaban monotherapy or single antiplatelet plus rivaroxaban for AF patients and those who underwent PCI at >1 year earlier [19]. The study reported bleeding event rates of 1.62% and 2.76% per patient-year for the rivaroxaban monotherapy group and the single antiplatelet plus rivaroxaban group, respectively. When considering cancer patients, it is easy to imagine that advanced cancer patients had more bleeding events. Nevertheless, the available evidence for bleeding events after PCI is limited. In one of the few studies involving cancer patients who underwent PCI, the prevalence of cancer was an independent determinant of cumulative incidence of hospitalization for bleeding [12]. Another important study reported the bleeding risks of DAPT among 9240 ACS patients on DAPT with a median follow-up period of 17 months such that 1.8% patients had a confirmed neoplasm event, and the rate of Global Use of Strategies to Open Occluded Coronary Arteries severe/moderate bleeding was higher in those with neoplasms than in those without neoplasms (11.2 vs. 1.5%) [13]. Considering the follow-up period, the bleeding event rate of 11.2% was similar to that for our active cancer group (22%).
Our study, taken together with previous studies, indicates that non-active cancer patients experienced lower rates of BARC types 2, 3, and 5 bleeding events (2%), which is similar to the results of previous studies mostly involving non-cancer patients. Conversely, active cancer patients had a relatively higher bleeding rate (22%) than those without a cancer history, but they had a consistent bleeding rate compared to those with neoplasms, as reported previously.
Impact of Activeness of Cancer on 3P-MACE Rates in Patients After PCI
As the secondary endpoint, we assessed the 3P-MACE rate in the 2 groups. There was no difference between active and non-active cancer groups according to both Kaplan-Meier and Cox regression hazards model analyses. The rates of 3P-MACE were 5% and 13% in the non-active and active cancer groups, respectively after a median follow-up period of 2.5 years. According to the AFIRE study [19], the rate of MACE including stroke, MI, unstable angina requiring PCI, and all-cause death was 4.14% per year for the DOAC monotherapy group and 5.75% per year for DOAC plus SAPT group. Patients after PCI with hypertension had significantly higher 2-year rates of MACE (cardiac death, MI, or stent thrombosis) than patients without hypertension (7.0% vs. 4.4%) [20]. Additionally, in the AUGUSTUS study, AF patients who underwent elective PCI experienced 5.6% and 5.4% of death or ischemic events (stroke, MI, stent thrombosis, and urgent revascularization), respectively, when treated with apixaban or vitamin K antagonist plus P2Y12 inhibitor over at least 6-month follow-up [21]. The composite endpoint of cardiovascular death, MI, and stroke was reported to occur more frequently in patients with neoplasm than in those without (18.2% vs. 13.5%) [13]. Compared to that in previous studies, the 3P-MACE rate in our cancer patients seemed to be reasonable and was not higher than the rate in studies that included mostly non-cancer patients.
Implications for Patients Undergoing PCI
In the real-world clinical setting, it is difficult for cardiologists to decide on the timing of PCI and cancer surgery. Furthermore, DAPT duration after PCI is controversial. In our study, patients with BMS received 1 month of DAPT and those with DES received 6 to 12 months of DAPT. As reported by the STOPDAPT-2 study, a short DAPT duration significantly reduced bleeding events after PCI; thus, DAPT duration has been reduced for PCI in non-cancer patients. However, bleeding events during the SAPT period were also detected during the 3-year follow-up period. In addition, although bleeding was mostly from the digestive tract, the primary cancers also included the lung, renal, larynx, and pharynx. There are 2 major risk stratifications of bleeding after PCI, the PRECISE DAPT score [22] and the Academic Research Consortium High Bleeding Risk (ARC-HBR) criteria [23]. The PRECISE DAPT score may not provide additional information on cancer patients, because the scores and criteria include the white blood cell count, hemoglobin, and platelet levels, which are unstable in patients undergoing chemotherapy. Although the ARC-HBR criteria include the presence of cancer as a bleeding risk factor, we now need further risk stratification of cancer patients since the results of accumulated evidence have shown that cancer patients have a higher bleeding risk than cancer-naïve patients. However, our study may contribute to the improvement in decision-making with respect to indications for PCI in cancer patients.
Limitations
The present study was a retrospective observational study with a relatively small sample size; thus, it was underpowered for the evaluation of clinical outcomes such as bleeding or MACE. As our institute does not have an emergency room and all patients who come to our institute are cancer patients, the number of PCI procedures was relatively low. However, all PCI procedures were performed by well-trained and certified interventionists. Another limitation was that since cancer type varied in each group, the effects of cancer type could not be considered due to the small sample size. Furthermore, as the event rate was very low, some factors could not be correctly assessed in Cox regression hazards model analysis.