There are limited data on readmission with ischemic and major bleeding events in patients with acute myocardial infarction (AMI) with active cancer. The purpose of our study was to evaluate in-hospital characteristics and 30-day readmission rates for recurrent AMI and major bleeding by cancer type in patients with AMI and active cancer. From 2016 through 2018, patients in the Nationwide Readmission Database admitted with AMI and underlying active colon, lung, breast, prostate, and hematological cancers were included. Thirty-day readmission for recurrent AMI and major bleeding were reported. Of 1,524,677 index hospitalizations for AMI, 35,790 patients (2.2%) had cancer (0.9% hematological; 0.5% lung; 0.4% prostate; 0.2% breast; and 0.1% colon). Compared with patients without cancer, patients with cancer were about 6 to 10 years older and had a higher proportion of atrial fibrillation, valvular heart disease, previous stroke, and a greater co-morbidity burden. Of all cancer types, only active breast cancer (adjusted odds ratios 1.82, 95% CI 1.11 to 2.98) was found to be significantly associated with elevated odds of readmission for major bleeding; no such association was observed for recurrent AMI. In conclusion, AMI in patients with breast cancer is associated with significantly greater odds of readmission for major bleeding within 30 days after discharge. Management of patients with concomitant AMI and cancer is challenging but should be based on a multidisciplinary approach and estimation of an individual patient’s risk of major coronary thrombotic and bleeding events.
Patients with cancer represent a cohort with high burden of coronary artery disease (CAD) due to numerous shared risk factors between the 2 disease processes. Additionally, patients with active cancer are also vulnerable to acute myocardial infarction (AMI) due to ongoing inflammation, as well as treatment for cancer with cardiotoxic chemotherapeutic agents, immunomodulators, , and hormonal therapies. Patients with active cancer who present with AMI are very challenging to treat due to a paucity of guidelines because of their exclusion from conventional clinical trials. A concomitant cancer diagnosis among patients with AMI is associated with lower utilization of invasive procedures and worse clinical outcomes compared with those without cancer depending on the type of cancer and the presence of metastases. Patients with cancer represent a cohort of patients who are paradoxically at high risk of bleeding as well as ischemic events. There are limited data regarding the long-term outcomes of patients with active cancer after AMI, particularly regarding readmission with bleeding or ischemic complications. This is clinically important because procedural decisions and antithrombotic strategies are often based on the perceived risk of major bleeding versus ischemic events after discharge. The few previous studies, which have evaluated readmission in patients with AMI with cancer are either relatively small in sample size, single-center perspective, or have only focused on patients receiving percutaneous coronary interventions (PCIs) or specific clinical presentations such as ST-segment elevation myocardial infarctions (STEMIs). Additionally, most studies have ‘pooled’ all patients with cancer together, including those with a history of cancer as well as active cancer, and lack granularity in terms of the type of cancer having an impact on readmission. , Therefore, we sought to analyze patients with AMI with active cancer from a large real-world dataset for readmission due to either re-infarction or major bleeding events based on cancer type.
Methods
The Nationwide Readmission Database is a publicly available dataset produced by the Healthcare Cost and Utilization Project (HCUP) of the Agency of Healthcare Research and Quality, designed to support various types of analyses of national readmission rates for all patients regardless of the expected payer for hospital stay. The database contains anonymized discharge-level hospitalization data from approximately 18 million annual discharges from 21 geographically dispersed states, which upon weighting roughly estimate to 35 million discharges. The hospitalizations and re-hospitalizations occurring within a calendar year can be determined by using a unique de-identified patient linkage number assigned to each patient to track patients across different hospitals within a state.
All patients with a principal discharge diagnosis of AMI (including STEMI and non-STEMI) between January and November for each of the years from 2016 to 2018 were retrospectively analyzed, stratified by their 30-day readmission status for AMI and major bleeding. We excluded patients younger than 18 years of age and those with missing values for age, length of stay, and death during the index admission ( Figure 1 ). Furthermore, we excluded all index AMI admissions during December of each year because the Nationwide Readmission Database does not track patients over multiple calendar years, meaning that patients admitted in December would not have 30-day follow-up hospital census data. The study cohort was stratified by the presence or absence of active cancer into 6 groups: colon cancer, lung cancer, breast cancer, prostate cancer, hematological malignancies, and no cancer. The cancer type was identified by using the following International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes: C18*, C34*, C399, C50*, C61*, C81*, C82*, C83*, C84*, C85*, C86*, C88*, C90*, C91*, C92*, C93*, C94*, C95*, and C96*. Other patient characteristics and outcomes (other than death) were also extracted using ICD-10 codes.
The primary outcome of this study was to assess 30-day re-admission rates for recurrent AMI and major bleeding in patients with and without cancer, after hospital discharge with a principal diagnosis of AMI. The ICD-10 codes used for identifying AMI and major bleeding events are provided in Supplementary Table 1.
All statistical analyses were conducted in Stata/MP (StataCorp, Texas) and R v 4.0.5 (Vienna, Austria). We followed the methodology suggested by the HCUP for all analyses and used the survey estimation command to weigh individual records by their designated discharge weights (variable DISCWT) to generate a national estimate. The Charlson co-morbidity score was calculated by using “Charlson” package in Stata. We further produced tables to delineate differences in characteristics of patients for each of the cancers stratified by the readmission status. The continuous variables were presented as mean ± standard deviation or median (interquartile range), whereas categoric variables were presented as percentages or frequencies.
We also performed multivariable logistic regression analyses to examine the odds of 30-day readmission for both recurrent AMI and major bleeding across different cancer groups using no cancer as the reference group. The regression models were adjusted for the following variables captured during the index admission: age, gender, smoking, alcohol abuse, hypertension, hyperlipidemia, obesity, diabetes mellitus, CAD, previous myocardial infarction, previous PCI, previous coronary artery bypass graft (CABG), atrial fibrillation, valvular heart disease, peripheral vascular disease, previous stroke or transient ischemic attack (TIA), chronic lung disease, renal failure, liver disease, fluid and electrolyte disorders, anemia, thrombocytopenia, hypothyroidism, pulmonary circulatory disorder, peptic ulcer disease, depression, dementia, mechanical circulatory support, invasive angiography, cardiogenic shock, in-hospital stroke/TIA, and vascular complications. For all analyses, a 2-sided p value <0.05 was deemed statistically significant.
Results
A total of 1,524,677 index hospitalizations for AMI were included in the final analysis. Of the total index hospitalizations, 1,490,966 were identified as patients with no active cancer (97.8%), followed by 13,757 patients with hematological cancers (0.9%), 7,877 with lung cancer (0.5%), 7,014 with prostate cancer (0.4%), 3,125 with breast cancer (0.2%), and 1,938 with colon cancer (0.1%). The baseline demographic, clinical, and in-hospital characteristics for patients readmitted with AMI and major bleeding stratified by individual cancer type and readmission status are detailed in Tables 1 and 2 , respectively.
| Variable | No cancer(n = 1,490,966) | Colon cancer(n = 1,938) | Lung cancer(n = 7,877) | Breast cancer(n = 3,125) | Prostate cancer(n = 7,014) | Hematological cancer(n = 13,757) | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Readmission | No (n=1,422,510) | Yes (n=68,455) | No (n=1,836) | Yes (n=102) | No (n=7,400) | Yes (n=477) | No (n=2,969) | Yes (n=156) | No (n=6,624) | Yes (n=390) | No (n=12,984) | Yes (n=773) | |
| % within group | (95.4%) | (4.6%) | (94.7%) | (5.3%) | (93.9%) | (6.1%) | (95.0%) | (5.0%) | (94.4%) | (5.6%) | (94.4%) | (5.6%) | |
| Characteristics | |||||||||||||
| Age, median (IQR), (years) | 66 (57–76) | 69 (59–79) | 74 (65–81) | 70 (61 – 78) | 72 (65–79) | 73 (67–78) | 73 (65–81) | 75 (66–81) | 77 (70–84) | 80 (73–86) | 74 (66–82) | 76 (66 – 82) | |
| Women | 37.2% | 40.1% | 39.5% | 38.8% | 43.3% | 39.6% | 98.4% | 99.1% | 0% | 0% | 33.3% | 30.8% | |
| Weekend admission | 27.0% | 26.9% | 22.0% | 26.9% | 25.1% | 28.7% | 27.7% | 27.3% | 26.7% | 27.9% | 26.2% | 29.9% | |
| Year | |||||||||||||
| 2016 | 33.0% | 36.7% | 33.0% | 44.3% | 32.9% | 37.2% | 33.4% | 36.5% | 33.1% | 41.4% | 32.0% | 34.7% | |
| 2017 | 34.1% | 35.9% | 36.7% | 29.6% | 35.7% | 34.1% | 34.0% | 37.4% | 32.3% | 30.3% | 35.4% | 37.0% | |
| 2018 | 32.8% | 27.4% | 30.2% | 26.0% | 31.3% | 28.6% | 32.6% | 26.0% | 34.6% | 28.2% | 32.5% | 28.2% | |
| Primary payer | |||||||||||||
| medicare | 56.3% | 67.3% | 73.5% | 71.4% | 77.2% | 78.8% | 78.8% | 83.0% | 81.9% | 90.9% | 77.8% | 83.7% | |
| Medicaid | 8.8% | 10.9% | 8.0% | 9.7% | 6.5% | 6.2% | 5.9% | 7.9% | 2.6% | 4.0% | 3.8% | 3.1% | |
| private | 26.8% | 14.9% | 15.4% | 10.2% | 12.2% | 9.2% | 13.4% | 7.1% | 12.0% | 3.8% | 15.2% | 10.3% | |
| self-pay | 4.4% | 3.6% | 0.9% | 3.8% | 0.9% | 2.0% | 0.9% | 1.0% | 0.4% | 0% | 0.8% | 0% | |
| no charge | 0.5% | 0.5% | 0% | 0% | 0.1% | 0% | 0.1% | 0% | 0% | 0% | 0.1% | 0.2% | |
| others | 3.0% | 2.6% | 2.2% | 4.9% | 2.9% | 3.6% | 0.7% | 0.9% | 3.0% | 1.1% | 2.2% | 2.6% | |
| Income quartile based on ZIP code | |||||||||||||
| 0 – 25 th | 30.3% | 34.3% | 26.9% | 35.8% | 31.7% | 28.5% | 29.5% | 24.3% | 25.0% | 21.9% | 24.9% | 22.2% | |
| 26 – 50th | 28.8% | 28.7% | 32.2% | 24.3% | 29.2% | 29.5% | 27.8% | 29.1% | 28.3% | 29.7% | 27.6% | 27.1% | |
| 51 – 75th | 24.1% | 22.5% | 23.2% | 35.8% | 22.3% | 22.7% | 24.6% | 30.4% | 25.3% | 26.4% | 25.6% | 26.5% | |
| 76 – 100th | 16.7% | 14.4% | 17.6% | 4.0% | 16.7% | 19.3% | 18.1% | 16.1% | 21.4% | 21.8% | 21.8% | 24.1% | |
| Hospital bed size | |||||||||||||
| small | 13.8% | 15.3% | 13.8% | 16.3% | 14.1% | 17.3% | 17.2% | 20.0% | 14.0% | 16.5% | 13.2% | 12.9% | |
| medium | 28.4% | 30.0% | 26.8% | 32.0% | 28.7% | 32.2% | 27.6% | 28.7% | 29.4% | 29.6% | 28.3% | 30.2% | |
| large | 57.8% | 54.6% | 59.3% | 51.7% | 57.2% | 50.5% | 55.1% | 51.2% | 56.5% | 53.8% | 58.4% | 56.8% | |
| Urban | 99.1% | 98.8% | 99.0% | 100% | 98.8% | 99.5% | 98.7% | 98.7% | 98.8% | 96.0% | 99.0% | 99.4% | |
| Teaching | 68.8% | 66.4% | 68.4% | 77.3% | 66.6% | 66.8% | 70.2% | 73.6% | 70.1% | 66.7% | 71.3% | 69.0% | |
| Smoking | 28.2% | 29.8% | 30.8% | 39.2% | 46.5% | 47.8% | 25.3% | 20.1% | 36.4% | 33.3% | 33.1% | 29.8% | |
| Alcohol abuse | 3.5% | 3.4% | 2.3% | 0% | 3.2% | 2.8% | 0.9% | 0% | 2.8% | 2.2% | 1.4% | 1.1% | |
| Hypertension | 80.4% | 87.9% | 81.3% | 88.9% | 79.1% | 80.5% | 81.6% | 93.3% | 83.5% | 85.0% | 81.7% | 88.3% | |
| Dyslipidemia | 68.2% | 70.7% | 61.2% | 55.1% | 58.3% | 62.7% | 61.8% | 78.5% | 68.1% | 65.0% | 64.2% | 67.9% | |
| Diabetes | 38.5% | 53.2% | 41.6% | 66.0% | 32.9% | 37.2% | 40.3% | 55.5% | 35.6% | 46.8% | 37.3% | 50.1% | |
| Obesity | 20.3% | 19.8% | 12.6% | 14.2% | 8.4% | 6.6% | 16.4% | 17.6% | 12.4% | 14.2% | 12.8% | 13.2% | |
| Previous coronary artery disease | 60.9% | 62.0% | 55.3% | 66.7% | 56.4% | 53.6% | 54.5% | 66.0% | 60.6% | 62.7% | 58.8% | 59.8% | |
| Previous myocardial infarction | 15.0% | 22.8% | 16.0% | 28.6% | 15.9% | 22.8% | 13.1% | 28.6% | 16.0% | 21.7% | 16.6% | 22.6% | |
| Previous PCI | 16.1% | 24.4% | 15.6% | 17.3% | 15.7% | 27.0% | 13.4% | 26.8% | 18.8% | 18.5% | 17.1% | 24.0% | |
| Previous CABG | 21.8% | 34.3% | 21.3% | 26.0% | 23.7% | 33.1% | 16.5% | 31.5% | 28.1% | 32.0% | 24.6% | 35.4% | |
| Atrial fibrillation | 7.0% | 7.2% | 8.3% | 12.6% | 9.3% | 10.1% | 3.6% | 8.1% | 10.5% | 9.2% | 9.8% | 9.1% | |
| Valvular heart disease | 9.8% | 12.2% | 12.9% | 19.0% | 9.9% | 9.5% | 11.5% | 14.0% | 13.6% | 14.3% | 13.2% | 17.5% | |
| Peripheral vascular disease | 8.6% | 13.6% | 11.4% | 9.6% | 15.9% | 19.3% | 7.8% | 17.9% | 11.2% | 13.0% | 10.7% | 14.4% | |
| Previous stroke/ TIA | 7.7% | 9.6% | 9.4% | 13.8% | 9.2% | 10.2% | 7.9% | 11.1% | 8.7% | 12.0% | 8.9% | 11.0% | |
| Chronic lung disease | 21.1% | 26.4% | 21.0% | 27.0% | 58.2% | 60.4% | 25.1% | 24.2% | 19.6% | 17.6% | 23.1% | 22.7% | |
| Renal failure | 21.6% | 36.4% | 28.5% | 36.6% | 24.5% | 32.9% | 24.7% | 40.3% | 32.4% | 38.7% | 35.6% | 49.1% | |
| Liver failure | 2.1% | 2.2% | 3.2% | 4.8% | 2.5% | 2.0% | 2.4% | 4.4% | 2.4% | 1.9% | 2.7% | 1.3% | |
| Fluid and electrolyte disorder | 23.1% | 25.3% | 34.0% | 48.6% | 33.0% | 33.8% | 28.8% | 31.9% | 27.3% | 23.2% | 30.9% | 29.2% | |
| Hypothyroidism | 12.1% | 13.8% | 11.8% | 20.4% | 14.4% | 15.3% | 21.4% | 15.3% | 9.9% | 11.6% | 17.1% | 16.6% | |
| Pulmonary circulatory disorder | 5.7% | 7.2% | 10.3% | 10.0% | 10.7% | 10.4% | 9.4% | 9.6% | 7.5% | 4.8% | 9.7% | 8.7% | |
| Peptic ulcer disease | 0.7% | 0.9% | 1.9% | 4.8% | 1.0% | 1.4% | 0.9% | 4.0% | 1.2% | 1.3% | 1.3% | 0.9% | |
| Depression | 9.5% | 11.1% | 9.8% | 11.6% | 12.3% | 11.8% | 13.7% | 10.6% | 7.6% | 5.7% | 10.9% | 11.1% | |
| Dementia | 5.2% | 6.0% | 5.5% | 1.4% | 5.6% | 4.8% | 7.2% | 5.8% | 8.7% | 6.1% | 6.0% | 6.8% | |
| Charlson co-morbidity index, median (IQR) | 2 (1–4) | 4 (2–6) | 7 (5–10) | 8 (5–10) | 7 (5–10) | 6 (5–9) | 6 (4–9) | 7 (5–9) | 6 (4–9) | 7 (5–10) | 5 (4–7) | 6 (5–8) | |
| Procedural/ In-hospital variables | |||||||||||||
| Angiography | 73.5% | 60.6% | 60.3% | 59.1% | 48.0% | 46.5% | 58.5% | 52.7% | 62.2% | 45.9% | 61.6% | 50.4% | |
| PCI | 54.0% | 42.0% | 37.7% | 43.9% | 32.0% | 27.5% | 36.9% | 34.4% | 41.9% | 27.8% | 41.6% | 31.3% | |
| CABG | 10.0% | 3.2% | 7.3% | 3.4% | 2.7% | 0.6% | 3.4% | 1.6% | 11.0% | 2.0% | 8.9% | 4.5% | |
| AKI | 17.1% | 21.4% | 24.2% | 29.9% | 19.6% | 20.7% | 17.6% | 22.7% | 24.7% | 23.1% | 25.9% | 28.9% | |
| IABP or assist | 0.8% | 0.6% | 1.2% | 0% | 0.8% | 1.3% | 0% | 0% | 0.7% | 0% | 0.8% | 0.8% | |
| Cardiac arrest | 1.8% | 1.0% | 1.7% | 0% | 1.5% | 1.2% | 1.2% | 1.1% | 1.5% | 0.3% | 2.0% | 0.9% | |
| Cardiogenic shock | 4.3% | 3.3% | 5.7% | 2.7% | 4.0% | 3.0% | 4.1% | 3.1% | 4.2% | 2.9% | 4.8% | 3.4% | |
| In-hospital stroke/ TIA | 1.3% | 1.2% | 1.6% | 4.8% | 2.9% | 2.1% | 1.7% | 0% | 1.8% | 3.4% | 1.6% | 0.9% | |
| Vascular complication | 0.04% | 0.04% | 0% | 0% | 0.02% | 0% | 0.05% | 0% | 0% | 0% | 0.05% | 0% | |
| Discharge location | |||||||||||||
| home/ self-care | 71.9% | 62.9% | 54.1% | 65.2% | 51.3% | 60.4% | 60.6% | 54.6% | 57.9% | 54.8% | 60.0% | 55.5% | |
| transfer to other hospital | 2.7% | 7.8% | 2.2% | 2.5% | 2.1% | 5.1% | 2.3% | 10.0% | 2.8% | 10.1% | 2.5% | 5.8% | |
| nursing facility | 10.9% | 11.0% | 21.1% | 7.6% | 17.9% | 11.7% | 17.0% | 11.9% | 18.1% | 12.2% | 15.5% | 16.1% | |
| discharge against medical advice | 1.1% | 3.4% | 0.8% | 1.6% | 1.1% | 2.6% | 0.4% | 21.5% | 0.6% | 2.1% | 0.9% | 1.5% | |
| Length of stay (days), median (IQR) | 3 (2–5) | 3 (2–5) | 4 (2–8) | 5 (3–7) | 4 (2–7) | 4 (2–6) | 3 (2–6) | 4 (2–6) | 4 (2–7) | 3 (2–5) | 4 (2–7) | 4 (2–7) | |
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