Acute coronary syndromes (ACS) are a leading cause of mortality, yet patients with active cancer are often under-represented in clinical trials, leaving a gap in evidence for their management. We conducted a PRISMA-compliant systematic review and meta-analysis (PROSPERO-registered) searching PubMed, Cochrane, Web of Science, and Scopus through August 2025. We compared mortality, myocardial infarction (MI), and bleeding risks between ACS patients with and without active cancer using random-effects models to calculate risk ratios (RR). Twenty studies involving 1,154,050 patients were analyzed; 5.0% had active cancer. Patients with cancer had significantly higher in-hospital (RR 2.56; 95% CI 1.07 to 6.15) and long-term mortality (RR 3.55; 95% CI 1.71 to 7.36). Notably, the increased in-hospital mortality risk was significant only in those not undergoing percutaneous coronary intervention (PCI) (RR 4.02) and was non-significant in the PCI group (RR 1.45). While cancer patients faced higher long-term mortality regardless of treatment, the risk was lower for those treated with PCI (RR 2.16) compared to those without (RR 6.13). Bleeding risk was consistently higher in cancer patients (RR 1.47) across all management strategies, while MI risk (RR 1.01) did not differ significantly between groups. In conclusion, active cancer is associated with increased mortality and bleeding in ACS patients. PCI appears to mitigate early mortality risk and reduce the magnitude of long-term mortality risk. These findings suggest that invasive management may be beneficial for this vulnerable population, though further prospective studies are required.
Graphical Abstract
Acute coronary syndromes (ACS) remain a leading cause of cardiovascular morbidity and mortality worldwide, with percutaneous coronary intervention (PCI) firmly established as the cornerstone of contemporary management for most patients. However, despite technological and pharmacological advances, outcomes remain suboptimal in vulnerable cohorts, such as those with active cancer. ,, The prevalence of patients living with cancer is rising owing to advances in oncological therapies and increasing life expectancy. The intersection of malignancy and coronary artery disease creates a uniquely challenging clinical scenario, with simultaneously heightened thrombotic and hemorrhagic risks. Cancer itself, along with its treatments, promotes a prothrombotic milieu through mechanisms such as systemic inflammation, endothelial dysfunction, and chemotherapy-induced cardiotoxicity, while bleeding risk is amplified by thrombocytopenia, metastatic burden, and the need for intensive pharmacological regimens. ,
Observational data suggest that cancer patients undergoing PCI experience significantly worse outcomes compared with non-cancer patients, including higher in-hospital mortality, excess bleeding events, and increased rates of repeat revascularization. Yet, the persistent under-representation of cancer patients in randomized clinical trials has resulted in an absence of robust recommendations for this population.
We therefore performed a comprehensive evaluation of the clinical outcomes of patients with ACS with and without cancer who were managed with and without PCI.
Methods
This systematic review and meta-analysis were conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews (PROSPERO), and methodology used followed the registered protocol.
Search strategy
A comprehensive search was performed in PubMed, Cochrane Library, Web of Science, and Scopus, from inception through August 2025. The PubMed search strategy was as follows: (“ST Elevation Myocardial Infarction”[Mesh] OR “STEMI”[tiab] OR “ST-segment elevation myocardial infarction”[tiab] OR “Acute ST elevation myocardial infarction”[tiab] OR “acute coronary syndrome”[tiab]) AND (“Neoplasms”[Mesh] OR cancer[tiab] OR cancers[tiab] OR carcinoma[tiab] OR neoplasm*[tiab] OR malignan*[tiab] OR tumor[tiab] OR tumour[tiab] OR oncolog*[tiab] OR “cancer patient*”[tiab]) Equivalent search strategies were adapted for the other databases accordingly. The selection process was conducted using Rayyan, with 2 independent reviewers screening titles and abstracts. Disagreements were resolved by a third reviewer.
Inclusion criteria and study selection
Studies were included if they met all of the following criteria: (1) observational design (prospective or retrospective); (2) comparison of patients with ACS, with or without PCI, between groups with and without active cancer; and (3) reporting at least 1 clinical outcome of interest. Eligible outcomes were all-cause mortality, myocardial infarction (MI), and bleeding. There were no restrictions on publication date, follow-up duration, or language. Studies were excluded if they (1) did not include a comparator group without cancer, (2) did not report at least 1 of the prespecified outcomes, or (3) did not involve patients diagnosed with ACS.
Data extraction and endpoints
Data were extracted using a standardized form and included study characteristics such as author, year, country, design, sample size, and follow-up duration; baseline patient characteristics including sex, age, diabetes mellitus, hypertension, previous ACS, previous CABG, previous stroke, history of heart failure, chronic kidney disease, and history of bleeding; and clinical outcomes including in-hospital mortality, long-term mortality, MI, bleeding events, stroke, and acute kidney injury. The primary endpoints were all-cause mortality, MI, and bleeding events. Mortality was analyzed separately as in-hospital mortality and long-term mortality (≥1-year) when reported. Secondary outcomes included stroke, and acute kidney injury. Subgroup and sensitivity analyses were planned to explore heterogeneity across studies, including analyses according to study design, follow-up duration, and outcomes in patients treated with vs. without PCI.
Quality assessments
The methodological quality of the included studies were evaluated with the ROBINS I tool. This tool is segmented into 7 domains of potential bias: confounding, selection of participants, classification of interventions, deviations from intended interventions, missing data, outcomes measurement and reporting.
Statistical analysis
Analyses followed PRISMA guidelines. For dichotomous outcomes, pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Between-study heterogeneity was quantified with the I² statistic. Small-study and publication bias were evaluated through funnel plots and formally tested with Egger’s regression test. Sensitivity analyses were performed using a leave-one-out approach in which the pooled effect was recalculated after sequential exclusion of each individual study. Analyses were performed with R version 4.3.2 (R Foundation for Statistical Computing, Vienna, Austria) and the meta package.
Results
Study selection and baseline characteristics
The study selection process is summarized in Figure 1 . A total of 9,405 records were identified through the systematic database search. After removal of duplicate records and ineligible studies, 107 remained and were fully reviewed. Ultimately, 20 studies (18 retrospective and 2 prospective) met the inclusion criteria and were incorporated into the final analysis. ,,,,,,,,,,,,,,,,,,, These studies collectively included 1,154,050 patients with ACS, of whom 57,733 (5.0%) had active cancer and 1,096,317 (95.0%) had no cancer. Baseline characteristics of the included populations from each study are detailed in Table 1 , Table 2 . In aggregate, PCI was performed in 11,806/57,733 (20.4%) patients with cancer and in 155,676/1,096,317 (14.2%) patients without cancer (p <0.001). Follow-up in these studies ranged from 30 days to 10 years.
PRISMA flow diagram.
Table 1
Characteristics of the included studies
| Study | Study design | Groups | N patients (total/cancer/without cancer) | Follow-up |
|---|---|---|---|---|
| Iannaccone | Retrospective | cancer and non-cancer |
14,631 C: 858
wC: 13,773 |
1 year |
| Jacobs | Retrospective | with or without a history of cancer |
609 C: 58
wC: 551 |
30 days |
| Mohamed et al , | Retrospective | cancer and non-cancer |
55,850 C: 3,763
wC: 52,087 |
In-hospital |
| Wang et al | Retrospective | with or without a history of cancer |
2,346 C: 263
wC: 2,083 |
10 years |
| Hess et al | Retrospective | with or without a history of cancer |
15,008 C: 496
wC: 14,512 |
5.3 years (median follow-up in cancer group), 7.7 years (median follow-up in control group) |
| Kanenawa et al | Retrospective | cancer and non-cancer |
1,303 C: 185
wC: 1,118 |
1 year |
| Rohrmann | Retrospective | cancer and non-cancer |
3,962 C: 1,981
wC: 1,981 |
In-hospital |
| Nakatsuma et al | Retrospective | cancer and non-cancer |
12,180 C: 1,109
wC: 11,071 |
5.3 years (median follow-up) |
| Osman | Retrospective | Cancer and non-cancer |
385,522 C: 5,956
wC: 379,566 |
30 days |
| Takeuchi et al | Prospective | Cancer and non-cancer |
3,499 C: 462
wC: 3,037 |
5 years |
| Velders et al | Prospective | With or without a history of cancer |
3,423 C: 208
wC: 3,215 |
1 year |
| Agmon et al | Retrospective | Active cancer and no active cancer |
4,913 C: 90
wC: 4,823 |
1 year |
| Ben Zadok et al | Retrospective | Cancer and cancer-naive |
3,089 C: 152
wC: 2,937 |
1 year |
| Bima et al |
Retrospective |
Cancer and non-cancer |
8,267 C: 711
wC: 7,556 |
1449 days (median follow-up) |
| Dafaalla et al | Retrospective | Cancer and non-cancer |
322,776 C: 7,050
wC: 315,726 |
1 year |
| Ederhy et al | Retrospective | With or without a history of cancer |
3,664 C: 246
wC: 3,418 |
5 years |
| Guo et al | Retrospective | Cancer and non-cancer |
1,184 C: 416
wC: 768 |
5 years |
| Kurisu et al | Retrospective | Cancer and non-cancer |
77 C: 18
wC: 59 |
1 year |
| Lange et al , | Retrospective | Cancer and non-cancer |
175,262 C: 27,213
wC: 148,049 |
1 year, 8 years |
| Leiva et al | Retrospective | Cancer and non-cancer |
140,205 C: 6,118
wC: 134,087 |
180 days |
Abbreviations: C = active cancer; NR = not reported; wC = without cancer.
Table 2
Baseline characteristics of the patients in each study
| STEMI (vs. NSTE ACS) | Sex (male) | Age | Diabetes | Hypertension | Previous ACS | Previous CABG | Previous stroke | Previous HF | CKD | History of bleeding | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C | wC | C | wC | C | wC | C | wC | C | wC | C | wC | C | wC | C | wC | C | wC | C | wC | C | wC | |
| Iannaccone |
440
(51.3) |
8,043
(58.4) |
612 (71.3) | 10,633(77.2) | 70.8 ± 10.3 | 62.8 ± 12.6 | 246 (28.7) | 3,237 (23.5) | 558 (65) | 7,961 (57.8) | 132 (15.4) | 1,584 (11.5) | 40 (4.7) | 427 (3.1) | 71 (8.3) | 744 (5.4) | 46 (5.4) | 399 (2.9) | 55 (6.4) | 399 (2.9) |
94 (11)
/ |
675 (4.9) |
| Jacobs |
58
(100) |
551
(100) |
33 (56.9) | 423 (76.8) | 63.6 ± 11.7 | 59.4 ± 11.5 | 20 (34.5) | 143 (26.0) | 40 (69.0) | 338 (61.3) | 10 (17.2) | 89 (16.2) | 7 (12.1) | 20 (3.6) | 9 (15.5) | 31 (5.6) | 1 (1.7) | 33 (6.0) | NR | NR | NR | NR |
| Mohamed et al |
38,932
(100) |
1,831,883
(100) |
2,362 (62.7) | 29,429 (56.5) | 75.8 ± 10.9 | 73 ± 14 | 941 (25) | 21,043 (40.4) | 2,224 (59.1) | 32,919 (63.2) | 226 (6) | 3,856 (7.4) | 203 (5.4) | 5,105 (9.8) | 79 (2.1) | 1,667 (3.2) | 1,604 (42.6) | 27,033 (51.9) | 756 (20.1) | 14,116 (27.1) | NR | NR |
| Wang et al | 261 (100) | 2,085 (100) | 178 (67.7) | 1,480 (71.1) | 72.0 ± 10.7 | 63.3 ± 13.7 | 44 (16.7) | 381 (18.3) | 199 (75.7) | 1,429 (68.6) | 44 (16.7) | 301 (14.5) | 32 (12.2) | 146 (7.0) | 39 (14.8) | 161 (7.7) | 4 (1.5) | 30 (1.4) | 10 (3.8) | 49 (2.4) | NR | NR |
| Hess | NR | NR | 354 (71.4) | 9,586 (66.1) | 68 ± 7 | 62 ± 9 | 129 (26.0) | 4,013 (27.7) | 334 (67.3) | 9,478 (65.3) | 246 (49.6) | 7,414 (51.1) | NR | NR | 66 (13.3) | 1,196 (8.2) | 99 (20.2) | 2,191 (15.4) | NR | NR | NR | NR |
| Kanenawa et al | NR | NR | 128 (69.2) | 752 (67.3) | 75.5 ± 9.1 | 70.5 ± 11.8 | 74 (40.0) | 428 (38.3) | 156 (84.3) | 882 (78.9) | 4 (2.2) | 35 (3.1) | NR | NR | 20 (10.8) | 104 (9.3) | 89 (8.0) | 21 (11.4) | 86 (46.4) | 466 (41.7) | 4 (2.2) | 7 (0.6) |
| Rohrmann | 1,033 (52.1) | 987 (49.8) | 1,432 (72.3) | 1,443 (72.8) | 73.1 ± 10.9 | 73.1 ± 11.6 | 439 (23.2) | 476 (25.2) | 1,309 (69.7) | 1,313 (69.9) | 444 (22.4) | 404 (20.4) | NR | NR | 164 (8.3) | 153 (7.7) | 122 (6.2) | 102 (5.1) | 283 (14.3) | 267 (13.5) | NR | NR |
| Nakatsuma | NR | NR | 825 (74) | 7,976 (72) | 73.2 ± 8.5 | 67.8 ± 11.1 | 440 (40) | 4,154 (38) | 904 (82) | 9,100 (82) | 119 (11) | 1,141 (10) | NR | NR | 142 (13) | 1,149 (10) | 222 (20) | 2,183 (20) | 89 (8.1) | 814 (7.4) | NR | NR |
| Osman |
5,949
(100) |
17,931
(100) |
3,710 (62.3) | 254,688 (67.1) | 72 ± 11.8 | 64.3 ± 14.0 | 1,679 (28.2) | 120,322 (31.7) | 4,318 (72.5) | 273,667 (72.1) | NR | NR | 113 (1.9) | 18,978 (5) | NR | NR | NR | NR | NR | NR | NR | NR |
| Takeuchi et al | 388 (85) | 2,669 (89) | 339 (73) | 2,375 (78) | 72.3 ± 8.5 | 64.3 ± 11.5 | 149 (33) | 986 (33) | 283 (63) | 1,692 (57) | 47 (10) | 323 (11) | NR | NR | NR | NR | 68 (16) | 414 (14) | NR | NR | NR | NR |
| Velders et al |
208
(100) |
3,215
(100) |
141 (67.8) | 2,427 (75.5) | 69.6 ± 11.0 | 62.8 ± 12.4 | 23 (11) | 361 (11.2) | 88 (42.7) | 1,135 (35.4) | 35 (17.0) | 335 (10.4) | 5 (2.4) | 79 (2.5) | 24 (11.7) | 191 (5.9) | NR | NR | 17 (8.3) | 109 (3.4) | NR | NR |
| Agmon et al |
36
(40) |
1,929 (40) | 70 (78) | 3,858 (80) | 71.5 (65 to 79.7) | 63.0 (55 to 72) | 42 (47) | 1,977 (41) | 70 (78) | 3,087 (64) | 37 (41) | 1,784 (37) | 4 (4) | 386 (8) | 12 (13) | 386 (8) | 12 (13) | 386 (8) | 23 (26) | 482 (10) | NR | NR |
| Ben Zadok et al |
62
(41) |
1,431
(49) |
99
(65) |
2,332 (79) | 75 (68 to 81) |
63
(54 to 73) |
64 (42) | 1,135 (39) | 116 (77) | 1,860 (64) | 46 (31) | 962 (33) | 15 (10) | 247 (8) | 23 (15) | 224 (8) | NR | NR | 33 (22) | 331 (11) | NR | NR |
| Bima et al |
1
(0.8) |
18
(1.6) |
485 (68.2) | 4,997 (66.1) | 75 (66 to 81) | 60 (48 to 72) | 179 (25.2) | 1,288 (17.1) | 544 (76.5) | 4,365 (57.8) | 208 (29.3) | 1,652 (21.9) | NR | NR | 60 (8.4) | 369 (4.9) | NR | NR | 150 (21.1) | 639 (8.5) | NR | NR |
| Dafaalla et al |
7,050
(100) |
315,726
(100) |
5,924 (75) | 226,841 (71.8) | 74.1 (66.4 to 81) | 64.7 (55 to 75.1) | 1,167 (17.4) | 46,365 (15.6) | 2,978 (47) | 121 205 (43.1) | 1,173 (18.4) | 39,883 (14.2) | 267 (4.3) | 7,550 (2.7) | 465 (7.5) | 14 115 (5.1) | 207 (3.3) | 8,016 (2.2) | 348 (5.6) | 6,938 (2.5) | NR | NR |
| Ederhy et al |
117
(47.6) |
1,764
(51.6) |
179 (72.7) | 2,332 (68.2) |
74 ±
11 |
67 ±
14 |
92 (37.4) | 1,221 (35.7) | 167 (67.9) | 2,017 (59.0) | 52 (21.1) | 612 (17.9) | 15 (6.1) | 195 (5.7) | 32 (13.0) | 270 (7.9) | 27 (11.0) | 187 (5.5) | 25 (10.2) | 185 (5.4) | NR | NR |
| Guo et al | 84 (20.2) | 154 (20.1) | 279 (67) | 519 (67.5) | 72.5 ± 9.8 | 72.3 ± 9.7 | 116 (27.9) | 187 (24.3) | 323 (77.6) | 607 (79.0) | 52 (21.1) | 612 (17.9) | 69 (16.6) | 127 (16.5) | 43 (10.3) | 79 (10.3) | 76 (18.3) | 130 (16.9) | 13 (3.3) | 38 (5.0) | NR | NR |
| Kurisu et al | NR | NR | 13 (72) | 44 (75) | 70.4 ± 8.1 | 68.8 ± 11.8 | 7 (39) | 25 (42) | 11 (61) | 37 (63) | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR | NR |
| Lange et al |
27,213
(100) |
148,049 (100) | 16,956 (62.3) | 96,351 (65) | 76.25 ± 10.6 | 66.8 ± 21.83 | 12,123 (44.5) | 55,549 (37.52) | 25067 (92.1) | 125,398 (84.7) | 9,566 (35.1) | 43,699 (29.5) | 1,492 (5.4) |
5,430
(3.67) |
3,590 (13.1) | 12,994 (8.78) | 15,190 (55.8) | 69,503 (46.95) | 10,471 (38.4) | 35,588 (24) | NR | NR |
| Leiva et al |
2,962
(48.4) |
73,753
(55) |
4,252 (69.4) | 87,314 (65.1) | 72.3 ± 11 | 68.5 ± 12.5 | 2,184 (35.7) | 56,244 (41.9) | 4,527 (74.0) | 98,927 (73.8) | 721 (11.8) | 15,853 (11.8) | 359 (5.9) | 8,394 (6.3) | 370 (6.0) | 8,149 (6.1) | 4,292 (70.2) | 93,061 (69.4) | 1,960 (32.0) | 38,027 (28.4) | NR | NR |
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