European Journal of Cardiovascular Medicine

Coronary artery disease is the leading cause of death both in developed and developing countries and often presents as Acute coronary syndrome (ACS).Acute Coronary Syndrome (ACS) includes Unstable Angina (UA) and developing Myocardial Infarction (MI), often classified as ST-segment elevation Myocardial Infarction (STEMI) or new onset Left Bundle Branch Block (LBBB) and ACS without ST-segment elevation (NSTEMI).¹ Antiplatelet drugs and revascularization treatments are efficacious in reducing recurring ischemia episodes or mortality in patients diagnosed with acute coronary syndromes.

At present, Percutaneous Coronary Intervention (PCI) is considered a fundamental aspect of the treatment. The supplementary antiplatelet medication, including intraprocedural parenteral anticoagulation, together with mid-to-long-term dual antiplatelet therapy (DAPT) involving the combination of aspirin and a P2Y12 inhibitor, are necessary for the success for procedure. However, bleeding complications have been the Achilles’ heel of antiplatelet drugs. Bleeding events remain one of the most frequent complications post PCI and are associated with increased risk of subsequent MI and death. Approximately 5% of post PCI patients are being readmitted for bleeding with highest occurrence occurring in first two months.² Given that proper antiplatelet therapy is a fundamental aspect of PCI treatment, it is crucial to evaluate the risk of thrombosis and hemorrhage.^3,4 The efficacy of DAPT in reducing unfavorable ischemic events is well-established.^5,6 Significant bleeding is found to be independently linked to a negative prognosis, which includes higher fatality rates.⁷ Many factors independently predict significant bleeding, such as advanced age, female gender, diabetes, hypertension, renal insufficiency, anemia, elevated cardiac biomarkers, and ST-segment deviation.

With the growing use of PCI, the occurrence of bleeding in patients with ACS both in-hospital and out-of-hospital has increased from 2.9% to 6.3%. However, there has been a correspondingly considerable overall survival advantage from 1995 to 2018, with rates of 24.4% and 14.6% respectively.⁸

These findings emphasize the importance of bleeding risk identification and the need for individualized antiplatelet therapies. The ARC-HBR criteria is a clinical practical instrument due to its uncomplicated scoring process and inclusion of elements that are not conventionally regarded as risk factors. High bleeding risk (HBR) is anticipated to indicate a prevalence of Bleeding Academic Research Consortium (BARC) class 3 to 5 bleeding of at least 4% after 1 year.⁹ This study aimed to investigate the association between the number of ARC-HBR criteria and bleeding outcomes in patients with ACS after PCI, and to compare the diagnostic ability of the ARC-HBR criteria with PRECISE DAPT score.

The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) risk score has been reported to demonstrate equal or superior diagnostic accuracy in predicting mortality and major adverse events among patients with ST-segment elevation myocardial infarction (STEMI) compared with other available scores.¹⁰

Therefore, the present study was designed to examine the relationship between the number of ARC-HBR criteria and bleeding outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), while also comparing the diagnostic ability of the ARC-HBR criteria with the PRECISE-DAPT score; in addition, it aimed to evaluate the prognostic utility of the CADILLAC risk score for predicting major adverse cardiovascular and ischemic events in the same patient population.

This Hospital based, Cross-sectional Analytical study was conducted in the Department of Cardiology, at SMS Medical College and Hospitals, Jaipur after obtaining approval of the research protocol from the Institutional Research Review Board and the Institutional Ethical Committee. The recruitment of subjects was taken from December 2024 to February 2025. And the follow up was done for 6 months from recruitment an additional two months were utilized for data compilation, statistical analysis, and report writing.

A total of 151 cases of acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) were included in the study. The sample size was calculated at 95% confidence and 80% power to predict patient outcomes based on six independent variables, with special emphasis on the ARC-HBR criteria.

The study population comprised patients of ACS following PCI presenting to the Department of Cardiology. Patients who provided written informed consent were included, while those who did not give consent or had unsuccessful reperfusion were excluded from the study.

Baseline data for all major and minor ARC-HBR criteria was obtained from medical records. The ARC-HBR score was calculated by assigning 1 point to each major criterion and 0.5 points to each minor criterion. Based on the total score, patients were categorized into three groups: low bleeding risk (score <1), intermediate bleeding risk (score 1–<2), and high bleeding risk (score ≥2). In addition, the CADILLAC risk score was calculated for every patient according to published methods. Patients were then classified into low-risk (score 0–2), intermediate-risk (score 3–5), and high-risk groups (score ≥6). Clinical and follow-up data were retrospectively obtained at the time of outpatient visit and by telephone interview

Clinical outcome measures

The primary outcome measure was to determine the correlation of ARC-HBR score with major bleeding events (BARC-3 and BARC-5) in patients with acute coronary syndrome (ACS) following PCI and to find out better criteria among the ARC-HBR criteria and PRECISE DAPT as a prognostic risk rating for bleeding events. The Secondary objective was to determine the efficacy of CADILLAC score in prediction of ischemic events (non-fatal stroke and non-fatal MI) and MACE (All cause death, non-fatal stroke and non-fatal MI) in patients with acute coronary syndrome (ACS) following PCI.

Statistical Analysis

The data collected were entered into a Microsoft Excel sheet. Continuous or quantitative variables were summarized as mean and standard deviation, and the significance of differences between two means was analysed using the student’s t test. Discrete or qualitative variables were summarized as proportions, and differences in proportions were analysed using the Chi-square test. The level of significance was kept at 95% for all statistical analyses. In addition, receiver operating characteristic (ROC) curves were plotted for bleeding events to quantify the predictive accuracy of the PRECISE-DAPT and ARC-HBR criteria.

Table 1] In this study of 151 patients with acute coronary syndrome undergoing PCI, the majority were in the 61–70 year age group (39.1%), followed by those aged 51–60 years (24.5%). Male predominance was observed (73.5% vs. 26.5% females). The most frequent presentation was ST-elevation MI (41%) then unstable angina (31.8%), followed by Non-ST Elevation MI (27.2%). Smoking (55.6%) and hypertension (49.7%) were most prevalent co-morbidities. 53.0% of patients were classified as low risk by ARC-HBR, while 23.8% were high risk and 23.2% intermediate. The CADILLAC score placed a higher proportion in the high-risk group (39.7%), with 31.8% low and 28.5% intermediate. On ECG evaluation, the majority of patients were in sinus rhythm (86.8%), while complete heart block (7.3%) and atrial fibrillation (6.0%) were less frequent.

Table 1: Baseline demographic, clinical, and risk score distribution of patients with Acute Coronary Syndrome undergoing PCI

[Table 2] At one-month, major bleeding events occurred in 4.6%, mainly gastrointestinal, with no intracranial bleeding. Major Bleeding events at 6 months were reported in 8.6% with gastrointestinal bleeding being the most common with 2 episodes of intracranial hemorrhage (1.3%). At one month, MACE occurred in 4.6%, with 2.0% mortality and 1.3% each of non-fatal MI and stroke and at six months follow-up, MACE occurred in 20.5% of patients, with all-cause mortality of 8.6%, non-fatal MI in 7.9%, and stroke in 4.0%. Ischemic events occurred in 11.9% of patients at 6 months. The mean LVEF was 43.8% and angiographic evaluation showed predominantly double-vessel (41.7%) and triple-vessel disease (39.1%). Most patients were on dual antiplatelet therapy with aspirin and clopidogrel (47.7%).

Table 2: Clinical outcomes, bleeding events, ischemic events, angiographic profile, stent characteristics, and antiplatelet therapy during follow-up

[Table 3] At one-month, major bleeding events occurred in 4.6%, mainly gastrointestinal, with no intracranial bleeding. At six months, bleeding rose to 8.6%, with mainly GI bleeding in 6 % and intracranial bleeding in 1.3%, showing a significant association with ARC-HBR (p<0.001).

Table 3: Association of Bleeding Outcomes with ARC-HBR

[Table 4] At one month, MACE occurred in 4.6%, with 2.0% all cause- mortality and 1.3% each of non-fatal MI and stroke. At six months, MACE increased to 20.5%, with all-cause mortality at 8.6%, non-fatal MI at 7.9%, and stroke at 4.0%. Ischemic events occurred in 18 (11.9%) patients at 6 months that were more common in high CADILLAC score category. CADILLAC score was significantly associated with both MACE (p=0.006) and ischemic events (p=0.039).

Table 4: Association of Clinical Outcomes with CADILLAC Score

Figure 1- ROC curve for Bleeding events at 1 month and 6 months

At one month, patients with ischemic events had a mean stent length of 52.75 mm compared to 40.63 mm in those without (p=0.221), and patients with MACE had a mean stent length of 50.29 mm versus 40.49 mm (p=0.195). At six months, ischemic events were associated with a longer mean stent length (48.44 mm vs. 39.93 mm, p=0.082), though not statistically significant. Importantly, patients with MACE at six months had significantly longer stent lengths (47.90 mm vs. 39.15 mm, p=0.025), indicating stent length as a potential predictor of adverse outcomes.

In our study, there were no statistically significant differences found in terms of major bleeding events and ischemic outcomes among the three antiplatelet regimens (Aspirin + clopidogrel, Aspirin +prasugrel, Aspirin +Ticagrelor; p >0.05). The mean PRECISE-DAPT scores were higher in patients who developed bleeding, both at one month (23.86 vs. 21.22) and at six months (24.77 vs. 21.01). However, these differences were not statistically significant (p=0.605 and p=0.326, respectively), suggesting limited discriminatory ability of the PRECISE-DAPT score in predicting bleeding in this cohort.

[Figure 1] The ARC-HBR score had an area under the curve (AUC) of 0.730 (SE = 0.093, 95% CI: 0.547–0.913, p = 0.040), indicating a fair ability for predicting major bleeding events at 1 month. In comparison, the PRECISE-DAPT score showed an AUC of 0.588 (SE = 0.110, 95% CI: 0.373–0.804, p = 0.431), suggesting poor discrimination as compared to ARC-HBR. At 6 months, the ARC-HBR score demonstrated stronger predictive accuracy with an AUC of 0.812 (SE = 0.058, 95% CI: 0.698–0.926, p < 0.001), reflecting good discriminatory power. The PRECISE-DAPT score yielded an AUC of 0.623 (SE = 0.071, 95% CI: 0.483–0.763, p = 0.144), which was not statistically significant. At a cutoff value of 1.250, the ARC-HBR score demonstrated a sensitivity of 92.3% and a specificity of 75.4%, as calculated using Youden's index.

Bleeding Outcomes by ARC-HBR

In our study, at one-month, major bleeding events occurred in 7(4.6%) patients, in which gastrointestinal bleeding was there in 6(4.0%), and other bleeding (haematuria) in 1 (0.7%), while no cases of intracranial bleeding were reported. At six months, major bleeding events were observed in 13 patients that includes specifically gastrointestinal bleeding was there in 9 (6.0%), intracranial bleeding in 2 (1.3%), and other bleeding in 2 (1.3%). Higher ARC-HBR categories were significantly associated with total bleeding at six months (p<0.001).

These findings are consistent with the consensus definition by Urban et al.¹¹ (2019), who established the ARC-HBR criteria, and with external validation by Ueki et al.¹² (2020), who showed that patients fulfilling ARC-HBR had significantly higher rates of BARC 3 and 5 bleeding after PCI. Furthermore, comparative studies such as Choi et al.¹³ (2021) confirmed that ARC-HBR performs at least as well as or better than PRECISE-DAPT in bleeding prediction.

Clinical Outcomes by CADILLAC Score

In our study, at one-month, MACE was observed in 7 (4.6%) patients that includes all-cause mortality in 3 (2.0%) patients, all of which were cardiovascular deaths. Non-fatal myocardial infarction and ischemic stroke were noted in 2 (1.3%) patients each. while ischemic events occurred in 4 (2.6%). At six months, MACE was documented in 31 (20.5%) patients, and ischemic events in 18 (11.9%).All-cause death was recorded in 13 (8.6%) patients, including cardiovascular death in 9 (6.0%), non-fatal MI in 12 (7.9%), and non-fatal stroke in 6 (4.0%). CADILLAC score showed a significant association with MACE (p=0.006) and ischemic events (p=0.039) at six months.

These results align with the original derivation of the CADILLAC score by Halkin et al.¹⁴ (2005), who demonstrated its predictive value for mortality after primary PCI, and with more recent validation by Sato et al.¹⁵ (2021) and Wilson et al.¹⁶ (2021), confirming its prognostic role in STEMI and contemporary PCI cohorts.

Stent Length and Outcomes

In our study, mean stent length was greater among patients with ischemic events and MACE compared to those without events. Although the differences were not statistically significant for ischemic events at one and six months, but stent length was significantly longer in patients who developed MACE at six months (47.90 mm vs. 39.15 mm, p=0.025). This suggests that longer stent length may contribute to worse clinical outcomes.

This is in agreement with Chandrasekhar et al.¹⁷ (2018), who showed that longer stent length was independently associated with higher 3-year MACE and MI with new-generation DES, and Kong et al.¹⁸ (2021), who reported worse outcomes with very long or overlapping stents in the GRAND-DES registry. Our study findings reinforce these observations, emphasizing the importance of minimizing stent length whenever clinically feasible.

Outcomes by Antiplatelet Therapy

In our study, there were no statistically significant differences among the three antiplatelet regimens (clopidogrel, ticagrelor and prasugrel) along with aspirin in terms of major bleeding events, ischemic events as well as MACE at 1 and 6 months.

In contrast, pivotal randomized trials demonstrated outcome differences: the PLATO trial¹⁹ showed ticagrelor reduced cardiovascular death (4.0% vs 5.1%), MI, or stroke compared with clopidogrel, overall bleeding was slightly higher than clopidogrel group (11.6 vs 11.2%=p=0.43), intracranial bleeding was more frequent in ticagrelor group while the TRITON-TIMI 38 trial²⁰ showed prasugrel having decreased MI, Stent thrombosis death, stroke as compared to clopidogrel. However, bleeding risks were significantly higher in prasugrel group (2.4% vs 1.8%, p=0.01). Our findings differ somewhat, showing no significant variation among regimens, possibly reflecting sample size and patient selection.

Precise DAPT and Bleeding Outcomes

In our study, mean PRECISE-DAPT scores were higher in patients who experienced major bleeding, both at one month (23.86 vs. 21.22) and at six months (24.77 vs. 21.01). However, these differences were not statistically significant (p=0.605 and p=0.326). This suggests that PRECISE-DAPT did not provide strong discriminatory value for bleeding prediction in this cohort.

The score was originally derived and validated by Costa et al.²¹ (2017), who showed it could predict bleeding in DAPT patients. However, subsequent external evaluations, such as Choi et al.¹³ (2021) and Ueki et al.¹² (2020), have highlighted variable discriminatory ability depending on patient population. Our findings similarly suggest that PRECISE-DAPT may be less effective than ARC-HBR in predicting bleeding risk in real-world Indian patients undergoing PCI.

This study has certain limitations. Being a single-centre study, the external validity is limited and the findings may not be generalisable to wider populations. The relatively small sample size reduces the statistical power and may not adequately capture the variability in the larger patient population. In addition, the absence of long-term follow-up prevents assessment of long-term outcomes, while the cross-sectional nature of the study restricts conclusions to associations rather than causal relationships. Despite these limitations, the study has notable strengths. We evaluated three widely used risk scores—ARC-HBR, PRECISE-DAPT, and CADILLAC—in the same cohort of patients with acute coronary syndrome undergoing PCI, allowing a direct head-to-head comparison of their predictive performance. The use of robust statistical methods, including ROC curve analysis and sensitivity and specificity calculations, ensured a reliable assessment of predictive accuracy. Furthermore, the collection of detailed clinical, angiographic, and therapeutic data provided a comprehensive dataset, enabling an in-depth analysis of factors associated with bleeding, ischemic events, and MACE.

In our study, the majority of patients were middle-aged to elderly males presenting with acute coronary syndrome, most commonly ST Elevation MI. Smoking and hypertension were the predominant comorbidities. Angiographic evaluation showed a predominance of multivessel coronary artery disease, and new-generation drug-eluting stents were used.

With regard to risk stratification, more than half of the patients belonged to the low ARC-HBR category, whereas a larger proportion were classified into the high-risk group by CADILLAC. During follow-up, ischemic events and MACE were significantly more frequent in higher CADILLAC categories, while major bleeding events at six months were strongly associated with higher ARC-HBR categories.

Stent length was found to be an important determinant, with significantly longer stents associated with MACE at six months. Choice of antiplatelet regimen did not significantly influence ischemic or bleeding outcomes in this cohort. The PRECISE-DAPT score did not reliably predict bleeding events, whereas the ARC-HBR score demonstrated good discriminatory ability for bleeding, especially at six months.

Overall, the findings indicate that the ARC-HBR score is a valuable tool for predicting bleeding risk, while the CADILLAC score is more reliable for ischemic outcomes in patients with acute coronary syndrome undergoing PCI. Incorporation of both scores in clinical decision-making may help achieve a more balanced assessment of ischemic and bleeding risks, thereby guiding individualized treatment strategies.

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