Comparison of bleeding complications between patients with peripheral and coronary artery disease after revascularization: Insights from ASPARAGUS,a prospective observational study

Abstract

Introduction:

This study compared the risks and incidences of major bleeding between patients undergoing revascularization for peripheral (PAD) and coronary artery disease (CAD).

Methods:

A subanalysis of the ASPARAGUS study (ASsessment of Prognosis in PAtients with CoRonary or Peripheral Artery Disease UnderGoing PercUtaneouS or Surgical Intervention) was conducted to compare the incidence of bleeding complications between patients with PAD and CAD. Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria were applied in 4343 patients with PAD and 6238 with CAD, respectively. The primary study endpoint was the cumulative incidence of major bleeding, defined as Bleeding Academic Research Consortium types 3 and 5.

Results:

At least one major bleeding criterion and one minor bleeding criterion were found in 61.5% and 79.3% of patients with PAD, compared with 32.0% and 65.9% of patients with CAD, respectively. During a median follow-up of 27.4 months, 385 incidences of major bleeding were recorded. In the PAD group, the crude incidence rate of major bleeding was 19.1 per 1000 person-years, which was higher than the 10.7 per 1000 person-years in the CAD group. Multivariable Poisson regression analysis demonstrated that PAD versus CAD was not significantly associated with incident major bleeding after adjusting for ARC-HBR major and minor criteria (adjusted incidence risk ratio = 1.14, 95% CI, 0.93–1.40; p = 0.22).

Conclusion:

Patients with PAD had higher ARC-HBR scores and a higher incidence rate of major bleeding than those with CAD. Their higher risk of major bleeding was driven by their higher prevalence of ARC-HBR-defined risk factors.

Keywords

bleeding complication coronary artery disease (CAD)endovascular therapy percutaneous intervention peripheral artery disease (PAD)

Introduction

Recently, the prevalence of peripheral artery disease (PAD) has increased worldwide, similar to that of coronary artery disease (CAD).^1,2 Symptomatic PAD specifically is estimated to affect up to 10% of the global population, increasing to nearly 30% in individuals older than 50 years.³ A previous study analyzed presentation patterns of PAD and CAD using nationwide databases.² Between 2012 and 2017, the annual number of revascularization procedures performed increased for patients with both PAD and CAD.² Compared with that of claudication and stable angina pectoris, the incidence rate of more severe diseases, including chronic limb-threatening ischemia (CLTI) and acute coronary syndrome, has increased substantially.²

Several studies have demonstrated that bleeding events after percutaneous coronary intervention (PCI) are associated with increased mortality and poor clinical outcomes in patients with CAD.^4
–6 Accordingly, the definition of high bleeding risk (HBR) was standardized with the proposal of the Academic Research Consortium for High Bleeding Risk (ARC-HBR) in 2019.⁷ In a previous study that validated the ARC-HBR criteria in 9623 patients with CAD undergoing PCI, Cao et al. reported that 44% of patients met the ARC-HBR criteria.⁸ Furthermore, the incidence of primary major bleeding at 1 year in patients with HBR was higher than the 4% cutoff assumed by the ARC-HBR consensus.⁸ Moreover, it was nearly three times higher than that in patients without HBR.⁸ By contrast, previous studies suggested that patients with PAD might meet the ARC-HBR criteria more frequently than those with CAD; thus, the criteria might be helpful in stratifying patients with PAD to predict the incidence of major bleeding.^9,10 However, no studies have directly compared the prevalence of ARC-HBR scores and its clinical impact on prognosis between patients with PAD and CAD. Therefore, the present study aimed to compare the risks and incidences of major bleeding between patients undergoing revascularization for symptomatic PAD and CAD.

Methods

Study population

This study used the 3-year database of the ASsessment of Prognosis in PAtients with CoRonary or Peripheral Artery Disease UnderGoing PercUtaneouS or Surgical Intervention (ASPARAGUS) study. The ASPARAGUS study is an ongoing prospective multicenter observational study that registered patients undergoing revascularization for either symptomatic PAD or CAD between September 2019 and June 2021 at 56 cardiovascular centers in Japan.⁴ All participants were registered at the index revascularization, and an annual follow-up was scheduled for 5 years. For this registry, the inclusion criteria were as follows: age ⩾ 20 years and consent for follow-up surveillance after revascularization; patients who underwent revascularization for nonatherosclerotic PAD or CAD were excluded. The study was performed in accordance with the guidelines of the Declaration of Helsinki and approved by the local ethics committees of the participating institutions. Informed consent was obtained from the participants or their families when the patients were unable to do so. Patients were permitted to opt out of the study.

Among the 10,683 patients in the 3-year database, 102 patients with missing data were excluded. The remaining 10,581 patients (i.e., 4343 and 6238 patients in the PAD and CAD groups, respectively) were analyzed in the present study. Each operator prescribed antithrombotic agents in accordance with the guidelines. However, low-dose rivaroxaban was not commercially available in Japan during the study enrolment period and therefore was not used at baseline.^11,12

Study definition and endpoints

The primary study endpoint was incident major bleeding during follow-up. Major bleeding was defined as Bleeding Academic Research Consortium (BARC) types 3 or 5.¹³ BARC type 3 bleeding referred to overt bleeding in addition to a decrease in hemoglobin ⩾ 3.0 g/dL, any transfusion with overt bleeding, bleeding requiring surgical intervention, bleeding requiring intravenous vasoactive agents, and intracranial bleeding.¹³ BARC type 5 bleeding was defined as fatal bleeding, including both probable and definite cases.¹³ Major bleeding was classified into cerebral, gastrointestinal, procedure-related, and traumatic bleedings.¹³ Traumatic bleeding referred to hemorrhage resulting from mechanical injury without access-site complications during revascularization procedures, leading to rapid blood loss that might cause tissue hypoperfusion and coagulopathy.¹⁴

Based on literature review and expert consensus, HBR was defined as a BARC type 3 or 5 bleeding risk ⩾ 4.0% at 1 year or a risk of an intracranial hemorrhage ⩾ 1.0% at 1 year for patients after intervention.⁷ The ARC-HBR criteria comprise major and minor criteria. Patients are considered to have HBR if they fulfil at least one major criterion or two minor criteria.⁷ Major criteria included a diagnosis of severe or end-stage chronic kidney disease (CKD, defined as an estimated glomerular filtration rate < 30.0 mL/min/1.73 m²), liver cirrhosis with portal hypertension, active malignancy within the past 12 months, severe anemia (defined as hemoglobin < 11.0 g/dL), moderate or severe thrombocytopenia (defined as platelet count < 10.0 × 10⁴/μL), previous spontaneous intracranial hemorrhage, previous traumatic intracranial hemorrhage within the past 12 months, presence of a brain arteriovenous malformation, moderate or severe ischemic stroke within the past 6 months, spontaneous bleeding requiring hospitalization or transfusion during the past 6 months, chronic bleeding diathesis, use of anticoagulation medication (excluding vascular protection doses), nondeferrable major surgery while undergoing dual antiplatelet therapy (DAPT), and recent major surgery or trauma within 30 days before revascularization. Minor criteria included age ⩾ 75 years, moderate CKD (defined as an estimated glomerular filtration rate of 30.0–59.0 mL/min/1.73 m²), mild anemia (defined as hemoglobin 11.0–12.9 g/dL for men and 11.0–11.9 g/dL for women), previous ischemic stroke, history of spontaneous bleeding requiring hospitalization or transfusion, and long-term use of steroids or nonsteroidal antiinflammatory drugs.⁷

Repeat procedure was defined as re-intervention performed on the index vascular segment. Vulnerabilities were measured in terms of clinical and social aspects, including malnutrition, frailty, receiving nursing care, receiving welfare, and staying in a nursing home.⁴ Malnutrition was defined as a Geriatric Nutritional Risk Index score < 92 points.¹⁵ Frailty was defined as a Clinical Frailty Scale score ⩾ 5 points.¹⁶ Receiving nursing care indicated that patients were certified for receiving long-term nursing care services with public nursing insurance, whereas receiving welfare meant that patients were certified for receiving public welfare benefits. Staying in a nursing home was defined as spending a daily life in a nursing home.

Statistical analysis

Baseline characteristics data are presented as mean ± SD for continuous variables and percentage for discrete variables, if not otherwise mentioned. Statistical significance was defined as p < 0.05. Accordingly, 95% CIs were reported where appropriate. Differences in the baseline characteristics between the PAD and CAD groups were tested by Welch’s t-test and the chi-squared test for continuous and discrete variables, respectively. The incidence rates of major bleeding are expressed in person-years. We also estimated the cumulative incidence rate of major bleeding using the Kaplan–Meier method. The association of baseline characteristics with major bleeding risk was investigated using the Poisson regression model. The difference in incidence risk ratios (RRs) between types of bleeding events was tested using 2000 bootstrap resamples. All statistical analyses were performed with R version 4.1.1 (R Development Core Team).

Results

The baseline characteristics of patients are summarized in Table 1. Compared with the CAD group, the PAD group met more major and minor HBR criteria. At least one major bleeding criterion and one minor bleeding criterion were found in 61.5% and 79.3% of patients with PAD, respectively, whereas this was 32.0% and 65.9% in patients with CAD. The PAD group had significantly higher ARC-HBR scores compared with the CAD group (p < 0.001). Among the major criteria, severe or end-stage CKD was most frequently recognized, followed by hemoglobin < 11.0 g/dL and the anticipated use of long-term oral anticoagulation in both groups (Table 1). The prevalence rates of the representative ARC-HBR criteria between the two groups are presented in Figure 1. Patients meeting ARC-HBR criteria were found in 79.7% of the PAD group and 52.2% of the CAD group (p < 0.001; Table 1 and Figure 1).

Table 1.

Baseline patient characteristics of patients undergoing revascularization for PAD or CAD.

	PAD group	CAD group	p-value
	(n = 4343)	(n = 6238)
Male sex, n (%)	3092 (71.2)	4935 (79.1)	< 0.001
Age (years), mean ± SD	74 ± 9	71 ± 11	< 0.001
Major criteria for HBR, n (%)
Anticipated use of long-term oral anticoagulation	797 (18.4)	734 (11.8)	< 0.001
Severe or end-stage CKD (eGFR < 30 mL/min)	1726 (39.7)	737 (11.8)	< 0.001
Hemoglobin < 11.0 g/dL	909 (20.9)	610 (9.8)	< 0.001
Spontaneous bleeding requiring hospitalization or transfusion in the past 6 months or at any time, if recurrent	58 (1.3)	44 (0.7)	0.002
Moderate or severe baseline thrombocytopenia (platelet count < 100 × 10⁹/L)	18 (0.4)	11 (0.2)	0.034
Chronic bleeding diathesis	2 (0.1)	2 (0.1)	> 0.99
Liver cirrhosis with portal hypertension	4 (0.1)	7 (0.1)	0.99
Active malignancy (excluding nonmelanoma skin cancer) within the past 12 months	202 (4.7)	300 (4.8)	0.74
Previous spontaneous ICH (at any time)	126 (2.9)	105 (1.7)	< 0.001
Previous traumatic ICH within the past 12 months	6 (0.1)	8 (0.1)	> 0.99
Presence of a bAVM	18 (0.4)	16 (0.3)	0.22
Moderate or severe ischemic stroke within the past 6 months	86 (2.0)	62 (1.0)	< 0.001
Nondeferrable major surgery on DAPT	18 (0.4)	11 (0.2)	0.034
Recent major surgery or major trauma within 30 days before the index revascularization	7 (0.2)	14 (0.2)	0.62
Number of major criteria met, n (%)			< 0.001
No criterion	1672 (38.5)	4239 (68.0)
1 criterion	1616 (37.2)	1433 (23.0)
2 criteria	837 (19.3)	481 (7.7)
3 criteria	190 (4.4)	77 (1.2)
4 criteria	23 (0.5)	5 (0.1)
5 criteria	5 (0.1)	3 (0.0)
More criteria	0 (0.0)	0 (0.0)
Minor criteria for HBR, n (%)
Age ⩾ 75 years	2259 (52.0)	2501 (40.1)	< 0.001
Moderate CKD (eGFR 30–59 mL/min)	1309 (30.1)	2332 (37.4)	< 0.001
Hemoglobin 11–12.9 g/dL for men and 11–11.9 g/dL for women	1403 (32.3)	1279 (20.5)	< 0.001
Spontaneous bleeding requiring hospitalization or transfusion within the past 12 months not meeting the major criteria	35 (0.8)	24 (0.4)	0.006
Long-term use of oral NSAIDs or steroids	334 (7.7)	200 (3.2)	< 0.001
Any ischemic stroke at any time not meeting the major criteria	752 (17.3)	629 (10.1)	< 0.001
Number of minor criteria met, n (%)			< 0.001
No criterion	901 (20.7)	2128 (34.1)
1 criterion	1513 (34.8)	1975 (31.7)
2 criteria	1308 (30.1)	1495 (24.0)
3 criteria	525 (12.1)	560 (9.0)
4 criteria	92 (2.1)	80 (1.3)
5 criteria	4 (0.1)	0 (0.0)
More criteria	0 (0.0)	0 (0.0)
ARC-HBR (at least 1 major or 2 minor criteria met), n (%)	3463 (79.7)	3256 (52.2)	< 0.001
Antiplatelet therapy, n (%)			< 0.001
SAPT	1366 (31.5)	454 (7.3)
DAPT	2791 (64.3)	5756 (92.3)
Repeat revascularization, n (%)	1808 (42.3)	2132 (34.2)	< 0.001
(missing data)	71 (1.6)	6 (0.1)	< 0.001
Transfemoral access	3823 (88.1)	1217 (19.5)	< 0.001
(missing data)	2 (0.1)	3 (0.1)	> 0.99
Vulnerabilities
Malnutrition, n (%)	1215 (28.3)	815 (13.3)	< 0.001
(missing data)	51 (1.2)	90 (1.4)	0.27
Frailty, n (%)	1162 (26.8)	490 (7.9)	< 0.001
(missing data)	3 (0.1)	5 (0.1)	> 0.99
Receiving nursing care, n (%)	899 (20.8)	339 (5.5)	< 0.001
(missing data)	11 (0.3)	22 (0.4)	0.47
Receiving welfare, n (%)	460 (10.6)	315 (5.0)	< 0.001
Staying in nursing home, n (%)	195 (4.5)	67 (1.1)	< 0.001
(missing data)	6 (0.1)	14 (0.2)	0.44

Categorical variables are expressed as number and percentage. Continuous variables are indicated as mean ± SD.

ARC, Academic Research Consortium; bAVM, brain arteriovenous malformation; CAD, coronary artery disease; CKD, chronic kidney disease; DAPT, dual antiplatelet therapy; eGFR, estimated glomerular filtration rate; HBR, high bleeding risk; ICH, intracranial hemorrhage; NSAIDs, nonsteroidal antiinflammatory drugs; PAD, peripheral artery disease; SAPT, single antiplatelet therapy.

During a median follow-up of 27.4 months, 385 incidences of major bleeding were recorded. Figure 2 shows that the crude incidence rate of major bleeding was 19.1 (95% CI, 16.7–21.9) per 1000 person-years in the PAD group, which was higher than that in the CAD group (10.7 [95% CI, 9.2–12.4] per 1000 person-years). The incidence RR of PAD versus CAD was 1.79 (95% CI, 1.46–2.18; p < 0.001). The 3-year cumulative incidence rates of major bleeding were 3.9% (95% CI, 3.3–4.6%) and 2.6% (95% CI, 2.2–3.1%) in the PAD and CAD groups, respectively (Figure 3). The details of major bleeding events are shown in Table 2. Among nonfatal major bleeding events, gastrointestinal bleeding was most frequently observed in the PAD and CAD groups (i.e., 7.3 and 3.6 per 1000 person-years, respectively), with the PAD group having a significantly higher incidence (incidence RR: 2.01). However, the incidence RR was not statistically different from that of other bleeding events (all p > 0.05 vs GI bleeding) (Table 2).

Table 2.

Incidence and details of major bleeding by revascularization group.

Bleeding type	Incidence rate(per 1000 person-years)		Incidence risk ratio	p-value vs GI bleeding
Bleeding type	PAD group	CAD group	Incidence risk ratio	p-value vs GI bleeding
Major bleeding (overall)	19.1 (16.7–21.9)	10.7 (9.2–12.4)	1.79 (1.46–2.18)
Fatal bleeding
Fatal cerebral hemorrhage	1.1 (0.6–2.0)	0.8 (0.4–1.3)	1.50 (0.68–3.28)	0.52
Other fatal bleeding	2.4 (1.6–3.5)	1.4 (0.9–2.1)	1.69 (0.96–2.96)	0.65
Nonfatal major bleeding
Cerebral hemorrhage	3.8 (2.8–5.2)	2.5 (1.8–3.3)	1.54 (1.00–2.38)	0.42
GI bleeding	7.3 (5.8–9.1)	3.6 (2.8–4.6)	2.01 (1.44–2.81)	ref.
Procedure-related bleeding	1.9 (1.2–2.9)	0.9 (0.6–1.5)	2.03 (1.05–3.91)	0.98
Traumatic bleeding	0.7 (0.3–1.4)	0.1 (0.0–0.5)	5.67 (1.18–27.3)	0.22
Other bleeding	2.0 (1.3–3.0)	1.4 (0.9–2.1)	1.42 (0.79–2.55)	0.39

The incidence rates of major bleeding events are expressed in person-years.

Values in parentheses are 95% CIs.

CAD, coronary artery disease; GI, gastrointestinal; PAD, peripheral artery disease.

The results of multivariable Poisson regression analysis demonstrated that PAD versus CAD was not significantly associated with incident major bleeding after adjusting for major and minor HBR criteria (Table 3). In multivariable model 1, the adjusted incidence RR was 1.14 (95% CI, 0.93–1.40; p = 0.22). Meeting one or more major criteria and two or more minor criteria for ARC-HBR was independently associated with incident major bleeding. Baseline DAPT was prescribed for more patients in the CAD than in the PAD group (Table 1). However, DAPT was not an independent predictor of incident major bleeding after adjusting for ARC-HBR in multivariable model 2 (Table 3). In multivariable model 3, transfemoral access was another independent risk factor for incident major bleeding in the whole population, but not other factors including repeat procedure and background characteristics related to vulnerability (Table 3).

Table 3.

Risk ratios of major bleeding events in the PAD and CAD revascularization groups.

	Unadjusted incidence RR(univariable model)	p-value	Adjusted incidence RR(multivariable model 1)	p-value	Adjusted incidence RR(multivariable model 2)	p-value	Adjusted incidence RR(multivariable model 3)	p-value
PAD versus CAD	1.79 (1.46–2.18)	< 0.001	1.14 (0.93–1.40)	0.22	1.14 (0.92–1.42)	0.22	0.87 (0.66–1.14)	0.31
Number of major criteria for HBR
No criterion	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
1 criterion	2.80 (2.17–3.62)	< 0.001	2.52 (1.95–3.27)	< 0.001	2.53 (1.95–3.29)	< 0.001	2.43 (1.86–3.17)	< 0.001
2 criteria	6.28 (4.81–8.20)	< 0.001	6.15 (4.68–8.08)	< 0.001	6.18 (4.67–8.16)	< 0.001	5.72 (4.26–7.68)	< 0.001
3 or more	10.4 (7.06–15.30)	< 0.001	10.77 (7.24–16.02)	< 0.001	10.8 (7.23–16.20)	< 0.001	10.3 (6.76–15.80)	< 0.001
Number of minor criteria for HBR
No criterion	1.00 (ref.)		1.00 (ref.)		1.00 (ref.)		1.00 (ref.)
1 criterion	1.39 (1.03–1.89)	0.033	1.16 (0.85–1.57)	0.35	1.16 (0.85–1.57)	0.35	1.16 (0.85–1.58)	0.35
2 criteria	2.03 (1.51–2.74)	< 0.001	1.72 (1.27–2.32)	< 0.001	1.72 (1.27–2.32)	< 0.001	1.75 (1.29–2.37)	< 0.001
3 or more	3.75 (2.75–5.11)	< 0.001	3.60 (2.63–4.92)	< 0.001	3.61 (2.64–4.94)	< 0.001	3.63 (2.63–5.02)	< 0.001
DAPT	0.51 (0.41–0.63)	< 0.001	N/I		1.02 (0.80–1.29)	0.89	0.99 (0.78–1.26)	0.93
Male sex	0.79 (0.63–0.99)	0.039	N/I		N/I		0.95 (0.76–1.20)	0.68
Transfemoral access	2.12 (1.72–2.60)	< 0.001	N/I		N/I		1.54 (1.17–2.03)	0.002
Repeat revascularization	1.03 (0.84–1.27)	0.76	N/I		N/I		0.88 (0.72–1.08)	0.23
Malnutrition	2.11 (1.68–2.64)	< 0.001	N/I		N/I		1.04 (0.82–1.33)	0.74
Frailty	2.28 (1.80–2.90)	< 0.001	N/I		N/I		1.23 (0.94–1.61)	0.14
Receiving nursing care	2.10 (1.60–2.76)	< 0.001	N/I		N/I		0.90 (0.66–1.24)	0.53
Receiving welfare	0.91 (0.60–1.37)	0.65	N/I		N/I		0.82 (0.54–1.24)	0.34
Staying in nursing home	1.39 (0.66–2.94)	0.39	N/I		N/I		0.68 (0.31–1.48)	0.33

Data are incidence RRs for major bleeding (95% CIs).

Explanatory variables included in multivariable model 1: PAD versus CAD, number of major criteria for HBR, and number of minor criteria for HBR.

Explanatory variables included in multivariable model 2: multivariable model 1 plus DAPT.

Explanatory variables included in multivariable model 3: multivariable model 2 plus male sex, transfemoral access, repeat revascularization, malnutrition, frailty, receiving nursing care, receiving welfare, and staying in nursing home.

CAD, coronary artery disease; DAPT, dual antiplatelet therapy; HBR, high bleeding risk; N/I, not included; PAD, peripheral artery disease; RR, risk ratio.

Discussion

The principal finding of this study is that patients with PAD met more major and minor ARC-HBR criteria than those with CAD. According to previous studies, bleeding events after PCI are closely associated with adverse outcomes in patients with CAD.^5
–8 The ARC-HBR criteria were developed to identify high-risk patients and guide antithrombotic strategies.^7,8 Recent studies suggested that the ARC-HBR criteria could also be associated with bleeding events in patients with PAD after revascularization.^9,10 Tomoi et al. demonstrated that HBR was observed in 80.3% of 542 patients with femoropopliteal artery disease treated with endovascular therapy (EVT).⁹ Meanwhile, Yoshioka et al. suggested that the accumulation of ARC-HBR criteria was associated with increased risk of incident major bleeding after EVT in 732 patients with PAD.¹⁰ However, these studies were retrospective and included relatively few patients with PAD. Furthermore, although the ARC-HBR consensus was proposed based on previous studies investigating patients with CAD treated with PCI, the difference in its clinical impact between patients with PAD and CAD has not yet been assessed in large-scale clinical registries.^7
–10

One of the key strengths of our study lies in its prospective, multicenter design that leverages the large-scale ASPARAGUS registry, which has systematically documented bleeding events and baseline risk profiles across PAD and CAD populations. Unlike previous studies that focused on PAD or CAD separately, our integrated approach allowed for a direct head-to-head comparison using the standardized ARC-HBR criteria. The present study showed that patients with PAD met ARC-HBR criteria more frequently than those with CAD, reflecting a higher burden of comorbidities (e.g., severe CKD and anemia) and greater need for long-term oral anticoagulation.

Our study demonstrated that patients with PAD had a higher risk of incident major bleeding after revascularization than those with CAD, and that the risk of bleeding events can largely be explained by the prevalence of ARC-HBR factors. After multivariable adjustment (Table 3), including major and minor ARC-HBR criteria, PAD per se was not independently associated with incident major bleeding and may be a marker of higher bleeding risk compared with CAD. This finding underscores the clinical utility of the ARC-HBR criteria in both PAD and CAD and supports their application in patients with PAD for bleeding risk stratification.

We evaluated whether incident major bleeding was influenced by baseline characteristics other than ARC-HBR. The results of multivariable analysis showed that transfemoral access was an independent predictor of bleeding in the whole population. Transfemoral access is a classical bleeding risk compared with other arterial access sites.^17,18 In our study, revascularization was frequently performed via femoral arteries in patients with PAD (Table 1). However, according to multivariable analysis (Table 3), the higher incidence of major bleeding in patients with PAD was explained by their higher ARC-HBR scores. Transfemoral access was another important risk factor for major bleeding apart from ARC-HBR, in patients with PAD and those with CAD.

We also assessed whether the incidence of major bleeding was influenced by baseline DAPT, frailty, and factors related to vulnerability. Our results showed that these factors were not independently associated with the bleeding risk. DAPT was received by more patients in the CAD group, and univariate analysis showed that DAPT was inversely associated with incident major bleeding (Table 3). The possible reason might be that intensive antithrombotic therapy tended to be avoided in patients with PAD, who were at higher risk of bleeding complications. Multivariable model 2 (Table 3) showed that DAPT may not have additional impact on incident major bleeding after adjustment for ARC-HBR. Similarly, other factors related to frailty and vulnerability were also not significantly associated with bleeding risk in the multivariable analysis (Table 3). However, the lack of significance may come from the methods used to define and evaluate these patient backgrounds. Further investigations will be needed to clarify their influence on incident bleeding events.

This study has several limitations. First, this work included only Asian patients. Hence, the clinical outcomes might not be generalize to other populations. Second, we focused only on major bleeding (BARC types 3 or 5) and did not capture clinically relevant nonmajor bleeding. Third, we exclusively analyzed patients who were undergoing revascularization. Patients who do not require revascularization may have different characteristics. Moreover, whether these findings can be extrapolated to broader PAD and CAD populations remains unknown. Fourth, we did not collect detailed data on antithrombotic agents, including the type, dose, and continuation. Fifth, the breakdown of bleeding events other than cerebral, gastrointestinal, procedure-related, and traumatic hemorrhage remains unknown. Finally, treatment strategies and procedural characteristics, including details of access sites (e.g., single or multiple cannulations) and arterial approaches other than transfemoral, could not be fully accounted for in the analysis.

Conclusion

This study suggests that patients undergoing revascularization for symptomatic PAD had higher crude incidence rates of major bleeding compared with those with CAD. Their higher incidence of major bleeding is largely driven by their higher prevalence of ARC-HBR-defined risk factors. The ARC-HBR criteria may be useful to stratify bleeding risk in both populations.

Supplemental Material

sj-docx-1-vmj-10.1177_1358863X251415140 – Supplemental material for Comparison of bleeding complications between patients with peripheral and coronary artery disease after revascularization: Insights from ASPARAGUS, a prospective observational study

Supplemental material, sj-docx-1-vmj-10.1177_1358863X251415140 for Comparison of bleeding complications between patients with peripheral and coronary artery disease after revascularization: Insights from ASPARAGUS, a prospective observational study by Kazunori Horie, Mitsuyoshi Takahara, Yoshimitsu Soga, Norio Tada and Osamu Iida in Vascular Medicine

Footnotes

Acknowledgements

The authors thank all collaborators at the participating centers (please refer to the ) for their great contributions to the conduct of the ASPARAGUS study.

An editorial by Ujueta and Secemsky¹⁹ accompanies this article.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The ASPARAGUS study was supported by the Research Association for Lower Limb Artery Revascularization (LIBERAL), which is sponsored by the following companies (in alphabetical order): Althent, Inc.; Fides-one, Inc.; Kaneka Corporation; Miyano Medical Instruments Co., Ltd; OrbusNeich Medical K.K.; SUN MEDICAL Co., Ltd; TOWN Homecare Clinic; Terumo Corp.; and YAGAMI Co., Ltd. The funding companies played no roles in study design, selection of enrolled patients, treatment strategy, revascularization procedures, data collection, analysis, and preparing the manuscript.

ORCID iDs

Kazunori Horie

Mitsuyoshi Takahara

Yoshimitsu Soga

Norio Tada

Osamu Iida

Supplemental material

Supplemental material for this article is available online.

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