Sex Differences in Outcomes of Complex Percutaneous Coronary Interventions Assisted With Mechanical Circulatory Support Devices

Abstract

Background

Sex-based disparities persist in the management of patients with coronary artery disease undergoing complex percutaneous coronary intervention (PCI).

Objectives

The purpose of this study was to evaluate sex differences in early and late outcomes among patients undergoing mechanical circulatory support (MCS)–assisted complex PCI.

Methods

We conducted a retrospective analysis of hemodynamically stable patients who underwent complex PCI assisted with either an intra-aortic balloon pump or Impella (Abiomed) at a single center between 2017 and 2022. The primary endpoint was 1-year major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction, and stroke. Secondary endpoints included individual MACE components, target vessel revascularization, bleeding, and procedural complications.

Results

Among the 605 included patients, 24% were women (n = 145). Women had a higher comorbidity burden, presented more frequently with non–ST-segment elevation myocardial infarction, and experienced significantly more in-hospital complications, particularly bleeding. At 1 year, women had higher rates of MACE compared with men (25.5% vs 13.8%; P = 0.002), driven largely by excess mortality (20.8% vs 10.2%; P = 0.003), irrespective of MCS device type. After multivariable adjustment, the difference in MACE was no longer statistically significant (adjusted HR: 1.34; 95% CI: 0.74-3.03; P = 0.337).

Conclusions

Women undergoing complex PCI with MCS support experienced higher procedural risk and worse early outcomes, yet adjusted 1-year MACE rates were comparable to men. The marked absolute differences in bleeding and mortality highlight the need for sex-specific approaches to patient selection, procedural planning, and post-PCI management in this high-risk population.

Central Illustration

Sex-based disparities continue to exist in the diagnosis, management, and outcomes of cardiovascular disease, including patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI).1, 2, 3 Compared to men, women presenting with stable ischemic heart disease and acute coronary syndromes (ACS) have less use of guideline-directed therapies and less access to revascularization resulting in higher unadjusted mortality.4, 5, 6 Such disparities are also evident among patients undergoing complex coronary interventions, which usually involve multivessel or multilesion coronary disease and/or treatment of left main disease, bifurcation lesions, chronic total occlusions, graft lesions, and severely calcified lesions.7, 8, 9 Recently, the use of mechanical circulatory support (MCS) devices such as intra-aortic balloon pumps (IABP) and the microaxial flow pump Impella (Abiomed) has been shown to improve outcomes by stabilizing hemodynamics and reducing the risk of complications and has emerged as an important intervention for patients undergoing complex PCI.¹⁰ However, studies on MCS devices were mainly conducted in cohort of patients with male predominance leading to a knowledge gap in understanding outcomes in females.^10,11

The aim of our study is to assess sex differences in patients undergoing high-risk PCI protected with MCS in a large single-center cohort, comparing procedural, early, and late complications.

Methods

Study population and design

We conducted a retrospective, sex-stratified analysis of all hemodynamically stable patients undergoing complex or high-risk PCI supported by MCS devices—either IABP or Impella—at Mount Sinai Hospital, a large tertiary academic center in New York, United States, between 2017 and 2022. As per our institutional practice, MCS is indicated for high-risk PCI, defined by the presence of complex anatomical feature, such as intervention on an unprotected left main coronary artery, bifurcation lesions, chronic total occlusions, graft lesions, multivessel disease, or severe calcification requiring atherectomy, and/or additional clinical risk factors, including last remaining vessel, reduced left ventricular ejection fraction, or significant comorbidities. Of note, patients presenting with cardiogenic shock were excluded from this analysis. Informed consent was obtained from all patients and the registry has been approved by local Institutional Review Board. PCI was performed according to standard technique, and device selection was left to clinician discretion.

Endpoints

The primary endpoint of this study was major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction (MI), and stroke at 1-year follow-up. Secondary endpoints included individual components of the primary endpoint, target vessel revascularization, postprocedural and in-hospital complications, including bleeding.

Statistical analysis

Continuous variables are presented as mean ± SD or as median (IQR) and compared using the Student’s t-test, Mann-Whitney U test, or Wilcoxon test based on data distribution. Categorical variables are shown as number (percent) and were compared using the chi-square test with Yates correction for continuity or the Fisher exact test, as appropriate. Clinical follow-up was censored at the date of death or at 1 year. Data for patients lost to follow-up were censored at the time of last contact. Risk estimates are presented as HR with 95% CIs. Multivariable adjustment was performed using the Cox regression method, including the following variables: age, body mass index, left main PCI, multivessel disease, calcification (moderate or severe), left ventricular ejection fraction<40%, oral anticoagulation, anemia, peripheral artery disease, cerebrovascular disease, and chronic kidney disease. The cumulative incidence of adverse events at 1 year was assessed using the Kaplan-Meier method and compared between groups using the log-rank test for time to first event. P values <0.05 were considered statistically significant. All statistical analyses were conducted at the Icahn School of Medicine at Mount Sinai, New York, NY, using Stata software version 18.0 (StataCorp) and SAS version 9.4 (SAS Institute, Inc).

Results

A total of 605 patients were included, with women comprising 24% of the study population (n = 145). Women presented with more advanced age, higher body mass index, and multiple comorbidities as noted in Table 1. Anemia (56.4% vs 45.3%; P = 0.025), insulin-dependent diabetes mellitus (35.9% vs 21.7%; P = 0.001), lung disease (15.9% vs 7.0%; P = 0.001), peripheral arterial disease (17.2% vs 9.8%; P = 0.014), cerebrovascular disease (20.0% vs 10.9%; P = 0.004), dialysis (12.4% vs 7.2%; P = 0.048), and chronic kidney disease (52.4% vs 35.2%; P = 0.001) were statistically higher in women. Most women undergoing PCI presenting in the setting of non–ST-segment elevation myocardial infraction (40.0% vs 26.6%; P = 0.002), while men mainly presented with stable angina (41.1% vs 27.9; P = 0.005). There was no statistically significant difference in target PCI vessels, procedural complexity, lesions morphology or length between the 2 groups (Table 2). At discharge, women were less likely to be on dual antiplatelet therapy (77.4% vs 84.8%; P = 0.042).

Table 1.

Baseline Clinical Characteristics

Outcome	Overall (N = 605)	Female (n = 145, 24.0%)	Male (n = 460, 76.0%)	P Value
Patient demographics
Age, y	69.7 ± 12.0	72.9 ± 11.6	68.6 ± 11.9	<0.001
BMI, kg/m2	27.7 ± 5.5	28.7 ± 6.2	27.4 ± 5.3	0.021
Race/ethnicity				0.005
Caucasian	250 (55.3%)	59 (53.6%)	191 (55.8%)
African American	58 (12.8%)	21 (19.1%)	37 (10.8%)
Asian	67 (14.8%)	7 (6.4%)	60 (17.5%)
Hispanic	77 (17.0%)	23 (20.9%)	54 (15.8%)
Medical history
Current smoker	60 (9.9%)	14 (9.7%)	46 (10.0%)	0.904
Family history of CAD	74 (12.2%)	9 (6.2%)	65 (14.1%)	0.011
Anemia	268 (47.9%)	75 (56.4%)	193 (45.3%)	0.025
Diabetes mellitus	311 (51.4%)	83 (57.2%)	228 (49.6%)	0.107
Insulin dependent	152 (25.1%)	52 (35.9%)	100 (21.7%)	<0.001
Hypertension	555 (91.7%)	138 (95.2%)	417 (90.7%)	0.085
Hyperlipidemia	505 (83.5%)	114 (78.6%)	391 (85.0%)	0.071
Lung disease	55 (9.1%)	23 (15.9%)	32 (7.0%)	0.001
Peripheral artery disease	70 (11.6%)	25 (17.2%)	45 (9.8%)	0.014
Cerebrovascular disease	79 (13.1%)	29 (20.0%)	50 (10.9%)	0.004
Atrial fibrillation	76 (12.6%)	17 (11.7%)	59 (12.8%)	0.727
Dialysis	51 (8.4%)	18 (12.4%)	33 (7.2%)	0.048
Chronic kidney disease	238 (39.3%)	76 (52.4%)	162 (35.2%)	<0.001
Prior PCI	262 (43.3%)	53 (36.6%)	209 (45.4%)	0.060
Prior MI	203 (33.6%)	43 (29.7%)	160 (34.8%)	0.254
Prior CABG	60 (9.9%)	10 (6.9%)	50 (10.9%)	0.163
LVEF, %	38.7 ± 14.9	40.6 ± 15.6	38.1 ± 14.7	0.081
PCI presentation
Asymptomatic	21 (3.6%)	3 (2.1%)	18 (4.0%)	0.297
Stable angina	223 (37.9%)	39 (27.9%)	184 (41.1%)	0.005
Unstable angina	90 (15.3%)	27 (19.3%)	63 (14.1%)	0.134
NSTEMI	175 (29.8%)	56 (40.0%)	119 (26.6%)	0.002
STEMI	79 (13.4%)	15 (10.7%)	64 (14.3%)	0.279

BMI = body mass index; CAD = coronary artery disease; PCI = percutaneous coronary intervention; MI = myocardial infarction; CABG = coronary artery bypass grafting; LVEF = left ventricular ejection fraction; NSTEMI = non–ST-segment elevation myocardial infarction; STEMI = ST-segment elevation myocardial infarction.

Table 2.

Baseline Procedural Characteristics

Outcome	Overall (N = 605)	Female (n = 145, 24.0%)	Male (n = 460, 76.0%)	P Value
Radial access	23 (3.8%)	2 (1.4%)	21 (4.6%)	0.080
Femoral access	534 (88.3%)	129 (89.0%)	405 (88.0%)	0.764
PCI vessels
Left main	189 (31.3%)	48 (33.1%)	141 (30.7%)	0.589
LAD	526 (87.1%)	128 (88.3%)	398 (86.7%)	0.624
LCX	443 (73.3%)	101 (69.7%)	342 (74.5%)	0.249
RCA	390 (64.6%)	86 (59.3%)	304 (66.2%)	0.129
Multivessel disease	529 (87.4%)	119 (82.1%)	410 (89.1%)	0.025
Lesions and stents
B2/C lesion	535 (88.4%)	125 (86.2%)	410 (89.1%)	0.337
Calcification (moderate/severe)	266 (44.0%)	73 (50.3%)	193 (42.0%)	0.076
Bifurcation	231 (38.2%)	54 (37.2%)	177 (38.5%)	0.789
Chronic total occlusion	55 (9.1%)	9 (6.2%)	46 (10.0%)	0.166
Total lesion length, mm	35.0 ± 20.9	34.6 ± 19.7	35.2 ± 21.3	0.782
Total stent length, mm	114.4 ± 73.5	111.2 ± 76.0	115.4 ± 72.7	0.588
No. of stents implanted	2.2 ± 1.2	2.1 ± 1.1	2.2 ± 1.2	0.342
No. of lesions treated	1.3 ± 0.7	1.3 ± 0.7	1.3 ± 0.7	0.728
Maximum stent diameter, mm	3.6 ± 0.5	3.6 ± 0.5	3.6 ± 0.5	0.301
Syntax score	28.8 ± 15.0	27.9 ± 15.1	29.1 ± 14.9	0.416
Discharge medication
DAPT	481 (83.1%)	106 (77.4%)	375 (84.8%)	0.042
Aspirin	487 (84.1%)	107 (78.1%)	380 (86.0%)	0.028
P2y12-inhibitors	559 (96.5%)	130 (94.9%)	429 (97.1%)	0.281
Oral anticoagulants	97 (17.1%)	23 (17.4%)	74 (17.1%)	0.921
Statin	543 (93.8%)	127 (92.7%)	416 (94.1%)	0.548
Beta-blocker	490 (84.6%)	114 (83.2%)	376 (85.1%)	0.599

DAPT = dual antiplatelet therapy; LAD = left anterior descending artery; LCX = left circumflex artery; RCA = right coronary artery; other abbreviation as in Table 1.

In-hospital outcomes

We observed higher periprocedural hemorrhagic complications (9.0% vs 4.4%; P = 0.033) and in-hospital bleeding (27.6% vs 14.3%; P < 0.001), post procedure transfusion (19.3% vs 8.7%; P = 0.001), post procedure congestive heart failure (6.9% vs 1.5%; P = 0.002), and death (8.3% vs 3.9%; P = 0.035) in women compared to men (Table 3). Occurrence of early in-hospital bleeding was strongly associated with higher risk of mortality in both women (HR: 3.16; 95% CI: 1.46-6.84; P = 0.004) and men (HR: 3.83; 95% CI: 2.01-7.31; P < 0.001), with no statistically significant interaction (P-interaction = 0.694), a finding that persisted after adjustment for multiple covariates (P-interaction = 0.796).

Table 3.

Periprocedural Complications

Outcome	Overall (N = 605)	Female (n = 145, 24.0%)	Male (n = 460, 76.0%)	P Value
Dissection, grade C or higher	16 (2.6%)	4 (2.8%)	12 (2.6%)	1.000
Side branch closure	25 (5.9%)	6 (5.5%)	19 (6.0%)	0.830
Tamponade	10 (1.7%)	4 (2.8%)	6 (1.3%)	0.263
Slow flow/no flow	53 (8.8%)	14 (9.7%)	39 (8.5%)	0.662
Vessel closure	15 (3.5%)	4 (3.6%)	11 (3.5%)	1.000
Post procedure death	30 (5.0%)	12 (8.3%)	18 (3.9%)	0.035
Post procedure MI	144 (23.8%)	29 (20.0%)	115 (25.1%)	0.213
Post procedure blood transfusion	68 (11.2%)	28 (19.3%)	40 (8.7%)	<0.001
Periprocedural bleeding	33 (5.5%)	13 (9.0%)	20 (4.4%)	0.033
In-hospital bleedinga	106 (17.5%)	40 (27.6%)	66 (14.3%)	<0.001
Post procedure stroke	5 (0.8%)	2 (1.4%)	3 (0.7%)	0.598
Post procedure HF	17 (2.8%)	10 (6.9%)	7 (1.5%)	0.002
Post procedure CABG	7 (1.2%)	2 (1.4%)	5 (1.1%)	0.676
Post procedure dialysis	9 (1.5%)	4 (2.8%)	5 (1.1%)	0.229

CABG = coronary artery bypass grafting; HF = heart failure; other abbreviation as in Table 1.

^aIncludes periprocedural bleeding, in-hospital bleeding requiring transfusion, and/or causing hemoglobin drop ≥3 g/dL.

Long-term clinical outcomes

A total of 447 patients completed 1-year follow-up or experienced MACE, representing 86.4% of the target population; patients lost to follow up were censored in the time-to-event analysis at their last contact date. At 1-year follow-up, the unadjusted rate of death, MI, and stroke was significantly higher in women compared to men (25.5%; 95% CI: 18.7%-34.2% vs 13.8%; 95% CI: 10.7%-17.7%; P = 0.002, Figure 1), mainly driven by excess in mortality (20.8%; 95% CI: 14.6%-29.1% vs 10.2%; 95% CI: 7.6%-13.6%; P = 0.003). However, after multivariable adjustment, no statistically significant difference in MACE was observed between the 2 groups (HR: 1.34; 95% CI: 0.74-3.03; P = 0.337). Notably, there was no difference in MI and target vessel revascularization, but women experienced a significantly higher rate of all-cause bleeding within 1 year post-PCI with a numerical, although nonsignificant, increase in postdischarge bleeding (Table 4). There was no evidence of heterogeneity by device type (IABP vs Impella), and the interaction term was not statistically significant for any of the outcomes (Table 5).

Figure 1.

One-Year Outcomes Following MCS-Assisted PCI Stratified by Sex

MCS = mechanical circulatory support; MI = myocardial infarction; PCI = percutaneous coronary intervention.

Table 4.

Unadjusted and Adjusted Association Between Sex and Outcomes at One Year After PCI

Outcome	Female (n = 145, 24.0%)	Male (n = 460, 76.0%)	HR (95% CI)	P Value	Adjusted HR (95% CI)	P Value
Death, MI, or stroke	32 (25.5%)	55 (13.8%)	1.96 (1.27-3.03)	0.002	1.34 (0.74-2.42)	0.337
All-cause death	26 (20.8%)	41 (10.2%)	2.12 (1.30-3.46)	0.003	1.45 (0.69-3.07)	0.329
MI	7 (6.6%)	16 (4.5%)	1.49 (0.61-3.63)	0.377	1.07 (0.42-2.70)	0.885
TVR	14 (13.2%)	52 (14.6%)	0.91 (0.50-1.63)	0.741	0.85 (0.46-1.59)	0.615
Stroke	1 (0.8%)	0 (0.0%)	N/A	N/A	N/A	N/A
Postdischarge bleeding	6 (5.2%)	9 (2.5%)	2.28 (0.81-6.41)	0.117	2.28 (0.74-6.96)	0.150
All bleeding	44 (30.8%)	72 (15.9%)	1.97 (1.35-2.87)	<0.001	1.94 (1.25-3.01)	0.003

The percentages mentioned above represent K-M rates at 1 year after procedure.

Model adjusted for: left main PCI, multivessel disease, calcification (moderate/severe), LVEF ≤ 40%, oral anticoagulation, age, BMI, anemia, PAD, CVD, CKD. Reference = male.

CKD = chronic kidney disease; CVD = cerebovascascular disease; PAD = peripheral artery disease; TVR = target vessel revascularization; other abbreviations as in Table 1.

Table 5.

Unadjusted and Adjusted Associations Between MCS Device and Outcomes at 1 Year After PCI Stratified by Sex

Outcomes	Female (N = 144)				Male (N = 454)
	Impella (n = 80)	IABP (n = 64)	HR (95% CI)	Adjusted HRa (95% CI)	Impella (n = 306)	IABP (n = 148)	HR (95% CI)	Adjusted HRa (95% CI)
Death, MI, or stroke	16 (23.2%)	15 (27.2%)	0.77 (0.38-1.55)	1.01 (0.34-3.02)	39 (14.8%)	13 (10.0%)	1.41 (0.75-2.63)	1.00 (0.42-2.35)
All-cause death	12 (17.6%)	13 (23.5%)	0.65 (0.30-1.42)	0.90 (0.22-3.75)	29 (10.8%)	9 (7.0%)	1.52 (0.72-3.21)	1.22 (0.39-3.88)
MI	5 (7.8%)	2 (4.9%)	1.75 (0.34-9.01)	1.01 (0.12-8.83)	12 (5.3%)	4 (3.1%)	1.41 (0.46-4.38)	1.04 (0.29-3.69)
TVR	8 (12.4%)	6 (14.5%)	0.93 (0.32-2.68)	0.95 (0.21-4.23)	33 (14.3%)	19 (15.6%)	0.80 (0.45-1.41)	1.05 (0.54-2.02)
Stroke	0 (0.0%)	1 (2.0%)	N/A	N/A	0 (0.0%)	0 (0.0%)	N/A	N/A
Postdischarge bleeding	3 (4.3%)	3 (6.8%)	0.69 (0.14-3.40)	0.50 (0.07-3.45)	6 (2.4%)	3 (2.6%)	0.94 (0.23-3.74)	0.49 (0.11-2.18)
All bleeding	22 (27.7%)	22 (35.4%)	0.79 (0.43-1.42)	0.86 (0.39-1.91)	44 (14.5%)	25 (17.3%)	0.85 (0.52-1.39)	0.76 (0.42-1.38)

The percentages mentioned above represent K-M rates at 12 months after index procedure. All interaction P values are not significant.

Reference = IABP.

Seven patients (6 males, 1 female) were removed from this analysis due to having both IABP and Impella.

IABP = intra-aortic balloon pump; other abbreviations as in Tables 1 and 4.

^aModel adjusted for: left main PCI, multivessel disease, calcification (moderate/severe), LVEF ≤40%, oral anticoagulation, age, BMI, anemia, PAD, CVD, and CKD.

Discussion

In contemporary practice, MCS is increasingly employed to mitigate hemodynamic compromise during complex PCIs, especially in the presence of high-risk clinical and/or procedural features.^12,13 In this study, we explored sex-based differences in clinical outcomes among hemodynamically stable patients undergoing complex high-risk PCI assisted with the use of MCS. The key findings of the study can be summarized as follows: 1) across a cohort of 605 patients meeting the inclusion criteria, women represented only 24% of the total; 2) women receiving MCS presented with a higher burden of comorbidities and were more likely to present with ACS; 3) they experienced worse in-hospital and 1-year outcomes, including higher rates of bleeding and mortality; and 4) no significant heterogeneity was observed in outcomes between patients supported with IABP vs Impella Central Illustration.

Central Illustration.

Sex-Based Characteristics and Outcomes in MCS-Assisted Complex PCI

Top panel: Baseline clinical and procedural characteristics of 605 patients undergoing MCS-assisted complex PCI, stratified by sex. Center panel: Unadjusted and adjusted 1-year clinical outcomes comparison in women vs men. Bottom panel: Distribution of MCS device use by sex types and associated clinical outcomes. adjHR = adjusted HR; BMI = body mass index; CCS = chronic coronary syndrome; CS = cardiogenic shock; IABP = intra-aortic balloon pump; LAD = left anterior descending artery; LCX = left circumflex artery; MACE = major adverse cardiovascular events; NSTEMI = non–ST-segment elevation myocardial infarction; RCA = right coronary artery; STEMI = ST-segment elevation myocardial infarction; other abbreviations as in Figure 1.

In our cohort, several important differences emerged between men and women in terms of clinical characteristics and periprocedural and postprocedural outcomes. Women comprised 24% of the total population, consistent with prior studies evaluating high-risk PCI with women ranging between 19% and 27%.^8,14,15 In addition, women were significantly older than men and had higher rates of comorbid conditions, including insulin-dependent diabetes mellitus, peripheral artery disease, chronic kidney disease, cerebrovascular disease, lung disease, and anemia. These findings are consistent with prior studies^16,17 and reflect a greater baseline risk profile in women undergoing complex PCI with MCS.^18,19 Despite similar procedural characteristics, women more often presented with ACS, particularly non–ST-segment elevation myocardial infarction, while men more frequently had stable CAD. This pattern may reflect referral or selection bias, suggesting that women are considered for MCS only when clinical acuity is high or after a greater accumulation of comorbidities. Such delayed or selective referral pathways may contribute to the more advanced disease state at presentation and partially explain the worse outcomes seen in women. These observations underscore the need for more tailored risk stratification, earlier identification of high-risk women, and equitable access to advanced support strategies.

In-hospital outcomes were notably worse among women, who experienced higher rates of bleeding, transfusion, heart failure, and mortality. These differences were likely multifactorial, driven by older age, greater comorbidity burden, and possibly anatomical factors such as smaller femoral artery size, which may increase the risk of vascular complications particularly in the context of large-bore access required for MCS. Notably, contemporary MCS technologies were largely developed and evaluated in predominantly male cohorts, raising concerns that device design and procedural strategies may be insufficiently tailored to women.^20,21 Vascular complications and bleeding are also powerful determinants of mortality,²² and in our analysis, early bleeding was strongly associated with death to a similar extent in both sexes although being more common in women.

At 1 year after PCI, the incidence of the primary outcome MACE was higher in women, primarily driven by higher all-cause death, although this difference was attenuated after multivariable adjustment. In the prospective, multicenter PROTECT III registry, which enrolled 1,237 patients (27% female) undergoing Impella-supported high-risk PCI, propensity-matched analyses demonstrated no significant sex differences in 90-day MACE.¹⁴ Taken together, these results suggest that the higher risk observed in women may be driven primarily by differences in baseline clinical characteristics. However, the absolute risk difference remains clinically meaningful and should not be discounted, particularly as our data also suggest that, in real-world practice, MCS may not be offered to women unless they present with very high risk. In addition, the adjusted HR for MACE indicated a 34% relative increase in risk, and the relatively small number of female patients may have limited the power to detect statistically significant differences even after adjustment. Crucially, the persistently higher event rates observed in women—both in the early and late phases—represent a concerning pattern that should prompt heightened clinical awareness and efforts to address potential gaps in care.

When comparing outcomes by MCS device type (Impella vs IABP), no statistically significant interaction was observed in our study. Importantly, however, the pattern we observed of worse outcomes in women appears to converge with observations from the recent randomized controlled trial DanGer Shock and its sex-specific analysis.^23,24 In this study of ST-segment elevation myocardial infarction–related cardiogenic shock patients randomized to Impella or standard of care, women (20.8% of total) had substantially higher 180-day mortality compared with men (64.9% vs 48.8%; P = 0.015). Moreover, although no statistically significant sex-by-treatment interaction was observed, women appeared to derive neutral benefit from microaxial pump support (HR: 1.01; 95% CI: 0.58-1.79) compared with a clear treatment benefit in men (HR: 0.66; 95% CI: 0.47-0.93). Of note, similarities should be interpreted cautiously since DanGer Shock examined patients with profound hemodynamic instability requiring emergent MCS, whereas our study evaluated MCS use in hemodynamically stable patients undergoing complex PCI. Nevertheless, the recurring pattern of worse outcomes or attenuated benefit in women across clinical contexts raises the possibility of a broader sex-specific signal that warrants further investigation. Determining whether these disparities arise from anatomical constraints, differences in clinical presentation, delayed referral, higher baseline risk, or potential underutilization of MCS in lower-risk women will be essential to improving outcomes in this population. The PROTECT IV trial (NCT04763200) is currently ongoing and is designed to provide definitive randomized evidence regarding the efficacy and safety of Impella in high-risk PCI compared to either no MCS or IABP. Until these results are available, careful patient selection for MCS is recommended.

Study limitations

This study has several important limitations. First, it was a retrospective, single-center analysis, which may limit the generalizability of the findings. While multivariable adjustment was performed to account for baseline imbalances, residual confounding cannot be excluded, particularly in light of significant differences in comorbidities and clinical presentation between sexes. Second, the relatively small number patients may have limited the statistical power to detect significant sex-specific differences in long-term outcomes, particularly in subgroup analyses comparing MCS devices. Third, device selection and use of MCS were left to operator discretion and might not be standardized across the cohort. Fourth, we lacked granular data on functional status, frailty, or patient-reported outcomes, which may have provided additional insight into sex-specific procedural risk and long-term prognosis. Finally, detailed data on sheath size, access-site imaging, closure device type, and specific access-management strategies were not available. Because these factors may influence bleeding and vascular complications, their absence limits our ability to fully interpret the higher bleeding rates observed in women. Future studies with standardized and comprehensive collection of access-related procedural variables will be essential to clarify these sex-specific differences and to guide targeted risk-mitigation strategies.

Conclusions

In this real-world cohort of hemodynamically stable patients undergoing complex high-risk PCI with MCS, women were fewer and presented with a greater comorbidity burden and clinical acuity. Despite significantly higher rates of in-hospital complications, including bleeding and mortality, adjusted 1-year MACE was comparable between sexes. No significant interaction was observed by device type, although a numerical trend favored Impella support in women. These findings highlight persistent sex-based disparities and underscore the need for tailored strategies to improve procedural safety and equitable care. Future randomized trials with adequate female representation are essential to validate these observations and guide sex-based decision-making in high-risk PCI.

Funding support and author disclosures

Dr Mehran has received institutional research payments from Abbott, Alleviant Medical, Beth Israel Deaconess Medical Center, Concept Medical, CPC Clinical Research, Cordis, Elixir Medical, Faraday Pharmaceuticals, Idorsia Pharmaceuticals, Janssen, MedAlliance, Mediasphere Medical, Medtronic, Novartis, Protembis GmbH, RM Global Bioaccess Fund Management, and Sanofi US Services, Inc; has received personal fees from Elixir Medical, IQVIA, Medtronic, Medscape/WebMD Global, and Novo Nordisk; has equity <1% in Elixir Medical, Stel, and ControlRad (spouse); has received no fees from SCAI (Women in Innovations Committee Member), Faculty Cardiovascular Research Foundation (CRF), and Women as One (Founding Director); and has received honorarium from AMA - JAMA Cardiology (Associate Editor) and the ACC (BOT Member, SC Member CTR Program). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.