DCB and Mortality: Systematic Review with ☸️SAIMSARA.

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Review Stats

Generated: 2025-10-06 17:00:28 CEST
Plan: Premium (expanded craft tokens; source: Europe PMC)
Source: Europe PMC
Scope: All fields
Keyword Gate: Fuzzy (≥60% of required terms, minimum 2 terms matched in title/abstract)
Total Abstracts/Papers: 1764
Downloaded Abstracts/Papers: 1764
Included original Abstracts/Papers: 246
Total study participants (naïve ΣN): 338100

Outcome-Sentiment Meta-Analysis (OSMA): (LLM-only)
Frame: Effect-of Predictor → Outcome • Source: Europe PMC
Outcome: mortality Typical timepoints: 12-mo, 2-y. Reported metrics: %, CI, p.
Common endpoints: Common endpoints: mortality, patency, survival.
Predictor: dcb — exposure/predictor. Doses/units seen: 6 μg. Routes seen: oral. Typical comparator: percutaneous transluminal, plain balloons, des in high-risk patients, dcb angioplasty alone….

1) Beneficial for patients — mortality with dcb — [9], [17], [18], [25], [26], [31], [32], [38], [74], [91], [92], [99], [109], [113], [114], [122], [123], [129], [136], [145], [149], [151], [156], [174], [175], [180], [192], [202], [209], [241] — ΣN=139744
2) Harmful for patients — mortality with dcb — [5], [8], [15], [16], [20], [51], [75], [85], [90], [93], [94], [115], [120], [124], [133], [143], [169], [210], [212], [213], [214], [216], [224], [226], [229], [232], [236], [242] — ΣN=26168
3) No clear effect — mortality with dcb — [1], [2], [3], [4], [6], [7], [10], [11], [12], [13], [14], [19], [21], [22], [23], [24], [27], [28], [29], [30], [33], [34], [35], [36], [37], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64], [65], [66], [67], [68], [69], [70], [71], [72], [73], [76], [77], [78], [79], [80], [81], [82], [83], [84], [86], [87], [88], [89], [95], [96], [97], [98], [100], [101], [102], [103], [104], [105], [106], [107], [108], [110], [111], [112], [116], [117], [118], [119], [121], [125], [126], [127], [128], [130], [131], [132], [134], [135], [137], [138], [139], [140], [141], [142], [144], [146], [147], [148], [150], [152], [153], [154], [155], [157], [158], [159], [160], [161], [162], [163], [164], [165], [166], [167], [168], [170], [171], [172], [173], [176], [177], [178], [179], [181], [182], [183], [184], [185], [186], [187], [188], [189], [190], [191], [193], [194], [195], [196], [197], [198], [199], [200], [201], [203], [204], [205], [206], [207], [208], [211], [215], [217], [218], [219], [220], [221], [222], [223], [225], [227], [228], [230], [231], [233], [234], [235], [237], [238], [239], [240], [243], [244], [245], [246] — ΣN=172188

1) Introduction
Drug-coated balloons (DCBs) represent a significant advancement in interventional cardiology and peripheral vascular disease treatment, designed to deliver antiproliferative agents directly to the vessel wall to prevent restenosis. While their efficacy in reducing target lesion revascularization has been widely explored, concerns regarding their long-term safety, particularly their association with all-cause mortality, have prompted extensive research. This paper synthesizes the current evidence on the relationship between DCB use and mortality outcomes across various vascular beds and patient populations.

2) Aim
The aim of this paper is to systematically review and synthesize the available evidence from recent scientific literature regarding the association between drug-coated balloon interventions and mortality, identifying key findings, clinical implications, and future research directions.

3) Methods
3.1 Eligibility criteria: This review included original studies investigating drug-coated balloon interventions and their association with mortality outcomes. Editorials, conference papers, and reviews were excluded.
3.2 Study selection: Studies were identified and filtered based on a strict keyword gate for "dcb and mortality" using an autonomous multilayer AI research agent. Only studies directly pertaining to drug-coated balloons in vascular interventions and reporting mortality data were considered for synthesis.
3.3 Risk of bias: The included studies comprised a mix of designs, including randomized controlled trials (RCTs), cohort studies (both prospective and retrospective), and mixed-design studies. RCTs generally offer the highest level of evidence, while retrospective cohort studies and mixed designs may be susceptible to confounding and selection bias. Sample sizes varied widely, from small case series to large registries and meta-analyses, impacting the statistical power to detect mortality differences. Follow-up periods also varied, ranging from short-term (e.g., 6 months) to long-term (up to 5 years or more), influencing the capture of late mortality events.
3.4 Synthesis: Autonomous multilayer AI research agent: keyword normalization, retrieval & structuring, and paper synthesis (see SAIMSARA About section for details).

4) Results
4.1 Study characteristics: The included studies predominantly featured cohort designs (both retrospective and prospective) and mixed methodologies, with a notable number of randomized controlled trials (RCTs). Populations frequently included patients with femoropopliteal artery disease, coronary artery disease, infrapopliteal lesions, and dysfunctional arteriovenous fistulas. Sample sizes ranged from as few as 8 [8] to over 9000 patients [3], with follow-up periods typically spanning 12 months to 5 years.
4.2 Main numerical result aligned to the query: Across studies reporting 12-month all-cause mortality rates following drug-coated balloon interventions, the median rate was 6.5% [206], with a range from 1.17% [159] to 12.1% [70]. While some studies indicated no significant differences in mortality between DCB and comparator groups (e.g., PTA, DES, BMS) [1, 3, 4, 13, 14, 30, 33, 34, 41, 44, 50, 54, 55, 60, 65, 67, 76, 77, 78, 81, 82, 83, 86, 87, 88, 89, 95, 96, 97, 101, 104, 112, 117, 128, 129, 131, 135, 151, 152, 153, 155, 158, 159, 162, 163, 166, 170, 172, 176, 179, 181, 183, 185, 186, 194, 196, 201, 203, 208], a few studies reported conflicting results, with one early study showing higher 24-month mortality in the DCB group (8.1% vs 0.9%, p=0.008) [210], and others suggesting a survival benefit for DCBs [9, 17, 123, 136, 151, 156, 202].
4.3 Topic synthesis:

DCB vs. Comparator Mortality: Many studies found no significant difference in all-cause mortality between DCB and plain old balloon angioplasty (PTA/POBA/UCB) [1, 30, 54, 55, 97, 101, 104, 131, 155, 162, 163, 170, 172, 176, 183], or between DCB and drug-eluting stents (DES) or bare metal stents (BMS) [44, 50, 53, 65, 76, 88, 146, 159, 196]. However, some reports indicated a lower mortality risk with DCB [9, 17, 123, 136, 151, 156, 202], while one early study showed a significantly higher 24-month mortality in DCB (8.1%) vs. PTA (0.9%) [210].
Paclitaxel Safety Concerns: Initial reports raised concerns about increased mortality with paclitaxel-coated balloons [75, 169]. However, numerous subsequent analyses and meta-analyses found no significant association between paclitaxel exposure and increased long-term mortality [1, 4, 30, 33, 34, 41, 44, 50, 54, 55, 60, 65, 67, 76, 77, 78, 81, 82, 83, 86, 87, 88, 89, 95, 96, 97, 101, 104, 112, 117, 128, 129, 131, 135, 136, 147, 149, 151, 152, 153, 155, 158, 159, 162, 163, 166, 170, 172, 175, 176, 179, 181, 183, 185, 186, 194, 196, 201, 203, 208].
Patient Comorbidities and Risk Factors: Chronic kidney disease (CKD) was consistently identified as an independent risk factor for unfavorable outcomes, including all-cause deaths, in patients undergoing PCI with DCB [5, 12, 20, 88, 124]. Diabetes mellitus (DM) was associated with higher mortality in some contexts [94], though DCB showed a survival benefit in high-risk DM patients in one study [9]. Higher iliac artery calcification burden was correlated with increased all-cause mortality [15]. Elderly patients had higher all-cause mortality rates attributed to age rather than DCB treatment [69].
Anatomical Location Specifics: For femoropopliteal lesions, 12-month all-cause mortality rates varied, e.g., 5.3% [64] to 11.6% [177], with no significant difference often reported against comparators. In infrapopliteal artery lesions, DCB was considered the worst treatment for 12-month all-cause mortality in one network meta-analysis [8], but other studies found no significant difference [13, 60, 77, 153, 172]. For coronary lesions, DCBs were associated with a trend toward lower all-cause mortality at 3 years [175] and lower incidence of myocardial infarction and all-cause mortality in de novo lesions [174], with similar outcomes to DES in small vessels [159].
Long-Term Mortality Outcomes: Freedom from all-cause mortality at 5 years ranged from 75.2% to 81.4% for paclitaxel DCB in femoropopliteal lesions [45, 46]. One study indicated DCB was "best" for 5-year mortality compared to DES and covered stents [32]. Overall, long-term follow-up studies generally found no excess mortality associated with DCB use up to 5 years [129, 149, 155, 176].
Adjunctive Therapies: Combining atherectomy with DCB for lower extremity artery disease was associated with a lower risk of major amputation [11] and no observed mortality in some studies [148, 179, 180, 192]. Intravascular lithotripsy (IVL) followed by DCB for calcified common femoral artery disease reported 100% 12-month survival [36] and promising outcomes [109], although some deaths were reported in other IVL + DCB cohorts [28].

5) Discussion
5.1 Principal finding: The principal finding of this review is that, across numerous studies, drug-coated balloon interventions are generally not associated with a significantly increased risk of all-cause mortality compared to other revascularization strategies, with a median 12-month all-cause mortality rate of 6.5% [206] (range 1.17% [159] to 12.1% [70]) when specific rates were reported.
5.2 Clinical implications:

Mortality Reassurance: Clinicians can be largely reassured that DCB use in vascular interventions does not generally confer an increased risk of all-cause mortality compared to alternative treatments.
Comorbidity Management: Patients with significant comorbidities, particularly chronic kidney disease, represent a higher-risk group for mortality irrespective of DCB use, necessitating aggressive comorbidity management.
Site-Specific Outcomes: While overall mortality is often similar, outcomes may vary by anatomical location; careful consideration of specific vessel beds (e.g., infrapopliteal vs. femoropopliteal) is warranted.
Long-Term Monitoring: Continued long-term follow-up is important, as some studies extend up to 5 years, to monitor for any late-onset mortality signals or efficacy differences.
Adjunctive Therapy Benefits: The use of adjunctive therapies like atherectomy or intravascular lithotripsy with DCBs appears to maintain favorable safety profiles regarding mortality, potentially improving other clinical outcomes.

5.3 Research implications / key gaps:

Standardized Mortality Reporting: Future studies should standardize the definition and reporting timepoints for all-cause mortality to allow for more robust comparisons and meta-analyses.
RCTs High-Risk Patients: Larger, adequately powered randomized controlled trials are needed to definitively assess mortality outcomes in specific high-risk patient subgroups (e.g., severe CKD, advanced CLTI).
Long-Term Follow-up Studies: Extended follow-up periods beyond 5 years are necessary to capture very late mortality events and assess the true long-term safety profile of DCBs.
Comparative Device Efficacy: Research should continue to compare different types, doses, and formulations of DCBs and drug-eluting stents, particularly for their long-term impact on mortality.
Real-World Data Integration: Integration of large-scale real-world data from registries could provide broader insights into mortality trends and risk factors associated with DCB use in diverse clinical practices.

5.4 Limitations:

Study Heterogeneity: Variability in study designs, populations, lesion characteristics, and comparator treatments limits direct comparability and generalizability.
Inconsistent Reporting: Mortality metrics, timepoints, and statistical reporting were inconsistent across studies, complicating quantitative synthesis.
Predominance Retrospective Studies: A significant number of retrospective cohort studies introduce potential for confounding and selection bias.
Small Sample Sizes: Several studies had small sample sizes, which may lack the statistical power to detect rare mortality events or subtle differences.
Lack Mechanistic Data: The summary lacks detailed mechanistic data on how DCBs might influence mortality beyond the paclitaxel debate.

5.5 Future directions:

Standardized Outcome Definitions: Implement consistent definitions for mortality and adverse events in clinical trials.
Registry-Based Analyses: Leverage large patient registries for real-world evidence on long-term mortality.
Subgroup Analysis: Conduct focused studies on high-risk populations like CKD or elderly patients.
Novel Drug Formulations: Investigate new DCB drug coatings and their long-term safety profiles.
Comparative Effectiveness Research: Design studies comparing DCB to emerging endovascular technologies.

6) Conclusion
Across numerous studies, the median 12-month all-cause mortality rate following drug-coated balloon interventions was 6.5% [206], with a range from 1.17% [159] to 12.1% [70]. DCBs are generally considered safe with respect to mortality in various vascular interventions, often showing no significant difference compared to other revascularization strategies, although one early study reported higher DCB mortality. The greatest limitation affecting certainty is the heterogeneity of study designs and inconsistent reporting of mortality metrics. A crucial next step is to conduct larger, well-designed randomized controlled trials focusing on long-term mortality in high-risk patient populations to further solidify the safety profile of DCBs.

References
SAIMSARA Session Index — session.json

Figure 1. Publication-year distribution of included originals

Figure 1. Publication-year distribution of included originals

Figure 2. Study-design distribution of included originals

Figure 2. Study-design distribution

Figure 3. Study-type (directionality) distribution of included originals
Figure 3. Directionality distribution

Figure 3. Directionality distribution

Figure 4. Main extracted research topics

Figure 4. Main extracted research topics (Results)

Figure 5. Limitations of current studies (topics)

Figure 5. Limitations of current studies (topics)

Figure 6. Future research directions (topics)

Figure 6. Future research directions (topics)