Drug-coated balloons are not inferior to drug-coated stents in the treatment of acute myocardial infarction and shorten the duration of dual antiplatelet treatment : Emergency and Critical Care Medicine

Secondary Logo

Journal Logo

Meta-analysis

Drug-coated balloons are not inferior to drug-coated stents in the treatment of acute myocardial infarction and shorten the duration of dual antiplatelet treatment

Yang, Jinga,b,c; Chang, Shutingb,c,d; Liu, Jinge; Zhang, Guanzhaoa,b,c; Wang, Yueb,c,f; Zhang, Baixueb,c,d; Nie, Zifana,b,c; Dong, Yuanbaog,∗; Li, Bob,c,∗

Author Information
Emergency and Critical Care Medicine 2(4):p 225-232, December 2022. | DOI: 10.1097/EC9.0000000000000050
  • Open

Abstract

Introduction

Coronary stent implantation is the first option of treatment for direct percutaneous coronary intervention in patients who suffered from acute myocardial infarctions. Kang et al.[1] pointed out that, when a comparison with bare metal stents was made, all extant drug-eluting stents (DESs) decrease the danger of revascularization, and that all DESs, except paclitaxel eluting stents, decrease the danger of myocardial infarction.

Nevertheless, after stent implantations, the possible complications may still ensue. These involve in-stent restenosis (ISR), late thrombosis, local chronic inflammation, and reocclusion.[2] Drug-coated balloons (DCBs) have come forth as a way to decrease the incidence and likelihood of complications.

A position paper statement from the Italian Society of Interventional Cardiology shows that, compared with stents, DCBs have additional benefits in that there is no need for permanent stents and polymers; the original anatomy of the coronary arteries is respected; and inflammatory stimulation is limited, so that short-term, dual antiplatelet therapy (DAPT) can be performed.[3] Drug-coated balloons offer a way of treating atherosclerotic lesions of small vessels and bifurcations an alternative. Furthermore, they confront peripheral artery segments in which stent implantation has been shown to be less beneficial.[4] Beyond that, DCBs are a new percutaneous coronary intervention therapy and have been turned out to be a up-and-coming strategy for treating ISR and coronary small vessel disease.[5]

A meta-analysis built on published trials was conducted to learn more about the efficacy of DCBs and DESs in patients who suffered from acute myocardial infarction.

Methods

For the methodology and recording of this meta-analysis, the Preferred Reporting Items for Systematic Reviews and Meta-analyses of Individual Participant Data statement was used.[6]

Literature search and search strategy

We searched the keywords “drug-coated balloon,” “paclitaxel-coated balloon,” “DCB,” “drug-eluting stents,” “DES,” and “acute myocardial infarction” individually or in combination through PubMed, Embase, and the Cochrane Library. Investigations were performed before August 2021, and articles were limited to those written in English. After screening according to the title and summary, relevant literature was downloaded for full-text reading and screening.

Data inclusion criteria and exclusion criteria

The inclusion criteria were as follows: (1) the type of investigation was a randomized controlled trial (RCT), observational study, or retrospective study; (2) the main content was that patients were treated with DCB or drug-eluding stent (DES) respectively who suffered from myocardial infarction with ST segment elevation or non-ST segment elevation; (3) the follow-up time was not less than 6 months; and (4) the main outcome was the incidence of a major adverse cardiovascular event (MACE), late lumen loss (LLL), target lesion revascularization (TLR), and other indicators. The exclusion criteria were as follows: (1) inability to extract effective outcome data from the literature; (2) literature repetition; (3) medical treatment other than DCB and DES in intervention measures; and (4) case reports, reviews, and animal experiments.

Data extraction and study quality assessment

The literature was screened independently by 2 researchers, and the data were extracted. The information extracted from the study included basic information derived from 7 trials, including the basic condition of the patients and clinical outcome indicators. The bias risk included in the study was assessed using the Ottawa Newcastle Cohort Study Scale, the Case-Control Study Scale, and the Cochrane risk assessment tool for RCTs.[7]

Data synthesis and statistical analysis

Review Manager Software version 5.3 and OpenMeta Analyst version 10.10 were used to analyze all studies. Potential publication bias was evaluated using an inverted funnel chart. The results of the included studies were generated from fixed-effect models (Mantel-Haenszel method) [8] or random-effect models in cases of significant heterogeneity between estimates.[9] The effect model was divided into fixed-effects model, which was used if I2 < 50%, and random-effects model, which was used if I2 ≥ 50%.[10]

Results

Literature search

After scanning databases and linked websites, the number of articles that were retrieved was 658 in total, 537 duplicate articles were excluded, and 98 documents of reviews, comments, guidelines and studies that did not satisfy the criteria were removed. After reading the full texts, a total of 7 articles[11–17] were chosen as meeting the criteria. Figure 1 depicts the flow chart for the literature screening process. Figures 2 and 3 depict the risk of bias analysis.

F1
Figure 1:
Flow-process diagram of the literature search.
F2
Figure 2:
Risk of bias graph: the distribution of methodological quality of involved studies.
F3
Figure 3:
Risk of bias summary: methodological quality of involved studies. + means low risk; ? means unclear risk; - means high risk.

The study and patients’ baseline characteristics

Four of the 7 research considered were RCTs, 2 were observational studies, and 1 was a retrospective study. A total of 922 patients (with 962 lesions) were involved in total, including 375 patients (with 402 lesions) in the DCB group and 547 patients (with 560 lesions) in the DES group (Table 1).

Table 1 - Characteristics of the Included Studies
Study Type of Study Number of Patients DCB/Stenting Number of Lesions DCB/
Stenting
Follow-up Time (months) Presentation Primary Endpoint DCB Type Stent Type Bailout Stenting Rate Continued DAPT
Vos et al.,[14] 2019 (Revelation) RCT 59/61 67/60 9 STEMI FFR of the infarct artery at 9 mo Pantera Lux (Biotronik, Berlin, Germany) Sirolimus or everolimus (Orsiro, Biotronik; or Xience, Abbott, Abbott Park, IL) 18% 1 year
Scheller
et al.,[13] 2020
(PEPCAD
NSTEMI)
RCT 104/106 123/120 9 NSTEMI Target lesion failure at 9 mo Sequent Please (B. Braun, Melsungen, Germany) 56% of patients were treated with BMS, 44% with current generation DESs 15% 1 year
Gobić et al.,[12]
2017
RCT 38/37 38/37 6 STEMI Major adverse cardiovascular events at 6 mo Sequent Please (B. Braun, Melsungen, Germany) Sirolimus (Biomime, Meril Life Sciences, Vapi, India) 4% with BMS (excluded from final analysis) 1 year
Nijhof et al.,[11]
2015
Observational 40/49 40/49 12 STEMI Angiographic LLL at 6 mo DIOR II (Eurocor GmbH, Bonn, Germany) Paclitaxel (Taxus Liberté, Boston Scientifc, Natick, MA) 10% with BMS Not mentioned
Tan et al.,[17] 2021 Retrospective 56/212 56/212 24 STEMI/NSTEMI Major adverse cardiovascular events at 24 mo SeQuent Please; B. Braun Melsungen, Germany Zotarolimus-eluting stent (Endeavor Resolute, Metronic company) or Rapamycin-eluting stent (Fire-bird-2, Microport company) None DCB group was used for 3 mo and DES group for 12 mo
Hao et al.,[16] 2021 RCT 38/42 38/42 12 STEMI Major adverse cardiovascular events, LLL at 1 y Not mentioned Not mentioned 9.52% with DESs (excluded from final analysis) DCB group was used for 6 mo and DES group for 12 mo
Sharif Khan et al.,[15] 2020 Observational 40/40 40/40 6 STEMI/NSTEMI Any subsequent MACCE during the ensuing 6 mo SeQuent Neo, B. Braun, Melsungen, Germany Xience Expedition, Abbott Laboratories, Abbott Park, IL None Not mentioned
BMS, bare-metal stent; DAPT, dual antiplatelet therapy; DCB, drug-coated balloon; DES, drug-eluding stent; FFR, fractional flow reserve; LLL, late lumen loss; MACCE, major adverse cardiovascular and cerebrovascular events; NSTEMI, non–ST-elevation myocardial infarction; RCT, randomized controlled trial; STEMI, ST-elevation myocardial infarction.

Clinical outcomes

The related outcome incidences of the 7 studies in which the average follow-up time was 15 months (range, 6–24 months) were statistically analyzed (Fig. 4).

F4
Figure 4:
Forest plots depicting the comparison of the outcomes in DCB and DESs patients. (A–E) Forest plots depicting the comparison of DCB and DES on MACEs, cardiac death, TLR, LLL, and DAPT, respectively. (F) Forest plots depicting the proportion of the bailout stenting rate. Heterogeneity analysis was carried out using the Q test and among the studies variation (I 2 index). Weights were calculated from binary random-effects model analysis. DAPT, dual antiplatelet therapy; DCB, drug-coated balloon; DES, drug-eluding stent; LLL, late lumen loss; MACE, major adverse cardiovascular event; TLR, target lesion revascularization.

The heterogeneity test result of MACE was I2 = 0%; hence, the analysis used a fixed-effect model. The results of 6 studies (a total of 772 cases) indicated that the incidence of MACEs in the DCB group was 12.7%, whereas it was 15.4% in the DES group. There was no statistically considerable difference between the 2 groups (odds ratio [OR]: 0.82; 95% confidence interval [CI]: 0.52–1.29), but the incidence of MACEs in the DCB group was numerically lower than in the DES group (Fig. 4A).

The results of the heterogeneity test of cardiac death showed that all studies had good homogeneity (I2 = 0%). Although DCB group had similar risk of cardiac death compared with DES group (OR: 0.92; 95% CI: 0.39–2.12), the mortality rate in the DCB group was numerically lower than in the DES group (Fig. 4B).

For TLR, the meta-analysis revealed that there was no statistically considerable difference between the 2 groups, but the incidence rate in the DCB group was numerically higher than in the DES group (4.6% vs. 4.0%; OR: 1.09; 95% CI: 0.53–2.25; Z = 0.24; P = 0.81) (Fig. 4C).

For the LLL with a median follow-up time of 15 months, there was significant heterogeneity among the studies (P < 0.00001, I2 = 90%); hence, a random-effect model was used. The results were similar between the 2 groups (mean difference: −0.05; 95% CI: −0.15 to 0.06; Z = 0.85; P = 0.40). Overall, the LLL of the DCB group was smaller than that of the DES group (Fig. 4D).

For DAPT, efficacy for 3 to 6 months after surgery in the DCB group was compared with that in the DES group at 12 months after surgery. The findings of a total of 348 cases were consistent with the results of the 2 studies. There was good homogeneity between the 2 groups (I2 = 0%) and no significant difference in the occurrence of MACE events (OR: 1.04; 95% CI: 0.53–2.05). The time of DAPT in the DEB group was importantly shorter than in the DES group (Fig. 4E).

Finally, we collected and analyzed the bailout stenting data offered by the five included studies (a total of 300 cases). The results indicated that 11.8% of the patients in the DCB group needed additional stents after surgery (95% CI: 7.1–16.5) (Fig. 4F). The results of the funnel plots show that the scatters of MACE, cardiac death, TLR, and DAPT are basically funnel-shaped and symmetrically distributed on either side of the pooled estimate but a nonsymmetrical distribution of the effect size of LLL (Fig. 5A−E). In addition, to reflect the publication bias of the 4 factors of RCT, the funnel analysis of the included literature was conducted by using MACE as the main outcome. The results showed that the scattered points representing the four items of RCT were basically funnel-shaped and distributed on both sides of the effective line. All the findings fell within the 95% linear range, and the publication bias was small (Fig. 5F).

F5
Figure 5:
Funnel plots of the comparisons of MACEs, cardiac death, TLR, dual antiplatelet, and LLL between DCB and DESs, respectively. (A–E) Funnel plots are used to describe the distribution of the effect size of MACE, cardiac death, TLR, LLL, and DAPT. (F) The funnel plot of MACE relating to 4 RCT studies. DAPT, dual antiplatelet therapy; DCB, drug-coated balloon; DES, drug-eluding stent; LLL, late lumen loss; MACE, major adverse cardiovascular event; RCT, randomized controlled trial; TLR, target lesion revascularization.

Among the 5 meta-analysis results, the LLL statistical results showed heterogeneity; however, no significant heterogeneity was found in the analysis, but the results obtained using the random effect and fixed model analyses were consistent.

Discussion

The findings of this study revealed that there was no importantly significant difference between the DCB group and the DES group in a median follow-up time of 15 months. In other words, the efficacy of DCBs in the treatment of acute myocardial infarction was not inferior to that of stent therapy. Despite the fact that there was no importantly significant difference in the incidence of each outcome, the LLL in the DCB group was lower than that in the DES group, and the time of DAPT in the DCB group was much shorter than that in the DES group. The DCB group also had a decreased danger of MACEs and cardiovascular death. The DCB group performed somewhat better than the DES group in terms of target vascular revascularization. However, the possibility of bailout stenting treatment after DCB treatment cannot be excluded.

At present, DES is undoubtedly the first option in the treatment of percutaneous coronary intervention, but there is a danger of late in-stent thrombosis and late restenosis.[18,19] Restenosis is still a main complication, limiting the clinical safety and effectiveness of DESs, the chance of which was 10% to 20%.[20–22] From a pathological perspective, restenosis is thought to be the outcome of a strong proliferation of smooth muscle cells and macrophage infiltrations in the stent. Arteries are rich in elastic fibers, which make them retract in various ways after dilation.[22] In-stent restenosis might cause recurrence of MACEs that involved angina pectoris, acute myocardial infarction, and even sudden cardiac death. Although DESs are associated with the inhibition of neointimal proliferations and reducing the probability of ISR, they can also lead to vascular healing dysfunction, persistent inflammation, platelet activation, and adverse immune reactions.[19]

The benefits of the DCBs over direct stenting include reducing restenosis rates in indications where DESs have limited efficacy; reducing DAPT, especially in patients with contraindications for prolonged DAPT; and reducing attachment to foreign bodies, which may lead to vascular remodeling and potential plaque regression, rather than new atherosclerosis.[18] Drug-coated balloons are the first-line treatment for in-stent stenosis, and this study and earlier trials suggest that DCBs may have benefits in treating acute myocardial infarction.

In respect of DAPT treatment, reducing the duration is essential for treating patients with a high-risk of bleeding.[23–25] Previous studies have shown that there is no significant difference in clinical outcomes, including all-cause mortality, myocardial infarction, and stent thrombosis, between shortening DAPT time ≤6 months and allowing for 1 year’s duration, except for the reduced probability of massive hemorrhaging.[25–27]

The research and development of a new generation of DCBs focus on enhancing the stability of drug coatings to reduce drug loss, promoting effective drug convey to the blood vessel wall, and improving drug uptake.[4]

Conclusion

DCBs with shorter DAPT durations may be as effective and safe as stent therapy in treating acute myocardial infarction.

Conflict of interest statement

The authors declare no conflict of interest.

Author contributions

Li B and Dong Y participated in research design. Yang J and Chang S participated in the writing of the paper. Liu J participated in the performance of the research. Zhang G and Nie Z contributed new reagents or analytic tools. Wang Y and Zhang B participated in data analysis.

Funding

This study was supported by the Natural Science Foundation of China (no. 81700321).

Ethical approval of studies and informed consent

Not applicable.

Acknowledgements

None.

References

1. Kang SH, Park KW, Kang DY, et al. Biodegradable-polymer drug-eluting stents vs. bare metal stents vs. durable-polymer drug-eluting stents: a systematic review and Bayesian approach network meta-analysis. Eur Heart J. 2014;35(17):1147–1158. doi:10.1093/eurheartj/eht570
2. Koo Y, Tiasha T, Shanov VN, Yun Y. Expandable Mg-based helical stent assessment using static, dynamic, and porcine ex vivo models. Sci Rep. 2017;7(1):1173. doi:10.1038/s41598-017-01214-4
3. Cortese B, Berti S, Biondi-Zoccai G, et al. Drug-coated balloon treatment of coronary artery disease: a position paper of the Italian Society of Interventional Cardiology. Catheter Cardiovasc Interv. 2014;83(3):427–435. doi:10.1002/ccd.25149
4. Ang H, Koppara TR, Cassese S, Ng J, Joner M, Foin N. Drug-coated balloons: technical and clinical progress. Vasc Med. 2020;6:577–587. doi:10.1177/1358863X20927791
5. Hu H, Shen L. Drug-coated balloons in the treatment of acute myocardial infarction (review). Exp Ther Med. 2021;21(5):464. doi:10.3892/etm.2021.9895
6. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg. 2010;8(5):336–341. doi:10.1016/j.ijsu.2010.02.007
7. Higgins JP, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi:10.1136/bmj.d5928
8. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev. 1987;9:1–30. doi:10.1093/oxfordjournals.epirev.a036298
9. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7(3):177–188. doi:10.1016/0197-2456(86)90046-2
10. Zhang Z, Wu P, Zhang J, Wang S, Zhang G. The effect of statins on microalbuminuria, proteinuria, progression of kidney function, and all-cause mortality in patients with non-end stage chronic kidney disease: a meta-analysis. Pharmacol Res. 2016;105:74–83. doi:10.1016/j.phrs.2016.01.005
11. Nijhoff F, Agostoni P, Belkacemi A, et al. Primary percutaneous coronary intervention by drug-eluting balloon angioplasty: the nonrandomized fourth arm of the DEB-AMI (drug-eluting balloon in ST-segment elevation myocardial infarction) trial. Catheter Cardiovasc Interv. 2015;86(Suppl 1):S34–S44. doi:10.1002/ccd.26060
12. Gobić D, Tomulić V, Lulić D, et al. Drug-coated balloon versus drug-eluting stent in primary percutaneous coronary intervention: a feasibility study. Am J Med Sci. 2017;354(6):553–560. doi:10.1016/j.amjms.2017.07.005
13. Scheller B, Ohlow MA, Ewen S, et al. Bare metal or drug-eluting stent versus drug-coated balloon in non-ST-elevation myocardial infarction: the randomised PEPCAD NSTEMI trial. EuroIntervention. 2020;15(17):1527–1533. doi:10.4244/EIJ-D-19-00723
14. Vos NS, Fagel ND, Amoroso G, et al. Paclitaxel-coated balloon angioplasty versus drug-eluting stent in acute myocardial infarction: the REVELATION randomized trial. JACC Cardiovasc Interv. 2019;12(17):1691–1699. doi:10.1016/j.jcin.2019.04.016
15. Sharif Khan H, Malik J, Mohsin M, Javed A, Farooq MU. Adverse events in primary percutaneous coronary angioplasty with drug-eluting stents compared with drug-coated balloons: a retrospective outlook. Cureus. 2020;12(6):e8500. doi:10.7759/cureus.8500
16. Hao X, Huang D, Wang Z, Zhang J, Liu H, Lu Y. Study on the safety and effectiveness of drug-coated balloons in patients with acute myocardial infarction. J Cardiothorac Surg. 2021;16(1):178. doi:10.1186/s13019-021-01525-8
17. Tan Q, Wang Q, Yang H, Jing Z, Ming C. Clinical outcomes of drug-eluting balloon for treatment of small coronary artery in patients with acute myocardial infarction. Intern Emerg Med. 2021;16(4):913–918. doi:10.1007/s11739-020-02530-w
18. Kleber FX, Rittger H, Bonaventura K, et al. Drug-coated balloons for treatment of coronary artery disease: updated recommendations from a consensus group. Clin Res Cardiol. 2013;102(11):785–797. doi:10.1007/s00392-013-0609-7
19. Borovac JA, D'Amario D, Vergallo R, et al. Neoatherosclerosis after drug-eluting stent implantation: a novel clinical and therapeutic challenge. Eur Heart J Cardiovasc Pharmacother. 2019;5(2):105–116. doi:10.1093/ehjcvp/pvy036
20. Mohan S, Dhall A. A comparative study of restenosis rates in bare metal and drug-eluting stents. Int J Angiol. 2010;19(2):e66–e72. doi:10.1055/s-0031-1278368
21. Park SJ, Kang SJ, Virmani R, Nakano M, Ueda Y. In-stent neoatherosclerosis: a final common pathway of late stent failure. J Am Coll Cardiol. 2012;59(23):2051–2057. doi:10.1016/j.jacc.2011.10.909
22. Zhang DM, Chen S. In-stent restenosis and a drug-coated balloon: insights from a clinical therapeutic strategy on coronary artery diseases. Cardiol Res Pract. 2020;2020:8104939. doi:10.1155/2020/8104939
23. Huynh K. Antiplatelet therapy: risks and benefits of extended DAPT after stenting. Nat Rev Cardiol. 2015;12(1):1. doi:10.1038/nrcardio.2014.192
24. Gori T, Polimeni A, Indolfi C, Räber L, Adriaenssens T, Münzel T. Predictors of stent thrombosis and their implications for clinical practice. Nat Rev Cardiol. 2019;16(4):243–256. doi:10.1038/s41569-018-0118-5
25. Torii S, Jinnouchi H, Sakamoto A, et al. Drug-eluting coronary stents: insights from preclinical and pathology studies. Nat Rev Cardiol. 2020;17(1):37–51. doi:10.1038/s41569-019-0234-x
26. Navarese EP, Andreotti F, Schulze V, et al. Optimal duration of dual antiplatelet therapy after percutaneous coronary intervention with drug eluting stents: meta-analysis of randomised controlled trials. BMJ. 2015;350:h1618. doi:10.1136/bmj.h1618
27. Palmerini T, Della Riva D, Benedetto U, et al. Three, six, or twelve months of dual antiplatelet therapy after DES implantation in patients with or without acute coronary syndromes: an individual patient data pairwise and network meta-analysis of six randomized trials and 11 473 patients. Eur Heart J. 2017;38(14):1034–1043. doi:10.1093/eurheartj/ehw627
Keywords:

Acute myocardial infarction; Drug-coated balloon; Dual antiplatelet therapy; Paclitaxel-coated balloon

Copyright © 2022 Shandong University, published by Wolters Kluwer, Inc.