Paclitaxel-coated balloon catheter versus paclitaxel-eluting stent for the treatment of coronary in-stent restenosis: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials

Abstract

Background:

Paclitaxel is an antimicrotubular agent and is used to coat balloons and stents used in percutaneous coronary intervention. This study aims to provide a pooled comparison of paclitaxel-coated balloons (PCB) and paclitaxel-eluting stents (PES) in terms of their efficacy in treating restenosis and their associated safety outcomes.

Methods:

We systematically searched PubMed, Scopus, Science Direct, and Clinicaltrials.gov from inception until August 2024 to evaluate the outcomes between PCB and PES for treating coronary in-stent restenosis. Studies were deemed eligible if they compared PCB with PES in patients with coronary in-stent restenosis. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference for continuous outcomes, along with 95% confidence intervals (CI). This systematic review and meta-analysis was registered with International Prospective Register of Systematic Reviews (CRD42024543509).

Results:

734 patients across 4 trials were included in this analysis. Descriptive analysis showed high device success in both groups (99.6% for PCB vs 97.9% for PES), while restenosis occurred in 20.6% of PCB patients and 23.7% of PES patients. Myocardial infarction rates were 1.9% for PCB and 3.0% for PES, while mortality was observed in 1.6% and 3.6% of patients, respectively. No significant differences between PCB and PES were revealed in terms of recurrent binary restenosis rates (RR: 0.76; 95% CI: 0.19 to 2.99) or late lumen loss (mean difference: −0.02; 95% CI: −0.25 to 0.22). Device success rates (RR: 1.01; 95% CI: 0.91 to 1.13), the incidence of myocardial infarction (RR: 0.64; 95% CI: 0.24 to 1.69), and the incidence of death (RR: 0.48; 95% CI: 0.16 to 1.41) were also comparable between the 2 groups.

Conclusion:

PCB provides a viable stent-free alternative to PES with comparable outcomes. Further studies, especially those focused on assessing patient-specific factors and lesion characteristics are required to guide optimal treatment selection.

1. Introduction

Percutaneous coronary intervention (PCI) is an intervention for revascularization in patients with severe coronary artery disease.^[1] More than a million PCIs are performed each year in the United States alone.^[2] The most common reason for target lesion failure after PCI is in-stent restenosis (ISR).^[3]

ISR is defined as stenosis within or next to an implanted coronary stent.^[4] The development of ISR is attributed to 2 pathological processes: it can occur either as a result of neointimal hyperplasia due to proliferation of smooth muscle cells, or due to accumulation of lipid-laden macrophages in the neointima leading to neoatherosclerosis.^[5]

It is said that the progressive evolution of the kind of intervention employed, from balloon angioplasty to bare-metal stents and drug-eluting stents (DES), has reduced the risk of ISR after PCI.^[6] The use of DES has been associated with a reduced risk of ISR in comparison to bare-metal stents, even in studies with a longer follow-up period,^[7] in addition to the added benefit of better clinical outcomes such as a reduced risk of myocardial infarction.^[8]

The occurrence of ISR leads to the need to repeat revascularization in the target vessel in order to reestablish blood flow.^[9] While the rate of ISR may be reduced with the use of newer interventions, the risk of this complication still remains and must be treated by the use of repeating PCI. A network meta-analysis comparing plain old balloon angioplasty, drug-coated balloons (DCB), and DES revealed a lower incidence of target lesion revascularization with the use of DCB or DES in comparison to plain old balloon angioplasty.^[10] DCB was also found to be associated with a lower risk of myocardial infarction when compared with plain old balloon angioplasty and DES.^[10]

Several therapeutic substances can be applied to the surface of a balloon catheter, including antiplatelet, anti-inflammatory, antihyperlipidemic, antiproliferative, and antithrombogenic agents.^[11] Out of these, paclitaxel and sirolimus are preferred.^[12] Newer drugs such as zotarolimus have also been investigated. However, zotarolimus was found to have an inferior effect on complex lesions in comparison to paclitaxel.^[13] Similarly, the same drugs have been used to coat stents as well.^[13]

Paclitaxel is an antimicrotubule agent that increases microtubule stability and inhibits cell replication by causing cell cycle arrest in the late G2 phase.^[14] This can impede smooth muscle cell proliferation and thus reduce the risk of the development of ISR.

We have undertaken this systematic review and meta-analysis to compare the efficacy and safety of paclitaxel-coated balloon (PCB) and paclitaxel-eluting stents (PES) for the treatment of ISR by pooling all relevant outcomes possible. Furthermore, we have provided robust evidence by evaluating the quality of the synthesized evidence utilizing the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, which will enable clinicians to decide whether the provided evidence should be followed by them or not.

2. Methods

The present study employed the Preferred Reporting Items for Systematic Review and Meta-Analysis 2020 guidelines to conduct a comprehensive systematic review and meta-analysis.^[15] The review is registered with the International Prospective Register of Systematic Reviews (CRD42024543509). Ethics approval was not required for this meta-analysis as it utilizes publicly available, previously published, and anonymized data, ensuring no direct involvement of human subjects.

2.1. Data sources & search strategy

We systematically searched PubMed/Medline, Scopus, ScienceDirect, Cochrane Library, and Clinicaltrials.gov for relevant studies, from inception to August 2024, to evaluate and compare the outcomes between PCB versus PES for the treatment of coronary ISR. We utilized the following keywords and Medical Subject Headings terms in our search strategy: “Paclitaxel-coated balloon,” “In-stent restenosis,” and “Paclitaxel-eluting stent.” The detailed search strategy for each database is provided in Table S1, Supplemental Digital Content, http://links.lww.com/MD/O669.

2.2. Eligibility criteria & study selection

Studies were considered eligible if they: (i) included adult participants with coronary ISR; (ii) compared PCB with PES; (iii) reported efficacy and safety outcomes; (iv) were randomized controlled trials; and (v) were in the English language. Exclusion criteria were participants < 18 years of age, no outcomes details specifically for PCB and PES, animal studies, not in the English language, and overlapping patients with another study. Initial screening based on titles and abstracts was done independently by 2 reviewers (A.H.; H.A) and in case of any discrepancies, a third reviewer was consulted (S.A).

2.3. Data extraction

Following the screening process, data was extracted by the 2 authors (S.A.; A.H.) and was entered into an Excel spreadsheet. This data included the first author’s last name, year of publication, study design, country, sample size, mean age, number of males, deaths, myocardial infarctions, late lumen loss, recurrent binary restenosis, and device success.

2.4. Risk of bias assessment

To assess the quality of included studies, the Cochrane risk-of-bias tool for randomized trials was utilized.^[16] This tool evaluates 5 domains of a randomized study to determine the overall risk of bias: (1) bias in the randomization process, (2) bias due to deviations from intended interventions, (3) bias due to missing outcome data, (4) bias in outcome measurement, and (5) bias due to selective reporting of results. Risk of bias assessment was performed by 1 author (S.A).

2.5. Certainty of evidence

The certainty of evidence was assessed using the GRADE approach.^[17] The summary of effects table was generated using the GRADEpro Guideline Development Tool.^[18]

2.6. Statistical analysis

R version 4.4 with “meta” package was used to conduct the statistical analyses. We calculated risk ratios (RR) and mean differences (MDs) along with their 95% confidence intervals (CIs) for dichotomous and continuous outcomes, respectively. Mantel-Haenszel method within a random effects model was utilized to pool the RRs, while the MDs were combined using the inverse variance method.^[19] Knapp-Hartung adjustment was applied to the CIs to account for any statistical heterogeneity.^[20] The variance was determined using the Paule-Mandel estimator for dichotomous outcomes and the restricted maximum likelihood estimator for continuous outcomes.^[21,22] Heterogeneity was reported in accordance with the threshold values in the Cochrane Handbook for Systematic Reviews of Interventions for the Higgins I² statistic, considering the results of the Chi² test.^[23] We used the “metasens” package in R to assess publication bias by Doi plots and reporting Luis-Furuya Kanamori index (LFK index), as the LFK index is sensitive and has more statistical power than Egger’s test when there are less than ten studies.^[24] Sensitivity analysis through the leave-one-out method was done whenever there were >2 studies for an outcome. A two-tailed P-value of < .05 was considered statistically significant for all outcomes.

3. Results

3.1. Study characteristics

Our meta-analysis included data from 4 trials, comprising a total of 734 patients.^[25–28] The search strategy yielded 771 titles and abstracts (PubMed: 13, Scopus: 291, Science Direct: 456, Cochrane library: 10, and ClinicalTrials.gov: 1), and the subsequent filtering process is depicted in a Preferred Reporting Items for Systematic Review and Meta-Analysis flow chart in Figure 1. 103 duplicate entries were identified and removed. Furthermore, articles that failed to meet the eligibility criteria based on title and abstract were excluded. A detailed evaluation of 8 potentially relevant full-text articles was conducted. Among the 8 articles, 4 were excluded for reasons mentioned in Figure 1. Ultimately, 4 studies met the eligibility criteria and were included in this systematic review.^[25–28]

Figure 1.

PRISMA flowchart. PRISMA = Preferred Reporting Items for Systematic Review and Meta-Analysis.

Of the 3 trials that reported gender distribution in their sample sizes, the patient population was predominantly male (n = 463). Notably, Xu et al reported the highest proportion of male participants, at 80.9%.^[28] Table 1 provides an overview of the study and patient characteristics.

Table 1.

Baseline and patient characteristics of included studies (NR: not reported; PEB: paclitaxel-eluting balloon; PES: paclitaxel-eluting stent).

Study name	Country	Sample size	Age (Mean ± SD)	Male	Diabetes	Hypertension	Hyperlipidemia	Predilation	Inflation time in seconds (Mean ± SD)
Cheng et al 2017[26]	China	120	NR	NR	NR	NR	NR	NR	NR
Xu et al 2014[28]	China	215	PEB: 61.8 ± 9.3 PES: 62.1 ± 9.3	174	79	147	73	PEB: 112/113 PES: 107/108	PEB: 44.5 ± 13.1 PES: 14.0 ± 10.8
Byrne et al 2013[27]	Germany	268	PEB: 67.7 ± 10.4 S: 68.8 ± 10.0	193	117	206	211	PEB: 139/137 PES: 145/131	NR
Unverdorben et al 2009[25]	Germany	131	B: 64.6 ± 9.7 S: 65.1 ± 8.7	98	39	107	98	PEB: 62/66 PES: 49/65	PEB: 40.42 ± 13.06 PES: 24.92 ± 11.92

3.2. Publication bias

Doi plots revealed major asymmetry for late lumen loss (LFK: −6.5, Fig. F1, Supplemental Digital Content, http://links.lww.com/MD/O670), recurrent binary restenosis (LFK: −4.02, Fig. F2, Supplemental Digital Content, http://links.lww.com/MD/O670), and device success (LFK: 4.37, Fig. F3, Supplemental Digital Content, http://links.lww.com/MD/O670), indicating significant publication bias. Minor asymmetry was observed for death (LFK: −1.78, Fig. F4, Supplemental Digital Content, http://links.lww.com/MD/O670), suggesting a smaller degree of bias. No publication bias was detected for myocardial infarction (LFK: −0.88, Fig. F5, Supplemental Digital Content, http://links.lww.com/MD/O670), as no asymmetry was found.

3.3. Risk of bias assessment and certainty of evidence

Unverdorben et al^[25] exhibited a high risk of bias, whereas some concerns were associated with the quality of Byrne et al^[27] Other studies exhibited a low risk of bias.^[26,28] Details of the risk of bias assessment are included in Figures F6 and F7, Supplemental Digital Content, http://links.lww.com/MD/O670. The GRADE assessment of certainty of evidence revealed the quality of the outcomes to be very low, the details of which are included in Table 2.

Table 2.

GRADE assessment of certainty of evidence.

Certainty assessment							No of patients		Effect		Certainty
No of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Paclitaxel-coated balloon	Paclitaxel-eluting stent	Relative (95% CI)	Absolute (95% CI)
3	Randomized trials	Very serious*	Serious†,‡	Not serious	Serious§	Publication bias strongly suspected∥	61/296 (20.6%)	66/278 (23.7%)	RR 0.76 (0.19–2.99)	57 fewer per 1000 (from 192 fewer to 472 more)	⨁◯◯◯ Very low*,†,‡,§,∥
4	Randomized trials	Very serious*,¶	Serious†,‡	Not serious	Not serious	Publication bias strongly suspected∥	356	338	–	MD 0.02 lower (0.25 lower to 0.22 higher)	⨁◯◯◯ Very low*,†,‡,∥,¶
3	Randomized trials	Serious*	Serious†	Not serious	Not serious	Publication bias strongly suspected∥	238/239 (99.6%)	228/233 (97.9%)	RR 1.01 (0.91–1.13)	10 more per 1000 (from 88 fewer to 127 more)	⨁◯◯◯ Very low*,†,∥
4	Randomized trials	Very serious*,¶	Not serious	Not serious	Serious#	None	7/372 (1.9%)	11/362 (3.0%)	RR 0.64 (0.24–1.69)	11 fewer per 1000 (from 23 fewer to 21 more)	⨁◯◯◯ Very low*,¶,#
3	Randomized trials	Very serious*,¶	Not serious	Not serious	Serious#	Publication bias strongly suspected**	5/312 (1.6%)	11/302 (3.6%)	RR 0.48 (0.16–1.41)	19 fewer per 1000 (from 31 fewer to 15 more)	⨁◯◯◯ Very low*,¶,#,**

CI = confidence interval, MD = mean difference, RR = risk ratio.

^*High risk of bias in Unverdorben et al 2009 due to bias arising from randomization process and measurement of outcomes.

^†High heterogeneity.

^‡Variation in effect.

^§Wide 95% confidence interval.

^∥Major asymmetry.

^¶Some concerns associated with Byrne et al 2013 due to bias in measurement of outcomes.

#95% confidence interval includes null effect and appreciable benefit.

^**Minor asymmetry.

3.4. Angiographic outcomes

Data on late lumen loss was available from all 4 trials. Between 6 and 9 months, late lumen loss was not significantly associated with the use of either PCB or PES (MD: −0.02; 95% CI: −0.25 to 0.22, Fig. 2). Restenosis rates were reported in 3 trials. Unverdorben et al observed lower restenosis in the PCB group, with 6.06% (4/66) compared to 18.46% (12/65) in the PES group. Similarly, Xu et al found rates of 19.35% (18/93) in the PCB group and 24.39% (20/82) in the PES group. In contrast, Byrne et al reported higher restenosis rates overall, with 28.47% (39/137) in the PCB group and 25.95% (34/131) in the PES group (Table S2, Supplemental Digital Content, http://links.lww.com/MD/O669). The pooled analysis demonstrated no significant difference in recurrent binary restenosis rates between PCB and PES (RR: 0.76; 95% CI: 0.19 to 2.99, Fig. 3).

Figure 2.

Forest plot of late lumen loss.

Figure 3.

Forest plot of recurrent binary restenosis rate.

Device success was assessed in 3 studies. Cheng et al observed a 100.00% success rate in both the PCB (60/60) and PES (60/60) groups. Similarly, Unverdorben et al reported 100.00% success in the PCB group (66/66), while the PES group had a slightly lower success rate of 92.31% (60/65). Xu et al found 99.12% success in the PCB group (112/113) and 100.00% success in the PES group (108/108) (Table S2, Supplemental Digital Content, http://links.lww.com/MD/O669). The device success rates were comparable between PCB and PES (RR: 1.01; 95% CI: 0.91 to 1.13, Fig. 4).

Figure 4.

Forest plot of device success rate.

For these angiographic outcomes, late lumen loss demonstrated high heterogeneity (I² = 89%), while moderate heterogeneity was observed in device success rates (I² = 66%) and recurrent binary restenosis rates (I² = 56%).

3.5. Adverse outcomes

The relative risk of major adverse events at 12 months, including myocardial infarction and death, was assessed across the trials.

Myocardial infarction rates varied among the studies. Cheng et al reported no myocardial infarctions in either the PCB (0/60) or PES (0/60) groups. Unverdorben et al observed no events in the PCB group (0/66) but recorded 1.54% (1/65) myocardial infarction in the PES group. Xu et al reported rates of 3.67% (4/109) in the PCB group and 6.60% (7/106) in the PES group. Similarly, Byrne et al observed low event rates, with 2.19% (3/137) in the PCB group and 2.29% (3/131) in the PES group (Table S2, Supplemental Digital Content, http://links.lww.com/MD/O669).

Mortality rates were also reported in 3 studies. Unverdorben et al recorded 3.03% (2/66) deaths in the PCB group and 4.62% (3/65) in the PES group. Xu et al observed no deaths in the PCB group (0/109) but 1.89% (2/106) in the PES group. Byrne et al reported 2.19% (3/137) mortality in the PCB group compared to 4.58% (6/131) in the PES group (Table S2, Supplemental Digital Content, http://links.lww.com/MD/O669). The incidence of myocardial infarction (RR: 0.64; 95% CI: 0.24 to 1.69, Fig. F8, Supplemental Digital Content, http://links.lww.com/MD/O670) and death (RR: 0.48; 95% CI: 0.16 to 1.41, Fig. F9, Supplemental Digital Content, http://links.lww.com/MD/O670) did not differ between PEB and PES In contrast with angiographic outcomes, myocardial infarction (I² = 0) and death (I² = 0) were found to have no heterogeneity.

3.6. Sensitivity analysis

Sensitivity analysis through the leave-one-out method revealed that the significant heterogeneity in late lumen loss was primarily due to Cheng et al (I² = 89% to I² = 55%, Fig. F10, Supplemental Digital Content, http://links.lww.com/MD/O670), while Unverdorben et al contributed to the heterogeneity in recurrent binary restenosis (I² = 56% to I² = 0%, Fig. F11, Supplemental Digital Content, http://links.lww.com/MD/O670) and device success rates (I² = 66% to I² = 0%, Fig. F12, Supplemental Digital Content, http://links.lww.com/MD/O670). However, leave-one-out analyses for myocardial infarction and death had no significant change in pooled results (Figs. F13 and F14, Supplemental Digital Content, http://links.lww.com/MD/O670).

4. Discussion

The results of our systematic review and meta-analysis revealed no significant difference in angiographic outcomes, including late lumen loss, binary restenosis rate and device success rate when comparing PCB with PES for coronary artery restenosis. Across the included studies, device success rates were consistently high, ranging from 99.1% to 100% in the PCB group and 92.3% to 100% in the PES group, reinforcing the equivalent performances of both interventions. Similarly, restenosis rates varied among trials but remained statistically comparable between groups. For instance, Unverdorben et al reported restenosis in 6.1% of PCB patients and 18.5% of PES patients, while Byrne et al found similar rates between both groups (28.5% vs 26.0%, respectively). Comparable results were observed for adverse effects including myocardial infarction and death. This shows that PCB is a feasible alternative to PES with similar results and safety profile.

We evaluated various angiographic outcomes, including the binary restenosis rate, late lumen loss, and device success rate. The term binary restenosis rate refers to stenosis that occupies more than half of the reference vessel diameter during angiographic follow-up.^[29] The observed overall restenosis rates (20.6% for PCB vs 23.7% for PES) reinforce the notion that coronary ISR remains a persistent clinical challenge regardless of the treatment strategy. While our meta-analysis demonstrated no statistically significant difference in restenosis risk, these event rates highlight that approximately 1 in 5 patients experience recurrent stenosis. Given that restenosis is influenced by factors such as lesion complexity, vessel diameter, and comorbid conditions like diabetes, further studies are warranted to determine whether specific patient subgroups may derive greater benefit from PCB or PES.^[4,30] In a trial that compared PCB, PES, and balloon angioplasty, both PCB and PES were found to be superior to balloon angioplasty alone, whereas PCB was found to be non-inferior when restenosis was compared with the group that underwent PES.^[27] Device success is defined as the success rate of DCB and DES in the respective groups,^[26] which we found to be comparable in our analysis (99.6% for PCB vs 97.9% for PES). While most studies reported success rates of 100% for both PCB and PES, some observed slightly lower rates for PES (as low as 92.3%), reinforcing the consistency of PCB’s performance. Since the results of both the binary restenosis rate as well as the device success rate, which can be a reflection of the binary restenosis rate, are both comparable with the use of PCB and PES, both interventions provide a more efficacious option than balloon angioplasty alone.

We also analyzed and compared late lumen loss between both groups. Late lumen loss refers to the discrepancy between the minimal lumen diameter after the procedure and at angiographic follow-up.^[25] Cortese et al found a statistically lower rate of late lumen loss with PCB when compared to stents, although the stent was covered with everolimus.^[31] Owing to the limited evidence in current literature, the angiographic outcomes between PCB and PES may be extrapolated from other studies, including DCB and DES. However, this shows a discrepancy in results, as is evident by the contradictory findings between our analysis and the study by Cortese et al Nevertheless, other studies have found comparable results between PCB and DES in terms of late lumen loss.^[29] This solidifies the need for more trials that directly compare PCB and PES in order to establish and conclude the superiority of one of these methods for PCI.

We found no significant difference in the risk of myocardial infarction and death between both groups. Myocardial infarction rates ranged from 0% to 3.7% in the PCB group and 0% to 6.6% in the PES group. While the incidence of myocardial infarction was low across both groups, the numerically lower total event rate in the PCB cohort (1.9% vs 3.0%) raises important considerations. Despite the lack of statistical significance regarding this outcome, these trends suggest that PCB may offer a theoretical safety advantage, particularly in high-risk patients. One possible explanation is that PCBs eliminate the need for additional metallic layers, thereby reducing the risk of stent thrombosis or delayed vascular healing.^[25,29] Similarly, mortality rates remained low in both the PCB and PES subgroups, at 1.6% and 3.6% respectively. Although this is consistent with a trial that compared DCB and DES, the trial also found a significant risk of major adverse cardiovascular events in the DES group.^[32] This underscores the need for assessing more adverse events associated with the use of PCB and PES.

Even if the efficacy and safety profiles of PCB and PES are comparable, PCBs possess the capability to uniformly distribute antiproliferative drugs, thereby reducing endothelial inflammation. Additionally, complex lesions may benefit from PCBs, as they can avoid the presence of multiple metal layers in previously implanted stents and can be used repeatedly to treat recurrent restenosis.^[25,29] Therefore, further clinical trials with subgroups of both simple and complex can provide better insights into the efficacy of PCB.

The limitations of this systematic review and meta-analysis must be considered while interpreting our findings. Despite a thorough literature review, we were able to find only 4 randomized controlled trials comparing PCB with PES in this patient population, limiting the sample size that was included in our analysis. Between-study heterogeneity may result from a difference in patient demographics and comorbidities as well. We employed the Paule-Mandel estimator for dichotomous outcomes and the restricted maximum likelihood estimator for continuous outcomes in our meta-analysis to account for this variance. It must be noted that restricted maximum likelihood requires a sufficient number of studies to determine accurate variances,^[33] which can be a source of limitation in our analysis as the number of included studies is <5. Furthermore, 2 of the included studies were from Germany, whereas 2 were from China, which is another limitation in terms of patient diversity. The quality of the outcomes was also concluded to be very low after an assessment of the certainty of evidence owing to various factors such as high risk of bias. In addition to that, we used prediction intervals in our meta-analysis, which can introduce limitations such as imprecise interval prediction when the number of included studies is <5 and there is evidence of publication bias.^[34] However, we have utilized the Mantel-Hanzel method, which is considered to be robust for meta-analyses with a smaller sample size,^[35] thus improving the quality of our analysis despite the limitations.

5. Conclusion

The results of this systematic review and meta-analysis exhibit comparable outcomes between PCB and PES in the treatment of coronary ISR. PCB offers a safe and comparable alternative to PES, and future studies should focus on assessing outcomes of PCB in subgroups made according to lesion types, and should also be conducted in diverse geographical settings to provide results that are applicable to a wider population.

Author contributions

Conceptualization: Shahzaib Ahmed, Eeman Ahmad, Arya Harikrishna.

Formal analysis: Shahzaib Ahmed, Eeman Ahmad.

Investigation: Shahzaib Ahmed, Eeman Ahmad, Mushood Ahmed, Hoor Ul Ain, Raheel Ahmed, Hritvik Jain, Shoaib Ahmad.

Methodology: Shahzaib Ahmed, Eeman Ahmad, Mushood Ahmed, Hoor Ul Ain, Raheel Ahmed, Hritvik Jain.

Project administration: Eeman Ahmad.

Supervision: Shoaib Ahmad.

Writing – original draft: Shahzaib Ahmed, Eeman Ahmad, Mushood Ahmed, Hoor Ul Ain, Arya Harikrishna, Danish Ali Ashraf.

Writing – review & editing: Raheel Ahmed, Hritvik Jain, Shoaib Ahmad.