Drug-eluting stents (DES) are widely used in contemporary PCI and have substantially reduced restenosis and repeat revascularization compared with bare-metal stents have revolutionized the management of coronary artery disease. Early generation DES markedly reduced angiographic restenosis and clinically driven repeat revascularization compared to bare-metal stents establishing DES as superior for restenosis prevention.
Today, second generation drug eluting stents have become the standard of care for most percutaneous coronary intervention (PCI) procedures. Advances in stent design including thinner struts, more biocompatible polymers, and improved drug-release technology, have enhanced safety and effectiveness. Their widespread adoption is supported by robust clinical evidence from numerous drug eluting stent clinical trials and long-term registries. This growing body of evidence has established DES effectiveness enabling clinicians to make informed, evidence-based treatment decisions and optimize patient outcomes.
The Evolution of Coronary Interventions
The effectiveness of DES began after first-generation devices such as the sirolimus-eluting Cypher (Cordis) and paclitaxel-eluting Taxus demonstrated superior efficacy over bare-metal stents in reducing target lesion revascularization (TLR).
Landmark trials for first-generation DES
- The RAVEL trial (2002): The first major randomized trial of a sirolimus-eluting stent demonstrated a reduction in restenosis. At 6 months, binary restenosis was 0% with the sirolimus-eluting stent versus 26.6% with the bare-metal stent.
- The SIRIUS trial confirmed these benefits in more complex lesions (including longer lesions, smaller vessels, and patients with diabetes or multivessel disease). It showed a reduction in target vessel failure from 21.0% to 8.6% and major adverse cardiac events (MACE) compared to bare-metal stents at 9 months.
- ISAR-TEST 4 trial (10-year follow-up): This landmark study compared clinical outcomes of new-generation drug-eluting stents (DES) against early-generation models. The findings showed comparable outcomes of new-generation DES, driven by significantly lower rates of major adverse cardiac events (MACE), and definite stent thrombosis.
ISAR TEST 4 is a randomized clinical trial that demonstrated non-inferiority of the biodegradable-polymer DES versus permanent-polymer DES for the primary composite endpoint at 12 months, with no significant differences between the groups. At 10-year follow-up, BP-SES and PP-EES showed comparable clinical outcomes. BP-SES had significantly lower rates of major adverse cardiac events (MACE: 47.7% and 46.0% vs 54.9%) and all-cause mortality (31.8% and 30.3% vs 37.2%). Definite stent thrombosis was also lower with the newer stents (1.1% and 0.8% vs 2.4%). Overall, the trial highlights that advancements in modern stent design have improved long-term safety and efficacy relative to early-generation devices out to 10 years.
Although these studies paved the way for regulatory approvals and widespread adoption, but included limitations such as an increased risk of late stent thrombosis. Concerns regarding late and very late stent thrombosis with some first-generation DES contributed to further development of stent platforms, polymers and drug-delivery technologies. Second generation drug eluting stents addressed such limitations through everolimus- or zotarolimus-eluting platforms with fluoropolymer or biodegradable coatings.
Key Second-Generation DES Trials and Outcomes
Modern second-generation drug eluting stents incorporate several important improvements including thinner metallic struts, biocompatible ploymers (available in both durable and fully biodegradable formulations), and anti-proliferative agents such as everolimus or zotarolimus. All of which synergistically contribute to enhanced DES effectiveness.
Landmark Trials for Second-Generation Drug Eluting Stent
ISAR-TEST 5 (10-year follow-up): This randomized trial compared a polymer free drug eluting stent sirolimus -probucol-eluting stent against a durable-polymer zotarolimus-eluting stent. At 10 years, there were no measurable differences between the two group of drug eluting stents regarding the primary device-oriented composite endpoint (43.8% vs. 43.0%, p=0.90). Both platforms demonstrated excellent safety regarding definite or probable stent thrombosis, which remained low and comparable (1.6% vs. 1.9%, p=0.58). However, the trial notably revealed high overall cumulative adverse event rates over the decade, with patient-oriented composite endpoints reaching 66.2% vs. 67.7% (p=0.22). These findings suggest that while contemporary DES maintain excellent long-term device safety, patient-level cardiovascular events continue to accrue over time, highlighting the importance of comprehensive secondary prevention strategies.
The SPIRIT and COMPARE trials compared everolimus-eluting stents with first-generation paclitaxel-eluting stents across multiple randomized studies.
Findings consistently demonstrated:
- Lower target lesion failure (TLF): In SPIRIT IV, TLF was reduced from 6.9% (paclitaxel) to 4.2% (everolimus) at 1 year. Similar reductions were observed in COMPARE.
- Reduced need for repeat revascularization: Target lesion revascularization (TLR) rates were approximately 40–50% lower with everolimus-eluting stents.
- Lower incidence of definite and probable stent thrombosis: SPIRIT and COMPARE demonstrated a significant reduction (often ~50% relative risk reduction) in stent thrombosis compared to paclitaxel-eluting stents.
Excellent long-term clinical outcomes: Follow-up data confirmed sustained benefits, with durable reductions in major adverse cardiac events over several years. These studies provided important evidence supporting the transition toward second generation drug eluting stents and reinforced overall DES effectiveness in routine clinical practice.
The RESOLUTE All Comers trial evaluated zotarolimus-eluting stents versus the Xience V everolimus-eluting stent (EES) in a broad range of patients, including those with diabetes, complex coronary lesions, and multivessel disease.
Key findings (final 5-year report, with ~98% follow-up completeness):
- Device-oriented composite endpoint / target lesion failure (cardiac death, target-vessel myocardial infarction, or clinically indicated target-lesion revascularization): 17.0% (ZES) vs 16.2% (EES); P = 0.61.
- Patient-oriented composite endpoint (all-cause death, any myocardial infarction, or any revascularization): 35.3% vs 32.0%; P = 0.11.
- Major adverse cardiac events: 21.9% vs 21.6%; P = 0.88.
- Definite/probable stent thrombosis: 2.8% vs 1.8%; P = 0.12.
These results confirmed non-inferiority of Resolute ZES to Xience V EES that was first shown at 1 year for the primary endpoint of target lesion failure (~8.2% vs ~8.3%), with sustained equivalence through 2 and 5 years and consistent performance across complex patient subsets.
BIOFLOW trials for the sirolimus-eluting stent (with ultrathin struts and biodegradable polymer) demonstrated favorable clinical outcomes. In BIOFLOW-V, this stent demonstrated significantly lower target lesion failure (TLF) at 12 months compared with a contemporary thin-strut durable-polymer everolimus-eluting stent, with the difference sustained through 2–3 years; at 5 years the TLF rates were similar, although target-vessel myocardial infarction and late/very late stent thrombosis remained significantly lower. These results underscores the clinical advantages of the combined design features (ultrathin struts plus biodegradable polymer).
Subsequent large-scale comparative studies, BIO-RESORT, and BIONYX, evaluated newer stent platforms with biodegradable and durable polymer technologies. Although individual trials occasionally reported advantages for specific devices in selected endpoints, the overall evidence consistently demonstrated Low rates of target lesion failure, myocardial infarction, and stent thrombosis across contemporary DES platforms
A 2025 network meta-analysis that pooled 29 randomized trials and more than 46,000 patients found no significant differences at five years among the leading contemporary platforms in rates of stent thrombosis, death, heart attack, target-lesion failure, or the need for repeat procedures. While individual stents ranked slightly differently depending on the endpoint, the overall picture is clear: modern DES platforms remain consistently safe and effective across a wide range of patients and lesions.
Importantly, most studies established non-inferiority rather than clear superiority of one stent over another, indicating that multiple approved DES technologies provide excellent clinical outcomes when used appropriately.
Translating Clinical Trial Evidence into Practice
Results from major drug eluting stent clinical trials directly influence guideline recommendations and everyday clinical decision-making. Contemporary DES have been studied across a broad- spectrum of clinical and anatomical settings.
Clinical trial data also help physicians balance procedural success with long-term outcomes, enabling evidence-based decisions regarding stent selection and duration of dual antiplatelet therapy according to individual patient characteristics.
What Landmark Studies Mean for Clinical Practice
Evidence from these drug-eluting stent clinical trials supports several practice-changing insights:
- Reduced Restenosis and Revascularization: Second-generation DES have lowered clinically-driven TLR to low single digits, improving long-term vessel patency and patient quality of life.
- Improved Safety Profile: Second-generation DES are associated with low prevalence of stent thrombosis beyond 1–3 months, facilitating more personalized antiplatelet therapy.
- Broader Patient Applicability: Trials like All Comers designs confirm efficacy in real-world populations, including diabetics, acute coronary syndromes, and complex anatomy.
- Regulatory and Evidence Standards: As highlighted in EuroIntervention review sufficient clinical evidence for novel stents includes non-inferiority trials against benchmarks like XIENCE, using surrogates like late lumen loss, followed by large-scale outcome studies. This framework ensures patient safety under MDR/FDA requirements.
Understanding “Best Drug Eluting Stent”
Healthcare professionals and patients frequently search for the best drug eluting stent. However, from a scientific and regulatory perspective, no single device can universally be described as the “best.”
Clinical outcomes depend on several factors, including:
- Coronary anatomy
- Lesion complexity
- Patient comorbidities
- Procedural technique
- Appropriate antiplatelet therapy
- Individual device characteristics
Current international guidelines recommend selecting an approved DES with demonstrated clinical safety and efficacy rather than assuming superiority on one device. Comparative performance should always be interpreted within the context of published evidence from randomized trials, meta-analyses, and real-world registries.
Conclusion
More than two decades of clinical research have firmly established the role of drug-eluting stents (DES) in contemporary interventional cardiology. Randomized trials and long-term follow-up studies support the safety and efficacy of contemporary DES, particularly in reducing restenosis and repeat revascularization while maintaining a favorable safety profile. Continuous advancements in stent engineering, biomaterials, and drug-delivery technologies have driven the evolution of second -generation drug eluting stents. While clinicians and patients often seek the best drug eluting stent, treatment decisions should be guided by robust clinical evidence, individual patient characteristics, lesion complexity, and current evidence-based clinical practice guidelines.
Reference
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