Drug-Eluting Coronary Stents: Evolution, Evidence and Stent Choice

Introduction

Drug-eluting stents (DES) are the predominant device used during percutaneous coronary intervention (PCI). They evolved from balloon angioplasty and bare-metal stents (BMS) in response to restenosis caused principally by neointimal hyperplasia. Contemporary DES combine a metallic scaffold, a polymeric or polymer-free drug-delivery system, and an antiproliferative agent. Their development has improved procedural safety, reduced repeat revascularization, and broadened the range of lesions amenable to PCI.

Stent selection must nevertheless be integrated with lesion anatomy, clinical presentation, bleeding risk, the anticipated need for non-cardiac surgery, procedural complexity, and the relative merits of PCI and coronary artery bypass grafting (CABG).

Definition and Pathophysiology

From balloon angioplasty to coronary stents

Balloon angioplasty was initially limited by acute vessel closure and later restenosis. Coronary stents provided a scaffold that tacked down dissection flaps, counteracted elastic recoil, reduced emergency vessel closure and decreased the need for emergency CABG.

Metal-only stents, now termed BMS, reduced restenosis compared with balloon angioplasty but did not eliminate it. Angiographic restenosis—defined in the source material as follow-up diameter stenosis greater than 50%—occurred in 20–30% of patients, while clinically evident restenosis, manifested by recurrent angina attributable to the treated segment, occurred in 10–15% during the first year. The dominant mechanism was excessive intimal hyperplasia within the stent.

Restenosis was more likely with:

• Small reference-vessel diameter

• A small post-procedural lumen

• Substantial residual stenosis

• Long lesions

• Diabetes mellitus

• Untreated edge dissection

Components and mechanisms of DES

A conventional durable-polymer DES consists of:

• A balloon-expandable metallic scaffold

• A durable or resorbable polymer coating

• An antiproliferative drug

The drug is delivered from the stent surface and suppresses cellular proliferation and neointimal growth. Modern stent platforms use thinner struts and improved delivery systems, reducing vascular injury and improving flexibility and deliverability.

Contemporary durable polymers are more biocompatible than those used in early DES. Fluoropolymer coatings have been associated with reduced vascular injury and inflammation, faster endothelialization, less neointimal proliferation and lower thrombogenicity.

Stent thrombosis

Early metallic stents reduced acute closure but introduced the risk of thrombosis related to the intravascular foreign body. First-generation DES, particularly sirolimus- and paclitaxel-eluting devices, were associated with increased late and very-late stent thrombosis compared with BMS. Modern DES have substantially lower thrombotic risk; contemporary durable-polymer DES have reported stent-thrombosis rates as low as 0.4–0.5% at 1 year and below 1% at 5 years.

Stent thrombosis remains clinically important because interruption of antiplatelet therapy, particularly in the perioperative period, may increase risk. The risk is greatest relatively soon after implantation and declines over time.

Evolution of Coronary Stent Platforms

Bare-metal stents

BMS consist of a metallic scaffold without an antiproliferative coating. Their advantages historically included a shorter required duration of dual-antiplatelet therapy (DAPT), which could be as brief as 4–6 weeks. This made BMS attractive in patients requiring urgent non-cardiac surgery, those with high bleeding risk, or those considered unlikely to adhere to medication.

However, contemporary data support the use of DES in most PCI procedures, including many patients with high bleeding risk, because newer DES provide greater efficacy with acceptable safety even when shorter DAPT regimens are used. BMS now account for less than 10% of contemporary PCI procedures according to the source material.

First-generation DES

The first widely used DES included sirolimus- and paclitaxel-eluting stents. They substantially reduced restenosis but were associated with a higher risk of late and very-late stent thrombosis compared with BMS.

The pivotal experience with sirolimus-eluting stents demonstrated a marked reduction in target-vessel failure compared with BMS. In the cited trial, target-vessel failure at 8 months was 8.6% with sirolimus-eluting stents compared with 21% with BMS, predominantly because of fewer target-vessel revascularizations. The difference remained evident at 5 years.

Contemporary durable-polymer DES

Current durable-polymer DES have improved safety, efficacy, deliverability and thrombogenicity compared with earlier devices. Everolimus- and newer zotarolimus-eluting stents are prominent examples.

In a large randomized comparison, everolimus-eluting stents (EES) reduced 1-year target-lesion failure compared with paclitaxel-eluting stents: 4.2% versus 6.8%. Myocardial infarction and stent thrombosis were also lower with EES, at 1.9% versus 3.1% and 0.17% versus 0.85%, respectively.

The two described durable-polymer EES platforms include:

• Cobalt-chromium Xience

• Platinum-chromium Promus

Both use an 81 µm strut thickness and a PBMA/PVDF-HFP polymer system.

Bioabsorbable-polymer DES

Bioabsorbable-polymer DES are designed so that the drug and polymer are released or degraded over time, leaving a metallic scaffold behind. This differs from a bioresorbable vascular scaffold, in which both the polymer and scaffold are eventually resorbed.

The principal examples described are Synergy and Orsiro.

The Synergy stent uses an abluminal polymer coating. Imaging studies showed complete resorption of the drug and polymer within approximately 4 months. In the EVOLVE II trial, Synergy was non-inferior to a durable-polymer DES for 12-month target-lesion failure: 6.7% versus 6.5%.

Orsiro is an ultrathin-strut sirolimus-eluting platform with a 60 µm strut thickness. In comparative studies, it had outcomes similar to contemporary durable-polymer DES for myocardial infarction, target-lesion revascularization and stent thrombosis at 12 months. In the BIONYX trial, Orsiro was non-inferior to Resolute Onyx for target-vessel failure at 1 year, although stent thrombosis was higher with Orsiro: 0.7% versus 0.1%.

Across studies, bioabsorbable-polymer DES generally have similar 1- to 2-year outcomes to contemporary durable-polymer DES. Ultrathin-strut bioabsorbable-polymer DES, defined in the source material as having struts less than 70 µm, have been associated with lower target-lesion failure and myocardial infarction rates than thicker-strut bioabsorbable-polymer or durable-polymer DES.

Polymer-free drug-coated stents

Polymer-free stents apply the drug directly to the metallic frame. Drug transfer occurs rapidly, after which a metallic scaffold remains.

The BioFreedom stent delivers umirolimus, also termed biolimus A9, predominantly during the first month; approximately 90% is transferred within 48 hours. In high-bleeding-risk patients receiving only 1 month of DAPT, BioFreedom reduced the composite of cardiac death, myocardial infarction and stent thrombosis compared with BMS at 390 days: 9.4% versus 12.9%. Target-lesion revascularization was also lower: 5.1% versus 9.8%.

Definite or probable stent thrombosis was similar between the groups, at 2.0% and 2.2%, respectively. However, the efficacy of BioFreedom appears intermediate between BMS and contemporary DES, and its role relative to modern DES remains uncertain.

Bioresorbable vascular scaffolds

Bioresorbable vascular scaffolds differ from bioabsorbable-polymer DES because both the polymer and the scaffold are eventually resorbed, leaving no permanent metallic structure. The source material identifies this as an important conceptual distinction but does not provide sufficient information to define their current clinical role or establish a preferred indication.

Pharmacological Agents Used in DES

Sirolimus

Sirolimus is an immunosuppressive and antiproliferative agent that produces cytostatic inhibition of cell proliferation. The Cypher stent contained 140 µg/cm2 of sirolimus, released from a biostable polymer over approximately 30 days. Although Cypher manufacture ceased in 2011, other durable-polymer sirolimus-eluting stents continue to be produced outside the United States.

Everolimus

Everolimus is a semisynthetic sirolimus analogue with both immunosuppressive and antiproliferative properties. Everolimus-eluting stents demonstrated lower target-lesion failure, myocardial infarction and stent thrombosis than first-generation paclitaxel-eluting stents.

Zotarolimus

Early zotarolimus-eluting stents released approximately 95% of the drug within 2 weeks. The Endeavor stent reduced 9-month target-vessel failure compared with BMS: 7.9% versus 15.1%. A later platform, Resolute, used a polymer that extended drug release, with approximately 85% released within 60 days and the remainder by 180 days.

Resolute was non-inferior to EES for target-lesion failure at 1 year: 8.2% versus 8.3%. At 5 years, there were no significant differences between the two platforms in target-lesion failure, its components or stent thrombosis.

Evidence Comparing Stent Types

DES versus BMS

New-generation DES are preferred over BMS because they reduce repeat revascularization and improve protection against restenosis. In acute myocardial infarction, contemporary DES have also shown lower rates of reinfarction, target-lesion revascularization and stent thrombosis compared with BMS, with benefits maintained during longer-term follow-up.

The Norwegian Coronary Stent Trial found comparable death or myocardial infarction rates between new-generation DES and BMS, but lower target-lesion revascularization and stent thrombosis with DES.

Relative performance of DES platforms

A network meta-analysis including 117,762 patient-years of follow-up reported the following short-term target-vessel revascularization rates:

Definite or probable stent thrombosis rates were lowest with everolimus-eluting stents, followed by Resolute zotarolimus- and sirolimus-eluting stents. Reported rates were 0.04%, 0.07% and 0.08%, respectively; paclitaxel-eluting and BMS platforms had higher rates.

Five-year rates of repeat revascularization and stent thrombosis appeared comparable between the Xience and Promus EES platforms.

Procedural and Imaging Considerations

Vascular access

Radial access permits PCI with lower risks of vascular complications and bleeding, greater patient comfort and shorter hospitalization. Same-day discharge is possible in selected low-risk patients.

Intravascular imaging

Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) can assist lesion assessment and stent implantation. Imaging is particularly relevant as lesion complexity and plaque burden increase.

IVUS permits assessment of:

• Lumen area

• Minimum and maximum lumen diameters

• External elastic membrane area

• Atheroma area

• Plaque burden

IVUS-guided PCI has been associated with larger minimum stent areas and reductions in major adverse cardiovascular events, including cardiovascular death, myocardial infarction and target-lesion revascularization. In the ULTIMATE trial, IVUS-guided DES implantation reduced target-vessel failure at 12 months compared with angiography-guided PCI.

IVUS may be especially valuable in complex lesions, including left main disease. In the EXCEL trial, IVUS was used in 77.2% of patients undergoing PCI.

Important limitations include the requirement for a coaxial catheter position, relatively low resolution for differentiating thrombus from plaque, cost, additional procedure time and dependence on operator expertise. IVUS also does not directly show plaque lipid content. Near-infrared spectroscopy may help address this limitation.

OCT provides higher-resolution imaging than IVUS, and a systematic review and network meta-analysis evaluated angiography, IVUS and OCT for PCI guidance. The source material does not provide sufficient information to define a universal preference among these imaging modalities.

Physiological lesion assessment

Fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are methods used to assess the functional significance of coronary stenoses and guide PCI. FFR-guided PCI has been studied in stable coronary artery disease and multivessel disease. iFR has also been compared with FFR for PCI guidance, with long-term follow-up reported.

Quantitative flow ratio-guided intervention has likewise been evaluated. The source material does not provide procedural thresholds or dosing details for these techniques.

Clinical Context for Stent Choice

Stable coronary disease

PCI is an important treatment option for patients with stable ischaemic heart disease, especially those with chronic angina that persists despite optimal guideline-directed medical therapy. It can be performed during the same encounter as diagnostic angiography, and symptom relief may be immediate and substantial.

The source material does not establish a single preferred DES platform for stable disease. Contemporary DES are generally favoured because of their lower restenosis and repeat-revascularization rates.

Acute coronary syndromes

New-generation DES are preferred to BMS in acute coronary syndromes. Evidence from acute myocardial infarction studies demonstrates lower reinfarction, target-lesion revascularization and stent-thrombosis rates with DES.

For non-ST-elevation acute coronary syndrome, a routine invasive strategy with inpatient coronary angiography is recommended in confirmed NSTEMI and in patients with a working diagnosis of NSTE-ACS with a high suspicion of unstable angina. A routine invasive approach reduces composite ischaemic endpoints, particularly in high-risk patients, but may increase peri-procedural complications and bleeding.

The use of drug-coated balloon angioplasty without stenting in NSTE-ACS remains insufficiently established. Small studies have shown non-inferiority or similar physiological outcomes in selected settings, but the source material states that further investigation is required before definitive recommendations can be made.

Multivessel disease

The choice between PCI and CABG is not determined by stent technology alone. In multivessel disease, CABG generally has more favourable long-term outcomes, particularly with higher SYNTAX scores.

In triple-vessel disease, PCI was associated with higher 5-year major adverse cardiac and cerebrovascular events than CABG: 37.5% versus 24.2%. PCI also resulted in more all-cause mortality, myocardial infarction and repeat revascularization, while stroke risk was similar.

In patients with low SYNTAX scores, major adverse event rates were more comparable, although repeat revascularization remained more frequent after PCI. FFR-guided PCI using contemporary EES did not meet non-inferiority criteria compared with CABG in multivessel disease in the cited trial.

Diabetes mellitus

Patients with diabetes have worse outcomes after either PCI or CABG than patients without diabetes and experience more recurrent cardiovascular events after PCI.

For diabetes with multivessel disease, the overall evidence and society recommendations favour CABG. In the cited trial of patients with type 2 diabetes and multivessel disease, CABG reduced the composite of death, myocardial infarction and stroke at both 1 and 5 years compared with PCI. At 5 years, death and myocardial infarction were lower with CABG, while repeat revascularization was more frequent after PCI. Stroke was more common after CABG.

CABG also carries greater risks of wound infection, acute kidney injury, heart failure and death in patients with diabetes, so decisions remain individualized.

Older adults and frailty

Older adults often present with symptoms other than angina, which may delay diagnosis. Frailty, comorbidity, cognitive status, biological rather than chronological age and health-related quality of life should influence treatment decisions.

Older patients are more vulnerable to bleeding, renal failure and neurological complications from both conservative and invasive strategies. Contemporary DES combined with short-duration DAPT provides safety and efficacy advantages compared with BMS in older adults. Frailty is central to individualized decision-making.

Antiplatelet Therapy and Non-Cardiac Surgery

Perioperative risk

Coronary stenting creates a period during which interruption of antiplatelet therapy may expose the patient to stent thrombosis and cardiovascular events. Drug-eluting stents historically presented greater perioperative concern than BMS, and the risk of thrombosis may persist for at least 1 year, particularly if antiplatelet agents are stopped.

Observational data indicate that perioperative cardiovascular risk is highest soon after PCI and declines with time. In patients with BMS, the cardiovascular event rate was 6.7% when surgery occurred within 45 days and 2.6% when surgery occurred 45–180 days after implantation. With DES, the rate was 20.2% during the first 45 days and became similar to that in patients without stenting once implantation had occurred more than 180 days previously.

Recommended delay before elective surgery

The cited ACC/AHA recommendations specify the following intervals:

A 3-month delay may be considered when surgery is time-sensitive. Elective surgery may be considered more than 180 days after DES implantation for chronic coronary disease when delaying surgery appears riskier than potential stent thrombosis.

If a P2Y12 inhibitor must be discontinued and further delay is not acceptable, surgery may be considered after 3 months in selected patients. Intravenous eptifibatide or tirofiban have been proposed as bridging strategies, but the source material emphasizes that these approaches lack rigorous testing and outcomes data.

Guideline Recommendations

The principal recommendations supported by the source material are:

• New-generation DES are preferred to BMS for PCI.

• The ACC/AHA revascularization guideline gives DES over BMS a class I recommendation with level of evidence A.

• ESC guidance affirms the superiority of newer-generation DES over earlier-generation DES and BMS for PCI in acute coronary syndromes.

• Routine invasive management is recommended for confirmed NSTEMI or high-suspicion NSTE-ACS.

• Intravascular imaging should be used more extensively as lesion complexity and plaque burden increase; IVUS-guided PCI has demonstrated reductions in adverse cardiovascular outcomes.

• CABG is generally favoured over PCI for diabetes with multivessel disease.

• CABG is generally favoured for complex two- or three-vessel disease, especially with higher SYNTAX scores.

• Drug-coated balloons in NSTE-ACS remain investigational from the standpoint of definitive guideline recommendations.

• In older adults, DES with short DAPT is associated with safety and efficacy advantages compared with BMS, with treatment individualized according to frailty and comorbidity.

• Elective non-cardiac surgery should generally be delayed according to the interval required after balloon angioplasty, BMS or DES implantation.

Treatment Strategy in Practice

Stent selection should follow a structured assessment:

Confirm that revascularization is appropriate. In stable disease, PCI is particularly relevant when symptoms persist despite optimal medical treatment. In acute coronary syndromes, the invasive strategy depends on the clinical presentation and risk profile.

Assess whether PCI or CABG is the more appropriate revascularization strategy. Diabetes, multivessel disease, left main disease and a high SYNTAX score may favour CABG.

Prefer a contemporary DES when PCI is selected. DES provide lower restenosis and repeat-revascularization rates than BMS, with lower stent-thrombosis rates for newer platforms than for early DES.

Incorporate bleeding and surgical risk. Polymer-free and selected newer-generation DES have been studied in high-bleeding-risk patients with 1 month of DAPT, but device-specific evidence should not be generalized indiscriminately.

Optimize implantation. Appropriate lesion preparation, stent sizing and expansion are essential. Intravascular imaging may improve stent deployment, particularly in complex anatomy.

Consider access strategy. Radial access reduces vascular complications and bleeding and may facilitate shorter hospitalization.

Prognosis and Follow-up

Procedural outcomes

Contemporary PCI has high procedural success. Registry data cited in the source material reported:

• Angiographic success: 96%

• Procedural success without death, myocardial infarction or emergency revascularization: 93%

• In-hospital death: less than 1%

• Emergency CABG: 0.3%

• Periprocedural myocardial infarction: 1%

With modern-generation DES, restenosis is reported at less than 10%.

Long-term considerations

The principal long-term concerns after DES implantation are:

• Stent thrombosis

• In-stent restenosis

• Target-lesion or target-vessel revascularization

• Myocardial infarction

• The need for repeat PCI or CABG

• Interruption of antiplatelet therapy for surgery or bleeding

Current-generation DES have low late stent-thrombosis rates compared with early DES and BMS. Nevertheless, risk is not eliminated, particularly when antiplatelet therapy is interrupted prematurely.

Follow-up should therefore include assessment of recurrent angina or alternative symptoms, adherence to antiplatelet treatment, bleeding, the need for non-cardiac surgery, and the broader revascularization strategy. Patients with diabetes, complex or multivessel disease, older age, frailty or high bleeding risk require particularly careful longitudinal assessment.