What is the history and development of stents in treating coronary artery disease?

History and Development of Coronary Stents

Early Era: Balloon Angioplasty Limitations (1970s-1980s)

Balloon angioplasty alone had critical limitations that necessitated the development of stents, including abrupt vessel closure rates of 4-7%, suboptimal acute angiographic results with 30% residual stenosis, frequent dissections, and in-stent restenosis rates of 20-40%. 1, 2, 3

• Percutaneous coronary intervention was introduced in the late 1970s but was plagued by high complication rates and poor durability 3
• In the 1980s and early 1990s, balloon angioplasty in acute coronary syndromes performed worse than in stable angina because balloon dilation induced plaque disruption and enhanced thrombogenicity 1
• Emergency surgery rates were unacceptably high due to acute vessel closure 1

Introduction of Bare-Metal Stents (1990s)

The introduction of coronary stents revolutionized treatment by effectively preventing abrupt vessel closure and reducing emergency surgery rates, though bare-metal stents still suffered from in-stent restenosis rates of 20-40% due to smooth muscle cell proliferation and neointimal hyperplasia. 1, 2, 4

• Stenting became the dominant therapy, with the NHLBI registry showing 83.6% of PCI patients receiving stents by the mid-2000s 1
• Bare-metal stents proved more successful than balloon angioplasty in mid-sized coronary lesions, chronic total occlusions, and saphenous vein grafts 1
• Stenting reduced acute complication rates and achieved better acute outcomes with reduced residual diameter stenosis 1

First-Generation Drug-Eluting Stents (Early 2000s)

First-generation drug-eluting stents with antiproliferative drug coatings reduced in-stent restenosis from 20-40% with bare-metal stents to 6-8%, but introduced the hazard of late stent thrombosis due to design limitations including thick struts, durable polymers causing local hypersensitivity, delayed vessel healing, and endothelial dysfunction. 2, 4, 5, 6

• The BENESTENT II Trial demonstrated that stent implantation was safe with lower 6-month restenosis rates than balloon dilation in unstable angina patients 1
• Drug-eluting stents demonstrated significantly lower restenosis (6% vs 22%) and target lesion revascularization (2% vs 16%) compared to bare-metal stents 7
• Safety concerns emerged regarding late stent thrombosis, prompting development of newer generations 2, 5

Adjunctive Therapies and Techniques (2000s)

The combination of stent implantation with GP IIb/IIIa inhibitors (particularly abciximab) significantly reduced major complication rates during PCI, with benefits sustained at 6-month follow-up, and this combination proved superior to either stenting alone or balloon angioplasty with GP IIb/IIIa inhibitors. 1

• The EPISTENT trial demonstrated that stent plus abciximab had lower complication rates than stent plus placebo 1
• Intracoronary brachytherapy with gamma and beta radiation sources was FDA-approved specifically for in-stent restenosis, with beta-radiation systems achieving approximately 50% reduction in reintervention needs over 9 months 1
• Other adjunctive therapies including cutting balloon, rotary ablation, and excimer laser showed mixed results with no clear superiority over balloon angioplasty for in-stent restenosis 1

Second-Generation Drug-Eluting Stents (Late 2000s)

Second-generation drug-eluting stents (Endeavor zotarolimus-eluting and Xience-V everolimus-eluting stents) improved upon first-generation designs with thinner struts, enhanced polymer formulations, and more potent antiproliferative agents, providing superior safety profiles in randomized controlled trials (SPIRIT, ENDEAVOR) and registries (E-Five, COMPARE). 2, 5

• These stents addressed the late stent thrombosis concerns while maintaining low restenosis rates 5
• The ISAR-LEFT MAIN trial found that sirolimus-eluting and paclitaxel-eluting stents were equally effective and safe in left main coronary artery disease, with 2-year definite or probable stent thrombosis rates of only 0.5-1.0% 1

Expansion to Complex Lesions (Late 2000s-2010s)

The introduction of coronary stenting led to reevaluation of PCI as a viable treatment option for left main coronary artery disease, with the widespread availability of drug-eluting stents and improved stenting techniques lowering the threshold for PCI instead of CABG in selected patients. 1

• Data from extensive registries showed that stenting resulted in mortality and morbidity rates comparing favorably with CABG, suggesting that Class III recommendations against PCI for unprotected left main disease may no longer be justified 1
• IVUS guidance became advocated for optimal stent deployment in left main coronary artery stenting 1, 7
• Distal embolic protection devices received Class I recommendation for use in saphenous vein graft interventions 1

Third-Generation and Future Technologies (2010s-Present)

Third-generation stent technology introduced biodegradable polymers, polymer-free stents, and bioresorbable scaffolds based on poly-L-lactide or magnesium to overcome limitations of permanent metallic prostheses, including vascular inflammation, neoatherosclerosis, and impaired vasomotor function restoration. 5, 6, 3

• Biodegradable polymer drug-eluting stents demonstrated proven reductions in very late stent thrombosis compared to first-generation drug-eluting stents 6
• Bioresorbable scaffolds provide temporary scaffolding then disappear, liberating the treated vessel from its cage 6
• Over 20 different drug-eluting stent types are now available, each with unique features and characteristics 2

Current Standard of Care

Stenting has become the most widely used percutaneous technique, with most U.S. laboratories employing stents in 80-85% of PCI procedures, and drug-eluting stents have markedly reduced restenosis risk compared to bare-metal stents while maintaining acceptable safety profiles. 1

• Dual antiplatelet therapy with aspirin plus clopidogrel for at least 12 months after drug-eluting stent placement is mandatory, as premature discontinuation dramatically increases stent thrombosis risk 7
• The latest generation of drug-eluting stents achieves the lowest rates of restenosis, stent thrombosis, and recurrent myocardial infarction 3