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Page 2 of 12 Onea et al. Vessel Plus 2023;7:13 https://dx.doi.org/10.20517/2574-1209.2023.11

adopting advanced modifying/debulking strategies, such as atherectomy, intravascular lithotripsy, cutting
and scoring balloons; the increase in the usage of routine intravascular imaging and physiological
assessment in the complex lesion setting has led to terrific clinical improvements for our patients. Despite
the current armamentarium, long-term outcomes in complex lesions, such as calcified or diffuse stenoses,
are still under expectations.

Historically, the incidence of diffuse coronary artery disease (CAD) was reported to be approximately
20% , but daily practice has shown that even a larger number of patients require long lengths of drug-
[1]
[2]
eluting stents (DES), which currently represent the gold standard in treating CAD . However, Costopoulos
et al. had shown that total stent length represents an independent predictor for target-vessel failure (TVF),
reporting target-lesion revascularization (TLR) rates of up to 24% when more than 60 mm DES were
[3]
overlapped .
A surgical approach for diffuse CAD is frequently impossible, and even when it is performed, it does not
seem to improve mid- and long-term results, as recent studies showed no difference between optimal
medical therapy and coronary artery bypass grafting (CABG) in terms of mortality, myocardial infarction
[4]
(MI), revascularization and symptom reduction after 2 years of follow-up .

Taking all these into consideration, drug-coated balloons (DCB) alone or in combination with DES have
emerged as a valid alternative for long or multiple metal devices , as cardiac death, target-vessel MI and
[5]
TLR at 1-year follow-up are not influenced by the use of a single ultra-long 48 mm DES in comparison to
[6]
multiple stenting , thus suggesting that a reduction in the total stent length could be associated with
improved outcomes.

PREDICTORS OF STENT FAILURE
Current second-generation DES have led to high angiographic and clinical performance and remain the
standard of care in most countries.

Although on extended long-term follow-up, this technology offers reduced rates of patient- and device-
oriented composite endpoints compared to traditional bare-metal stents (BMS) (32.4% vs. 38.0%, HR 0.81;
95%CI: 0.68 - 0.96; P = 0.013 and 13.6% vs. 18.4%, HR 0.72; 95%CI: 0.55 - 0.93; P = 0.012), there are no
advantages in terms of TLR and stent thrombosis (ST) between years 1 - 10 (1.4% vs. 1.3%, P = 0.96; 0.6% vs.
[7]
0.4%, P = 0.70) .

What is more, due to various mechanical, technical or biological factors, stent failure remains a pressing
matter [Table 1], as data from the ISAR-TEST-5 trial shows 10-year device-oriented composite endpoint
[8]
rates of up to 43% .
Although DES implantation reduces intima proliferation compared to BMS, hypersensitivity to the polymer
and drug or local inflammation can occur, which can trigger in-stent restenosis (ISR), the most frequent
mechanism of stent failure . Neoatherosclerosis is usually responsible for late-occurring ISR . Konigstein
[9]
[10]
et al. analyzed over 10,000 patients and found total stent length to be the only short-term predictor of
target-lesion failure (TLF), while small vessel diameter was the only lesion-related predictor at 5 years .
[11]
Complex lesion morphology, particularly when accompanied by a high calcium burden, is a strong
[12]
predictor for ISR, which is associated with elevated rates of stent underexpansion and malapposition .