Amphilimus- vs zotarolimus-eluting stents: Any preference in patients with diabetes?

Updated results of the SUGAR* trial showed that using polymer-free amphilimus-eluting stents (AES) was not a superior option to durable-polymer zotarolimus-eluting stents (ZES) in patients with diabetes mellitus who required percutaneous coronary intervention (PCI).

“At 2 years, there is insufficient evidence that AES are superior to ZES with regard to target lesion failure (TLF) in patients with diabetes undergoing PCI,” remarked study author Dr Pablo Salinas from the Hospital Clínico San Carlos and Instituto de Investigación Sanitaria del Hospital Clínico San Carlos in Madrid, Spain, at TCT 2022.

Participants in this 23-centre study from Spain were 1,175 patients with diabetes mellitus (95.5 percent with type 2 diabetes) who required PCI. They were randomized 1:1 to undergo PCI with polymer-free AES (70–80 µm thickness) or durable-polymer ZES (92–102 µm thickness). Patients who were pregnant, had cardiogenic shock, life expectancy <2 years, required mechanical ventilation, or with a contraindication to dual antiplatelet therapy were excluded. At baseline, 32 percent of patients were on insulin therapy. Fifty-one percent had multivessel disease.

One-year results showed non-inferiority between stents for the outcome of TLF (defined as a composite of cardiac death, target vessel myocardial infarction [MI], or target vessel revascularization; 7.2 percent [AES] vs 10.9 percent [ZES]; hazard ratio [HR], 0.65, 95 percent confidence interval [CI], 0.44–0.96; p_{noninferiority}<0.001). [Eur Heart J 2022;43:1320-1330]

However, the pre-specified exploratory analysis for superiority at 1 year suggested that AES may be superior to ZES (p_superiority=0.030), noted Salinas.

The present analysis at 2 years, which was powered for superiority and included 578 and 586 patients in the AES and ZES groups, respectively, did not demonstrate superiority of AES over ZES in terms of TLF (10.4 percent vs 12.1 percent; HR, 0.84, 95 percent CI, 0.60–1.19; p=0.331). [TCT 2022, session: Late-Breaking Clinical Science in Coronary Artery Disease]

The results were consistent across the individual components of the composite namely cardiac death (3.1 percent vs 3.4 percent; HR, 0.81, 95 percent CI, 0.42–1.55; p=0.519), target vessel MI (6.6 percent vs 7.6 percent; HR, 0.89, 95 percent CI, 0.56–1.42; p=0.627), and target vessel revascularization (4.3 percent vs 4.6 percent; HR, 0.93, 95 percent CI, 0.54–1.60; p=0.782).

Secondary outcomes analysed also did not differ between patients in the AES and ZES groups. These included all-cause mortality (7.1 percent vs 6.8 percent; HR, 1.03; p=0.890), any MI (9.0 percent vs 9.2 percent; HR, 0.89; p=0.595), all new revascularizations (7.6 percent vs 9.4 percent; HR, 0.79; p=0.265), definite stent thrombosis (1.0 percent vs 1.2 percent; HR, 0.87; p=0.795), probable or definite stent thrombosis (1.4 percent vs 1.7 percent; HR, 0.81; p=0.655), and major adverse cardiovascular events (18.3 percent vs 20.8 percent; HR, 0.88; p=0.371).

According to Salinas, PCI in patients with diabetes is associated with an increased risk of adverse events. However, there are few studies on this outcome in this population. “SUGAR is the first randomized trial to compare second-generation drug-eluting stents in patients with diabetes and an all-comers pragmatic design,” he said.

“This year we have definitive results. What we saw is that the differences [between the two stents that were noted at 1 year] attenuated with time,” he continued.

While the study did not demonstrate the superiority of AES over ZES, both stents “are behaving quite well,” said Salinas. However, longer follow-up is warranted in this patient population, he added, noting that the patients will be followed up to 5 years.

“Picking one stent over the other … might have some impact on short-term or mid-term outcomes,” said Salinas. However, the high rate of all-cause mortality suggests the need for “a more comprehensive approach for these patients.”

He also highlighted the lack of “late events” in the ZES group at 2 years which points to the safety of durable-polymer stents.