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Effectiveness and Safety of Sirolimus-eluting Stents in Patients with Diabetes
significantly reduced angiographic late loss, binary restenosis, TVR and most widely used DES are as different as the results of their use.
MACE at the same extent observed in previous large randomised trials not The indirect comparison between the two DES in the meta-analysis of the
devoted to diabetic patients. RCTs of DES versus BMS
24
show not only a significant reduction of MACE
with DES but also a significant heterogeneity between subgroups according
In the recently published Drug Eluting Stents Evaluation; a Randomized Trial to the type of DES (p<0.001), with a major reduction of MACE in the
(DESsERT),
14
75 diabetic patients were treated with SES on 109 lesions and sirolimus compared with the paclitaxel group (odds ratio [OR] 0.28, 95% CI
75 with BMS on 109 lesions. In each patient, the PCI procedure was 0.25–0.35 for SES; OR 0.62, 95% CI 0.53–0.73 for PES). In a recent meta-
performed on top of a glycoprotein (GP) IIa/IIIb inhibitor. An eight-month analysis of head-to-head trials, Kastrati
25
reported a similar difference in
angiographic and a 12-month clinical follow-up were performed. In-stent favour of SES, although the risk of death or myocardial infarction was not
lumen late loss decreased from 0.96mm for BMS to 0.14mm for SES different between the two DES.
(p<0.001) and in-segment binary restenosis resulted in 38.8 versus
3.6%, respectively (p<0.001). At 12 months, MACE were 40 versus 22.1% Only one study, the Innovative Stratification of Arrhythmic Risk (ISAR):
(p=0.023) and TLR 30 versus 5.9% (p<0.001) in the two groups, Diabetes study
26
enrolled 250 diabetic patients in a direct non-inferiority trial
respectively. The beneficial effect on binary restenosis of SES regarding BMS that compared the sirolimus and the paclitaxel stents. The primary end-point
was present in each subgroup analysed, irrespective of the vessel diameter, was in-segment late luminal loss, which was lower with sirolimus (0.43mm)
lesion length and insulin use; however, MACE reduction was marginal and than with paclitaxel (0.67mm) DES, but the study was not sufficiently
no more statistically significant for women and previous insulin use. powered to assess differences in terms of TVR or MACE. The analysis of the
diabetic subgroup (378 patients) of the Reproductive Hormones And
Besides routine use of GPIIb/IIIa inhibitors as the standard optimal therapy for Pre-Clinical CVD In Women (REALITY) study
27
showed a greater late loss in
PCI in diabetic patients,
15–17
for the first time a metabolic control parameter the paclitaxel than in the sirolimus group, but this loss was not associated
as expressed by glycated haemoglobin (HbA
1c
) levels was determined in with a higher rate of TLR.
DESsERT at baseline and after 30 days. An uncontrolled metabolic situation
with HbA
1c
>7% decreased from 63% at the time of enrolment to 54% at Stettler et al.
28
conducted an indirect meta-analysis of six trials with SES
30 days and insulin-treated patients increased from 25 to 36%. Of note, (SIRIUS, E-SIRIUS, C-SIRIUS, DIABETES, the Randomized, Double-blind Study
HbA
1c
together with stent type was the only independent predictor of 12- with the Sirolimus-eluting Bx-Velocity Balloon Expandable Stent in the
month target vessel failure – composite end-point of death, target-vessel- Treatment of Patients with de Novo Native Coronary Artery Lesions [RAVEL],
related myocardial infarction and TVR – at multivariate analysis (p=0.024). SES-Smart)
29–33
and four trials with PES (TAXUS I, II, IV, VI)
34–37
in patients
Only one case of angiographic stent thrombosis in each group was with and without diabetes. Although sirolimus was superior to paclitaxel
documented within the per protocol six-month double antiplatelet regimen DES in patients without diabetes, in those with diabetes the two DES did not
prescribed to SES-treated patients without events after discontinuation of differ significantly in any angiographic or clinical end-points. The relative
clopidogrel. If sudden deaths are taken into account (one in each group), the incidence rate ratios for SES versus PES were 0.82 (0.31–2.18; p= 0.694) for
total incidence of definite plus possible stent thrombosis as defined by the in-stent restenosis, 1.51 (0.68–3.33; p=0.312) for in-segment restenosis,
Academic Research Consortium (ARC)
18
reached 2.6% in both groups, but 0.86 (0.4–1.86; p=0.703) for TLR and 0.6 (0.21–1.71; p=0.336) for MACE.
was not related to stent type.
Furthermore, in the Taxus Stent Evaluated At Rotterdam Cardiology Hospital
Safety (T-SEARCH) and RESEARCH registries,
38
there was no difference in diabetic
Diabetes has been observed to be an independent predictor of stent patients in unadjusted one-year outcome by stent type (MACE 20.4% for
thrombosis in patients treated with DES,
19–22
concomitant with premature SES and 15.6% for PES) and after adjustment for multivariate predictors.
antiplatelet therapy discontinuation, renal function impairment, bifurcation Furthermore, in a published meta-analysis
39
of RCTs, head-to-head trials and
lesion and low left ventricular ejection fraction. The inflammatory and registries, including over 11,000 diabetic patients treated with DES,
prothrombotic milieu favoured by diabetes associated with delayed revascularisation and MACE estimates were similar for both PES and SES.
re-endothelisation of the vessel wall determined by DES are responsible for
this increased risk. Registry studies
23
report a two-year incidence of Drug-eluting Stents versus Coronary
angiographic thrombosis of 4.4% for SES and 2.4% for paclitaxel-eluting Artery Bypass Graft in Diabetics
stents (PES). In the largest registry of PCI in diabetic patients,
10
there was a All of the historical RCTs between PCI and CABG in multivessel coronary
two-fold increase in the incidence of angiographically proven stent disease showed a better medium- to long-term prognosis in the surgical arm
thrombosis at two years in DES compared with the BMS group (1.5 versus of diabetics for both the incidence of new revascularisations and death.
0.7%; p=0.48), with a typical trend after the first six months towards a Conflicting results are reported in the treatment of multivessel diabetic
disappearance of the event in BMS together with a constant incidence in patients with DES. Diabetics and non-diabetics treated with SES in the
DES-treated patients. This observation has been confirmed by several Arterial Revascularization Therapy Study (ARTS) II
40
had satisfying results in
experiences and makes prudent the prolonging of double antiplatelet comparison with the historical cohorts treated with BMS or CABG, findings
therapy until one year or more in diabetics,
22
and also questions the long- also confirmed in single-centre experiences with both DES,
41,42
with a similar
term efficacy and safety of treatment with numerous DES for extended three-year mortality in the DES and CABG groups in diabetics also reported
periods in diffuse multivessel coronary artery disease of diabetic patients. by the Korean group. However, numerous other reports show a higher
incidence of cardiovascular adverse events in multivessel diabetics treated
Sirolimus- versus Paclitaxel-eluting Stents in Diabetics with DES in relation to CABG.
43–45
In the study by Javaid et al.,
44
diabetics
The components – i.e. stent platform, polymer and drug, the treated with DES for two-vessel disease (in contrast to non-diabetics) has
immunosuppressive sirolimus and the antineoplastic paclitaxel – of the two more MACE and cerebrovascular events than those receiving CABG, while
INTERVENTIONAL CARDIOLOGY 53
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