Inclisiran, a small interfering RNA that targets
PCSK9
mRNA, was given as a single injection at baseline or in two doses at baseline and 90 days. At 180 days, LDL cholesterol was significantly ...lowered among persons at high cardiovascular risk who had elevated levels at baseline.
Low-density lipoprotein (LDL) cholesterol is a causal factor in atherosclerotic cardiovascular disease. Statins have been shown to reduce LDL cholesterol levels and cardiovascular events in large outcome trials, findings that have made them the therapeutic cornerstone of clinical practice.
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Despite the proven efficacy of statins, there is considerable variability in individual responses to these drugs.
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Furthermore, some observational data suggest that as many as half of persons who begin statin therapy discontinue it within a year.
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Moreover, among patients receiving statin therapy who are at high risk for cardiovascular disease and who have persistent elevation of LDL cholesterol levels, the . . .
MiStent is a drug-eluting stent with a fully absorbable polymer coating containing and embedding a microcrystalline form of sirolimus into the vessel wall. It was developed to overcome the limitation ...of current durable polymer drug-eluting stents eluting amorphous sirolimus. The clinical effect of MiStent sirolimus-eluting stent compared with a durable polymer drug-eluting stents has not been investigated in a large randomised trial in an all-comer population.
We did a randomised, single-blind, multicentre, phase 3 study (DESSOLVE III) at 20 hospitals in Germany, France, Netherlands, and Poland. Eligible participants were any patients aged at least 18 years who underwent percutaneous coronary intervention in a lesion and had a reference vessel diameter of 2·50–3·75 mm. We randomly assigned patients (1:1) to implantation of either a sirolimus-eluting bioresorbable polymer stent (MiStent) or an everolimus-eluting durable polymer stent (Xience). Randomisation was done by local investigators via web-based software with random blocks according to centre. The primary endpoint was a non-inferiority comparison of a device-oriented composite endpoint (DOCE)—cardiac death, target-vessel myocardial infarction, or clinically indicated target lesion revascularisation—between the groups at 12 months after the procedure assessed by intention-to-treat. A margin of 4·0% was defined for non-inferiority of the MiStent group compared with the Xience group. All participants were included in the safety analyses. This trial is registered with ClinicalTrials.gov, number NCT02385279.
Between March 20, and Dec 3, 2015, we randomly assigned 1398 patients with 2030 lesions; 703 patients with 1037 lesions were assigned to MiStent, of whom 697 received the index procedure, and 695 patients with 993 lesions were asssigned to Xience, of whom 690 received the index procedure. At 12 months, the primary endpoint had occurred in 40 patients (5·8%) in the sirolimus-eluting stent group and in 45 patients (6·5%) in the everolimus-eluting stent group (absolute difference −0·8% 95% CI −3·3 to 1·8, pnon-inferiority=0·0001). Procedural complications occurred in 12 patients (1·7%) in the sirolimus-eluting stent group and ten patients (1·4%) in the everolimus-eluting stent group; no clinical adverse events could be attributed to these dislodgements through a minimum of 12 months of follow-up. The rate of stent thrombosis, a safety indicator, did not differ between groups and was low in both treatment groups.
The sirolimus-eluting bioabsorbable polymer stent was non-inferior to the everolimus-eluting durable polymer stent for a device-oriented composite clinical endpoint at 12 months in an all-comer population. MiStent seems a reasonable alternative to other stents in clinical practice.
The European Cardiovascular Research Institute, Micell Technologies (Durham, NC, USA), and Stentys (Paris, France).
BACKGROUND:Numerous randomized clinical trials have demonstrated the superiority of thin-strut biodegradable polymer second-generation drug-eluting stent to the first-generation drug-eluting stent ...and the noninferiority to the thin-strut second-generation permanent polymer drug-eluting stent. Data on long-term clinical outcomes with a novel ultrathin drug-eluting stent, to date, are limited.
METHODS:The DESSOLVE III trial (Multicenter Randomized Study of the MiStent Sirolimus Eluting Absorbable Polymer Stent System for Revascularization of Coronary Arteries; n=1398) is a prospective, multicenter, single-blinded, all-comers, randomized controlled trial (NCT02385279), allocating in a 1:1 ratio to either ultrathin-strut biodegradable polymer MiStent sirolimus-eluting stent or to thin-strut permanent polymer Xience everolimus-eluting stent. The primary end point was device-oriented composite end point, defined as the composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization. The secondary end point was patient-oriented composite end point, defined as the composite of all-cause mortality, any myocardial infarction, or any revascularization.
RESULTS:At 3 years, follow-up data were available in 1381 patients (98.8%). The primary end point of device-oriented composite end point occurred in 10.5% for MiStent sirolimus-eluting stent and in 11.5% for Xience everolimus-eluting stent (P=0.55). Rates of cardiac death (3.9% versus 3.8%; P=0.88), target vessel myocardial infarction (3.2% versus 2.5%; P=0.43), and clinically indicated target lesion revascularization (5.2% versus 6.5%; P=0.30) did not differ significantly between the 2 devices. The rate of definite or probable stent thrombosis was infrequent and similar between the 2 arms (1.2% versus 1.5%; P=0.64). The 90-day landmark analysis showed no significant difference in device-oriented composite end point between the 2 groups after polymer degradation of MiStent. The risk of patient-oriented composite end point was comparable between the 2 groups (22.7% versus 22.9%; P=0.34).
CONCLUSIONS:In the DESSOLVE III trial, early safety and efficacy with MiStent sirolimus-eluting bioabsorbable polymer-coated stent are confirmed at a longer term follow-up when compared with Xience everolimus-eluting permanent polymer-coated stent in a large all-comers population.
REGISTRATION:URLhttps://www.clinicaltrials.gov; Unique identifierNCT02385279.
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