On the role of specific drug binding in modelling arterial eluting stents

In this paper we consider drug binding in the arterial wall following delivery by a drug-eluting stent. Whilst it is now generally accepted that a non-linear saturable reversible binding model is required to properly describe the binding process, the precise form of the binding model varies between authors. Our particular interest in this manuscript is in assessing to what extent modelling specific and non-specific binding in the arterial wall as separate phases is important. We study this issue by extending a recently developed coupled model of drug release and arterial tissue distribution, and comparing simulated profiles of drug concentration and drug mass in each phase within the arterial tissue

Long-term Safety and Efficacy of New-Generation Drug-Eluting Stents inWomenWith AcuteMyocardial Infarction From theWomen in Innovation and Drug-Eluting Stents (WIN-DES) Collaboration

Importance Women with acute myocardial infarction (MI) undergoing mechanical reperfusion remain at increased risk of adverse cardiac events and mortality compared with their male counterparts. Whether the benefits of new-generation drug-eluting stents (DES) are preserved in women with acute MI remains unclear. Objective To investigate the long-term safety and efficacy of new-generation DES vs early-generation DES in women with acute MI. Design, Setting, and Participants Collaborative, international, individual patient-level data of women enrolled in 26 randomized clinical trials of DES were analyzed between July and December 2016. Only women presenting with an acute coronary syndrome were included. Study population was categorized according to presentation with unstable angina (UA) vs acute MI. Acute MI included non–ST-segment elevation MI (NSTEMI) or ST-segment elevation MI (STEMI). Interventions Randomization to early- (sirolimus- or paclitaxel-eluting stents) vs new-generation (everolimus-, zotarolimus-, or biolimus-eluting stents) DES. Main Outcomes and Measures Composite of death, MI or target lesion revascularization, and definite or probable stent thrombosis at 3-year follow-up. Results Overall, the mean age of participants was 66.8 years. Of 11 577 women included in the pooled data set, 4373 (37.8%) had an acute coronary syndrome as clinical presentation. Of these 4373 women, 2176 (49.8%) presented with an acute MI. In women with acute MI, new-generation DES were associated with lower risk of death, MI or target lesion revascularization (14.9% vs 18.4%; absolute risk difference, −3.5%; number needed to treat [NNT], 29; adjusted hazard ratio, 0.78; 95% CI, 0.61-0.99), and definite or probable stent thrombosis (1.4% vs 4.0%; absolute risk difference, −2.6%; NNT, 46; adjusted hazard ratio, 0.36; 95% CI, 0.19-0.69) without evidence of interaction for both end points compared with women without acute MI (P for interaction = .59 and P for interaction = .31, respectively). A graded absolute benefit with use of new-generation DES was observed in the transition from UA, to NSTEMI, and to STEMI (for death, MI, or target lesion revascularization: UA, −0.5% [NNT, 222]; NSTEMI, −3.1% [NNT, 33]; STEMI, −4.0% [NNT, 25] and for definite or probable ST: UA, −0.4% [NNT, 278]; NSTEMI, −2.2% [NNT, 46]; STEMI, −4.0% [NNT, 25]). Conclusions and Relevance New-generation DES are associated with consistent and durable benefits over 3 years in women presenting with acute MI. The magnitude of these benefits appeared to be greater per increase in severity of acute coronary syndrome

Neurological outcomes with embolic protection devices in patients undergoing transcatheter aortic valver replacement a systematic review and meta-analysis of randomized controlled trials

Objectives The aim of this study was to investigate the efficacy and safety of intraprocedural embolic protection (EP) during transcatheter aortic valve replacement (TAVR). Background Randomized controlled trials (RCTs) investigating the efficacy of EP devices during TAVR were relatively underpowered. Methods A systematic review and study-level meta-analysis was performed of randomized controlled trials that tested the efficacy and safety of EP during TAVR. Trials using any type of EP and TAVR vascular access were included. Primary imaging efficacy endpoints were total lesion volume and number of new ischemic lesions. Primary clinical efficacy endpoints were any deterioration in National Institutes of Health Stroke Scale and Montreal Cognitive Assessment scores at hospital discharge. Primary analyses were performed using the intention-to-treat approach. Results Four randomized clinical trials (total n = 252) were included. Use of EP was associated with lower total lesion volume (standardized mean difference −0.65; 95% confidence interval [CI]: −1.06 to −0.25; p = 0.002) and smaller number of new ischemic lesions (standardized mean difference −1.27; 95% CI: −2.45 to −0.09; p = 0.03). EP was associated with a trend toward lower risk for deterioration in National Institutes of Health Stroke Scale score at discharge (risk ratio: 0.55; 95% CI: 0.27 to 1.09; p = 0.09) and higher Montreal Cognitive Assessment score (standardized mean difference 0.40; 95% CI: 0.04 to 0.76; p = 0.03). Risk for overt stroke and all-cause mortality were nonsignificantly lower in the EP group. Conclusions Use of EP seems to be associated with reductions in imaging markers of cerebral infarction and early clinical neurological effectiveness in patients undergoing TAVR