Percutaneous coronary intervention with drug-eluting stents or coronary artery bypass surgery in subjects with type 2 diabetes : evaluation of: Farkouth ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367(25):2375-84, and Contini GA, Nicolini F, Fortuna D, et al. Five-year outcomes of surgical or percutaneous myocardial revascularization in diabetic patients. Int J Cardiol 2012. [Epub ahead of print]

There is debate as to whether percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass surgery (CABG) is the best procedure for subjects with type 2 diabetes and coronary artery disease requiring revascularization. There is some evidence that following these procedures there is less further revascularization with CABG than PCI in subjects with diabetes. Two recent studies; the FREEDOM (Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal Management of Multivessel Disease) trial, and a trial using a real world diabetic population from a Registry, have shown that the benefits of CABG over PCI in subjects with type 2 diabetes extends to lower rates of death and myocardial infarct, in addition to lower rates of revascularization. However, the rates of stroke may be higher with CABG than PCI with drug-eluting stents in this population. Thus, if CABG is going to be preferred to PCI in subjects with type 2 diabetes and multivessel coronary disease, consideration should be given to how to reduce the rates of stroke with CABG.

The application of electrostatic dry powder deposition technology to coat drug-eluting stents

Purpose: A novel methodology has been introduced to effectively coat intravascular stents with sirolimus-loaded polymeric microparticles. Methods: Dry powders of the microparticulate formulation, consisting of non-erodible polymers, were produced by a supercritical, aerosol, solvent extraction system (ASES). A design of experiment (DOE) approach was conducted on the independent variables, such as organic/CO2 phase volume ratio, polymer weight and stirring-rate, while regression analysis was utilized to interpret the influence of all operational parameters on the dependent variable of particle size. The dry powders, so formed, entered an electric field created by corona charging and were sprayed on the earthed metal stent. Furthermore, the thermal stability of sirolimus was investigated to define the optimum conditions for fusion to the metal surfaces. Results: The electrostatic dry powder deposition technology (EDPDT) was used on the metal strut followed by fusion to produce uniform, reproducible and accurate coatings. The coated stents exhibited sustained release profiles over 25 days, similar to commercial products. EDPDT-coated stents displayed significant reduced platelet adhesion. Conclusions: EDPDT appeared to be a robust accurate and reproducible technology to coat eluting stents.

Late clinical outcomes after implantation of drug-eluting stents coated with biodegradable polymers: 3-year follow-up of the PAINT randomised trial

Aims: The long-term clinical performance of drug-eluting stents (DES) coated with biodegradable polymers is poorly known. Methods and results: A total of 274 coronary patients were randomly allocated to paclitaxel-eluting stents, sirolimus-eluting stents, or bare metal stems (2:2:1 ratio). The two DES used the same biodegradable polymers and were identical except for the drug. At three years, the pooled DES population had similar rates of cardiac death or myocardial infarction (9.0% vs. 7.1; p=0.6), but lower risk of repeat interventions (10.0% vs. 29.9%; p<0.01) than controls with bare stents. The cumulative 3-year incidence of definite or probable stent thrombosis in the pooled DES group was 2.3% (first year: 1.8%; second year: 0.4%; third year: zero). There were no significant differences in outcomes between paclitaxel- and sirolimus-eluting stents. Conclusions: The biodegradable-polymer coated DES releasing either paclitaxel or sirolimus were effective in reducing the 3-year rate of re-interventions.

Impact of arterial injury on neointimal hyperplasia after implantation of drug-eluting stents in coronary arteries: an intravascular ultrasound study

Aims: We investigated the impact of arterial injury on neointimal hyperplasia following implantation of drug-eluting stents (DES). Methods and results: A total of 196 patients with 223 segments (sirolimus-eluting stents [SES]: 104, paclitaxel-eluting stents [PES]: 119) underwent intravascular ultrasound eight months after DES implantation. Arterial injury was defined as the balloon-to-artery ratio (BAR). Segments were categorised into two groups: high BAR defined as BAR>1.1 (120 segments), and low BAR defined as BAR ≤1.1 (103 segments). Baseline clinical characteristics were similar for both groups. Although reference vessel diameter was smaller, stent diameter, maximal balloon pressure and balloon diameter were higher in the high BAR compared with the low BAR group. Lumen (7.10±1.91 vs. 6.25±1.69, p=0.001), stent (7.31±1.95 vs. 6.41±1.80, p=0.001), and external elastic membrane (17.1±4.9 vs. 14.8±4.0, p<0.0001) areas (mm2) were higher, but neointimal hyperplasia (0.21±0.36 vs. 0.16±0.48, p=0.42) area (mm2) was similar in the high BAR compared with the low BAR group. Arterial injury as assessed by BAR was not associated with the amount of neointimal hyperplasia (R2=0.003, p=0.40). Conclusions: Arterial injury does not correlate with the amount of neointimal hyperplasia following DES implantation. Conventionally aggressive DES implantation techniques do not adversely affect long-term outcome with respect to restenosis. - See more at: http://www.pcronline.com/eurointervention/30th_issue/79/#sthash.1do4X31G.dpuf

Drug-eluting stents: limitations of early generation and progress with newer generation devices

The success of first generation drug-eluting stents, namely by reducing restenosis and the need of repeat revascularization procedures is hampered by some limitations affecting device safety. Intense research efforts helped to identify these shortcomings and direct research to develop newer generation drug-eluting stents with the potential to circumvent these drawbacks. This review will discuss limitations of early generation drug-eluting stents, focus on solutions provided by newer generation devices, and shed light on unresolved issues and potential future solutions.

A randomised determination of the effect of fluvastatin and atorvastatin on top of dual antiplatelet treatment on platelet aggregation after implantation of coronary drug-eluting stents. The EFA-Trial

Drug-drug interaction between statins metabolised by cytochrome P450 3A4 and clopidogrel have been claimed to attenuate the inhibitory effect of clopidogrel. However, published data regarding this drug-drug interaction are controversial. We aimed to determine the effect of fluvastatin and atorvastatin on the inhibitory effect of dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel. One hundred one patients with symptomatic stable coronary artery disease undergoing percutaneous coronary intervention and drug-eluting stent implantation were enrolled in this prospective randomised study. After an interval of two weeks under dual antiplatelet therapy with ASA and clopidogrel, without any lipid-lowering drug, 87 patients were randomised to receive a treatment with either fluvastatin 80 mg daily or atorvastatin 40 mg daily in addition to the dual antiplatelet therapy for one month. Platelet aggregation was assessed using light transmission aggregometry and whole blood impedance platelet aggregometry prior to randomisation and after one month of receiving assigned statin and dual antiplatelet treatment. Platelet function assessment after one month of statin and dual antiplatelet therapy did not show a significant change in platelet aggregation from 1st to 2nd assessment for either statin group. There was also no difference between atorvastatin and fluvastatin treatment arms. In conclusion, neither atorvastatin 40 mg daily nor fluvastatin 80 mg daily administered in combination with standard dual antiplatelet therapy following coronary drug-eluting stent implantation significantly interfere with the antiaggregatory effect of ASA and clopidogrel.

Current status of drug-eluting stents

First-generation drug-eluting stents (DES) with controlled release of sirolimus or paclitaxel from durable polymers compared with bare-metal stents have been consistently shown to reduce the risk of repeat revascularization procedures due to restenosis. The superior efficacy was found across a wide range of patients and lesion subsets and persisted up to 5 years whereas similar outcomes have been observed in terms of death and myocardial infarction. Newer generation DES have been developed with the goal to further improve upon the safety profile of first-generation DES while maintaining efficacy. These platforms include DES with improved and more biocompatible durable polymers, DES using bioabsorbable polymers for drug release, DES with polymer-free drug release, and fully bioabsorbable DES. Newer generation DES with durable polymers such as zotarolimus-eluting or everolimus-eluting XIENCE V stents have been directly compared with first-generation DES. Most recent results of large scale clinical trials are encouraging in terms of similar or increased efficacy while improving safety by reducing the rates of myocardial infarctions and stent thrombosis. DES using biodegradable polymers for drug release represent the next technological modification and preliminary results are favorable and demonstrate similar angiographic and clinical efficacy as first-generation DES, but only longer term follow-up and investigation in larger patient cohorts will determine whether their use is associated with improved long-term safety. Fully bioabsorbable stents represent another innovative approach. Whether this innovative concept will enter into clinical routine remains yet to be determined.

Risk of target lesion failure in relationship to vessel angiographic geometry and stent conformability using the second generation of drug-eluting stents

Vessel angulation and large changes in vessel geometry after stent implantation have been associated with an increased risk of target lesion failure (TLF) using bare-metal stents. Second-generation drug-eluting stents (DES)offer superior conformability and inhibition of neointima. The aim of the study is to investigate the relationship between pre and post-implant vessel geometry and the occurrence of TLF at 1 year after treatment with second-generation DES; and to compare the conformability of Resolute and Xience stents.

Delayed coverage in malapposed and side-branch struts with respect to well-apposed struts in drug-eluting stents: in vivo assessment with optical coherence tomography

Background—Pathology studies on fatal cases of very late stent thrombosis have described incomplete neointimal coverage as common substrate, in some cases appearing at side-branch struts. Intravascular ultrasound studies have described the association between incomplete stent apposition (ISA) and stent thrombosis, but the mechanism explaining this association remains unclear. Whether the neointimal coverage of nonapposed side-branch and ISA struts is delayed with respect to well-apposed struts is unknown. Methods and Results—Optical coherence tomography studies from 178 stents implanted in 99 patients from 2 randomized trials were analyzed at 9 to 13 months of follow-up. The sample included 38 sirolimus-eluting, 33 biolimus-eluting, 57 everolimus-eluting, and 50 zotarolimus-eluting stents. Optical coherence tomography coverage of nonapposed side-branch and ISA struts was compared with well-apposed struts of the same stent by statistical pooled analysis with a random-effects model. A total of 34 120 struts were analyzed. The risk ratio of delayed coverage was 9.00 (95% confidence interval, 6.58 to 12.32) for nonapposed side-branch versus well-apposed struts, 9.10 (95% confidence interval, 7.34 to 11.28) for ISA versus well-apposed struts, and 1.73 (95% confidence interval, 1.34 to 2.23) for ISA versus nonapposed side-branch struts. Heterogeneity of the effect was observed in the comparison of ISA versus well-apposed struts (H=1.27; I2=38.40) but not in the other comparisons. Conclusions—Coverage of ISA and nonapposed side-branch struts is delayed with respect to well-apposed struts in drug-eluting stents, as assessed by optical coherence tomography.

Impact of body mass index on the five-year outcome of patients having percutaneous coronary interventions with drug-eluting stents

The purpose of this study was to assess the impact of body mass index (BMI) on clinical outcome of patients treated by percutaneous coronary intervention (PCI) using drug-eluting stents. Patients were stratified according to BMI as normal (<25 kg/m(2)), overweight (25 to 30 kg/m(2)), or obese (>30 kg/m(2)). At 5-year follow-up all-cause death, myocardial infarction, clinically justified target vessel revascularization (TVR), and definite stent thrombosis were assessed. A complete dataset was available in 7,427 patients, of which 45%, 22%, and 33% were classified according to BMI as overweight, obese, and normal, respectively. Mean age of patients was significantly older in those with a normal BMI (p <0.05). Incidence of diabetes mellitus, hypertension, and dyslipidemia increased as BMI increased (p <0.05). Significantly higher rates of TVR (15.3% vs 12.8%, p = 0.02) and early stent thrombosis (1.5% vs 0.9%, p = 0.04) were observed in the obese compared to the normal BMI group. No significant difference among the 3 BMI groups was observed for the composite of death/myocardial infarction/TVR or for definite stent thrombosis at 5 years, whereas the normal BMI group was at higher risk for all-cause death at 5 years (obese vs normal BMI, hazard ratio 0.74, confidence interval 0.53 to 0.99, p = 0.05; overweight vs normal BMI, hazard ratio 0.73, confidence interval 0.59 to 0.94, p = 0.01) in the multivariate Cox proportional hazard model. Age resulted in a linearly dependent covariate with BMI in the all-cause 5-year mortality multivariate model (p = 0.001). In conclusion, the "obesity paradox" observed in 5-year all-cause mortality could be explained by the higher rate of elderly patients in the normal BMI group and the existence of colinearity between BMI and age. However, obese patients had a higher rate of TVR and early stent thrombosis and a higher rate of other risk factors such as diabetes mellitus, hypertension, and hypercholesterolemia.

The impact of anemia on long-term clinical outcome in patients undergoing revascularization with the unrestricted use of drug-eluting stents

Anemia is frequent among patients with cardiovascular disease and adversely affects prognosis. The objective of this analysis was to assess the impact of anemia on long-term clinical outcomes among patients undergoing percutaneous coronary intervention (PCI) with the unrestricted use of drug-eluting stents (DES).

Impact of sex on clinical and angiographic outcomes among patients undergoing revascularization with drug-eluting stents

The goal of this study was to investigate sex-based differences in long-term clinical and angiographic outcomes after coronary revascularization with drug-eluting stents (DES).

Comparison of drug-eluting stents with bare metal stents in patients with ST-segment elevation myocardial infarction

To evaluate safety and effectiveness of early generation drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), and to determine whether benefits and risks vary over time.

Very late coronary stent thrombosis of a newer-generation everolimus-eluting stent compared with early-generation drug-eluting stents: a prospective cohort study

Early-generation drug-eluting stents releasing sirolimus (SES) or paclitaxel (PES) are associated with increased risk of very late stent thrombosis occurring >1 year after stent implantation. It is unknown whether the risk of very late stent thrombosis persists with newer-generation everolimus-eluting stents (EES).

Biodegradable polymer drug-eluting stents reduce the risk of stent thrombosis at 4 years in patients undergoing percutaneous coronary intervention: a pooled analysis of individual patient data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials

The efficacy of durable polymer drug-eluting stents (DES) is delivered at the expense of delayed healing of the stented vessel. Biodegradable polymer DES aim to avoid this shortcoming and may potentially improve long-term clinical outcomes, with benefit expected to accrue over time. We sought to compare long-term outcomes in patients treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES).