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Background: Limus-eluting stents are dominating coronary interventions, although paclitaxel is the only drug on balloon catheters with proven inhibition of restenosis. Neointimal inhibition by limus-coated balloons has been shown in few animal studies, but data from randomized clinical trials are not available. The aim of the present preclinical studies was to achieve high and persistent sirolimus levels in the vessel wall after administration by a coated balloon., Methods and Results: Different coating formulations and doses were studied in the porcine coronary model to investigate sirolimus tissue levels at different time points as well as efficacy at 1 month using quantitative coronary angiography and histomorphometry. Loss of the selected coating in the valve, guiding catheter, and blood was low (2±14% of dose). Acute drug transfer to the vessel wall was 14.4±4.6% with the crystalline coating, whereas the amorphous coatings were less effective in this respect. Persistence of sirolimus in the vessel wall until 1 month was 40% to 50% of the transferred drug. At 1-month follow-up, a modest but significant reduction of neointimal growth was demonstrated in a dose range from 4 μg/mm(2) to 2×7 μg/mm(2), for example, maximum neointimal thickness of 0.38±0.13 versus 0.65±0.21 mm in the uncoated control group., Conclusions: Various sirolimus-coated balloons effectively reduce neointimal proliferation in the porcine coronary model but differ considerably in retention time in the vessel wall. It has to be determined if such a formulation with persistent high vessel concentration will result in a relevant clinical effect., (© 2016 American Heart Association, Inc.)

Background: In selected patients with hypertension, renal artery (RA) stenting is used to treat significant atherosclerotic stenoses. However, blood pressure often remains uncontrolled after the procedure. Although catheter-based renal denervation (RDN) can reduce blood pressure in certain patients with resistant hypertension, there are no data on the feasibility and safety of RDN in stented RA., Methods and Results: We report marked blood pressure reduction after RDN in a patient with resistant hypertension who underwent previous stenting. Subsequently, radiofrequency ablation was investigated within the stented segment of porcine RA, distal to the stented segment, and in nonstented RA and compared with stent only and untreated controls. There were neither observations of thrombus nor gross or histological changes in the kidneys. After radiofrequency ablation of the nonstented RA, sympathetic nerves innervating the kidney were significantly reduced, as indicated by significant decreases in sympathetic terminal axons and reduction of norepinephrine in renal tissue. Similar denervation efficacy was found when RDN was performed distal to a renal stent. In contrast, when radiofrequency ablation was performed within the stented segment of the RA, significant sympathetic nerve ablation was not seen. Histological observation showed favorable healing in all arteries., Conclusions: Radiofrequency ablation of previously stented RA demonstrated that RDN provides equally safe experimental procedural outcomes in a porcine model whether the radiofrequency treatment is delivered within, adjacent, or without the stent struts being present in the RA. However, efficacious RDN is only achieved when radiofrequency ablation is delivered to the nonstented RA segment distal to the stent., (© 2014 American Heart Association, Inc.)

Background: The purpose of this study was to investigate the elimination of paclitaxel from the arterial wall after a single short administration with a coated balloon., Methods and Results: Slightly oversized paclitaxel-coated balloons (dose 3 or 9 μg/mm(2)) without or with premounted stents were inflated in nonatherosclerotic coronary arteries of either young domestic pigs or adult Goettingen minipigs. The paclitaxel content of plasma, arterial segments, and residual hearts (without treated arteries) was measured for up to 180 days using high-performance liquid chromatography/ultraviolet detection or mass spectrometry. Angiograms were evaluated for lumen narrowing. The paclitaxel concentration in plasma remained <10 ng/mL. In arteries of domestic pigs and minipigs treated with paclitaxel-coated balloons with premounted stents, 10%±5% or 21%±8% of dose, respectively, was initially detected and decreased to 3.5%±3.1% of dose (domestic pig) by Day 7. Within 6 months it fell with a half-life of 1.9 months to 0.40%±0.35%. After 3 months the concentration in the arterial wall was 17±11 μmol/L. Without a stent, drug transfer to the vessel wall was somewhat reduced and elimination faster. Immediately after treatment up to 26%±4% of dose was detected in the residual whole hearts. It dropped with a half-life of 45 days to 1.5%±0.6% of dose (0.3 μmol/L) within 6 months., Conclusions: After a single local administration with coated balloons, paclitaxel stays in the vessel wall of pigs long enough to explain persistent inhibition of neointimal proliferation. The pharmacokinetics of paclitaxel does, however, not exclude other reasons for sustained efficacy such as early blocking of processes initiating excessive and prolonged neointimal proliferation.

Background: Optimal reperfusion strategy in ST-elevation myocardial infarction is controversial. Failure of fibrinolytic therapy is related to limited efficacy, high reocclusion rates, reinfarction, and systemic bleeding complications. Data on the impact of percutaneous coronary intervention (PCI) after fibrinolysis are conflicting. The Southwest German Interventional Study in Acute Myocardial Infarction (SIAM III) evaluated the effects of transfer for early PCI in acute ST-elevation-myocardial infarction compared with a delayed PCI strategy., Methods and Results: SIAM III was a multicenter, randomized, prospective, controlled trial in patients with ST-elevation-myocardial infarction receiving fibrinolysis <12 hours after onset of symptoms. All patients received reteplase, aspirin in combination with ticlopidine, and heparin. Patients of the early PCI group were transferred within 6 hours after fibrinolysis for PCI. The delayed PCI group received elective PCI 2 weeks after fibrinolysis. In total, 197 patients were included; 163 were treated by PCI. The primary end point was the composite of death, reinfarction, target lesion revascularization, and ischemic events. During a mean follow-up time of 7.9±3.4 years (maximum, 11.2 years), early PCI was associated with a significant reduction of the primary end point (hazard ratio, 0.61 [95% confidence interval, 0.42 to 0.88]; P=0.008). Long-term survival was higher in the early PCI group (P=0.057). Ischemic events were significantly reduced after early PCI (P=0.003)., Conclusions: Early PCI after fibrinolysis improves long-term event-free survival compared with a delayed PCI treatment strategy.