Utilisation des ballons actifs dans l’angioplastie coronaire : indications actuelles et perspectives

The paclitaxel-eluting balloon is an emerging percutaneous coronary angioplasty tool which aim is to prevent restenosis by delivering a high intravessel paclitaxel dose during balloon inflation. It has been already approved in the treatment of bare metal stent restenosis and is being investigated in drug-eluting stent restenosis. For the treatment of de novo lesions, it could be used alone or in combination with bare metal stent implantation. Most interesting results were obtained by a drug-eluting balloon alone strategy in small vessels angioplasty. Current and upcoming results of this evolving technology are reviewed.     

Effectiveness of drug-eluting stents in patients with bare-metal in-stent restenosis: meta-analysis of randomized trials.

OBJECTIVES: We sought to synthesize the available evidence on the effectiveness of drug-eluting stents for bare-metal in-stent restenosis. BACKGROUND: Although there is clinical evidence that drug-eluting stents are associated with better results than other treatments for in-stent restenosis, they are not yet approved for this indication. Meta-analysis of randomized trials may yield more precise estimates of treatment effects and enable a rapid adoption of effective treatments in clinical practice. METHODS: Data sources included PubMed and conference proceedings. Prespecified criteria were met by 4 randomized studies comparing sirolimus- or paclitaxel-eluting stents versus balloon angioplasty or vascular brachytherapy in 1,230 patients with bare-metal in-stent restenosis. Studies reported the clinical outcomes of efficacy and safety during a minimum of 9 months. The primary outcome was target lesion revascularization. RESULTS: No significant heterogeneity was found across trials, thus showing a similar effect size regardless of the use of balloon angioplasty or vascular brachytherapy as comparators. The risk of target lesion revascularization (odds ratio 0.35, 95% confidence interval [CI] 0.25 to 0.49; p < 0.001) and that of angiographic restenosis (odds ratio 0.36, 95% CI 0.27 to 0.49; p = 0.001) were markedly lower in patients treated with drug-eluting stents. There were no differences between patients treated with drug-eluting stents and those treated with other techniques with respect to the composite of death or myocardial infarction (odds ratio 1.04, 95% CI 0.54 to 2.03; p = 0.55). CONCLUSIONS: Drug-eluting stents are markedly superior to conventional techniques (balloon angioplasty and vascular brachytherapy) and should be considered as first-line treatment for patients with bare-metal in-stent restenosis.     

Impact of coronary culprit lesion calcium in patients undergoing paclitaxel-eluting stent implantation (a TAXUS-IV sub study)

Randomized clinical trials have shown that paclitaxel-eluting stents significantly reduce restenosis after percutaneous coronary intervention. The impact of lesion calcification on the efficacy of paclitaxel-eluting stents is unknown. In the TAXUS-IV trial, 1,314 patients who underwent percutaneous coronary intervention were randomly assigned to a bare-metal or paclitaxel-eluting stent. By core laboratory analysis, 247 lesions (19%) were moderately or severely calcified. At the 9-month angiographic follow-up examination, the paclitaxel-eluting stent had significantly reduced the amount of late loss compared with the control stent (0.26 +/- 0.56 vs 0.51 +/- 0.48 mm, p = 0.015) within the analysis segment in the calcific lesions. The analysis segment restenosis rate was similar in patients with calcified and noncalcified lesions after paclitaxel-eluting stent implantation (7.5% vs 8.0%, respectively; p = 1.0). The rate of ischemia-driven target lesion revascularization (TLR) at 1 year was reduced by 56% in patients with calcified lesions (11.9% vs 5.1%, p = 0.09) and by 75% in noncalcified lesions (15.7% vs 4.3%, p <0.0001). By interaction testing, the efficacy of the paclitaxel-eluting stent in reducing TLR at 1 year was similar in the calcified and noncalcified lesions (p = 0.30). Moreover, by multivariate analysis, implantation of the paclitaxel-eluting stent was a powerful independent predictor of freedom from TLR, with similar hazard ratios for efficacy in calcified and noncalcified lesions (0.30 and 0.26, respectively). In conclusion, implantation of paclitaxel-eluting stents in patients with de novo coronary lesions significantly reduced restenosis in patients with and without calcified lesions.     

Classification and Current Treatment Options of In-Stent Restenosis

Coronary stent implantation is currently performed in > 80% of percutaneous coronary interventions. Its main late complication is the development of in-stent restenosis (ISR), occurring in 10-80% of lesions treated in daily practice. The classification by Mehran et al. is most commonly used. Current therapeutic options to treat ISR include repeat balloon angioplasty, repeat stenting, cutting balloon angioplasty, directional coronary atherectomy, rotational coronary atherectomy, brachytherapy, and drug-eluting stents (DES). DES have been effective in reducing binary restenosis in de novo lesions in randomized controlled trials. The novel use of DES to treat ISR has been shown to be safe and effective in multiple studies involving sirolimus- and paclitaxel-eluting stents. As DES implantation becomes more widespread, ISR in DES is emerging as a new problem. The use of debulking techniques to treat ISR in DES is to be cautioned against. In this new era, the optimal treatment of this new problem is currently unknown. We await further data to see whether repeat DES implantation may help solve this vexing clinical problem.     

Therapy insight: diabetes and drug-eluting stents

Individuals with diabetes mellitus usually present with accelerated atherosclerosis, more diffuse disease, concomitant comorbidities and have an increased risk for restenosis. Evidence confirmed the superiority of CABG surgery over balloon angioplasty with or without bare-metal stenting for diabetic patients requiring multivessel revascularization. More recently, drug-eluting stents (DESs) have emerged as the predominant percutaneous strategy in patients with coronary artery disease. This Review summarizes the knowledge on coronary stenting in diabetics. Although the rate of restenosis is dramatically reduced with the use of DESs compared with bare-metal stents, diabetic patients continue to face higher adverse cardiac event rates when compared with nondiabetic patients. Whether there are differences in the effectiveness of paclitaxel-eluting or sirolimus-eluting stents is still debated. Late outcome might be overshadowed by clinical issues such as late stent thrombosis or restenosis, particularly in diabetic patients with renal failure or complex lesions, and after premature interruption of antiplatelet agents. Longer follow-up in larger populations is thus needed to confirm the long-term safety and efficacy. The superiority or the equivalence of DESs over CABG surgery for multivessel disease has not yet been demonstrated. Thus, although evidence supports DES use in diabetics, further data are needed to better define the management of diabetic patients with coronary artery disease.     

Opportunities and limitations of drug-coated balloons in interventional therapies

Drug-coated balloons (DCB) represent a novel clinical treatment modality for coronary and peripheral artery disease. Advantages over standard angioplasty and stent technologies including homogeneous drug delivery to the vessel wall, immediate drug release without the use of a polymer, the option of using balloon catheters alone or in combination with a bare metal stent, no foreign object that remains in the body, the potential of reducing antiplatelet therapy, and lower restenosis rates in some indications. As with drug-eluting stents (DES), one cannot assume a class effect for DCB. So far, data from randomized clinical trials identify the treatment of coronary in-stent restenosis (ISR) and of de novo and restenotic lesions in peripheral artery disease as viable options. Furthermore, treatment of de novo lesions in small coronary vessels, bifurcation lesions, long lesions, pediatric interventions, and cerebrovascular applications are potential beneficial indications. In the coronary application, a strategy of DCB angioplasty with provisional spot-stenting in the case of severe dissections may become a better alternative in long and complex lesions, bifurcations, or in patients with contraindications for DES.     

The paclitaxel-eluting stent in percutaneous coronary intervention: Part II. Comparison with the sirolimus-eluting stent, economics, and unanswered questions

The paclitaxel- and sirolimus-eluting stents are currently the only drug-eluting stents approved for use in the United States. These 2 stents differ in terms of mechanism of drug action, the construct of the stent itself, and the drug delivery polymer. Clinical trials have demonstrated superiority of both paclitaxel- and sirolimus-eluting stents when compared with bare-metal stents in terms of reducing restenosis and the need for target vessel revascularization. Recently published head-to-head trials have not conclusively shown 1 drug-eluting stent to be superior to the other, but have demonstrated more favorable angiographic results with the sirolimus-eluting stent compared with the paclitaxel-eluting stent; however, no significant difference has been demonstrated in clinical outcomes such as myocardial infarction or death. In terms of economics, the paclitaxel-eluting stent is substantially more expensive than the bare-metal stent. However, by significantly reducing the risk of restenosis and need for repeat revascularization, the higher direct cost of the paclitaxel-eluting stent may in theory be offset by lower overall healthcare costs, although economic analyses have yet to definitively establish that the paclitaxel-eluting stent is truly cost-effective. There is still much to be discovered regarding the paclitaxel-eluting stent, specifically the optimal stent design and drug release mechanism, the relative safety and efficacy of the paclitaxel-eluting stent compared with other drug-eluting stents, the long-term effects of the paclitaxel-eluting stent, the ideal antiplatelet regimen to use in patients with a paclitaxel-eluting stent, the safety and efficacy of the paclitaxel-eluting stent in various high-risk patient groups, and the ultimate cost-effectiveness of this device.     

Randomized trial of paclitaxel- and sirolimus-eluting stents in small coronary vessels.

AIMS: Sirolimus- and paclitaxel-eluting stents effectively reduce restenosis in small coronary vessels. The relative efficacy of these drug-eluting stents in this high-risk subset is not known. METHODS AND RESULTS: A total of 360 patients undergoing percutaneous coronary intervention for de novo lesions in native coronary vessels with a diameter of <2.80 mm received randomly paclitaxel-eluting stents (n=180) or sirolimus-eluting stents (n=180). The primary endpoint was in-stent late luminal loss. Secondary endpoints were angiographic restenosis and need of target lesion revascularization. The study intended to show that the paclitaxel-eluting stent is not inferior to the sirolimus-eluting stent with respect to the primary endpoint. The non-inferiority margin was set at 0.16 mm. Follow-up angiography was performed in 87% of the patients. In-stent late luminal loss in the paclitaxel-eluting stent group was 0.32 mm (upper 95% boundary, 0.42 mm), which was greater than that in the sirolimus-eluting stent group, failing to show the non-inferiority of the paclitaxel-eluting stent to the sirolimus-eluting stent (P>0.99). Angiographic restenosis was found in 19.0% of the lesions in the paclitaxel-eluting stent group and 11.4% of the lesions in the sirolimus-eluting stent group (P=0.047). Target lesion revascularization was performed in 14.7% of the lesions treated with paclitaxel-eluting stents and 6.6% of the lesions treated with sirolimus-eluting stents (P=0.008). CONCLUSION: The paclitaxel-eluting stent is associated with a greater late luminal loss and is less effective in reducing restenosis in small coronary vessels than the sirolimus-eluting stent.     

Intracoronary radiation therapy for multi-drug resistant in-stent restenosis: initial clinical experience.

While randomized clinical trials have demonstrated the excellent efficacy of sirolimus-eluting stents (SES) for de novo lesions, the optimal treatment for SES-restenosis is not known. Management may include stand-alone balloon angioplasty, repeat SES implantation, or placement of a drug-eluting stent (DES) with an alternative antiproliferative agent (i.e., a paclitaxel-eluting stent, PES). The appropriate management strategy for recurrent restenosis after PES implantation for SES restenosis is even less clear. We report the initial clinical experience with intracoronary radiation therapy (ICRT) for multi-DES resistant restenosis. We performed ICRT in five patients with recurrent restenosis after treatment with both SES and PES. Over a median follow-up of 256 days (range 75-489 days), one patient had a target lesion revascularization at 182 days and subsequently died at 483 days following the procedure. Our findings support the further study of this management approach.     

Six-month clinical and angiographic results of a dedicated drug-eluting stent for the treatment of coronary bifurcation narrowings

Percutaneous intervention for coronary bifurcation lesions has been associated with increased clinical complication rates compared with nonbifurcation lesions, primarily as a result of restenosis. Therefore, there is a need for new techniques. The purpose of this study was to evaluate a new drug-eluting stent and implantation technique for the treatment of de novo coronary bifurcation lesions. The Axxess Plus trial was a prospective multicenter single-arm study that enrolled 139 patients. Each patient received a self-expanding, conically shaped nickel-titanium Axxess Plus biolimus A9-eluting stent at the level of the carina. Depending on the lesion anatomy, additional nonstudy stents were placed distally if necessary. Clinical and angiographic follow-up were scheduled at 6 months after the procedure. The overall rate of target lesion revascularization was 7.5% at 6 months. A mean of 2.4 stents were implanted per patient; 51.2% of patients received a stent to the side branch, 29.4% received balloon angioplasty only, and 20.6% of side branches were not treated. In-stent late loss in the Axxess stents was 0.09 mm. Incidences of angiographic in-stent restenosis were 7.1% in the parent vessel stents and 9.2% in the group receiving stents in the side branch (7.9% excluding bare metal stents placed distal to the Axxess stent), compared with 25% for balloon angioplasty treatment and 12% for no treatment. Late stent thrombosis was observed in 3 cases, 2 of which were associated with confirmed premature cessation of antiplatelet therapy. In conclusion, the Axxess Plus conical stent effectively treats bifurcation lesions alone or in conjunction with other drug-eluting stents.     

Outcomes of paclitaxel-eluting stent implantation in patients with stenosis of the left anterior descending coronary artery

OBJECTIVES: We sought to examine the efficacy of paclitaxel-eluting stent implantation in the left anterior descending coronary artery (LAD). BACKGROUND: Restenosis and recurrent cardiac events after percutaneous intervention are more common for lesions in the LAD than other native coronary arteries, and often necessitate bypass surgery. Drug-eluting stents may improve the long-term prognosis of this high-risk group. METHODS: In the TAXUS-IV trial, 1,314 patients with single de novo coronary lesions were assigned to implantation of the slow-release, polymer-based, paclitaxel-eluting TAXUS stent or an identical bare-metal stent; 536 (41%) randomized patients had LAD lesions. RESULTS: Baseline characteristics of patients with LAD lesions were well-matched between the randomized groups. Late lumen loss at nine months after paclitaxel-eluting and control stent implantation were 0.28 +/- 0.51 mm and 0.54 +/- 0.57 mm, respectively (p = 0.0004), and binary restenosis rates were 11.3% and 26.9%, respectively (p = 0.004). At one year, major adverse cardiac events (MACE) occurred in 13.5% of TAXUS-treated patients versus 21.2% treated with the control stent (p = 0.01). The need for bypass surgery at one year was reduced among patients randomized to the TAXUS stent (2.6% vs. 6.3%, p = 0.02). In the proximal LAD subgroup (n = 126), the one-year target vessel revascularization rate was 7.9% with the TAXUS stent and 18.6% with the bare-metal stent (p = 0.009). CONCLUSIONS: Compared to bare-metal stents, implantation of polymer-based, paclitaxel-eluting stents in LAD lesions is safe, and reduces angiographic restenosis and MACE one year. Notably, the need for bypass graft surgery due to restenosis is reduced after TAXUS stent implantation in LAD lesions.     

Contemporary use of drug-eluting stents

Optional statement Since the era of balloon angioplasty, stents have been a revolutionary advance in the treatment of severe coronary artery disease. However, one of the major limitations is in-stent restenosis. Although brachytherapy was found to be an effective treatment, the goal remains to develop a kind of stent that will not restenose. The emergence of drug-eluting stents provided a novel solution for the reduction of restenosis. The currently approved indication for drug-eluting stents by the US Food and Drug Administration is for discrete, de novo lesions in native vessels with reference vessel diameters of 2.5 to 3.5 mm. However, in the worldwide daily practice, there have been numerous off-label uses of drug-eluting stents, and their long-term follow-up and experience in more complex lesions are accumulating. This article reviews the current off-label uses of drug-eluting stents. The majority of the supporting data are from registry and observational studies, yet many studies are limited by small sample sizes. Therefore, large, prospective, randomized, double-blind, and controlled trials are definitely warranted to further support current practice. Nevertheless, the “real world” unrestricted uses of drug-eluting stents seem to be the current trend in the interventional field.     

Drug-eluting stents for treatment of focal infrapopliteal lesions

We have investigated the role of drug-eluting stents on patency rates after treatment of focal infrapopliteal lesions in patients with intermittent claudication and critical limb ischemia. Reports indicate that drug-eluting stents reduce the risk of restenosis after percutaneous infrapopliteal artery revascularization. A Pub Med, EMBASE, Cochrane database review search of non-randomized studies investigating patency rates, target lesion revascularisation rates, limb salvage rates and mortality rates in an up to 3-year follow-up period after drug-eluting stent placement was conducted. In addition, preliminary results of randomized studies comparing drug-eluting stents with bare-metal stents and plain balloon angioplasty in treatment of focal infrapopliteal lesions were included in this review. A total of 1039 patients from 10 non-randomized and randomized studies were included. Most commonly used drug-eluting stents were sirolimus-eluting. The mean follow-up period was 12.6 (range 8 - 24). The mean 1-year primary patency rate was 86 ± 5 %. The mean target lesion revascularization rate and limb salvage rate was 9.9 ± 5 % and 96.6 %±4 %, respectively. Results from non-randomized and preliminary results from prospective, randomized trials show a significant advantage for drug-eluting stents in comparison to plain balloon angioplasty and bare-metal stents concerning target lesion patency and in parts target lesion revascularisation. No trial reveals an advantage for drug-eluting stents with regard to limb salvage and mortality.     

Drug-Eluting Stents for In-Stent Restenosis and Acute Myocardial Infarction

In-stent restenosis (ISR) remains the "Achilles' heel" of percutaneous stent angioplasty treatment of patients with atherosclerotic disease of the coronary arteries. Recently, drug-eluting stents (DES) have ushered in a revolution in the treatment of these patients, yet, to date, their efficacy and safety have been demonstrated primarily for native de novo coronary lesions. For ISR, intracoronary brachytherapy using beta- or gamma-radiation is considered the standard of care. Nevertheless, DES are used for ISR lesions in clinical practice. This review outlines the few results currently available from small observational studies and larger registries. The designs of two ongoing randomized trials evaluating the sirolimus-eluting and the paclitaxel-eluting stent versus brachytherapy in patients with ISR lesions are also presented. Patients with acute myocardial infarction (AMI) have mostly been investigated in the context of small, uncontrolled studies and registries. The incomplete evidence to date is that implantation of sirolimus-eluting stents in patients with AMI is safe and effective.     

Role of adjunct pharmacologic therapy in the era of drug-eluting stents

The success of percutaneous coronary intervention (PCI) has historically been limited by a relatively high rate of restenosis, a response of the coronary artery to trauma induced during PCI. Bare-metal stents, by providing a supportive intravascular scaffolding, have significantly reduced the incidence of restenosis compared with traditional balloon PCI. However, significant loss of lumen within the bare-metal device (in-stent restenosis) occurs in 10-30% of patients within 6 months of the procedure. The recent introduction of drug-eluting stents, permitting local delivery of high concentrations of immunosuppressive or anti-proliferative agents, promises to prevent the processes underlying restenosis. Although these devices have been successful in providing an incremental reduction in rates of restenosis, they are expensive. To date, clinical trials of pharmacologic treatment have failed to demonstrate a clinically significant impact on restenosis. Recently, results of the Cilostazol for Restenosis (CREST) trial, a randomized, double-blind study, show that cilostazol reduces the risk of restenosis in patients who receive bare-metal stents, including high-risk patients. Effective adjunct pharmacologic therapy to prevent in-stent restenosis, therefore, remains desirable, particularly in patients receiving bare-metal stents, and potentially in patients receiving drug-eluting stents who are at high risk for restenosis (i.e., those with diabetes, long lesions, and small vessels).     

Is Palmaz-Schatz stenting effective for second restenosis?

The long-term outcome after coronary stent placement in restenotic lesions after balloon angioplasty (percutaneous transluminal coronary angioplasty: PTCA)may be less favorable compared to stent treatment of de novo lesions, but the role of stents in restenotic lesions after 2 prior PTCA procedures is unknown. Elective Palmaz-Schatz stent placement was performed in 124 consecutive patients. Stents were placed in 70 patients(56%) in the native coronary arteries for de novo lesions(de novo group), in 33 patients (27%)for restenotic lesions after one prior PTCA(restenosis group), and 21 patients(17%)for restenotic lesions after 2 prior PTCA(second restenosis group). The 3 groups were well matched with respect to lesion type, lesion length, and reference diameter. Stent size was similar in the 3 groups. Follow-up angiograms taken about 6 months after stenting were available for all patients. The restenosis rate after stenting was similar for the de novo group and restenosis group(19% vs 27%, NS). The second restenosis group tended to have a higher restenosis rate after stenting than the de novo group(38% vs 19%, p = 0.06). The frequency of diffuse type in-stent restenosis of the second restenosis group tended to be higher than that of the de novo group(63% vs 13%, p = 0.08). Our results suggest that the restenosis rate after stenting was higher in patients with repeated restenosis. Therefore, other therapeutic methods should be considered.     

Drug-eluting coronary stents

The introduction and widespread use of coronary stents have been the most important advancement in the percutaneous treatment of coronary artery disease since the introduction of balloon angioplasty. Coronary artery stents reduce the rate of angiographic and clinical restenosis compared to balloon angioplasty. This angiographic restenosis was further reduced with the introduction of drug-eluting stents and hence further reduction in the frequency of major adverse cardiac events. Herein we present a comprehensive and up-to-date review about the use of drug-eluting stents in the treatment of coronary artery disease.     

Provisional stenting for multivessel PCI

Background: Bare stents reduce acute complications and repeat revascularization following percutaneous coronary intervention (PCI), but are costly and may lead to in‐stent restenosis. It remains unclear whether stents should be universally implanted or whether provisional stenting mainly to suboptimal balloon dilatation results is an acceptable approach for multivessel PCI. Objective: To compare the long‐term clinical restenosis and target lesion revascularization (TLR) of stented and non‐stented coronary artery lesions in patients who had multivessel PCI. Methods: We performed retrospective analysis of matched data from 129 consecutive patients who underwent multivessel PCI (at least optimal balloon angioplasty to one coronary artery segment and balloon angioplasty plus stenting to another coronary artery in the same patient, all lesions are de novo native coronary artery lesions with vessel diameter ?2.5?mm). The study endpoint was restenosis and repeat revascularization at one‐year follow‐up. Results: Baseline characteristics were similar in both groups. Low in‐hospital MACE (3.1%). Acute myocardial infarction, emergency revascularization via either PCI or CABG was detected and angiographic success was achieved in 99.3% of lesions in both groups. The rate of clinically driven angiographic restenosis and TLR at one‐year (follow‐up?100%) was similar (17.1% versus 18.6%, P?=?0.871, and 13.9% versus 16.3%, P?=?0.728, for optimal balloon angioplasty versus provisional stenting. Conclusions: The main findings from this study are that long‐term angiographic restenosis and TLR was comparable for optimal balloon angioplasty and provisional stenting, suggesting that provisional stenting is an acceptable approach for multivessel PCI.     

Covered stent for the treatment of recurrent bilateral renal artery in-stent restenosis

The optimal treatment for renal artery in-stent restenosis (ISR) is not well established. Reintervention with different strategies including balloon angioplasty, cutting-balloon angioplasty, additional stenting with bare-metal, drug-eluting or covered stents and brachytherapy are effective in achieving immediate angiographic success. However, recurrent ISR rates are high irrespective of treatment strategy. We present a case describing the use of a covered stent for the treatment of recurrent bilateral renal artery ISR after bare-metal and drug-eluting stent implantation and cutting-balloon angioplasty.     

A case of takotsubo cardiomyopathy associated with Kounis syndrome

In-stent restenosis (ISR) occurs in 20% to 40% of de novo coronary lesions treated with bare-metal stents (BMS), depending on lesion and patient-related factors. Drug-eluting stents coated with antiproliferative agents, represent a valid rationale for treatment and prevention of recurrent ISR, with low MACE rates. However, case reports and observational studies reported a definite increase in the incidence of late stent thrombosis after drug-eluting stents use, particularly in off-label cases and after clopidogrel withdrawal. The case we present shows target vessel occlusion occurring at the site of a previously implanted BMS, suggesting that in-stent restenosis was the main pathological mechanism leading to abrupt thrombotic vessel closure and acute myocardial infarction.