Trials Of Drug-eluting Stents Research Articles

Drug‐eluting or bare metal stents for diabetics: Clinical judgment still wins

Once it is determined to pursue mechanical revascularization with percutaneous coronary intervention in a diabetic patient capable of taking dual antiplatelet therapy (DAPT), what is the optimal type of stent to place? Meta-analysis of the 2,422 diabetic patients randomized in the 13 pivotal randomized trials (RCTs) of drug-eluting stents (DES) versus bare metal stents (BMS) documented an 84% reduction in the odds of restenosis with DES compared with BMS [1,2]. In the DECODE and DIABETES studies, DES reduced angiographic restenosis from 50% to 10% and target vessel revascularization (TVR) from 30% to single digits compared with BMS in diabetics, with particular advantage in reference vessel diameters <3.0 mm [3,4]. The meta-analyses of the RCTs also demonstrate a nonsignificant trend toward reduction in death and myocardial infarction (MI) in patients assigned to DES, both diabetic and nondiabetic subgroups [5]. The putative mechanisms of DES possibly reducing death and nonfatal MI in randomized comparisons is that restenosis is not always a benign event and/or possible benefit from more prolonged DAPT associated with DES treatment. Given the selection biases of less complex lesions and healthier patients in the RCTs, what results can reasonably be expected in consecutive routine practice? Legitimate concerns about the prothrombotic state as well as reduced response to aspirin and clopidogrel in diabetics raise the specter of late and very late stent thrombosis (ST) undermining some of the potential revascularization benefits. The EVASTENT registry in France reported a DES ST rate of 4.3% with multivessel disease and 2.3% with single-vessel disease in 356 diabetics (compared with 3.0% and 0.8% in nondiabetics) [6]. Insulin requirement was an independent significant risk factor for ST. Reassuringly, Ramanath et al. [7] in this issue of Catheterization and Cardiovascular Interventions observe no signal of increased mortality or major adverse cardiovascular events in 1,319 consecutive diabetics undergoing stenting with DES compared with BMS. Although optimal statistical methods to control bias are used in this observational study, a significantly lower in-hospital and 30-day mortality remains associated with operator selection of DES [8]. As the authors suggest, this almost certainly reflects residual confounding from unknown and unmeasured covariates in the nonrandomized comparison. A mechanism by which DES implantation might save lives at 30 days compared with BMS is difficult to imagine. Surely, operators are successfully optimizing the match between stent type and patient comorbidities using additional information and clinical intuition not captured in these most robust of statistical methods for leveling observational comparisons. In late follow-up, likely less contaminated with patient selection biases, Ramanath et al. observe a small nonsignificant trend toward better survival with DES consistent with the RCTs. Does the revascularization benefit observed in diabetics in the RCTs hold up in the real world? After propensity score matching, Ramanath et al. report a hazard ratio of subsequent TVR 35% lower with DES than BMS. Extrapolating this to absolute rates, TVR with BMS is 14% compared to 6% with DES at 1 year. TVR is 21% with BMS at 3 years compared to 13% with DES. So the incremental absolute difference in subsequent TVR with DES is roughly 8%. About 12 diabetic patients need to be treated with DES instead of BMS to prevent one TVR event. What explains the smaller magnitude of TVR benefit in observational studies compared to RCTs? Again, operators are likely considering additional unknown and unmeasured confounders in matching stent type with patient that optimizes restenosis risk. Supporting this hypothesis, a considerably larger observational analysis comparing DES with BMS outcomes documented an even smaller additional revascularization

TCT-224: Use of a Low-Dose (LD) Paclitaxel Formulation on the Novel, Biodegradable, Minimal Polymer JACTAX Stent: Primary Endpoint Results from the JACTAX LD Drug-Eluting Stent Trial

TCT-224: Use of a Low-Dose (LD) Paclitaxel Formulation on the Novel, Biodegradable, Minimal Polymer JACTAX Stent: Primary Endpoint Results from the JACTAX LD Drug-Eluting Stent Trial

The Clinical Impact of Routine Angiographic Follow-Up in Randomized Trials of Drug-Eluting Stents: A Critical Assessment of “Oculostenotic” Reintervention in Patients With Intermediate Lesions

The aim of this study was to study the long-term clinical effects of routine angiographic follow-up and related reintervention after drug-eluting stenting. Prior stent trials have shown that protocol-mandated angiographic follow-up increases repeat interventions compared with clinical follow-up alone. The long-term clinical impact of this practice is unknown. Long-term outcomes of patients assigned to routine angiographic follow-up in 3 large-scale TAXUS (Boston Scientific, Natick, Massachusetts) trials were compared with patients assigned to clinical follow-up alone, in a propensity score-adjusted patient-level meta-analysis. Outcomes were also compared in patients with treated versus untreated nonischemic intermediate lesions (quantitative angiographic stenosis between >or=40% and <70%) detected at angiographic follow-up. Target lesion revascularization (TLR) rates at 5 years were significantly higher in the angiographic compared with clinical follow-up cohort (18.3% vs. 11.1%, p < 0.001). This was due to more frequent treatment of intermediate lesions, but there was no associated reduction in rates of cardiac death or myocardial infarction (8.9% vs. 8.8%, p = 0.93). Of patients with nonischemic intermediate lesions, 17% who were not revascularized at the time of angiographic follow-up had a subsequent TLR, whereas 7% of patients who had TLR at this follow-up angiogram required additional revascularization during long-term follow-up. A strategy of routine angiographic follow-up increases oculostenotic revascularization of nonischemic intermediate lesions without affecting subsequent rates of cardiac death or myocardial infarction, and TLR was not required in 83% of those lesions. A conservative approach, in which repeat angiography is limited to patients with recurrent ischemia or progressive symptoms, minimizes repeat revascularization of nonischemic intermediate lesions and optimizes long-term event-free survival after drug-eluting stent implantation.

A Novel Paclitaxel-Eluting Stent With an Ultrathin Abluminal Biodegradable Polymer: 9-Month Outcomes With the JACTAX HD Stent

The JACTAX HD trial ("JACTAX" Trial Drug Eluting Stent Trial) evaluated the safety and clinical performance of a novel JACTAX HD (Boston Scientific Corporation, Natick, Massachusetts) paclitaxel-eluting stent (PES) in de novo coronary lesions. The JACTAX HD (Boston Scientific) stent consists of a pre-crimped bare-metal Liberté (Boston Scientific) stent coated on its abluminal aspect with an ultrathin (<1 microm) 1/1 mixture of biodegradable polylactide polymer and paclitaxel applied as discrete microdots (nominal totals of 9.2 microg each of polymer and paclitaxel per 16-mm stent). In this prospective, single-arm, multicenter, first-human-use study (n = 103), the primary end point of 9-month major adverse cardiac events (MACE) (cardiac death, myocardial infarction, ischemia-related target vessel revascularization) was compared with an objective performance criterion (OPC) of 17% (11% MACE based on TAXUS ATLAS [TAXUS Liberté-SR Stent for the Treatment of de Novo Coronary Artery Lesions] trial results plus a pre-specified noninferiority margin of 6%). The composite primary end point occurred in 7.8% of JACTAX HD patients with an upper 1-sided 95% confidence limit of 13.6%, thus meeting the pre-specified criteria for noninferiority. There was no death, Q-wave myocardial infarction, or stent thrombosis through 9 months. In-stent late loss was 0.33 +/- 0.45 mm, with an in-stent binary restenosis of 5.2% and net volume obstruction by intravascular ultrasound of 11.4 +/- 11.2%. The JACTAX HD stent with an abluminal biodegradable polymer showed 9-month MACE, in-stent late loss, restenosis, and net volume obstruction comparable to that observed with the TAXUS Liberté (Boston Scientific) stent coated with a conformal durable polymer. Further studies are underway to better evaluate the potential of this new PES design, which might allow for more rapid endothelialization and improved vessel healing. ("JACTAX" Trial Drug Eluting Stent Trial; NCT00754728).

Re-examining minimal luminal diameter relocation and quantitative coronary angiography – intravascular ultrasound correlations in stented saphenous vein grafts: methodological

Angiographic parameters (such as late luminal loss) are common endpoints in drug-eluting stent trials, but their correlation with the neointimal process and their reliability in predicting restenosis are debated. Using quantitative coronary angiography (QCA) data (49 bare metal stent and 44 sirolimus-eluting stent lesions) and intravascular ultrasound (IVUS) data (39 bare metal stent and 34 sirolimus-eluting stent lesions) from the randomised Reduction of Restenosis In Saphenous vein grafts with Cypher stent (RRISC) trial, we analysed the "relocation phenomenon" of QCA-based in-stent minimal luminal diameter (MLD) between post-procedure and follow-up and we correlated QCA-based and IVUS-based restenotic parameters in stented saphenous vein grafts. We expected the presence of MLD relocation for low late loss values, as MLD can "migrate" along the stent if minimal re-narrowing occurs, while we anticipated follow-up MLD to be located close to post-procedural MLD position for higher late loss. QCA-based MLD relocation occurred frequently: the site of MLD shifted from post-procedure to follow-up an "absolute" distance of 5.8 mm [2.5-10.2] and a "relative" value of 29% [10-46]. MLD relocation failed to correlate with in-stent late loss (rho = 0.14 for "absolute" MLD relocation [p = 0.17], and rho=0.03 for "relative" relocation [p = 0.811). Follow-up QCA-based and IVUS-based MLD values well correlated in the overall population (rho = 0.76, p < 0.001), but QCA underestimated MLD on average 0.55 +/- 0.49 mm, and this was mainly evident for lower MLD values. Conversely, the location of QCA-based MLD failed to correlate with the location of IVUS-based MLD (rho = 0.01 for "absolute" values--in mm [p = 0.911, rho = 0.19 for "relative" values--in % [p = 0.111). Overall, the ability of late loss to "predict" IVUS parameters of restenosis (maximum neointimal hyperplasia diameter, neointimal hyperplasia index and maximum neointimal hyperplasia area) was moderate (rho between 0.46 and 0.54 for the 3 IVUS parameters). These findings suggest the need for a critical re-evaluation of angiographic parameters (such as late loss) as endpoints for drug-eluting stent trials and the use of more precise techniques to describe accurately and properly the restenotic process.

Mounting Evidence for Safety and Improved Outcomes of Drug-Eluting Stenting

Mounting Evidence for Safety and Improved Outcomes of Drug-Eluting Stenting

Assessing the Landscape of Stent Thrombosis: The Drug-Eluting Versus Bare-Metal Stent Controversy

Within labeled indications, drug-eluting stents (DES) are as safe as bare-metal stents (BMS). Data from key randomized, controlled trials comparing paclitaxel-eluting stents with BMS or sirolimus-eluting stents with BMS show no difference in risk of death/myocardial infarction or stent thrombosis using uniform definitions of stent thrombosis. However, these trials and other analyses indicate a difference in time distribution of stent thrombosis, with more cases of stent thrombosis occurring later (ie, after 1 year) in patients with DES--a problem to which the lack of adequate antiplatelet therapy appears to be a main contributor. A consistent finding from randomized, controlled trials of DES versus BMS is the significantly reduced need for reintervention associated with DES use. In the absence of any other differences in safety between DES and BMS, this reduced need for reintervention constitutes a significant advantage for DES in clinical practice.

Stent Thrombosis in Randomized Clinical Trials of Drug-Eluting Stents

Stent Thrombosis in Randomized Clinical Trials of Drug-Eluting Stents

Long-term Clinical Outcomes Following Coronary Stenting

Clinical trials of drug-eluting stents (DES) vs bare metal stents (BMS) report a reduced need for target lesion revascularization with no difference in death or myocardial infarction. However, these trials selectively enrolled patients with lower risk, single-vessel coronary artery disease (CAD) and limited the follow-up period to 1 year or less. Thus, it is not known how these short-term results apply to patients with higher risk, multivessel CAD seen in community practice settings. The objective of this study was to compare the long-term clinical outcomes of patients receiving DES vs BMS in a clinical practice setting. Patients from the Duke Databank for Cardiovascular Disease undergoing their initial revascularization with DES or BMS from January 1, 2000, through July 31, 2005, were included in the study population. Propensity scores and inverse probability weighted estimators were used to adjust for treatment group imbalances. The study population included 1501 patients who received DES and 3165 who received BMS. After adjustment, DES reduced target vessel revascularization (TVR) rates at 6, 12, and 24 months compared with BMS (24-month rates: DES, 6.6%; BMS, 16.3%; difference, -9.7%; 95% confidence interval [CI], -11.7% to -7.7%; P < .001). The TVR benefit for DES increased among patients with multivessel CAD (1-vessel CAD: -8.3%; 95% CI, -10.9% to -5.8%; P < .001; 2-vessel CAD: -9.7%; 95% CI, -3.6% to -5.8%; P < .001; 3-vessel CAD: -16.2%; 95% CI, -25.2% to -7.2%; P < .001). However, in the overall cohort there were no statistically significant differences in the composite of death or myocardial infarction. Patients receiving DES vs BMS in a clinical practice setting have lower TVR rates, albeit with less absolute benefit than those observed in clinical trials. Patients with multivessel vs single-vessel disease experience a greater reduction in TVR.

Clinical Outcomes Following Drug‐Eluting versus Bare Metal Stent Implantation for Lesion Subsets Excluded from Pivotal Clinical Trials: Findings from the GHOST Study (Guthrie Health System Off‐Label StenT Study)

We assessed outcomes of patients undergoing drug-eluting stent (DES) vs. bare metal stent (BMS) implantation for complex lesions excluded from pivotal clinical trials of DES. Although DES improve target vessel revascularization (TVR) and major adverse cardiovascular events (MACE) compared to BMS in randomized trials, data on safety and efficacy of DES in complex lesions are insufficient. In a single-center registry of 1,354 patients who underwent stent implantation for complex lesions between July 2001 and December 2005, we compared the incidence of death, death or myocardial infarction (MI), stent thrombosis [definite or probable by the Academic Research Consortium (ARC) criteria], TVR, and MACE between patients who received DES (n = 483) versus those who received BMS (n = 871). Mean duration of follow-up was 494 versus 838 days in DES and BMS groups, respectively. Clinical outcomes in DES versus BMS groups were as follows: death 5.2% versus 11.5% (log-rank P = 0.042); death/MI 11.2% versus 16.7% (P = 0.47), stent thrombosis 2.9% versus 2.6% (P = 0.61), TVR 6.6 versus 18.5% (P < 0.0001), MACE 14.9% versus 29.7% (P = 0.0002), respectively. After adjustment for baseline differences, DES implantation was associated with lower TVR (adjusted hazards ratio HR = 0.38, 95% CI 0.26-0.56, P < 0.0001) and MACE (HR = 0.56, CI 0.42-0.74, P < 0.0001) without significant impact on other outcomes. In 933 patients who underwent DES (n = 483) or BMS (n = 450) implantation in the year 2003 or later, DES implantation similarly lowered TVR and MACE without affecting other outcomes. Our findings support the safety and efficacy of DES in patient subsets excluded from pivotal randomized clinical trials of DES.

Impact of duration of clopidogrel prescription on outcome of DES as compared to BMS in primary angioplasty: a meta-regression analysis of randomized trials

Recent concerns have emerged on the potential higher risk of stent thrombosis after Drug-eluting stents (DES) implantation, that might be even more pronounced among ST-segment elevation myocardial infarction (STEMI) patients. The aim of the current study was to evaluate, by a meta-analytic approach, whether the benefits and safety of DES as compared to bare-metal stents (BMS) in patients undergoing primary angioplasty for STEMI may be influenced by the duration of prescription of dual oral antiplatelet therapy. The literature was scanned by formal searches of electronic databases (MEDLINE and CENTRAL). We examined all completed randomized trials of DES for STEMI. The following key words were used for study selection: randomized trial, myocardial infarction, reperfusion, primary angioplasty, stenting, DES, sirolimus-eluting stent (SES), Cypher, paclitaxel-eluting stent (PES), Taxus. Information on study design, type of stent, inclusion and exclusion criteria, primary endpoint, number of patients, angiographic and clinical outcome, were extracted by two investigators. Disagreements were resolved by consensus. A total of 12 trials were included in the meta-analysis, involving 4,351 patients (2,260 or 51.9% randomized to DES and 2,091 or 48.1% randomized to BMS). In five trials (involving 1690 patients) dual oral antiplatelet therapy was prescribed for at least 1 year. The outcome of DES as compared to BMS was not affected by the duration of dual antiplatelet therapy in terms of death (P interaction = 0.16), reinfarction (P interaction = 0.91) and in-stent thrombosis (P interaction = 0.26) and TVR (P interaction = 0.38). These data were confirmed by the use of a meta-regression analysis. This meta-analysis shows that among selected STEMI patients undergoing primary angioplasty, DES (SES and PES), as compared to BMS, are safe and their benefits are not affected by the duration of clopidogrel prescription.

Safety and effectiveness of drug eluting stent in patients with ST elevation myocardial infarction undergoing primary angioplasty

Drug eluting stents (DES) have recently been proven to further reduce restenosis and revascularization rate in comparison to bare metal stents in elective procedures. Most early DES trials did not include patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation MI, because these patients tend to have lower restenosis rates than other patient groups and delayed endothelization of these stents raises concern about a possible increase of thrombotic complications in the setting of STEMI. To confirm the safety and effectiveness of DES in patients with STEMI in a real-world scenario. From January 2004 to December 2006, clinical and angiographic data of 370 patients with STEMI treated with primary PCI have been analyzed. Patients were retrospectively followed for the occurrence of major adverse cardiac events (MACE): death, reinfarction and target vessel revascularization (TVR). Overall, 120 patients received DES (32%, DES group) and 250 received bare metal stents (68%, BMS group) in the infarct related artery. Compared with the BMS group, DES patients were younger, (mean age 56 +/- 12 vs. 65 +/- 10; P < 0.001) had more often diabetes mellitus (47% vs. 14% P < 0.001), anterior localization (65% vs. 45%; P < 0.0011) and less cardiogenic shock at admission (4% vs. 7%; P < 0.001). The angiographic characteristics in the DES group showed longer lesions (23 mm vs. 19 mm) and smaller diameter of vessels (2.5 mm vs. 3.0 mm). After a median follow-up of 24 +/- 9 months, there was no significant difference in the rate of stent thrombosis (1.6% in the DES group vs. 1.2% in the BMS group, P = ns). The incidence of MACE was significantly lower in the DES group compared with the BMS group (HR 0.56 [95% CI: 0.3-0.8]; P = 0.01), principally due to the lower rate of TVR (HR 0.41 [95% CI: 0.2-0.85]; P = 0.01). Utilization of DES in the setting of primary PCI for STEMI, in our "real world," was safe and improved the 3-year clinical outcome compared with BMS reducing the need of TVR.

Current Status of Off-Pump Coronary Artery Bypass Surgery

The expanding indications for angioplasty coupled with the successful short and mid-term results of randomized controlled trials of drug-eluting stents have already had an unquestionable impact on the practice of coronary revascularization operations. However, coronary artery bypass grafting remains a major mode of therapy for coronary artery disease. It is likely that surgery will continue to be preferred for more complex subsets and that surgeons will have to continue to maintain good results in patients with more complex problems. Concerns regarding morbidity associated with conventional surgical myocardial revascularization on cardiopulmonary bypass have led to a resurgence of interest in off-pump bypass surgery during the last decade, with the expectation that it would be safer if cardiopulmonary bypass could be avoided. This review summarizes the impact of off-pump bypass surgery in reducing the morbidity and mortality associated with conventional coronary artery bypass on cardiopulmonary bypass by evaluating the current best-available evidence from randomized controlled trials and meta-analyses comparing off-pump surgery with conventional bypass grafting.

Studies of Drug-Eluting Stents

All technology has limitations, some of which are not recognized at the time of introduction. Once adopted, technology may be challenged as to whether the initial promise of patient benefit demonstrated in clinical trials has been achieved in the setting of routine practice. This challenge is the objective of observational studies. Among interventional cardiologists, the jury on drug-eluting stents is still out. Article p 2071 Progress has not been linear for coronary stenting technology. The introduction of 2 new stents that largely prevented the problem of restenosis1,2 was met by an explosive adoption of these techniques by physicians and requests by patients. Within the first 8 months of introduction in Massachusetts, the rate of drug-eluting stents (DES) as a proportion of total stent procedures reached 90%.3 However, reports of late adverse events and stent thrombosis, a rare but morbid event, raised alarm in patients and prompted caution from regulators and physicians. The net outcome has been a return to increased use of bare-metal stents, with DES use decreasing to 64% in the United States (Millenium Research Group, Waltham, Mass, written communication, 2007). The benefits of restenosis prevention observed in randomized trials comparing DES to bare-metal stents were far greater in magnitude than many other incremental changes in medicine. Relative reductions in the need for repeat procedures to treat restenosis reached 75% to 80%,1,2 a larger jump forward than that achieved with the introduction of bare-metal stents to replace balloon angioplasty.4,5 Although the composite end points in the pivotal trials of drug-eluting stents included myocardial infarction and death and patients were followed for 5 years after stenting, the trials were not powered to detect harm in these important end points.6,7 Some have voiced concern that the trials leading to DES approval did not anticipate the broad …

Overview of the 2007 Food and Drug Administration Circulatory System Devices Panel Meeting on the Endeavor Zotarolimus-Eluting Coronary Stent

Initial trials comparing stenting with balloon angioplasty demonstrated improved angiographic and clinical outcomes with the former.1–3 The main clinical problem with bare metal stents (BMS) became the development of in-stent restenosis.4–6 Early data suggested that drug-eluting stents (DES) could mitigate, if not abolish, this problem.7–9 Since the approval of DES, these devices have become the predominant stents used in percutaneous coronary interventions, regardless of indication. As of September 2007, the Cypher sirolimus-eluting stent (SES) (Cordis Johnson & Johnson, Miami Lakes, Fla) had been deployed in >3 million patients worldwide,10 and the millionth Taxus paclitaxel-eluting stent (PES) (Boston Scientific, Natick, Mass) was implanted as of January 2005.11 Over the past 2 years, numerous reports of very late stent thrombosis (ST) with first-generation DES have surfaced. This highly morbid complication and data suggesting that death and myocardial infarction (MI) may be more common with DES12,13 have altered the focus of trials and registries working to determine optimal DES use. There is a hope that second-generation DES will be less prone to ST as a result of differences in drug, stent design, and polymer. Medtronic, Inc (Minneapolis, Minn) presented safety and efficacy data to a public meeting of the US Food and Drug Administration (FDA) Circulatory System Devices Panel (CSDP) in October 2007 on its Endeavor zotarolimus-eluting stent (ZES), seeking approval for the indication of treating de novo native coronary lesions ≤27 mm with reference vessel diameters of 2.5 to 3.5 mm. The FDA asked the CSDP to determine whether the data presented demonstrated a reasonable level of safety and effectiveness, with clinical benefits clearly outweighing short- and long-term risks of ZES use. Important efficacy end points included ischemia-driven target lesion revascularization (TLR) or target vessel revascularization (TVR); safety end points included death, MI, and ST. The …

Differential outcomes after sirolimus-eluting stent implantation: comparing on-label versus off-label patients in the ‘real world’

Randomized controlled trials indicate that sirolimus-eluting stents (SES) reduce the rates of restenosis and need for subsequent revascularization procedures, but patients enrolled in randomized trials represent a highly selected population. This study examined the performance of SES in a 'real world' setting by comparing the outcomes of trial-eligible versus ineligible patients undergoing percutaneous coronary intervention. From the US commercial introduction of SES in April 2003 until December 2003, all patients that received an SES at our institution were followed in a prospective registry (n=838). For the purpose of this analysis, the registry population was divided into two groups based on the inclusion and exclusion criteria of the stenosis in a native coronary artery (SIRIUS) trial. The primary endpoint of the study was the rate of target lesion revascularization (TLR) at follow-up. Secondary endpoints included major adverse cardiac events (MACE) such as cardiac death, myocardial infarction, and target vessel revascularization. Clinical follow-up was complete for 92% of patients with a median duration of 14.2 months. Overall, 296 patients (35.3%) met entry criteria for the SIRIUS trial and thus comprised the SIRIUS eligible group. Patients in the SIRIUS ineligible group (n=542) were more likely to have chronic kidney disease and earlier bypass surgery and had longer mean stent length. At 1 year, TLR occurred in 3.0% of the SIRIUS eligible population and in 9.2% of the SIRIUS ineligible group (P=0.001). The secondary endpoint of cumulative MACE occurred in 6.6% of the SIRIUS eligible versus in 17.7% of the SIRIUS ineligible population (P<0.001). Two patients (0.4%) in the SIRIUS ineligible group had a late stent thrombosis on days 39 and 99, respectively, versus none in the SIRIUS eligible group. Among 'real world' patients treated with SES, the incidence of TLR and MACE at 1 year was substantially greater among SIRIUS ineligible patients compared with SIRIUS eligible patients. These findings confirm that pivotal clinical trials of drug-eluting stents tend to enroll low-risk patients and that the estimated rates of TLR and MACE derived from such trials may not reflect subsequent outcomes with unrestricted clinical use.

Safety and Efficacy of the Drug-Eluting Stent: A Double-Edged Sword?

Like the introduction of bare metal stents (BMS), that of drug-eluting stents (DES) represented a quantum leap in the interventional cardiology community's ongoing efforts to conquer restenosis. However, recent concerns over late thrombosis (LT) have tempered the initial enthusiasm. Nonetheless, when compared with BMS, the slightly higher DES-LT is counterbalanced by the device's markedly lower incidence of restenosis, resulting in net equivalent rates of death, myocardial infarction, and overall major adverse cardiovascular events. This article summarizes for the noncardiology practitioner the benefits and risks of DES, as well as essentials of postprocedural care of the DES patient. We discuss the pathophysiology of stent thrombosis, pivotal DES trials, and adjunct antiplatelet pharmacology. In December 2006, the Food and Drug Administration convened an expert panel to review these devices. Their recommendations, as well as the joint statement from the American College of Cardiology/American Heart Association/Society of Cardiovascular Angiography and Interventions, are outlined.

Drug-Eluting Stents — Pushing the Envelope beyond the Labels?

Unlike jurors, clinicians frequently must make decisions without the luxury of the totality of evidence. When we speak of evidence-based medicine, it is important to remember that available data may be incomplete, outdated, and of questionable relevance to particular patients, especially those excluded from randomized trials. Nowhere is this more apparent than in the controversies surrounding the use of drug-eluting stents in patients with coronary disease.Pivotal trials of drug-eluting stents reported significant reductions in the rate of repeat revascularization without excess adverse events in the first year after placement of the stent.1,2 Although these randomized trials were well . . .

Angiographic Surrogate End Points in Drug-Eluting Stent Trials: A Systematic Evaluation Based on Individual Patient Data From 11 Randomized, Controlled Trials

Angiographic Surrogate End Points in Drug-Eluting Stent Trials: A Systematic Evaluation Based on Individual Patient Data From 11 Randomized, Controlled Trials

Angiographic Surrogate End Points in Drug-Eluting Stent Trials: A Systematic Evaluation Based on Individual Patient Data From 11 Randomized, Controlled Trials

We sought to validate 4 angiographic measures as potential surrogates for clinical restenosis (target lesion revascularization [TLR]) after stent implantation. Given the low revascularization rates with drug-eluting stents (DES), an angiographic surrogate of TLR is desirable to reduce the sample size required to demonstrate efficacy in future trials of antirestenosis devices. We evaluated 4 potential angiographic measures (late loss [LL] and percent diameter stenosis [%DS], both in-stent and in-segment) as a surrogate for TLR at 1 year. From 11 multicenter, prospective randomized stent trials, 9 comparing DES with bare-metal stents (BMS) and 2 comparing different DES, individual data on 5,381 patients with a single treated lesion and follow-up angiography at 6 to 9 months were analyzed. By 4 well-defined criteria of surrogacy, LL and %DS strongly predicted the risk of TLR, with in-segment %DS being the most highly predictive (approximately 0.95). Differences in TLR risk were fully explained statistically by their differences in LL or %DS, although LL as a surrogate was dependent on vessel size whereas %DS was not. However, because of the curvilinearity of the logistic model, trials comparing 2 effective DES can have significant differences in mean LL and %DS but small expected differences in TLR risk, especially at the lower ranges of LL and %DS. From in-stent and in-segment LL and %DS measures, logistic models can reliably estimate TLR rates for DES and BMS. These angiographic measures are thus suitable surrogate markers for clinical stent efficacy and can be used as primary end points in future DES trials to significantly reduce sample size.