Early technology review: towards an expedited pathway.

OBJECTIVES: Evidence development for medical devices is often focused on satisfying regulatory requirements with the result that health professional and payer expectations may not be met, despite considerable investment in clinical trials. Early engagement with payers and health professionals could allow companies to understand these expectations and reflect them in clinical study design, increasing chances of positive coverage determination and adoption into clinical practice. METHODS: An example of early engagement through the EXCITE International model using an early technology review (ETR) is described which includes engagement with payers and health professionals to better inform companies to develop data that meet their expectations. ETR is based on an early evidence review, a framework of expectations that guides the process and identified gaps in evidence. The first fourteen ETRs were reviewed for examples of advice to companies that provided additional information from payers and health professionals that was thought likely to impact on downstream outcomes or strategic direction. Given that limitations were imposed by confidentiality, examples were genericized. RESULTS: Advice through early engagement can inform evidence development that coincides with expectations of payers and health professionals through a structured, objective, evidence-based approach. This could reduce the risk of business-related adverse outcomes such as failure to secure a positive coverage determination and/or acceptance by expert health professionals. CONCLUSIONS: Early engagement with key stakeholders exemplified by the ETR approach offers an alternative to the current approach of focusing on regulatory expectations. This could reduce the time to reimbursement and clinical adoption and benefit patient outcomes and/or health system efficiencies.

Quantifying the utilization of medical devices necessary to detect postmarket safety differences: A case study of implantable cardioverter defibrillators.

PURPOSE: To estimate medical device utilization needed to detect safety differences among implantable cardioverter defibrillators (ICDs) generator models and compare these estimates to utilization in practice. METHODS: We conducted repeated sample size estimates to calculate the medical device utilization needed, systematically varying device-specific safety event rate ratios and significance levels while maintaining 80% power, testing 3 average adverse event rates (3.9, 6.1, and 12.6 events per 100 person-years) estimated from the American College of Cardiology's 2006 to 2010 National Cardiovascular Data Registry of ICDs. We then compared with actual medical device utilization. RESULTS: At significance level 0.05 and 80% power, 34% or fewer ICD models accrued sufficient utilization in practice to detect safety differences for rate ratios <1.15 and an average event rate of 12.6 events per 100 person-years. For average event rates of 3.9 and 12.6 events per 100 person-years, 30% and 50% of ICD models, respectively, accrued sufficient utilization for a rate ratio of 1.25, whereas 52% and 67% for a rate ratio of 1.50. Because actual ICD utilization was not uniformly distributed across ICD models, the proportion of individuals receiving any ICD that accrued sufficient utilization in practice was 0% to 21%, 32% to 70%, and 67% to 84% for rate ratios of 1.05, 1.15, and 1.25, respectively, for the range of 3 average adverse event rates. CONCLUSIONS: Small safety differences among ICD generator models are unlikely to be detected through routine surveillance given current ICD utilization in practice, but large safety differences can be detected for most patients at anticipated average adverse event rates.

Lack of association between migraine headache and patent foramen ovale: results of a case-control study.

BACKGROUND: Clinical observations of migraine headache symptoms in patients with a patent foramen ovale (PFO), both of which conditions are highly prevalent, have raised the question of a possible pathophysiological relationship. We sought to evaluate the assumption of an association between migraine headaches and the presence of PFO by use of a large case-control study. METHODS AND RESULTS: We conducted a case-control study to assess the prevalence of PFO in subjects with and without migraine. Case subjects were those with a history of migraine (diagnosed by neurologists at a specialty academic headache clinic). Control subjects were healthy volunteers without migraine 1:1 matched on the basis of age and sex with case subjects. Presence of PFO was determined by transthoracic echocardiogram with second harmonic imaging and transcranial Doppler ultrasonography during a standardized procedure of infused agitated saline contrast with or without Valsalva maneuver and a review of the results by experts blinded to case-control status. PFO was considered present if both studies were positive. Odds ratios were calculated with conditional logistic regression in the matched cohort (n=288). In the matched analysis, the prevalence of PFO was similar in case and control subjects (26.4% versus 25.7%; odds ratio 1.04, 95% confidence interval 0.62 to 1.74, P=0.90). There was no difference in PFO prevalence in those with migraine with aura and those without (26.8% versus 26.1%; odds ratio 1.03, 95% confidence interval 0.48 to 2.21, P=0.93). CONCLUSIONS: We found no association between migraine headaches and the presence of PFO in this large case-control study.

Rationale and design of the MASS COMM trial: A randomized trial to compare percutaneous coronary intervention between MASSachusetts hospitals with cardiac surgery on-site and COMMunity hospitals without cardiac surgery on-site.

BACKGROUND: Emergency surgery has become an increasingly rare event after percutaneous coronary intervention (PCI). There have been no randomized trials evaluating whether cardiac surgery services on-site are essential for patient safety and optimal outcomes during and after PCI. STUDY DESIGN: The MASS COMM trial (ClinicalTrials.gov no. NCT01116882) is a randomized trial comparing the safety and effectiveness of nonemergency PCI at hospitals without surgery on-site (SOS) (non-SOS hospitals) and hospitals with SOS (SOS hospitals). A total of 3,690 subjects will be randomized in a 3:1 fashion to undergo PCI at non-SOS and SOS hospitals, with follow-up at hospital discharge, 30 days, and 12 months after PCI. The rate of major adverse cardiac events (all-cause mortality, myocardial infarction, repeat revascularization, and stroke) will serve as the primary safety end point at 30 days and the primary effectiveness end point at 12 months. The design is a 1-way randomized trial with a statistical hypothesis of noninferiority of nonemergency PCI at non-SOS hospitals for both safety and effectiveness end points. CONCLUSIONS: This multicenter, randomized trial will compare the relative safety and effectiveness of nonemergency PCI at sites with and without cardiac SOS.

Relative spatial distributions of coronary artery bypass graft insertion and acute thrombosis: a model for protection from acute myocardial infarction.

BACKGROUND: Randomized trials have demonstrated coronary artery bypass surgery (CABG) to be superior to percutaneous coronary intervention with respect to long-term mortality and morbidity from myocardial infarction within specific high-risk cohorts. The purpose of this study was to analyze the spatial distribution of coronary artery bypass graft anastomoses relative to acute thromboses in native coronary arteries. We hypothesized that insertion sites of bypass grafts are located distal to sites of acute thrombosis and consequently decrease cardiac morbidity and mortality associated with plaque rupture. METHODS: We analyzed 168 patients with prior CABG and 208 patients with ST-segment elevation myocardial infarctions (STEMI) presenting to the Brigham and Women's Hospital who underwent coronary angiography. We constructed a spatial map of the coronary arterial bypass graft insertion sites and compared these locations to sites of acute thrombosis leading to STEMI. RESULTS: Graft insertion sites were consistently located distal to acute thrombosis sites (left anterior descending artery median graft insertion versus median thrombosis site = 72 versus 34 mm, right coronary artery 91 versus 42 mm, left circumflex artery 44 versus 37 mm). Greater than 97% of thrombosis sites were located proximal to 75% of graft insertion sites. CONCLUSIONS: Coronary arterial bypass grafts provide the coverage of anatomic zones at risk for STEMI. The superior performance of CABG in high risk patients may be attributed to targeting of proximal coronary locations where thrombosis risk is clustered.

Attribution of Adverse Events Following Coronary Stent Placement Identified Using Administrative Claims Data.

Background More than 600 000 coronary stents are implanted during percutaneous coronary interventions (PCIs) annually in the United States. Because no real-world surveillance system exists to monitor their long-term safety, claims data are often used for this purpose. The extent to which adverse events identified with claims data can be reasonably attributed to a specific medical device is uncertain. Methods and Results We used deterministic matching to link the NCDR (National Cardiovascular Data Registry) CathPCI Registry to Medicare fee-for-service claims for patients aged ≥65 years who underwent PCI with drug-eluting stents (DESs) between July 1, 2009 and December 31, 2013. We identified subsequent PCIs within 1 year of the index procedure in Medicare claims as potential safety events. We linked these subsequent PCIs back to the NCDR CathPCI Registry to ascertain how often the revascularization could be reasonably attributed to the same coronary artery as the index PCI (ie, target vessel revascularization). Of 415 306 DES placements in 368 194 patients, 33 174 repeat PCIs were identified in Medicare claims within 1 year. Of these, 28 632 (86.3%) could be linked back to the NCDR CathPCI Registry; 16 942 (51.1% of repeat PCIs) were target vessel revascularizations. Of these, 8544 (50.4%) were within a previously placed DES: 7652 for in-stent restenosis and 1341 for stent thrombosis. Of 16 176 patients with a claim for acute myocardial infarction in the follow-up period, 4446 (27.5%) were attributed to the same coronary artery in which the DES was implanted during the index PCI (ie, target vessel myocardial infarction). Of 24 288 patients whose death was identified in claims data, 278 (1.1%) were attributed to the same coronary artery in which the DES was implanted during the index PCI. Conclusions Most repeat PCIs following DES stent implantation identified in longitudinal claims data could be linked to real-world registry data, but only half could be reasonably attributed to the same coronary artery as the index procedure. Attribution among those with acute myocardial infarction or who died was even less frequent. Safety signals identified using claims data alone will require more in-depth examination to accurately assess stent safety.

Saphenous vein graft stenting and major adverse cardiac events: a predictive model derived from a pooled analysis of 3958 patients.

BACKGROUND: Treatment of saphenous vein graft (SVG) stenosis with percutaneous coronary intervention has a 15% to 20% incidence of major adverse cardiac events (MACE) within 30 days. Although MACE rates are reduced significantly by the use of embolic protection devices (EPDs), neither the level of baseline risk nor the benefit provided by EPDs has been well characterized. METHODS AND RESULTS: Data from 5 randomized controlled trials and 1 registry evaluating EPDs in SVG percutaneous coronary intervention (n=3958 patients) were pooled for analysis. MACE was defined as a composite of death, myocardial infarction, and target vessel revascularization. Baseline variables and 2 summary angiographic variables (an SVG degeneration score and an estimate of lesion plaque volume) were included in a multivariable logistic regression model to predict 30-day MACE, with adjustment for the type of device used and inter-study variation. The angiographic variables were potent predictors of MACE (increasing SVG degeneration score, P<0.0001; larger estimated plaque volume, P<0.0001), with significant contributions from the presence of thrombus (P<0.01), increasing patient age (P<0.01), glycoprotein IIb/IIIa inhibitor use (P=0.02), and current tobacco abuse (P=0.03). The treatment benefit of EPDs was preserved across all categories of risk as categorized by SVG degeneration or plaque volume. CONCLUSIONS: The strongest predictors of 30-day MACE in SVG percutaneous coronary intervention are angiographic estimates of plaque volume and SVG degeneration. Identification of these predictors of 30-day MACE allows reliable prediction of patient outcomes and confirms consistent treatment benefit with the use of EPDs across the range of patients tested in randomized trials.

Location of acute coronary artery thromboses in patients with and without chronic kidney disease.

Patients with chronic kidney disease have high rates of myocardial infarction and death following an initial attack. Proximal location of coronary atherosclerotic lesions has been linked to the risk of acute myocardial infarction and to infarction-associated mortality. To examine if the spatial distribution of lesions differs in patients with and without chronic kidney disease, we used quantitative coronary angiography to measure this in patients with acute coronary thromboses who were having angiography following acute myocardial infarction. Multivariable linear regression was used to adjust for differences in baseline characteristics. Among 82 patients with stage 3 or higher chronic kidney disease, 55.6% of lesions were located within 30 mm and 87.7% were within 50 mm of the coronary ostia. This compared to 34.7 and 71.8%, respectively, among 299 patients without significant kidney disease. Chronic kidney disease was independently and significantly associated with a 7.0 mm decrease in the distance from the coronary ostia to the problem lesion. Our study suggests that a causal link between a more proximal culprit lesion location in patients with chronic kidney disease and their high mortality rates after myocardial infarct is possible and may have important implications for interventions to prevent infarction.

Overview and experience of the YODA Project with clinical trial data sharing after 5 years.

The Yale University Open Data Access (YODA) Project has facilitated access to clinical trial data since 2013. The purpose of this article is to provide an overview of the Project, describe key decisions that were made when establishing data sharing policies, and suggest how our experience and the experiences of our first two data generator partners, Medtronic, Inc. and Johnson & Johnson, can be used to enhance other ongoing or future initiatives.

Advancing the Science of Healthcare Service Delivery: The NHLBI Corporate Healthcare Leaders' Panel.

There is a growing gap between available science and evidence and the ability of service providers to deliver high-quality care in a cost-effective way to the entire population. We believe that the chasm between knowledge and action is due to a lack of concerted effort among all organizations that deliver health care services across the life span of patients. Broad participation is needed and necessitates a far more explicit and concerted public-private partnership focused on large-scale transformation. In this context, the National Heart, Lung, and Blood Institute convened a panel made up of leaders of corporate health care entities, including academic health centers, and government agency representatives to inform contemporary strategic partnerships with health care companies. This article provides insights from the meeting on how to execute a transformative innovation research agenda that will foster improvements in health care service delivery by leveraging the translation of biomedical research evidence in real-world settings.

Randomized, double-blind, multicenter study of the Endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions: clinical and angiographic results of the ENDEAVOR II trial.

BACKGROUND: The use of the Endeavor stent might reduce restenosis and stent thrombosis at 9 months. METHODS AND RESULTS: Patients (n = 1197) treated for single coronary artery stenosis were enrolled in a prospective, randomized, double-blind study and randomly assigned to receive the Endeavor zotarolimus-eluting phosphorylcholine polymer-coated stent (n = 598) or the same bare metal stent but without the drug or the polymer coating (n = 599). The 2 groups were well matched in baseline characteristics. Diabetes was present in 20.1% of patients; the mean reference vessel diameter was 2.75 mm; and the mean lesion length was 14.2 mm. The primary end point of target vessel failure at 9 months was reduced from 15.1% with the bare metal stent to 7.9% with the Endeavor (P = 0.0001), and the rate of major adverse cardiac events was reduced from 14.4% with the bare metal stent to 7.3% with the Endeavor (P = 0.0001). Target lesion revascularization was 4.6% with Endeavor compared with 11.8% with the bare metal stent (P = 0.0001). The rate of stent thrombosis was 0.5% with the Endeavor, which was not significantly different from 1.2% with the bare metal stent. In 531 patients submitted to angiographic follow-up, late loss was reduced from 1.03 +/- 0.58 to 0.61 +/- 0.46 (P < 0.001) in stent and from 0.72 +/- 0.61 to 0.36 +/- 0.46 (P < 0.001) in segment. The rate of in-segment restenosis was reduced from 35.0% to 13.2% with Endeavor (P < 0.0001). There was no excessive edge stenosis, aneurysm formation, or late acquired malapposition by intravascular ultrasound imaging. Differences in clinical outcome were maintained at 12 and 24 months (P < 0.0001). CONCLUSIONS: Compared with bare metal stents, the Endeavor stent is safe and reduces the rates of clinical and angiographic restenosis at 9, 12, and 24 months.

Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery.

BACKGROUND: Preliminary reports of studies involving simple coronary lesions indicate that a sirolimus-eluting stent significantly reduces the risk of restenosis after percutaneous coronary revascularization. METHODS: We conducted a randomized, double-blind trial comparing a sirolimus-eluting stent with a standard stent in 1058 patients at 53 centers in the United States who had a newly diagnosed lesion in a native coronary artery. The coronary disease in these patients was complex because of the frequent presence of diabetes (in 26 percent of patients), the high percentage of patients with longer lesions (mean, 14.4 mm), and small vessels (mean, 2.80 mm). The primary end point was failure of the target vessel (a composite of death from cardiac causes, myocardial infarction, and repeated percutaneous or surgical revascularization of the target vessel) within 270 days. RESULTS: The rate of failure of the target vessel was reduced from 21.0 percent with a standard stent to 8.6 percent with a sirolimus-eluting stent (P<0.001)--a reduction that was driven largely by a decrease in the frequency of the need for revascularization of the target lesion (16.6 percent in the standard-stent group vs. 4.1 percent in the sirolimus-stent group, P<0.001). The frequency of neointimal hyperplasia within the stent was also decreased in the group that received sirolimus-eluting stents, as assessed by both angiography and intravascular ultrasonography. Subgroup analyses revealed a reduction in the rates of angiographic restenosis and target-lesion revascularization in all subgroups examined. CONCLUSIONS: In this randomized clinical trial involving patients with complex coronary lesions, the use of a sirolimus-eluting stent had a consistent treatment effect, reducing the rates of restenosis and associated clinical events in all subgroups analyzed.

Protected carotid-artery stenting versus endarterectomy in high-risk patients.

BACKGROUND: Carotid endarterectomy is more effective than medical management in the prevention of stroke in patients with severe symptomatic or asymptomatic atherosclerotic carotid-artery stenosis. Stenting with the use of an emboli-protection device is a less invasive revascularization strategy than endarterectomy in carotid-artery disease. METHODS: We conducted a randomized trial comparing carotid-artery stenting with the use of an emboli-protection device to endarterectomy in 334 patients with coexisting conditions that potentially increased the risk posed by endarterectomy and who had either a symptomatic carotid-artery stenosis of at least 50 percent of the luminal diameter or an asymptomatic stenosis of at least 80 percent. The primary end point of the study was the cumulative incidence of a major cardiovascular event at 1 year--a composite of death, stroke, or myocardial infarction within 30 days after the intervention or death or ipsilateral stroke between 31 days and 1 year. The study was designed to test the hypothesis that the less invasive strategy, stenting, was not inferior to endarterectomy. RESULTS: The primary end point occurred in 20 patients randomly assigned to undergo carotid-artery stenting with an emboli-protection device (cumulative incidence, 12.2 percent) and in 32 patients randomly assigned to undergo endarterectomy (cumulative incidence, 20.1 percent; absolute difference, -7.9 percentage points; 95 percent confidence interval, -16.4 to 0.7 percentage points; P=0.004 for noninferiority, and P=0.053 for superiority). At one year, carotid revascularization was repeated in fewer patients who had received stents than in those who had undergone endarterectomy (cumulative incidence, 0.6 percent vs. 4.3 percent; P=0.04). CONCLUSIONS: Among patients with severe carotid-artery stenosis and coexisting conditions, carotid stenting with the use of an emboli-protection device is not inferior to carotid endarterectomy.

Understanding the drug-eluting stent trials.

The advent of intravascular stenting dramatically reduced the incidence of restenosis among patients undergoing percutaneous transluminal coronary angioplasty. However, a substantial percentage of patients, particularly those with risk factors such as diabetes mellitus or complicated lesions, remain at risk for restenosis. Drug-eluting stents overcome this problem by releasing bioactive agents from a polymeric coating directly into the vessel wall, inhibiting the cellular mechanisms of restenosis while avoiding systemic toxicity. Recent data indicate that local targeting of the proliferative process with drug-eluting stents dramatically reduces the risk for restenosis, even among high-risk patients. A range of bioactive coatings are currently available or in late clinical trials. Both sirolimus- and paclitaxel-eluting stents have demonstrated efficacy in a broad range of patient types; early data from clinical trials of second-generation stent coatings, such as everolimus and ABT-578 (zotarolimus), suggest that these agents are also effective in preventing restenosis. This article reviews the pathophysiology of in-stent restenosis and surveys recent key clinical trials of drug-eluting stents.

Zotarolimus-eluting stents in patients with native coronary artery disease: clinical and angiographic outcomes in 1,317 patients.

Early studies of a cobalt-based alloy stent coated with the novel antiproliferative agent zotarolimus and a phosphorylcholine polymer have demonstrated significant reductions in angiographic restenosis and target vessel revascularization compared with bare metal stents. However, the generalizability of the angiographic outcomes and clinical benefit of zotarolimus-eluting stents (ZESs) to a more real-world patient population is undetermined. Clinical and angiographic outcomes in 1,317 patients treated with the ZES in the first 4 trials of the Endeavor ZES (Medtronic Vascular, Santa Rosa, CA) clinical trials program were pooled for systematic analysis. Protocol-specified follow-up angiography was performed at 8 or 12 months for a subset of 750 of these patients, and clinical follow-up was performed at 9 months after the index procedures in all patients. Diabetes mellitus was present in 22.5% of patients, the mean reference vessel diameter was 2.73 mm, and the mean lesion length was 14.59 mm. At 8 months (12 months for ENDEAVOR I), mean +/- SD in-stent late luminal loss was 0.61 +/- 0.49 mm. In-stent late luminal loss was greatest in larger caliber (>2.9 mm) vessels (0.65 +/- 0.49 mm) and longer (>16.3 mm) lesions (0.70 +/- 0.52 mm) but did not statistically vary according to diabetic status. At 9 months, overall rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE) were 4.9% and 7.7%, respectively. The rate of TLR at 12 months was not significantly different relative to diabetes and lesion length >16.3 mm (7.2% and 7.7%, respectively), although TLR was significantly more common when reference vessel diameter was <2.5 mm (8.5%; p = 0.013). At 24 months, overall rates of TLR and MACE were 6.5% and 9.9%, respectively. The overall 24-month rate of stent thrombosis was 0.3%, with no events occurring >14 days after the procedure. Despite varied clinical and angiographic characteristics, treatment with the ZES is associated with consistently low rates of TLR and overall major adverse events, including stent thrombosis. Although these findings indicate the efficacy and safety of the ZES over the time course of the first 4 ENDEAVOR clinical trials, additional ongoing study with more open patient inclusion criteria (including long lesions, small vessels, bifurcations, etc) will be important for discerning whether comparable clinical outcomes can be extended to lesion subsets of higher complexity.

Safety of sirolimus-eluting stenting and its effect on restenosis in patients with unstable angina pectoris (a SIRIUS substudy).

The SIRIUS study was a double-blinded, randomized trial of the sirolimus-eluting stent (SES) to evaluate its effect on the rate of restenosis. The present report is a retrospective analysis of short- and long-term outcomes of SESs compared with bare metal stents (BMSs) in a subgroup of patients with unstable angina enrolled in the trial. Of 1,058 patients randomized in SIRIUS, 533 (50.4%) had unstable angina pectoris and 490 had stable angina. In the unstable angina group, patients treated with SESs and BMSs had similar clinical and angiographic characteristics. The stenting procedure was highly successful in the 2 groups (95.9% and 97.4%, respectively) with similar immediate angiographic results and short-term (in-hospital) clinical event rates. At 1-year follow-up, compared with BMSs, patients with unstable angina treated with SESs had significantly lower rates of target lesion revascularization (5.5% vs 22.3%, p <0.0001), target vessel failure (10.9% vs 26.3%, p <0.0001), and major adverse cardiac events (8.4% vs 24.8%, p <0.0001). Stent thrombosis was a rare event, with only 1 patient (0.4%) in each group during the first 30 days. Late thrombosis occurred in 2 patients (0.7%) in the BMS group but in none of the SES group. In conclusion, in the higher risk subgroup of patients with unstable angina, SESs are as safe as BMSs in decreasing restenosis and the need for repeat revascularization. This is reflected by a significant decrease in major adverse cardiac events and target vessel failure. Patients with unstable angina undergoing percutaneous coronary intervention who meet the entry criteria of the SIRIUS study should be preferentially treated with SESs.

Detailed intravascular ultrasound analysis of Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy stent in de novo coronary lesions (results from the ENDEAVOR II trial).

Zotarolimus-eluting phosphorylcholine-coated cobalt-chromium alloy Driver stents (ZES) demonstrated significant reductions in target lesion revascularization rate with few apparent adverse events compared with bare metal stents (BMS; uncoated Driver stents) in a prospective, multicenter, double-blind, randomized controlled trial in de novo coronary lesions. The aim of this study was to examine detailed vascular responses to ZES compared with BMS using serial intravascular ultrasound analysis. A total of 343 patients (ZES n = 178, BMS n = 165) were enrolled in this formal, prespecified intravascular ultrasound substudy of the Randomized Controlled Trial to Evaluate the Safety and Efficacy of the Medtronic AVE Zotarolimus-Eluting Driver Coronary Stent in de Novo Native Coronary Artery Lesions (ENDEAVOR II), a prospective, multicenter, double-blind, randomized controlled trial to compare ZES and BMS in de novo native coronary artery lesions. Quantitative and qualitative intravascular ultrasound analyses were performed postprocedurally and at 8-month follow-up in stented and reference segments. ZES showed significantly less neointima, with a larger lumen than BMS at 8 months (percentage neointimal volume 17.6 +/- 10.1% vs 29.4 +/- 17.2%, p <0.0001; maximum percentage neointimal area 32.9 +/- 13.0% vs 47.6 +/- 18.6%, p <0.0001; minimum luminal area 4.9 +/- 1.6 vs 4.0 +/- 1.7 mm(2), p <0.0001) and no unfavorable edge effect. In the 18-mm single stents, ZES showed evenly inhibited neointima compared with BMS. Neither persistent stent-edge dissection nor late-acquired incomplete stent apposition was observed in either group. In conclusion, ZES showed evenly inhibited neointima with no apparent adverse vascular response in stented and reference segments at 8 months compared with BMS.

Distribution of coronary artery disease and relation to mortality in asymptomatic hemodialysis patients.

BACKGROUND: Long-term dialysis patients have a high incidence of myocardial infarction and cardiovascular death, but the incidence of coronary artery disease (CAD) in asymptomatic patients, distribution of coronary obstruction, and relationship between lesion location and mortality are unknown. METHODS: We studied 67 asymptomatic hemodialysis patients who volunteered for coronary angiography. Coronary stenoses of 50% or greater were documented, and the location of each within the proximal, midportion, or distal segment of the coronary vessel was recorded. Patients were followed up until death or renal transplantation. Cox proportional hazards regression was performed to analyze the relationship of lesion location with mortality. RESULTS: Obstructive CAD was common. Twenty-eight subjects (41.7%) had 50% or greater stenosis in at least 1 epicardial vessel, and 19 subjects (28.5%) had evidence of CAD within the proximal third of an epicardial vessel. After a median follow-up of 2.7 years, the presence of proximal CAD was associated with a marked increase in risk of death (adjusted hazard ratio, 3.14; 95% confidence interval, 1.34 to 7.33; P = 0.008) and was associated more strongly with mortality than multivessel disease or left anterior descending disease. CONCLUSION: CAD is common in asymptomatic dialysis patients, and stenoses frequently are located within the proximal coronary arteries, where they are associated with markedly increased risks of death. Additional studies are needed to determine whether proximal disease is a modifiable risk factor for cardiovascular mortality in dialysis patients.