Manish S. Chauhan

Stent Thrombosis in the Modern Era

Background—There are limited studies of stent thrombosis in the modern era of second-generation stents, high-pressure deployment, and current antithrombotic regimens. Methods and Results—Six recently completed coronary stent trials and associated nonrandomized registries that enrolled 6186 patients (6219 treated vessels) treated with ≥1 coronary stent followed by antiplatelet therapy with aspirin and ticlopidine were pooled for this analysis. Within 30 days, clinical stent thrombosis developed in 53 patients (0.9%). The variables most significantly associated with the probability of stent thrombosis were persistent dissection NHLBI grade B or higher after stenting (OR, 3.7; 95% CI, 1.9 to 7.7), total stent length (OR, 1.3; 95% CI, 1.2 to 1.5 per 10 mm), and final minimal lumen diameter within the stent (OR, 0.4; 95% CI, 0.2 to 0.7 per 1 mm). Stent thrombosis was documented by angiography in 45 patients (0.7%). Clinical consequences of angiographic stent thrombosis included 64.4% incidence of death or myoc...

Clinical restenosis after coronary stenting: perspectives from multicenter clinical trials

OBJECTIVES We sought to evaluate clinical restenosis in a large population of patients who had undergone coronary stent placement. BACKGROUND One-year success after coronary stenting is limited mainly by restenosis of and requirement for repeat revascularization of the treated lesion. We studied 6,186 patients (6,219 lesions) pooled from several recently completed coronary stent trials. Clinical restenosis was defined using three different definitions: target lesion revascularization (TLR) beyond 30 days, target vessel revascularization (TVR) beyond 30 days, and target vessel failure (TVF), defined as TVR, any death, or myocardial infarction (MI) of the target vessel territory after hospital discharge. RESULTS By one year, 638 (12.2%) patients had TLR, 748 (14.3%) had TVR, and 848 (16.0%) had TVF, more than two-thirds higher than the rate of these end points at six months. The severity of angiographic restenosis (> or =50% follow-up diameter stenosis [DS]) in 419 of 1,437 (29%) patients undergoing routine angiographic follow-up correlated directly with the likelihood of TLR (73% vs. 26% for >70% DS compared with <60% DS). Smaller pretreatment minimum lumen diameter (MLD), smaller final MLD, longer stent length, diabetes mellitus, unstable angina, and hypertension were independent predictors of TLR. Prior MI and current smoking were negative predictors. CONCLUSIONS At one year after stenting, most clinical restenosis reflected TLR, which was predicted by the same variables previously associated with an increased risk of angiographic restenosis. The lower absolute rate of clinical restenosis relative to angiographic restenosis was due to infrequent TLR in lesions with less severe (<60% DS) angiographic renarrowing.

Beyond Restenosis Five-Year Clinical Outcomes From Second-Generation Coronary Stent Trials

Background—In the first year after coronary stent implantation, clinical failures are driven mainly by procedural complications and restenosis, but the subsequent relative contributions of restenosis and disease progression to late failures are less clear. Methods and Results—We observed 1228 patients for 5 years after the implantation of stents as part of pivotal second-generation coronary stent trials. Clinical events of death, myocardial infarction, repeat revascularization, and repeat hospitalization for acute coronary syndrome or congestive heart failure were attributed to the index stented (target) lesion or other distinct sites (either in the target or other coronary vessels) and further classified as procedural, restenosis, or nonrestenosis. During the first year the hazard rate was 18.3% for target-lesion events and 12.4% for events unrelated to the target lesion. After the first year the average annual hazard rate was 1.7% for target-lesion events and 6.3% for nontarget-lesion events. By the fifth year, restenosis events occurred in 20.3% of patients, whereas 30-day procedural complications or later nonrestenosis events occurred in 37.9%, including 11.4% who also experienced a restenosis event, for a combined cumulative event rate of 46.4%. Diabetes mellitus and multivessel disease were independently associated with increased risk for both restenosis and nonrestenosis events. Conclusion—In a low-risk clinical trial population, the clinical outcome beyond 1 year after stenting is determined by a high rate of events related to disease progression in segments other than the stented lesion, which itself remains relatively stable.

Cutting balloon angioplasty for the prevention of restenosis: results of the Cutting Balloon Global Randomized Trial ☆

The cutting balloon (CB) is a specialized device designed to create discrete longitudinal incisions in the atherosclerotic target coronary segment during balloon inflation. Such controlled dilatation theoretically reduces the force needed to dilate an obstructive lesion compared with standard percutaneous transluminal coronary angioplasty (PTCA). We report a multicenter, randomized trial comparing the incidence of restenosis after CB angioplasty versus conventional balloon angioplasty in 1,238 patients. Six hundred seventeen patients were randomized to CB treatment, and 621 to PTCA. The mean reference vessel diameter was 2.86 +/- 0.49 mm, mean lesion length 8.9 +/- 4.3 mm, and prevalence of diabetes mellitus in patients was 13%. The primary end point, the 6-month binary angiographic restenosis rate, was 31.4% for CB and 30.4% for PTCA (p = 0.75). Acute procedural success, defined as the attainment of <50% diameter stenosis without in-hospital major adverse cardiac events, was 92.9% for CB and 94.7% for PTCA (p = 0.24). Freedom from target vessel revascularization was slightly higher in the CB arm (88.5% vs 84.6%, log-rank p = 0.04). Five coronary perforations occurred in the CB arm only (0.8% vs 0%, p = 0.03). At 270 days, rates of myocardial infarction, death, and total major adverse cardiac events for CB and PTCA were 4.7% versus 2.4% (p = 0.03), 1.3% versus 0.3% (p = 0.06), and 13.6% versus 15.1% (p = 0.34), respectively. In summary, the proposed mechanism of controlled dilatation did not reduce the rate of angiographic restenosis for the CB compared with conventional balloon angioplasty. CB angioplasty should be reserved for difficult lesions in which controlled dilatation is believed to provide a better acute result compared with balloon angioplasty alone.

Percutaneous coronary revascularization in Elderly patients: Impact on functional status and quality of life

Ischemic heart disease affects more than 25% of persons older than 65 years of age in the United States. Although elderly patients with coronary artery disease tend to be treated less aggressively than nonelderly patients, the use of percutaneous coronary intervention (PCI) in the elderly is increasing rapidly; it more than doubled between 1979 and 1986 (1). Previous studies have examined the risks for PCI-related complications among elderly patients and found that elderly patients have a higher risk for vascular complications and in-hospital death than younger patients (2). Nonetheless, little is known about the critical outcomes of these procedures from the patients perspective. Although short- and long-term mortality rates are important outcomes to consider, PCI is generally done to improve the patients quality of life by relieving the signs and symptoms of myocardial ischemia. Improvement in quality of life may be particularly germane to older patients, for whom competing risks tend to limit any potential gains in longevity (3). We examined changes in health-related quality of life among elderly patients after PCI and compared these changes with those in nonelderly patients. Methods Study Sample Patients in this study had PCI as part of two randomized multicenter clinical trials: the Balloon versus Optimal Atherectomy Trial (BOAT; n =989), which compared directional atherectomy with balloon angioplasty (4), and the Advanced Cardiovascular System Multi-Link-Stent System Trial (ASCENT; n =1040), which compared the ACS Multi-Link stent to the PalmazSchatz stent (5). Only patients enrolled in U.S. hospitals who completed a baseline health-related quality-of-life survey (n =1789) were eligible for our substudy. Inclusion and exclusion criteria for the trials were similar. All patients had symptomatic coronary artery disease that required percutaneous revascularization of a single native coronary artery. Patients with a myocardial infarction within 5 days of treatment, stroke within the preceding 3 months, bifurcation lesions, or severe proximal tortuosity were excluded. The institutional review boards of each institution approved the studies, and all patients provided informed consent before participation. Quality-of-Life Assessment Health-related quality of life was assessed by using the physical and mental health summary scales of the Medical Outcomes Study Short-Form Survey (SF-36) (6, 7). These summary scales are standardized such that the mean ( SD) for the U.S. population is 50 10. Higher scores indicate better health. Patients in ASCENT also completed the Seattle Angina Questionnaire (SAQ), a validated disease-specific instrument that measures five health-related quality-of-life domains specific for coronary artery disease (physical functioning, anginal stability, anginal frequency, disease perception, and treatment satisfaction) (8, 9). The SAQ scores range from 0 to 100, and higher scores indicate better levels of functioning (that is, less physical limitation and less frequent angina). Baseline health-related quality of life was assessed by using self-administered questionnaires that were completed immediately before the index revascularization procedure. Follow-up measurements were obtained by surveys mailed to participants 6 months and 1 year after initial treatment. Patients who did not respond to the mailed survey within 2 weeks were administered the same instrument by telephone when possible. Statistical Analysis Baseline patient characteristics of elderly ( 70 years of age) and nonelderly (<70 years of age) patients were compared by using t-tests and Wilcoxon rank-sum tests for continuous variables and Fisher exact tests for categorical variables. Logistic regression was used to determine whether the likelihood of substantial improvement in health-related quality of life after PCI differed between elderly and nonelderly patients (10). For each health-related quality-of-life scale, each patient was classified as improved or not improved according to the level of change at which patients in previous studies had reported substantial improvement. Previous studies involving the SF-36 have demonstrated that changes in the physical component score of 3.8 points or more and changes in the mental component score of 7.2 points or more were meaningful to patients (6). For the SAQ subscales, an improvement of 10 or more points has been found to correlate with clinically meaningful changes (9) and was used to classify patients as improved or not improved for our analysis. Each regression model adjusted for patient demographic characteristics (sex, marital status, education, race or ethnicity) and medical conditions (previous myocardial infarction, congestive heart failure, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, arthritis, vision problems, number of comorbid conditions, smoking status). Standardized predicted probabilities derived from these models were used to estimate the percentage of patients in each age group who were expected to demonstrate substantial improvement after PCI. We also calculated standardized risk differences and associated confidence intervals (11). The main results were not altered in analyses that adjusted for clustering (data not shown). All analyses were done by using Stata software, version 6.0 (Stata Corp., College Station, Texas). P values less than 0.05 were considered statistically significant. Significance tests were not adjusted for multiple comparisons. All data were collected and analyzed by an independent data coordinating center (Cardiovascular Data Analysis Center, Boston, Massachusetts), without direct input from the study sponsor. Twenty percent of the data were missing because of patient nonresponse at follow-up. To examine whether our results were sensitive to differences between respondents and nonrespondents, we imputed the change scores of nonrespondents by using multiple imputation techniques (12) and re-estimated the models for the full study sample. Because the results of these sensitivity analyses were similar to our primary results, we report only the primary results. Results Of the patients who completed the baseline survey, 1445 (80%) completed the 6-month follow-up survey. These patients made up our analytic cohort. Compared with nonrespondents, respondents were more likely to be nonwhite and unmarried and were less likely to have congestive heart failure. Among respondents, the median age of the nonelderly group was 57 years (range, 38 to 69 years) and the median age of the elderly group was 74 years (range, 70 to 89 years). Compared with nonelderly patients, elderly patients were more likely to be female, white, and unmarried and were less well-educated. Elderly patients were less likely to smoke cigarettes but were more likely to have hypertension and congestive heart failure and had more comorbid conditions (data not shown). Clinical Events During the initial hospitalization and 1-year follow-up period, the incidence of major adverse cardiac events, including myocardial infarction, bypass surgery, and repeated PCI, was low in both groups. However, during the initial hospitalization, older patients were more likely than younger patients to sustain a major vascular complication (3.7% compared with 1.7%; P =0.04). Effect of Percutaneous Coronary Intervention on Health-Related Quality of Life At baseline, both elderly and nonelderly patients had substantial impairments in physical health and modest impairments in mental health relative to the overall U.S. population (Table). The SAQ subscales also demonstrated substantial physical limitations and impaired quality of life due to angina in both age groups. At 6-month follow-up, both elderly and nonelderly patients demonstrated substantial improvement in each quality-of-life domain, and these gains persisted at 1 year (Table). At both 6 months and 1 year, approximately 60% of patients reported no angina. Table. Distribution of Health-Related Quality-of-Life Scores at Baseline, 6 Months, and 1 Year In adjusted analyses, the change in health-related quality of life associated with PCI did not significantly differ between elderly and nonelderly patients (Figure). At 6-month follow-up, physical health improved substantially for 51% of elderly patients and 58% of nonelderly patients (difference, 7 percentage points [95% CI, 15 to 1 percentage point]). Similarly, mental health improved substantially for 29% of elderly patients and 30% of nonelderly patients (difference, 1 percentage point [CI, 9 to 6 percentage points]). At 6-month follow-up, most patients demonstrated substantial improvement in all three aspects of disease-specific quality of life, with nearly identical benefits regardless of age. Physical limitations related to angina improved substantially for 58% of elderly patients and 54% of younger patients (difference, 4 percentage points [CI, 7 to 13 percentage points]). Elderly and nonelderly patients demonstrated similar rates of improvement in frequency of angina (75% compared with 74% [difference, 1 percentage point; CI, 6 to 10 percentage points]) and in disease burden (77% compared with 71% [difference, 6 percentage points; CI, 6 to 10 percentage points]). Only 4% to 13% of patients reported meaningful declines in cardiovascular-specific quality of life, and the proportion did not vary with age. Similar changes were observed at 1-year follow-up as well (data not shown). Figure. Standardized estimates of the percentage of patients expected to have improvements in health-related quality of life ( QOL ) 6 months after percutaneous coronary intervention, according to age. Discussion We found that PCI resulted in substantial population-level benefits for elderly patients with regard to both physical and mental health as well as reductions in physical limitations due to angina, frequency of angina, and the perceived burden of coronary artery disease. During 6- to 12-

Coronary artery stenting in the aged

OBJECTIVES The study compared the safety and efficacy of coronary artery stenting in aged and nonaged patients and identified predictors of adverse clinical outcomes. BACKGROUND Limited data are available on the outcomes of stenting in the aged (> or = 80 years) compared to nonaged patients. METHODS The study was a pooled analysis of 6,186 patients who underwent coronary artery stenting in six recent multicenter trials. A clinical events committee adjudicated clinical end points, and quantitative angiography was performed by an independent core laboratory. RESULTS There were 301 (4.9%) aged patients (> or = 80 years). Compared to nonaged patients, aged patients had a higher prevalence of multivessel disease (16.5% vs. 9.6%, p = 0.001), unstable angina (50.8% vs. 42.1%, p = 0.003), moderate to severe target lesion calcification (30.4% vs. 15.3%, p = 0.001) and smaller reference vessel diameter (2.90 mm vs. 2.98 mm, p = 0.004). Procedural success rate (97.4% vs. 98.5%, p = 0.14) was similar in the two groups. In-hospital mortality (1.33% vs. 0.10%, p = 0.001), bleeding complications (4.98% vs. 1.00%, p < 0.001) and one-year mortality (5.65% vs. 1.41%, p < 0.001) were significantly higher for the aged patients. Clinical restenosis was similar for the two groups (11.19% vs. 11.93%, p = 0.78). Advanced age, diabetes, prior myocardial infarction and presence of three-vessel disease were independent predictors of long-term mortality. CONCLUSIONS Coronary artery stenting can be performed safely in patients > or = 80 years of age, with excellent acute results and a low rate of clinical restenosis, albeit with higher incidences of in-hospital and long-term mortality, and vascular and bleeding complications compared to nonaged patients.