Interruption of Dual Antiplatelet Therapy Within Six Months After Coronary Stents (from the Dual Antiplatelet Therapy Study).

The risk of major adverse cardiac and cerebrovascular events (MACCE) in subjects who interrupt temporarily or permanently thienopyridine therapy in the first 6 months after percutaneous coronary intervention (PCI) remains uncertain. In the dual antiplatelet therapy (DAPT) study subjects were enrolled within 72 hours of PCI and treated with aspirin and a thienopyridine for 12 months before being randomized to continued thienopyridine versus placebo. This analysis focuses on the 12-month period before randomization. Thienopyridine interruptions of greater than 24 hours, occurring in the first 6 months after PCI were evaluated. The incidence of MACCE and moderate or severe bleeding occurring within 12 months after PCI were compared between subjects with and without interruptions. Among 23,002 subjects, the incidence of interruption of thienopyridine was 5.1% (n = 1,173). Compared with subjects who adhered to treatment, subjects with an interruption had a higher incidence of MACCE (6.1% vs 4.3%, p = 0.005), death (2.2% vs 1.4%, p = 0.02), myocardial infarction (3.8% vs 2.7%, p = 0.03), and bleeding (3.1% vs 2.2%, p = 0.04) at 12 months. After adjusting for baseline characteristics, interruptions were associated with MACCE (adjusted odds ratio 1.3, 95% confidence interval 1.0, 1.7, p = 0.04) and had a borderline association with subsequent bleeding (adjusted odds ratio 1.4, 95% confidence interval 1.0, 2.0, p = 0.05). In conclusion, interruption of thienopyridine in the first 6 months after PCI occurs not infrequently and is associated with an increased risk of MACCE and subsequent bleeding between the time of interruption and 12 months after PCI.

Benefit and Risk of Prolonged DAPT After Coronary Stenting in Women.

BACKGROUND: Women may derive differential benefit from prolonged DAPT (dual antiplatelet therapy) after coronary stenting than men. We assessed whether the risks/benefits of prolonged DAPT differ between women and men. METHODS AND RESULTS: The DAPT study was a randomized double-blind, placebo-controlled trial comparing continued thienopyridine versus placebo beyond 12 months after coronary stenting. We compared rates of myocardial infarction, stent thrombosis, major adverse cardiovascular and cerebrovascular events, and bleeding by sex and randomized treatment. Of 11 648 patients, women (N=2925) were older, with higher prevalence of diabetes mellitus and lower rates of acute coronary syndrome than men. At 12 to 30 months, women had similar adjusted ischemic and bleeding events as men. The effects of continued thienopyridine therapy did not differ significantly by sex for stent thrombosis (women: hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.22-1.36; men: HR, 0.26; 95% CI, 0.15-0.44; interaction P=0.17), myocardial infarction (women: HR, 0.75; 95% CI, 0.50-1.14; men: HR, 0.46; 95% CI, 0.36-0.60; interaction P=0.052), major adverse cardiovascular and cerebrovascular events (women: HR, 0.87; 95% CI, 0.62-1.22; men: HR, 0.70; 95% CI, 0.58-0.85; interaction P=0.26), and bleeding (women: HR, 1.45; 95% CI, 0.88-2.40; men: HR, 1.78; 95% CI, 1.28-2.49; interaction P=0.50). CONCLUSIONS: Women had similar late risks of ischemia and bleeding as men after coronary stent procedures. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00977938.

A Prospective Randomized Trial of Apixaban Dosing During Atrial Fibrillation Ablation: The AEIOU Trial.

OBJECTIVES: This study sought to determine whether uninterrupted apixaban would have similar rates of bleeding and thromboembolic events as does minimally interrupted apixaban at the time of atrial fibrillation (AF) ablation and to compare those results with rates in historical patients treated with uninterrupted warfarin. BACKGROUND: The safety, efficacy, and optimal dosing regimen for apixaban at the time of AF ablation are uncertain. METHODS: This prospective, multicenter clinical trial enrolled 306 patients undergoing catheter ablation for nonvalvular AF and randomized 300 to uninterrupted versus minimally interrupted (holding 1 dose) periprocedural apixaban. A retrospective cohort of patients treated with uninterrupted warfarin at the same centers was matched to the apixaban-treated subjects for comparison. Endpoints included clinically significant bleeding, major bleeding, and nonhemorrhagic stroke or systemic embolism (SE) from the time of ablation through 30 days. RESULTS: There were no stroke or SE events. Clinically significant bleeding occurred in 11.3% of 150 evaluable patients on uninterrupted apixaban and 9.7% of 145 evaluable patients on interrupted apixaban (risk difference: 1.7% [95% confidence interval: -5.5% to 8.8%]; p = NS). Rates of major bleeding were 1.3% with uninterrupted apixaban, and 2.1% with interrupted (risk difference: -0.7%; p = NS). The rates of clinically significant and major bleeding were similar for all apixaban patients combined (10.5% and 1.7%), compared with the matched warfarin group (9.8% and 1.4%). CONCLUSIONS: Both uninterrupted and minimally interrupted apixaban at the time of AF ablation were associated with a very low rate of thromboembolic events, and rates of both major (<2%) and clinically significant bleeding were similar to uninterrupted warfarin. (Apixaban Evaluation of Interrupted Or Uninterrupted Anticoagulation for Ablation of Atrial Fibrillation [AEIOU]; NCT02608099).

Impact of Clopidogrel Therapy on Mortality and Cancer in Patients With Cardiovascular and Cerebrovascular Disease: A Patient-Level Meta-Analysis.

BACKGROUND: Clinical trial data associate extended clopidogrel therapy with increased mortality and cancer. We sought to determine the impact of continued clopidogrel use on mortality and cancer within a patient-level meta-analysis of randomized clinical trials. METHODS AND RESULTS: Meta-analytic clinical event rates for all-cause, cardiovascular, noncardiovascular, and cancer-related mortality; cancer; myocardial infarction; stroke; and fatal and major nonfatal bleeding were generated using patient-level data from 6 randomized trials comparing prolonged versus no or short-duration clopidogrel on a background of aspirin in patients with cardiovascular and cerebrovascular disease. Among 48 817 randomized patients (median follow-up 546 days), there was no difference in all-cause (7.23% versus 7.26%; P=0.97), cardiovascular (5.25% versus 5.22%; P=0.86), noncardiovascular (1.98% versus 2.03%; P=0.73), and cancer-related (0.93% versus 0.99%; P=0.59) mortality or in new cancer diagnoses (2.97% versus 2.96%; P>0.99). Rates of myocardial infarction (3.21% versus 4.05%; P<0.0001) and stroke (3.04% versus 3.75%; P<0.0001) were significantly lower in patients receiving continued clopidogrel. Fatal bleeding was more common with continued clopidogrel use (0.39% versus 0.27%; P=0.03), as were major nonfatal bleeding (4.06% versus 2.68%; P<0.0001) and intracranial hemorrhage (0.43% versus 0.30%; P=0.02). CONCLUSIONS: Across trials of cardiovascular and cerebrovascular disease, extended-duration clopidogrel on a background of aspirin has no overall effect on mortality or cancer but does reduce rates of myocardial infarction and stroke and increase rates of bleeding. These findings emphasize the need for selective use of extended clopidogrel therapy in patients in whom the risks of ischemia are not fully counterbalanced by the risks of bleeding.

Myocardial Infarction Risk After Discontinuation of Thienopyridine Therapy in the Randomized DAPT Study (Dual Antiplatelet Therapy).

BACKGROUND: Thienopyridine plus aspirin beyond 1 year after coronary stenting reduces myocardial infarction (MI) risk and increases bleeding risk in comparison with aspirin alone. The hazard associated with late thienopyridine discontinuation and risk factors for MI after discontinuation are poorly defined. METHODS: In the DAPT Study (Dual Antiplatelet Therapy), after percutaneous coronary intervention and 12 months of thienopyridine (clopidogrel or prasugrel) plus aspirin, eligible patients remained on aspirin and were randomly assigned to continued thienopyridine versus placebo for 18 months. At 30 months, patients stopped the study drug and were observed for 3 months. Cumulative incidence of MI was assessed over 3 months after randomization (months 12-15) and 3 months after study drug discontinuation (months 30-33). The MI hazard for each of these periods was assessed across randomized treatment arms and by DAPT score values <2 or ≥2. RESULTS: Among the 11 648 randomly assigned patients, the monthly cumulative incidence of MI was lower with continued thienopyridine versus placebo at 12 to 15 months (0.12% versus 0.37%, P<0.001, in all patients; 0.13% versus 0.27%, P=0.02, in patients not treated with paclitaxel-eluting stents), and higher at 30 to 33 months (0.30% versus 0.15%, P=0.013, in all patients; in patients without paclitaxel-eluting stents, 0.18% versus 0.17%, P=0.91). The majority of MIs in both time periods (74% and 76%) were not related to stent thrombosis. After multivariable adjustment, treatment arm independently predicted MI at months 12 to 15 (P<0.001) and 30 to 33 (P=0.011). During months 12 to 15, patients with DAPT scores <2 or ≥2 both had lower rates of MI with continued thienopyridine (MI monthly incidence 0.16% versus 0.51%, P<0.001, for scores ≥2; 0.08% versus 0.24%, P=0.012, for scores<2, interaction P=0.064). CONCLUSIONS: Discontinuing thienopyridine after either 12 or 30 months is associated with an early increase in MI risk, mainly unrelated to stent thrombosis; the magnitude of risk is highest in the earlier time frame, and lower in patients not treated with paclitaxel-eluting stents. Although higher DAPT scores identify patients with greater absolute ischemic benefit (relative to bleeding harm) with continued thienopyridine therapy, discontinuation at 12 months increases MI hazard regardless of DAPT score group. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.

Impact of Optimal Medical Therapy in the Dual Antiplatelet Therapy Study.

BACKGROUND: Continued dual antiplatelet therapy and optimal medical therapy (OMT) improve outcomes in selected patient populations with established coronary heart disease, but whether OMT modifies the treatment effect of dual antiplatelet therapy is unknown. METHODS: The DAPT (Dual Antiplatelet Therapy) Study, a double-blind trial, randomly assigned 11 648 patients who had undergone coronary stenting and completed 1 year of dual antiplatelet therapy without major bleeding or ischemic events to an additional 18 months of continued thienopyridine or placebo. OMT was defined as a combination of statin, ß-blocker, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use in patients with an American College of Cardiology/American Heart Association class I indication for each medication. Per protocol, all patients were treated with 75 to 325 mg aspirin daily. End points included myocardial infarction, major adverse cardiovascular and cerebrovascular events, and Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries moderate or severe bleeding events. RESULTS: Of 11 643 randomly assigned patients with complete medication data, 63% were on OMT. Between 12 and 30 months, continued thienopyridine reduced myocardial infarction in comparison with placebo in both groups (on OMT 2.1% versus 3.3%, hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.48-0.86; P=0.003; off OMT 2.2% versus 5.2%, HR, 0.41; CI, 0.29-0.58; P<0.001; interaction P=0.103). Comparing continued thienopyridine versus placebo, rates of major adverse cardiovascular and cerebrovascular events were 4.2% versus 5.0% among patients on OMT (HR, 0.82; CI, 0.66-1.02; P=0.077) and 4.5% versus 7.0% among those off OMT (HR, 0.63; CI, 0.49-0.82; P<0.001; interaction P=0.250); rates of bleeding for thienopyridine versus placebo in patients on OMT were 2.2% versus 1.0% (HR, 2.13; CI, 1.43-3.17; P<0.001), and in patients off OMT were 2.8% versus 2.2% (HR, 1.30; CI, 0.88-1.92; P=0.189; interaction P=0.073). Overall, patients on OMT had lower rates of myocardial infarction (2.7% versus 3.7%, P=0.003), major adverse cardiovascular and cerebrovascular events (4.6% versus 5.7%, P=0.007), and bleeding (1.6% versus 2.5%, P<0.001) in comparison with patients off OMT. Rates of stent thrombosis (0.8% versus 1.0%, P=0.171) and death (1.6% versus 1.9%, P=0.155) did not differ. CONCLUSIONS: Continued thienopyridine therapy reduced the rate of myocardial infarction regardless of OMT status and had consistent effects on reduction in major adverse cardiovascular and cerebrovascular events and increased bleeding. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT00977938.

Efficacy and Safety of Proton-Pump Inhibitors in High-Risk Cardiovascular Subsets of the COGENT Trial.

BACKGROUND: Proton-pump inhibitors (PPIs) have been demonstrated to reduce rates of gastrointestinal events in patients requiring dual antiplatelet therapy (DAPT). Data are limited regarding the efficacy and safety of PPIs in high-risk cardiovascular subsets after acute coronary syndrome or percutaneous coronary intervention. METHODS: All patients enrolled in COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) were initiated on DAPT (with aspirin and clopidogrel) for various indications within the prior 21 days. These post hoc analyses of the COGENT trial evaluated the efficacy and safety of omeprazole compared with placebo in subsets of patients requiring DAPT for the 2 most frequent indications: 1) patients undergoing percutaneous coronary intervention (for any indication) within 14 days of randomization (n = 2676; 71.2%); and 2) patients presenting with acute coronary syndrome managed with or without percutaneous coronary intervention (n = 1573; 41.8%). Unadjusted Cox proportional hazards models were used to estimate effect sizes through final follow-up. RESULTS: Median follow-up duration was 110 days (interquartile range 55-167). In percutaneous coronary intervention-treated patients, omeprazole significantly reduced rates of composite gastrointestinal events at 180 days (1.2% vs 2.7%; hazard ratio [HR] 0.43; 95% confidence interval [CI], 0.22-0.85; P = .02) without increasing composite cardiovascular events (5.4% vs 6.3%; HR 1.00; 95% CI, 0.67-1.50; P = 1.00). Similarly, omeprazole lowered risk of the primary gastrointestinal endpoint at 180 days in patients presenting with acute coronary syndrome (1.1% vs 2.7%; HR 0.37; 95% CI, 0.13-1.01; P = .05) without a significant excess in cardiovascular events (5.6% vs 4.5%; HR 1.40; 95% CI, 0.77-2.53; P = .27). CONCLUSIONS: PPI therapy attenuates gastrointestinal bleeding risk without significant excess in major cardiovascular events in high-risk cardiovascular subsets, regardless of indication for DAPT. Future studies will be needed to clarify optimal gastroprotective strategies for higher-intensity and longer durations of DAPT.

Proton-Pump Inhibitors Reduce Gastrointestinal Events Regardless of Aspirin Dose in Patients Requiring Dual Antiplatelet Therapy.

BACKGROUND: The COGENT (Clopidogrel and the Optimization of Gastrointestinal Events Trial) showed that proton-pump inhibitors (PPIs) safely reduced rates of gastrointestinal (GI) events in patients requiring dual antiplatelet therapy (DAPT). However, utilization of appropriate prophylactic PPI therapy remains suboptimal, especially with low-dose aspirin. OBJECTIVES: The authors investigated the safety and efficacy of PPI therapy in patients receiving DAPT in low- and high-dose aspirin subsets. METHODS: Randomized patients with available aspirin dosing information in COGENT (N = 3,752) were divided into "low-dose" (≤ 100 mg) and "high-dose" (>100 mg) aspirin groups. The primary GI and cardiovascular endpoints were composite upper GI events and major adverse cardiac events, respectively. All events were adjudicated by independent, blinded gastroenterologists and cardiologists. RESULTS: Median duration of follow-up was 110 days. Low-dose aspirin users (n = 2,480; 66.1%) were more likely to be older, female, and have higher rates of peripheral artery disease, prior stroke, and hypertension, whereas high-dose aspirin users (n = 1,272; 33.9%) had higher rates of hyperlipidemia, smoking, a history of percutaneous coronary intervention, and were more than twice as likely to be enrolled from sites within the United States (80.4% vs. 39.8%). High-dose aspirin was associated with similar 180-day Kaplan-Meier estimates of adjudicated composite GI events (1.7% vs. 2.1%; adjusted hazard ratio: 0.88; 95% confidence interval: 0.46 to 1.66) and major adverse cardiac events (4.8% vs. 5.5%; adjusted hazard ratio: 0.73; 95% confidence interval: 0.48 to 1.11) compared with low-dose aspirin. Randomization to PPI therapy reduced 180-day Kaplan-Meier estimates of the primary GI endpoint in low-dose (1.2% vs. 3.1%) and high-dose aspirin subsets (0.9% vs. 2.6%; p for interaction = 0.80), and did not adversely affect the primary cardiovascular endpoint in either group. CONCLUSIONS: Gastroprotection with PPI therapy should be utilized in appropriately selected patients with coronary artery disease requiring DAPT, even if the patients are on low-dose aspirin. (Clopidogrel and the Optimization of Gastrointestinal Events Trial [COGENT]; NCT00557921).

Diabetes Mellitus and Prevention of Late Myocardial Infarction After Coronary Stenting in the Randomized Dual Antiplatelet Therapy Study.

BACKGROUND: Patients with diabetes mellitus (DM) are at high risk for recurrent ischemic events after coronary stenting. We assessed the effects of continued thienopyridine among patients with DM participating in the Dual Antiplatelet Therapy (DAPT) Study as a prespecified analysis. METHODS AND RESULTS: After coronary stent placement and 12 months treatment with open-label thienopyridine plus aspirin, 11 648 patients free of ischemic or bleeding events and who were medication compliant were randomly assigned to continued thienopyridine or placebo, in addition to aspirin, for 18 more months. After randomization, patients with DM (n=3391), in comparison with patients without DM (n=8257), had increased composite outcome of death, myocardial infarction (MI), or stroke (6.8% versus 4.3%, P<0.001), increased death (2.5% versus 1.4%, P<0.001), and MI (4.2% versus 2.6%, P<0.001). Among patients with DM, in a comparison of continued thienopyridine versus placebo, rates of stent thrombosis were 0.5% versus 1.1%, P=0.06, and rates of MI were 3.5% versus 4.8%, P=0.058; and among patients without DM the rates were 0.4% versus 1.4%, P<0.001 (stent thrombosis, P interaction=0.21) and 1.6% versus 3.6%, P<0.001 (MI, P interaction=0.02). Bleeding risk with continued thienopyridine was similar among patients with or without DM (interaction P=0.61). CONCLUSIONS: In patients with DM, continued thienopyridine beyond 1 year after coronary stenting is associated with reduced risk of MI, although this benefit is attenuated in comparison with patients without DM. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00977938.

Benefits and Risks of Extended Dual Antiplatelet Therapy After Everolimus-Eluting Stents.

OBJECTIVES: The purpose of this study was to characterize outcomes for everolimus-eluting stent (EES)-treated subjects according to treatment with continued thienopyridine plus aspirin versus aspirin alone 12 to 30 months after stenting. BACKGROUND: In the DAPT (Dual Antiplatelet Therapy) study, continued thienopyridine plus aspirin beyond 1 year after coronary stenting reduced ischemic events. Given low rates of stent thrombosis and myocardial infarction (MI) for current drug-eluting stents, we examined outcomes among EES-treated subjects in the DAPT study. METHODS: The DAPT study enrolled 25,682 subjects (11,308 EES-treated) after coronary stenting. Following 12 months of treatment with thienopyridine and aspirin, eligible subjects continued treatment with aspirin and 9,961 (4,703 with EES) were randomized to 18 months of continued thienopyridine or placebo. Stent type was not randomized, and the EES subset analysis was post hoc. RESULTS: Among EES-treated patients, continued thienopyridine reduced stent thrombosis (0.3% vs. 0.7%, hazard ratio [HR]: 0.38, 95% confidence interval [CI]: 0.15 to 0.97; p = 0.04) and MI (2.1% vs. 3.2%, HR: 0.63, 95% CI: 0.44 to 0.91; p = 0.01) versus placebo but did not reduce a composite of death, MI, and stroke (4.3% vs. 4.5%, HR: 0.89, 95% CI: 0.67 to 1.18; p = 0.42), and increased moderate/severe bleeding (2.5% vs. 1.3%, HR: 1.79, 95% CI: 1.15 to 2.80; p = 0.01), and death (2.2% vs. 1.1%, HR: 1.80, 95% CI: 1.11 to 2.92; p = 0.02). Death due to cancer and not related to bleeding was increased (0.64% vs. 0.17%; p = 0.01). CONCLUSIONS: In EES-treated subjects, significant reductions in stent thrombosis and MI and an increase in bleeding were observed with continued thienopyridine beyond 1 year compared with aspirin alone. (The Dual Antiplatelet Therapy Study [DAPT Study]); NCT00977938).

Efficacy of dose increase among nonresponders to low-dose aripiprazole augmentation in patients with inadequate response to antidepressant treatment: a randomized, double-blind, placebo-controlled, efficacy trial.

OBJECTIVE: To examine the efficacy of a dose increase of aripiprazole to 5 mg/d in subjects with major depressive disorder (MDD) who did not respond to 4 weeks of treatment with aripiprazole 2 mg/d in a randomized, double-blind, placebo-controlled, parent study. METHOD: 221 Subjects with Structured Clinical Interview for DSM-IV Axis I Disorders-Patient Edition-diagnosed DSM-IV-TR MDD (mean ± SD age, 45 ± 11 years; 64% women) with inadequate antidepressant response were recruited from September 2008-July 2009 and randomized to 60 days of double-blind augmentation with either aripiprazole or placebo in two 30-day phases. The study was performed across 8 academic hospital sites and 14 nonacademic (private clinic) sites throughout the United States. Randomization in a 2:3:3 ratio per sequential parallel comparison design was drug/drug (aripiprazole 2 mg/d in phase 1 and 5 mg/d in phase 2), placebo/placebo (placebo in both phases), and placebo/drug (placebo in phase 1 and aripiprazole 2 mg/d in phase 2). In phase 2, we examined efficacy of an aripiprazole dose increase to 5 mg/d in nonresponders to 2 mg/d by assessing response rates (≥ 50% reduction in Montgomery-Asberg Depression Rating Scale [MADRS] score [primary outcome measure]) and score changes in MADRS, Quick Inventory of Depressive Symptomatology-Self-Report, 9-item Patient Health Questionnaire (PHQ-9), the Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales, and patient-rated versions of the CGI-I and CGI-S scales. RESULTS: Response rate for aripiprazole 2 mg/d in phase 1 was 18.5% (n/n = 10/54). Among 39 nonresponders who increased their dose to 5 mg/d, response rate was 12.8% (95% CI, 4.30%-27.43%), with significant overall mean ± SD reductions in MADRS scores (-9.46 ± 7.83 [95% CI, -12.00 to -6.92]; P < .0001), Symptoms Questionnaire Distress scores (19.51 ± 17.73 [95% CI, 13.60 to 25.43]; P < .0001), PHQ-9 scores (-7.92 ± 5.92 [95% CI, -9.89 to -5.94]; P < .0001), and CGI-S scores (-0.86 ± 0.86 [95% CI, -1.15 to -0.58]; P < .0001). Differences in efficacy between drug and placebo groups were nonsignificant, however. Aripiprazole and placebo were well tolerated. CONCLUSIONS: Augmentation with aripiprazole 5 mg/d may provide only a modest additional benefit in patients who do not benefit from lower doses. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00683852.

Cognitive status and change among Iowa centenarians.

Equivocal evidence exists regarding the degree of cognitive stability and prevalence of cognitive impairment in very late life. The objective of the current study was to examine mental status performance and change over time within a sample of Iowa centenarians. The baseline sample consisted of 152 community-dwelling and institutionalized centenarians. Twenty eight of these centenarians participated in the next phase of the study which involved up to four subsequent assessments conducted over a 6-month period. Centenarians' Short Portable Mental Status Questionnaire (SPMSQ; Pfeiffer, 1975) performance indicated that 40% of the baseline sample performed within the normal range while an additional 40% of centenarians' performed within the moderately or severely impaired range. Examination of individual-level change indicated four patterns of short-term longitudinal performance which depicted stability, enhancement, decrement, and variability in scores across the 8-month testing period. The degree of reliable change as assessed by standard error of measurement largely mirrored change as classified by the traditional scoring categories, however, the former approach appeared more sensitive to meaningful intraindividual change in later assessments.

Frequency of major noncardiac surgery and subsequent adverse events in the year after drug-eluting stent placement results from the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) Registry.

OBJECTIVES: This study sought to determine the frequency of noncardiac surgery and adverse post-operative events among patients who recently received a drug-eluting stent (DES) following noncardiac surgery. BACKGROUND: Little is known about frequency of and risks associated with noncardiac surgery after DES implantation. METHODS: In the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) registry, consecutive patients who underwent attempted stent placement at 42 hospitals between July 2004 and September 2005 were enrolled and followed for 1 year. In this study, we analyzed patients who received ≥ 1 DES to determine the frequency of noncardiac surgery and cardiac death, myocardial infarction, or stent thrombosis in the following week. RESULTS: Among 4,637 DES recipients, 206 (4.4%) underwent major noncardiac surgery in the following year (median days to surgery: 179 [interquartile range 112 to 266 days; range 13 to 360 days]). Overall, stent use averaged 1.5 per patient. The most frequent operations were orthopedic (36%), abdominal (31%), and vascular (20%). Compared with patients who did not undergo surgery, those who did were older, more likely to be women, and have had a prior stroke; the frequencies of prior myocardial infarction, prior coronary artery bypass graft, and diabetes were similar, as were left ventricular ejection fraction and indication for percutaneous coronary intervention. In the 7 days after surgery, 4 patients had a cardiac death, myocardial infarction, or stent thrombosis (1.9% [exact 95% confidence interval (CI): 0.5% to 4.9%]). The risk of the composite outcome was increased 27-fold in the week following noncardiac surgery compared with any other week after stent implantation (hazard ratio [HR]: 27.3 [95% CI: 10.0 to 74.2], p < 0.001). CONCLUSIONS: The frequency of major noncardiac surgery in the year after DES placement is >4%. Although the overall risk of adverse outcomes was less than previously reported when surgery is performed months after DES placement, it is significantly increased in the week after major noncardiac surgery.

Prevalence and prognostic significance of preprocedural cardiac troponin elevation among patients with stable coronary artery disease undergoing percutaneous coronary intervention: results from the evaluation of drug eluting stents and ischemic events registry.

BACKGROUND: Although cardiac troponin (cTn) elevation is associated with periprocedural complications during percutaneous coronary intervention (PCI) in the setting of acute coronary syndromes, the prevalence and prognostic significance of preprocedural cTn elevation among patients with stable coronary artery disease undergoing PCI are unknown. METHODS AND RESULTS: Between July 2004 and September 2006, 7592 consecutive patients who underwent attempted stent placement at 47 hospitals throughout the United States were enrolled in a prospective multicenter registry. We analyzed the frequency of an elevated cTn immediately before PCI and its relationship to in-hospital and 1-year outcomes among patients who underwent PCI for either stable angina or a positive stress test. Among the stable coronary artery disease population (n=2382, 31.4%), 142 (6.0%) had a cTn level above the upper limit of normal before the procedure. Compared with patients who had normal baseline cTn, patients with elevated cTn had a higher rate of in-hospital death or myocardial infarction (13.4% versus 5.6%; P<0.001) and a trend toward higher rates of urgent repeat PCI (1.4% versus 0.2%; P=0.06). In multivariable analyses adjusted for demographic, clinical, angiographic, and procedural factors, baseline cTn elevation remained independently associated with the composite of death or myocardial infarction at hospital discharge (odds ratio, 2.1; 95% confidence interval, 1.2 to 3.8; P=0.01) and at the 1-year follow-up (odds ratio, 2.0; 95% confidence interval, 1.2 to 3.3; P=0.005). CONCLUSIONS: Baseline elevation of cTn is relatively common among patients with stable coronary artery disease undergoing PCI and is an independent prognostic indicator of ischemic complications. If these data are confirmed in future studies, consideration should be given to routine testing of cTn before performance of PCI in this patient population.

Stent thrombosis in randomized clinical trials of drug-eluting stents.

BACKGROUND: Definitions of stent thrombosis that have been used in clinical trials of drug-eluting stents have been restrictive and have not been used in a uniform manner. METHODS: We applied a hierarchical classification of stent thrombosis set by the Academic Research Consortium (ARC) across randomized trials involving 878 patients treated with sirolimus-eluting stents, 1400 treated with paclitaxel-eluting stents, and 2267 treated with bare-metal stents. We then pooled 4 years of follow-up data. All events were adjudicated by an independent clinical-events committee. RESULTS: The cumulative incidence of stent thrombosis according to the original protocol definitions was 1.2% in the sirolimus-stent group versus 0.6% in the bare-metal-stent group (P=0.20; 95% confidence interval [CI], -0.4 to 1.5) and 1.3% in the paclitaxel-stent group versus 0.8% in the bare-metal-stent group (P=0.24; 95% CI, -0.3 to 1.4). The incidence of definite or probable stent thrombosis as defined by the ARC was 1.5% in the sirolimus-stent group versus 1.7% in the bare-metal-stent group (P=0.70; 95% CI, -1.5 to 1.0) and 1.8% in the paclitaxel-stent group versus 1.4% in the bare-metal-stent group (P=0.52; 95% CI, -0.7 to 1.4). The incidence of definite or probable events occurring 1 to 4 years after implantation was 0.9% in the sirolimus-stent group versus 0.4% in the bare-metal-stent group and 0.9% in the paclitaxel-stent group versus 0.6% in the bare-metal-stent group. CONCLUSIONS: The incidence of stent thrombosis did not differ significantly between patients with drug-eluting stents and those with bare-metal stents in randomized clinical trials, although the power to detect small differences in rates was limited.