Kevin F. Kennedy

Appropriateness of Percutaneous Coronary Intervention

CONTEXT Despite the widespread use of percutaneous coronary intervention (PCI), the appropriateness of these procedures in contemporary practice is unknown. OBJECTIVE To assess the appropriateness of PCI in the United States. DESIGN, SETTING, AND PATIENTS Multicenter, prospective study of patients within the National Cardiovascular Data Registry undergoing PCI between July 1, 2009, and September 30, 2010, at 1091 US hospitals. The appropriateness of PCI was adjudicated using the appropriate use criteria for coronary revascularization. Results were stratified by whether the procedure was performed for an acute (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, or unstable angina with high-risk features) or nonacute indication. MAIN OUTCOME MEASURES Proportion of acute and nonacute PCIs classified as appropriate, uncertain, or inappropriate; extent of hospital-level variation in inappropriate procedures. RESULTS Of 500,154 PCIs, 355,417 (71.1%) were for acute indications (ST-segment elevation myocardial infarction, 103,245 [20.6%]; non-ST-segment elevation myocardial infarction, 105,708 [21.1%]; high-risk unstable angina, 146,464 [29.3%]), and 144,737 (28.9%) for nonacute indications. For acute indications, 350,469 PCIs (98.6%) were classified as appropriate, 1055 (0.3%) as uncertain, and 3893 (1.1%) as inappropriate. For nonacute indications, 72,911 PCIs (50.4%) were classified as appropriate, 54,988 (38.0%) as uncertain, and 16,838 (11.6%) as inappropriate. The majority of inappropriate PCIs for nonacute indications were performed in patients with no angina (53.8%), low-risk ischemia on noninvasive stress testing (71.6%), or suboptimal (≤1 medication) antianginal therapy (95.8%). Furthermore, although variation in the proportion of inappropriate PCI across hospitals was minimal for acute procedures, there was substantial hospital variation for nonacute procedures (median hospital rate for inappropriate PCI, 10.8%; interquartile range, 6.0%-16.7%). CONCLUSIONS In this large contemporary US cohort, nearly all acute PCIs were classified as appropriate. For nonacute indications, however, 12% were classified as inappropriate, with substantial variation across hospitals.

Association Between Use of Bleeding Avoidance Strategies and Risk of Periprocedural Bleeding Among Patients Undergoing Percutaneous Coronary Intervention

CONTEXT Bleeding complications with percutaneous coronary intervention (PCI) are associated with adverse patient outcomes. The association between the use of bleeding avoidance strategies and post-PCI bleeding as a function of a patients preprocedural risk of bleeding is unknown. OBJECTIVE To describe the use of 2 bleeding avoidance strategies, vascular closure devices and bivalirudin, and associated post-PCI bleeding rates in a nationally representative PCI population. DESIGN, SETTING, AND PATIENTS Analysis of data from 1,522,935 patients undergoing PCI procedures performed at 955 US hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry from January 1, 2004, through September 30, 2008. MAIN OUTCOME MEASURE Periprocedural bleeding. RESULTS Bleeding occurred in 30,654 patients (2%). Manual compression, vascular closure devices, bivalirudin, or vascular closure devices plus bivalirudin were used in 35%, 24%, 23%, and 18% of patients, respectively. Bleeding events were reported in 2.8% of patients who received manual compression, compared with 2.1%, 1.6%, and 0.9% of patients receiving vascular closure devices, bivalirudin, and both strategies, respectively (P < .001). Bleeding rates differed by preprocedural risk assessed with the NCDR bleeding risk model (low risk, 0.72%; intermediate risk, 1.73%; high risk, 4.69%). In high-risk patients, use of both strategies was associated with lower bleeding rates (manual compression, 6.1%; vascular closure devices, 4.6%; bivalirudin, 3.8%; vascular closure devices plus bivalirudin, 2.3%; P < .001). This association persisted following adjustment using a propensity-matched and site-controlled model. Use of both strategies was used least often in high-risk patients (14.4% vs 21.0% in low-risk patients, P < .001). CONCLUSIONS In a large national PCI registry, vascular closure devices and bivalirudin were associated with significantly lower bleeding rates, particularly among patients at greatest risk for bleeding. However, these strategies were less often used among higher-risk patients.

Contemporary Incidence, Predictors, and Outcomes of Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions: Insights From the NCDR Cath-PCI Registry

OBJECTIVES This study sought to examine the contemporary incidence, predictors and outcomes of acute kidney injury in patients undergoing percutaneous coronary interventions. BACKGROUND Acute kidney injury (AKI) is a serious and potentially preventable complication of percutaneous coronary interventions (PCIs) that is associated with adverse outcomes. The contemporary incidence, predictors, and outcomes of AKI are not well defined, and clarifying these can help identify high-risk patients for proactive prevention. METHODS A total of 985,737 consecutive patients underwent PCIs at 1,253 sites participating in the National Cardiovascular Data Registry Cath-PCI registry from June 2009 through June 2011. AKI was defined on the basis of changes in serum creatinine level in the hospital according to the Acute Kidney Injury Network (AKIN) criteria. Using multivariable regression analyses with generalized estimating equations, we identified patient characteristics associated with AKI. RESULTS Overall, 69,658 (7.1%) patients experienced AKI, with 3,005 (0.3%) requiring new dialysis. On multivariable analyses, the factors most strongly associated with development of AKI included ST-segment elevation myocardial infarction (STEMI) presentation (odds ratio [OR]: 2.60; 95% confidence interval [CI]: 2.53 to 2.67), severe chronic kidney disease (OR: 3.59; 95% CI: 3.47 to 3.71), and cardiogenic shock (OR: 2.92; 95% CI: 2.80 to 3.04). The in-hospital mortality rate was 9.7% for patients with AKI and 34% for those requiring dialysis compared with 0.5% for patients without AKI (p < 0.001). After multivariable adjustment, AKI (OR: 7.8; 95% CI: 7.4 to 8.1, p < 0.001) and dialysis (OR: 21.7; 95% CI: 19.6 to 24.1; p < 0.001) remained independent predictors of in-hospital mortality. CONCLUSIONS Approximately 7% of patients undergoing a PCI experience AKI, which is strongly associated with in-hospital mortality. Defining strategies to minimize the risk of AKI in patients undergoing PCI are needed to improve the safety and outcomes of the procedure.

Cardiovascular safety of liraglutide assessed in a patient-level pooled analysis of phase 2—3 liraglutide clinical development studies

We assessed the cardiovascular safety of liraglutide, a glucagon-like peptide-1 receptor agonist, using existing clinical data. Patient-level results from all completed phase 2 and 3 studies from the liraglutide clinical development programme were pooled to determine rates of major adverse cardiovascular events (MACE): cardiovascular death, myocardial infarction, stroke. MACE were identified by querying the study database using Medical Dictionary for Regulatory Activities (MedDRA) terms combined with serious adverse events recorded by study investigators. Broad, narrow, and custom groups of MedDRA queries were used. Candidate events from each query were independently adjudicated post hoc. In 15 studies (6638 patients; 4257 liraglutide treated), there were 114 patients with MACE identified using the broad MedDRA query. Of these, 44 were classified as serious adverse events and 39 were adjudicated as MACE. The incidence ratio for adjudicated broad/serious MACE associated with liraglutide was 0.73 (95% CI 0.38—1.41) versus all comparator drugs (metformin, glimepiride, rosiglitazone, insulin glargine, placebo), within cardiovascular safety limits defined by the United States Food & Drug Administration for diabetes therapies under current investigation.

Oral Anticoagulant Therapy Prescription in Patients With Atrial Fibrillation Across the Spectrum of Stroke Risk: Insights From the NCDR PINNACLE Registry

IMPORTANCE Patients with atrial fibrillation (AF) are at a proportionally higher risk of stroke based on accumulation of well-defined risk factors. OBJECTIVE To examine the extent to which prescription of an oral anticoagulant (OAC) in US cardiology practices increases as the number of stroke risk factors increases. DESIGN, SETTING, AND PARTICIPANTS Cross-sectional registry study of outpatients with AF enrolled in the American College of Cardiology National Cardiovascular Data Registrys PINNACLE (Practice Innovation and Clinical Excellence) Registry between January 1, 2008, and December 30, 2012. As a measure of stroke risk, we calculated the CHADS2 score and the CHA2DS2-VASc score for all patients. Using multinomial logistic regression models adjusted for patient, physician, and practice characteristics, we examined the association between increased stroke risk score and prescription of an OAC. MAIN OUTCOMES AND MEASURES The primary outcome was prescription of an OAC with warfarin sodium or a non-vitamin K antagonist OAC. RESULTS The study cohort comprised 429 417 outpatients with AF. Their mean (SD) age was 71.3 (12.9) years, and 55.8% were male. Prescribed treatment consisted of an OAC (192 600 [44.9%]), aspirin only (111 134 [25.9%]), aspirin plus a thienopyridine (23 454 [5.5%]), or no antithrombotic therapy (102 229 [23.8%]). Each 1-point increase in risk score was associated with increased odds of OAC prescription compared with aspirin-only prescription using the CHADS2 score (adjusted odds ratio, 1.158; 95% CI, 1.144-1.172; P < .001) and the CHA2DS2-VASc score (adjusted odds ratio, 1.163; 95% CI, 1.157-1.169; P < .001). Overall, OAC prescription prevalence did not exceed 50% even in higher-risk patients with a CHADS2 score exceeding 3 or a CHA2DS2-VASc score exceeding 4. CONCLUSIONS AND RELEVANCE In a large quality improvement registry of outpatients with AF, prescription of OAC therapy increased with a higher CHADS2 score and CHA2DS2-VASc score. However, a plateau of OAC prescription was observed, with less than half of high-risk patients receiving an OAC prescription.

Prognostic Impact of Periprocedural Bleeding and Myocardial Infarction After Percutaneous Coronary Intervention in Unselected Patients: Results From the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) Registry

OBJECTIVES Our aim was to examine the prognostic importance of hemorrhagic and ischemic complications after percutaneous coronary intervention (PCI) in unselected patients. BACKGROUND In randomized trials of PCI, major bleeding and periprocedural myocardial infarction (pMI) have been associated with increased mortality. Whether similar associations exist among un-selected PCI patients is unknown. METHODS We used data from the EVENT (Evaluation of Drug Eluting Stents and Ischemic Events) registry-a multicenter registry of unselected patients undergoing PCI-to examine the association between both in-hospital bleeding and pMI and 1-year mortality. Cardiac enzyme levels were assessed in all patients, and pMI was defined as a peak creatine kinase-MB value >or=3x the upper limit of normal. Post-PCI bleeding was classified by Thrombolysis In Myocardial Infarction criteria. RESULTS After excluding patients with elevated pre-PCI creatine kinase-MB values and ST-segment elevation myocardial infarction at presentation (n = 1,626), a total of 5,961 patients were available for evaluation. Rates of post-PCI bleeding and pMI were 3.0% and 7.1%, respectively; 1-year all-cause mortality was 2.8%. After multivariable adjustment, both post-PCI bleeding (adjusted hazard ratio [HR]: 3.83, 95% confidence interval: 2.48 to 5.90, p < 0.001) and pMI (adjusted HR: 1.84, 95% confidence interval: 1.17 to 2.89, p = 0.009) were independently associated with 1-year mortality. Time period-specific analyses demonstrated that the adjusted HR for bleeding was similar for 30-day mortality and mortality between 1 month and 1 year, while the adjusted HR for pMI was greater for 30-day mortality as compared with mortality between 1 month and 1 year. CONCLUSIONS Among unselected PCI patients, both post-PCI bleeding and pMI are independently associated with increased 1-year mortality. Continued efforts to reduce these complications after PCI are warranted.

Changes in myocardial ischemic burden following percutaneous coronary intervention of chronic total occlusions

Objectives: We assessed the potential for percutaneous coronary intervention (PCI) of a chronic total occlusion (CTO) to decrease myocardial ischemia and established objective criteria to predict post‐procedure improvement. Background: Optimal treatment for CTO of coronary arteries is controversial, and selection criteria for PCI of CTO are subjective. Methods: All patients undergoing CTO PCI at a single center between 2002 and 2007 were included if myocardial perfusion imaging (MPI) was performed within 12 ± 3 months before and a follow‐up study within 12 ± 3 months after PCI. Average summed difference scores were calculated and converted to percent ischemic myocardium to classify patients as having normal/minimal, mild, moderate, or severe ischemia. A significant improvement in ischemia following PCI was classified as an absolute ≥5% decrease in ischemic myocardium. Receiver operating characteristic (ROC) curves were used to identify ischemic thresholds predictive of decreased and increased ischemic burden on follow‐up MPI. Results: In 301 patients, average baseline ischemic burden was 13.1% ± 11.9% and decreased to 6.9% ± 6.5% (P < 0.001) during follow‐up. Overall, 53.5% of patients met criteria for improvement following PCI. These patients were more likely to be male, without diabetes, with CTO in the left anterior descending artery, and classified as having high ischemic burden at baseline. ROC analysis identified a baseline 12.5% ischemic burden as optimal in identifying those most likely to have a significantly decreased ischemic burden post‐PCI. Those with a baseline ischemic burden less than 6.25% were more likely to have an increased ischemic burden post‐PCI. Conclusions: Ischemic burden is reduced following CTO PCI, and the decrease is greater at high ischemic burden. A threshold of 12.5% ischemic burden is suggested as a criterion for performing PCI in the setting of CTO.

Association Between Public Reporting of Outcomes With Procedural Management and Mortality for Patients With Acute Myocardial Infarction

BACKGROUND Public reporting of procedural outcomes may create disincentives to provide percutaneous coronary intervention (PCI) for critically ill patients. OBJECTIVES This study evaluated the association between public reporting with procedural management and outcomes among patients with acute myocardial infarction (AMI). METHODS Using the Nationwide Inpatient Sample, we identified all patients with a primary diagnosis of AMI in states with public reporting (Massachusetts and New York) and regionally comparable states without public reporting (Connecticut, Maine, Maryland, New Hampshire, Rhode Island, and Vermont) between 2005 and 2011. Procedural management and in-hospital outcomes were stratified by public reporting. RESULTS Among 84,121 patients hospitalized with AMI, 57,629 (69%) underwent treatment in a public reporting state. After multivariate adjustment, percutaneous revascularization was performed less often in public reporting states than in nonreporting states (odds ratio [OR]: 0.81, 95% confidence interval [CI]: 0.67 to 0.96), especially among older patients (OR: 0.75, 95% CI: 0.62 to 0.91), those with Medicare insurance (OR: 0.75, 95% CI: 0.62 to 0.91), and those presenting with ST-segment elevation myocardial infarction (OR: 0.63, 95% CI: 0.56 to 0.71) or concomitant cardiac arrest or cardiogenic shock (OR: 0.58, 95% CI: 0.47 to 0.70). Overall, patients with AMI in public reporting states had higher adjusted in-hospital mortality rates (OR: 1.21, 95% CI: 1.06 to 1.37) than those in nonreporting states. This was observed predominantly in patients who did not receive percutaneous revascularization in public reporting states (adjusted OR: 1.30, 95% CI: 1.13 to 1.50), whereas those undergoing the procedure had lower mortality (OR: 0.71, 95% CI: 0.62 to 0.83). CONCLUSIONS Public reporting is associated with reduced percutaneous revascularization and increased in-hospital mortality among patients with AMI, particularly among patients not selected for PCI.

Validated Contemporary Risk Model of Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions: Insights From the National Cardiovascular Data Registry Cath‐PCI Registry

Background We developed risk models for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI‐D) after percutaneous coronary intervention (PCI) to support quality assessment and the use of preventative strategies. Methods and Results AKI was defined as an absolute increase of ≥0.3 mg/dL or a relative increase of 50% in serum creatinine (AKIN Stage 1 or greater) and AKI‐D was a new requirement for dialysis following PCI. Data from 947 012 consecutive PCI patients and 1253 sites participating in the NCDR Cath/PCI registry between 6/09 and 7/11 were used to develop the model, with 70% randomly assigned to a derivation cohort and 30% for validation. AKI occurred in 7.33% of the derivation and validation cohorts. Eleven variables were associated with AKI: older age, baseline renal impairment (categorized as mild, moderate, and severe), prior cerebrovascular disease, prior heart failure, prior PCI, presentation (non‐ACS versus NSTEMI versus STEMI), diabetes, chronic lung disease, hypertension, cardiac arrest, anemia, heart failure on presentation, balloon pump use, and cardiogenic shock. STEMI presentation, cardiogenic shock, and severe baseline CKD were the strongest predictors for AKI. The full model showed good discrimination in the derivation and validation cohorts (c‐statistic of 0.72 and 0.71, respectively) and identical calibration (slope of calibration line=1.01). The AKI‐D model had even better discrimination (c‐statistic=0.89) and good calibration (slope of calibration line=0.99). Conclusion The NCDR AKI prediction models can successfully risk‐stratify patients undergoing PCI. The potential for this tool to aid clinicians in counseling patients regarding the risk of PCI, identify patients for preventative strategies, and support local quality improvement efforts should be prospectively tested.

Predicting Restenosis of Drug-Eluting Stents Placed in Real-World Clinical Practice Derivation and Validation of a Risk Model From the EVENT Registry

Background— Prediction of restenosis after percutaneous coronary intervention (PCI) remains challenging, and existing risk assessment algorithms were developed before the widespread adoption of drug-eluting stents (DES). Methods and Results— We used data from the EVENT registry to develop a risk model for predicting target lesion revascularization (TLR) in 8829 unselected patients undergoing DES implantation between 2004 and 2007. Using a split-sample validation technique, predictors of TLR at 1 year were identified from two thirds of the subjects (derivation cohort) using multiple logistic regression. Integer point values were created for each predictor, and the summed risk score (range, 0 to 10) was applied to the remaining sample (validation cohort). At 1 year, TLR occurred in 4.2% of patients, and after excluding stent thrombosis and early mechanical complications, the incidence of late TLR (more likely representing restenosis-related TLR) was 3.6%. Predictors of TLR were age <60, prior PCI, unprotected left main PCI, saphenous vein graft PCI, minimum stent diameter ≤2.5 mm, and total stent length ≥40 mm. Comparison of observed versus predicted rates of TLR according to risk score demonstrated good model fit in the validation set. There was more than a 3-fold difference in TLR rates between the lowest risk category (score=0; TLR rate, 2.2%) and the highest risk category (score ≥5; TLR rate, 7.5%). Conclusions— The overall incidence of TLR remains low among unselected patients receiving DES in routine clinical practice. A simple risk model incorporating 6 readily available clinical and angiographic variables helps identify individuals at extremely low ( 7%) risk of TLR after DES implantation.Background—Prediction of restenosis after percutaneous coronary intervention (PCI) remains challenging, and existing risk assessment algorithms were developed before the widespread adoption of drug-eluting stents (DES). Methods and Results—We used data from the EVENT registry to develop a risk model for predicting target lesion revascularization (TLR) in 8829 unselected patients undergoing DES implantation between 2004 and 2007. Using a split-sample validation technique, predictors of TLR at 1 year were identified from two thirds of the subjects (derivation cohort) using multiple logistic regression. Integer point values were created for each predictor, and the summed risk score (range, 0 to 10) was applied to the remaining sample (validation cohort). At 1 year, TLR occurred in 4.2% of patients, and after excluding stent thrombosis and early mechanical complications, the incidence of late TLR (more likely representing restenosis-related TLR) was 3.6%. Predictors of TLR were age <60, prior PCI, unprotected left main PCI, saphenous vein graft PCI, minimum stent diameter ⩽2.5 mm, and total stent length ≥40 mm. Comparison of observed versus predicted rates of TLR according to risk score demonstrated good model fit in the validation set. There was more than a 3-fold difference in TLR rates between the lowest risk category (score=0; TLR rate, 2.2%) and the highest risk category (score ≥5; TLR rate, 7.5%). Conclusions—The overall incidence of TLR remains low among unselected patients receiving DES in routine clinical practice. A simple risk model incorporating 6 readily available clinical and angiographic variables helps identify individuals at extremely low (<2%) and modestly increased (>7%) risk of TLR after DES implantation.