Impact of COVID-19 on percutaneous coronary intervention utilization and mortality in New York.

BACKGROUND: COVID-19 has disrupted the care of all patients, and little is known about its impact on the utilization and short-term mortality of percutaneous coronary intervention (PCI) patients, particularly nonemergency patients. METHODS: New York State's PCI registry was used to study the utilization of PCI and the presence of COVID-19 in four patient subgroups ranging in severity from ST-elevation myocardial infarction (STEMI) to elective patients before (December 01, 2018-February 29, 2020) and during the COVID-19 era (March 01, 2020-May 31, 2021), as well as to examine the impact of different COVID severity levels on the mortality of different types of PCI patients. RESULTS: Decreases in the mean quarterly PCI volume from the prepandemic period to the first quarter of the pandemic ranged from 20% for STEMI patients to 61% for elective patients, with the other two subgroups having decreases in between these values. PCI quarterly volume rebounds from the prepandemic period to the second quarter of 2021 were in excess of 90% for all patient subgroups, and 99.7% for elective patients. Existing COVID-19 was rare among PCI patients, ranging from 1.74% for STEMI patients to 3.66% for elective patients. PCI patients with COVID-19 and acute respiratory distress syndrome (ARDS) who were not intubated, and PCI patients with COVID-19 and ARDS who were either intubated or were not intubated because of Do Not Resuscitate//Do Not Intubate status had higher risk-adjusted mortality ([adjusted ORs = 10.81 [4.39, 26.63] and 24.53 [12.06, 49.88], respectively]) than patients who never had COVID-19. CONCLUSIONS: There were large decreases in the utilization of PCI during COVID-19, with the percentage of decrease being highly sensitive to patient acuity. By the second quarter of 2021, prepandemic volumes were nearly restored for all patient subgroups. Very few PCI patients had current COVID-19 throughout the pandemic period, but the number of PCI patients with a COVID-19 history increased steadily during the pandemic. PCI patients with COVID-19 accompanied by ARDS were at much higher risk of short-term mortality than patients who never had COVID-19. COVID-19 without ARDS and history of COVID-19 were not associated with higher mortality for PCI patients as of the second quarter of 2021.

Sex differences in the treatment and outcomes of patients hospitalized with ST-elevation myocardial infarction.

OBJECTIVES: To compare mortality for women and men hospitalized with ST-elevation myocardial infarction (STEMI) by age and revascularization status. BACKGROUND: There is little information on the mortality of men and women not undergoing revascularization, and the impact of age on relative male-female mortality needs to be revisited. METHODS AND RESULTS: An observational database of 23,809 patients with STEMI presenting at nonfederal New York State hospitals between 2013 and 2015 was used to compare risk-adjusted inhospital/30-day mortality for women and men and to explore the impact of age on those differences. Women had significantly higher mortality than men overall (adjusted odds ratio [AOR] = 1.15, 95% CI [1.04, 1.28]), and among patients aged 65 and older. Women had lower revascularization rates in general (AOR = 0.64 [0.59, 0.69]) and for all age groups. Among revascularized STEMI patients, women overall (AOR = 1.30 [1.10, 1.53]) and over 65 had higher mortality than men. Among patients not revascularized, women between the ages of 45 and 64 had lower mortality (AOR = 0.68 [0.48, 0.97]). CONCLUSIONS: Women with STEMI, and especially older women, had higher inhospital/30-day mortality rates than their male counterparts. Women had higher mortality among revascularized patients, but not among patients who were not revascularized.

Assessment of repeat target lesion percutaneous coronary intervention as a quality measure for public reporting and general quality assessment for PCIs.

BACKGROUND: Target lesion percutaneous coronary intervention (TLPCI) within 1 year of PCI has been proposed by critics of public reporting of short-term mortality as an alternative measure for PCI reporting. METHODS: New York's PCI registry was used to identify 1-year repeat TLPCI and 1-year repeat TLPCI/mortality for patients discharged between December 1, 2013 and November 30, 2014. Significant independent predictors of the outcomes were identified. Hospital and cardiologist risk-adjusted outcomes were calculated, and outlier status and correlations of risk-adjusted rates were examined for the three outcomes. RESULTS: The adverse outcome rates were 1.30, 4.21, and 8.97% for in-hospital/30-day mortality, 1-year repeat TLPCI, and 1-year repeat TLPCI/mortality. There were many commonalities but also many differences in significant predictors of the outcomes. Hospital and cardiologist risk-adjusted 1-year repeat TLPCI rates and repeat TLPCI/mortality rates were poorly correlated with risk-adjusted in-hospital/30-day mortality rates (eg, Spearman R = -.16 [p = .23] and .27 [p = .04], respectively, for hospital 1-year repeat TLPCI vs. in-hospital/30-day mortality). Many more providers were found to have significantly higher and lower rates for repeat TLPCI than for short-term mortality. CONCLUSIONS: Hospital and cardiologist quality assessments are very different for TLPCI and repeat TLPCI/mortality than they are for short-term mortality. Repeat TLPCI/mortality rates are highly correlated with repeat TLPCI rates, but outlier providers differ. More study of repeat TLPCI and all the patient, cardiologist, and hospital factors associated with it may be required before using it as a supplement to, or in lieu of, short-term mortality in public reporting of PCI outcomes.

Impact of Regionalization of ST-Segment-Elevation Myocardial Infarction Care on Treatment Times and Outcomes for Emergency Medical Services-Transported Patients Presenting to Hospitals With Percutaneous Coronary Intervention: Mission: Lifeline Accelerator-2.

BACKGROUND: Regional variations in reperfusion times and mortality in patients with ST-segment-elevation myocardial infarction are influenced by differences in coordinating care between emergency medical services (EMS) and hospitals. Building on the Accelerator-1 Project, we hypothesized that time to reperfusion could be further reduced with enhanced regional efforts. METHODS: Between April 2015 and March 2017, we worked with 12 metropolitan regions across the United States with 132 percutaneous coronary intervention-capable hospitals and 946 EMS agencies. Data were collected in the ACTION (Acute Coronary Treatment and Intervention Outcomes Network)-Get With The Guidelines Registry for quarterly Mission: Lifeline reports. The primary end point was the change in the proportion of EMS-transported patients with first medical contact to device time ≤90 minutes from baseline to final quarter. We also compared treatment times and mortality with patients treated in hospitals not participating in the project during the corresponding time period. RESULTS: During the study period, 10 730 patients were transported to percutaneous coronary intervention-capable hospitals, including 974 in the baseline quarter and 972 in the final quarter who met inclusion criteria. Median age was 61 years; 27% were women, 6% had cardiac arrest, and 6% had shock on admission; 10% were black, 12% were Latino, and 10% were uninsured. By the end of the intervention, all process measures reflecting coordination between EMS and hospitals had improved, including the proportion of patients with a first medical contact to device time of ≤90 minutes (67%-74%; P<0.002), a first medical contact to device time to catheterization laboratory activation of ≤20 minutes (38%-56%; P<0.0001), and emergency department dwell time of ≤20 minutes (33%-43%; P<0.0001). Of the 12 regions, 9 regions reduced first medical contact to device time, and 8 met or exceeded the national goal of 75% of patients treated in ≤90 minutes. Improvements in treatment times corresponded with a significant reduction in mortality (in-hospital death, 4.4%-2.3%; P=0.001) that was not apparent in hospitals not participating in the project during the same time period. CONCLUSIONS: Organization of care among EMS and hospitals in 12 regions was associated with significant reductions in time to reperfusion in patients with ST-segment-elevation myocardial infarction as well as in in-hospital mortality. These findings support a more intensive regional approach to emergency care for patients with ST-segment-elevation myocardial infarction.

Plasma Ceramides.

Objective- Ceramides are sphingolipids involved with cellular signaling. Synthesis of ceramides occurs in all tissues. Ceramides accumulate within tissues and the blood plasma during metabolic dysfunction, dyslipidemia, and inflammation. Elevations of ceramides are predictive of cardiovascular mortality. We sought to verify the utility of plasma concentrations of 4 ceramides: N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)], and N-lignoceroyl-sphingosine [Cer(24:0)] in predicting major adverse cardiovascular events in a diverse patient population referred for coronary angiography. Approach and Results- Plasma ceramides were measured in 495 participants before nonurgent coronary angiography. Coronary artery disease, defined as >50% stenosis in ≥1 coronary artery, was identified 265 (54%) cases. Ceramides were not significantly associated with coronary artery disease. Patients were followed for a combined primary end point of myocardial infarction, percutaneous intervention, coronary artery bypass, stroke, or death within 4 years. Ceramides were significantly predictive of outcomes after adjusting for age, sex, body mass index, hypertension, smoking, LDL (low-density lipoprotein) cholesterol, HDL (high-density lipoprotein) cholesterol, triglycerides, serum glucose, and family history of coronary artery disease. The fully adjusted per SD hazard ratios (95% confidence interval) were 1.50 (1.16-1.93) for Cer(16:0), 1.42 (1.11-1.83) for Cer(18:0), 1.43 (1.08-1.89) for Cer(24:1), and 1.58 (1.22-2.04) for the ceramide risk score. Conclusions- Elevated plasma concentrations of ceramides are independently associated with major adverse cardiovascular events in patients with and without coronary artery disease.

Regional Systems of Care Demonstration Project: American Heart Association Mission: Lifeline STEMI Systems Accelerator.

BACKGROUND: Up to 50% of patients fail to meet ST-segment-elevation myocardial infarction (STEMI) guideline goals recommending a first medical contact-to-device time of <90 minutes for patients directly presenting to percutaneous coronary intervention-capable hospitals and <120 minutes for transferred patients. We sought to increase the proportion of patients treated within guideline goals by organizing coordinated regional reperfusion plans. METHODS: We established leadership teams, coordinated protocols, and provided regular feedback for 484 hospitals and 1253 emergency medical services (EMS) agencies in 16 regions across the United States. RESULTS: Between July 2012 and December 2013, 23 809 patients presented with acute STEMI (direct to percutaneous coronary intervention hospital: 11 765 EMS transported and 6502 self-transported; 5542 transferred). EMS-transported patients differed from self-transported patients in symptom onset to first medical contact time (median, 47 versus 114 minutes), incidence of cardiac arrest (10% versus 3%), shock on admission (11% versus 3%), and in-hospital mortality (8% versus 3%; P<0.001 for all comparisons). There was a significant increase in the proportion of patients meeting guideline goals of first medical contact-to-device time, including those directly presenting via EMS (50% to 55%; P<0.001) and transferred patients (44%-48%; P=0.002). Despite regional variability, the greatest gains occurred among patients in the 5 most improved regions, increasing from 45% to 57% (direct EMS; P<0.001) and 38% to 50% (transfers; P<0.001). CONCLUSIONS: This Mission: Lifeline STEMI Systems Accelerator demonstration project represents the largest national effort to organize regional STEMI care. By focusing on first medical contact-to-device time, coordinated treatment protocols, and regional data collection and reporting, we were able to increase significantly the proportion of patients treated within guideline goals.

Incomplete revascularization for percutaneous coronary interventions: Variation among operators, and association with operator and hospital characteristics.

BACKGROUND: Many studies have compared outcomes for incomplete revascularization (IR) among patients undergoing percutaneous coronary interventions (PCIs), but little is known about the correlates of IR, the extent to which complete revascularization (CR) was attempted unsuccessfully, and the variation across operators in the use of IR. METHODS: New York's PCI registry was used to examine medium-term mortality for IR, the variables associated with the use of IR, and the variation across operators in the utilization of IR after controlling for patient factors. RESULTS: Incomplete revascularization occurred for 63% of all patients and was significantly associated with higher 3-year mortality (adjusted hazard ratio1.35, 95% CI 1.23-1.48) than for CR. A total of 96% of all attempted CRs were successful. Operators with 15 or fewer years in practice (the lowest half) used IR significantly more (65% vs 61%, adjusted odds ratio [AOR] 1.17, 95% CI 1.00-1.37) than other operators, and operators with annual volumes of 171 or lower (the lowest 3 quartiles) used IR more than other operators (68% vs 60%, AOR 1.35, 95% CI 1.14-1.59). Also, hospitals with annual volumes of 645 and lower (the lowest 50% of hospitals) used IR more (67% vs 62%, AOR 1.46, 95% CI 1.07-1.99) than other hospitals. CONCLUSIONS: Percutaneous coronary intervention patients without myocardial infarction who undergo IR continue to have higher medium-term (3-year) risk-adjusted mortality rates. There is a large amount of variability among operators in the frequency with which IR occurs. Operators who have been in practice longer, and higher-volume operators and hospitals have lower rates of IR. Failed attempts at CR occur very infrequently.

Influence of smoking on the antiplatelet effect of clopidogrel differs according to clopidogrel dose: Insights from the GRAVITAS trial.

OBJECTIVE: To examine the influence of smoking on the antiplatelet effect of clopidogrel following percutaneous coronary intervention (PCI). BACKGROUND: Certain studies suggest smokers may have enhanced clopidogrel-induced platelet inhibition compared to non-smokers after PCI. Whether this is affected by clopidogrel dose is unknown. METHODS: In this study, we conducted an analysis of 5,429 patients in the Gauging Responsiveness With A VerifyNow P2Y12 Assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Platelet reactivity was assessed 12-24 hr after PCI (baseline). Patients with high on-treatment platelet reactivity (OTR) (P2Y12 reaction units [PRU] ≥ 230) were randomized to clopidogrel 75 mg or 150 mg daily. Reactivity was subsequently assessed at 30-days, and 6-months. Patients were stratified by smoking status. RESULTS: Smoking was independently associated with lower PRU (P = 0.001), and smokers were less likely to have high OTR (odds ratio 0.80, 95% confidence interval 0.68-0.94; P = 0.006) at baseline. Among patients assigned to clopidogrel 75 mg, smokers had lower PRU and were less likely to still have high OTR at 30-days (P < 0.001) and 6-months (P < 0.001). However, in patients assigned clopidogrel 150 mg, PRU and high OTR did not differ by smoking status at any time. Tests demonstrated an interaction between smoking and dose at 30 days (P = 0.007), and a trend at 6-months (P = 0.098). CONCLUSIONS: Smokers treated with clopidogrel exhibit reduced platelet reactivity and are less likely to have persistent high OTR than non-smokers. This difference is mitigated by clopidogrel 150 mg, indicating non-smokers may require double-dose therapy to achieve a similar antiplatelet effect after PCI. © 2016 Wiley Periodicals, Inc.

Impact of pre-hospital electrocardiograms on time to treatment and one year outcome in a rural regional ST-segment elevation myocardial infarction network.

BACKGROUND: Pre-hospital electrocardiograms (ECGs) are believed to reduce time to reperfusion in ST Segment Elevation Myocardial Infarction (STEMI) patients. Little is known of their impact on clinical outcomes in a rural setting. Geisinger regional STEMI network provides percutaneous coronary intervention (PCI) care to over a 100-mile radius in rural central Pennsylvania. METHODS: A retrospective analysis identified 280 consecutive STEMI patients treated with PCI between 1/1/09 and 8/31/11. Comparison between two STEMI groups was performed: 205 patients who were taken by the emergency medical system (EMS) to the nearest hospital (a non-PCI center), underwent an ECG revealing a STEMI, and were transported immediately to Geisinger Medical Center (GMC) for PCI (transfer group) versus 75 patients in whom a pre-hospital ECG was obtained and who were transported by EMS directly to Geisinger for PCI, bypassing the nearest hospital that did not perform PCI (the pre-hospital ECG group). RESULTS: Analysis of baseline characteristics revealed that the pre-hospital ECG cohort was older (65 vs. 60 years); had a higher percentage of previous myocardial infarctions (MI) (28% vs. 15%), heart failure (11% vs. 4%), and prior PCI (23% vs. 13%; p < 0.05 all comparisons). Median time from EMS contact to pre-hospital ECG in the pre-hospital ECG group was 5 minutes; from pre-hospital ECG to the GMC ED was 34 minutes. Median time from first medical contact (EMS contact) to reperfusion (device activation) was 79 versus 157 minutes (P < 0.001), respectively in pre-hospital ECG vs. transfer groups. Mortality in the two groups at 1 year was 4.1% in the pre-hospital ECG group versus 8.3% in the transfer group (P-value = 0.34). After adjusting for the difference in age between the two groups, the 62% reduction in 1 year mortality associated with having obtained a pre-hospital ECG was still not statistically significant (P-value = 0.19). CONCLUSION: In a rural regional STEMI network, pre-hospital ECGs decreased time from first medical contact to reperfusion by 50% and were associated with an excellent clinical outcome at 1 year. © 2016 Wiley Periodicals, Inc.

Pre-treatment with P2Y12 inhibitors in ACS patients: who, when, why, and which agent?

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12receptor inhibitor is the mainstay of treatment for acute coronary syndrome (ACS) patients, whether they undergo a percutaneous coronary intervention (PCI) or are managed medically. In recent years, the most appropriate timing for initiation and duration of P2Y12receptor inhibition has been a focus of great interest. Many observational studies and a single prospective trial (CREDO) utilizing clopidogrel had focused on whether pre-treatment with clopidogrel, i.e. its administration upstream of coronary angiography and PCI, is beneficial. Although the rationale for pre-treatment is obvious, large-scale randomized trials supporting a pre-treatment strategy with clopidogrel or with the newer P2Y12inhibitors prasugrel and ticagrelor did not exist. Proponents of a pre-treatment strategy had to rely on their best guess, on non-randomized studies, or on negative studies in which a trend for a benefit had been demonstrated. Recently, however, two randomized trials directly evaluated the value of pre-treatment-one in patients with a non-STE elevation myocardial infarction (NSTEMI)-the Comparison of Prasugrel at the Time of Percutaneous Coronary Intervention or as Pretreatment at the Time of Diagnosis in Patients with Non-ST Elevation Myocardial Infarction (ACCOAST) trial, and a second trial evaluating the use of ticagrelor in ST-elevation myocardial infarction (STEMI) patients, the Administration of Ticagrelor in the Cath Lab or in the Ambulance for New ST-elevation myocardial Infarction to open the Coronary artery (ATLANTIC) trial. Neither of the two trials, however, answered all the questions clinicians have about pre-treatment. And given the recent approval of the intravenous and rapidly acting P2Y12inhibitor cangrelor, the choice of who should receive treatment with a P2Y12inhibitor, which one should be used, and when it should be administered, should be carefully re-evaluated for all patients. This clinical review aims at evaluating the available evidence regarding the value of pre-treatment with the now four available oral and intravenous P2Y12inhibitors that can be administered to patients in whom coronary angiography followed by a possible PCI is planned.

Appending Limited Clinical Data to an Administrative Database for Acute Myocardial Infarction Patients: The Impact on the Assessment of Hospital Quality.

BACKGROUND: Hospitals' risk-standardized mortality rates and outlier status (significantly higher/lower rates) are reported by the Centers for Medicare and Medicaid Services (CMS) for acute myocardial infarction (AMI) patients using Medicare claims data. New York now has AMI claims data with blood pressure and heart rate added. OBJECTIVE: The objective of this study was to see whether the appended database yields different hospital assessments than standard claims data. METHODS: New York State clinically appended claims data for AMI were used to create 2 different risk models based on CMS methods: 1 with and 1 without the added clinical data. Model discrimination was compared, and differences between the models in hospital outlier status and tertile status were examined. RESULTS: Mean arterial pressure and heart rate were both significant predictors of mortality in the clinically appended model. The C statistic for the model with the clinical variables added was significantly higher (0.803 vs. 0.773, P<0.001). The model without clinical variables identified 10 low outliers and all of them were percutaneous coronary intervention hospitals. When clinical variables were included in the model, only 6 of those 10 hospitals were low outliers, but there were 2 new low outliers. The model without clinical variables had only 3 high outliers, and the model with clinical variables included identified 2 new high outliers. CONCLUSION: Appending even a small number of clinical data elements to administrative data resulted in a difference in the assessment of hospital mortality outliers for AMI. The strategy of adding limited but important clinical data elements to administrative datasets should be considered when evaluating hospital quality for procedures and other medical conditions.

Contemporary use of platelet function and pharmacogenomic testing among patients with acute myocardial infarction undergoing percutaneous coronary intervention in the United States.

BACKGROUND: Although platelet function and pharmacogenomic testing have been studied in clinical trials, their adoption into contemporary practice is unknown. METHODS: We studied patterns of platelet function and pharmacogenomic testing among 10,048 patients with acute myocardial infarction treated with percutaneous coronary intervention at 226 US hospitals in the TRANSLATE-ACS observational study between April 2010 and October 2012, excluding those receiving research protocol-mandated testing. Inverse probability-weighted propensity adjustment was used to compare 1-year bleeding and major adverse cardiac event risks between patients with and without testing. RESULTS: Overall, 337 (3.4%) patients underwent predischarge platelet function testing, whereas 85 (0.9%) underwent pharmacogenomic testing; 82% and 93% of hospitals never performed any platelet function or pharmacogenomic testing, respectively. Patients undergoing testing were more likely to be on an adenosine diphosphate receptor inhibitor preadmission or to have percutaneous coronary intervention of a previously treated lesion. Tested patients were more likely than nontested patients to be switched from clopidogrel to prasugrel/ticagrelor (25.7% vs 9.7%, P < .001) and were more likely to be on prasugrel/ticagrelor 6 months postdischarge (33.8% vs 25.1%, P < .001). No significant differences in 1-year bleeding and major adverse cardiac event risks were observed between tested and nontested patients (adjusted hazard ratios 1.06 [95% CI 0.68-1.65] and 1.21 [95% CI 0.94-1.54], respectively). CONCLUSIONS: Platelet function and pharmacogenomic testing are rarely performed in contemporary myocardial infarction patients in the United States. When tested, patients were more likely to be treated with higher-potency adenosine diphosphate receptor inhibitors, yet no significant differences in longitudinal outcomes were observed.

Assessing hospital performance for acute myocardial infarction: how should emergency department transfers be attributed.

BACKGROUND: The Centers for Medicare and Medicaid Services publicly reports risk-standardized mortality rates (RSMRs) to assess quality of care for hospitals that treat acute myocardial infarction patients, and the outcomes for inpatient transfers are attributed to transferring hospitals. However, emergency department (ED) transfers are currently ignored and therefore attributed to receiving hospitals. METHODS: New York State administrative data were used to develop a statistical model similar to the one used by Centers for Medicare and Medicaid Services to risk-adjust hospital 30-day mortality rates. RSMRs were calculated and outliers were identified when ED transfers were attributed to: (1) the transferring hospital and (2) the receiving hospital. Differences in hospital outlier status and RSMR tertile between the 2 attribution methods were noted for hospitals performing and not performing percutaneous coronary interventions (PCIs). RESULTS: Although both methods of attribution identified 3 high outlier non-PCI hospitals, only 2 of those hospitals were identified by both methods, and each method identified a different hospital as a third outlier. Also, when transfers were attributed to the referring hospital, 1 non-PCI hospital was identified as a low outlier, and no non-PCI hospitals were identified as a low outlier with the other attribution method. About one sixth of all hospitals changed their tertile status. Most PCI hospitals (89%) that changed status moved to a higher (worse RSMR) tertile, whereas the majority of non-PCI hospitals (68%) that changed status were moved to a lower (better) RSMR tertile when ED transfers were attributed to the referring hospital. CONCLUSIONS: Hospital quality assessments for acute myocardial infarction are affected by whether ED transfers are assigned to the transferring or receiving hospital. The pros and cons of this choice should be considered.

Does Preoperative Platelet Function Predict Bleeding in Patients Undergoing Off Pump Coronary Artery Bypass Surgery?

OBJECTIVE: We sought to examine the relationship between preoperative platelet function and perioperative bleeding in patients undergoing CABG. BACKGROUND: There are many ways to measure platelet aggregability. Little is known about their correlations with one another, or with bleeding. METHODS: We prospectively studied 50 patients undergoing a first isolated off-pump CABG. Thirty-four were exposed to a thienopyridine prior to surgery; 16 were not. Preoperative platelet function was measured by VerifyNow®, TEG®, AggreGuide™, Plateletworks®, vasodilator-stimulated phosphoprotein (VASP) phosphorylation, and light transmission aggregometry. Bleeding was assessed 2 ways: drop from pre- to nadir postoperative hematocrit, and chest tube drainage. Correlation coefficients were calculated using Spearman's rank-order correlation. RESULTS: Mean age was 62 years. Patient characteristics and surgical details were similar between the thienopyridine-exposed and non-exposed patients. The correlation coefficients between the 4 point-of-care platelet function measurements and hematocrit change ranged from -0.2274 to 0.2882. Only Plateletworks® correlated with drop in hematocrit (r = 0.2882, P = 0.0470). The correlation coefficients between each of the 4 point-of-care platelet function tests and the chest tube drainage were also poor, ranging from -0.3073 to 0.2272. Both AggreGuide™ (r = -0.3073, P = 0.0317) and VASP (r = -0.3187, P = 0.0272) were weakly but significantly correlated with chest tube drainage. The correlation among the 4 point-of-care platelet function measurements was poor, with coefficients ranging from -0.2504 to 0.1968. CONCLUSIONS: We observed little correlation among 4 platelet function tests, and between those assays and perioperative bleeding defined 2 different ways. Whether any of these assays should be used to guide decision making in individual patients is unclear.

Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study.

BACKGROUND: Dual antiplatelet therapy (DAPT) cessation increases the risk of adverse events after percutaneous coronary intervention (PCI). Whether risk changes over time, depends on the underlying reason for DAPT cessation, or both is unknown. We assessed associations between different modes of DAPT cessation and cardiovascular risk after PCI. METHODS: The PARIS (patterns of non-adherence to anti-platelet regimens in stented patients) registry is a prospective observational study of patients undergoing PCI with stent implantation in 15 clinical sites in the USA and Europe between July 1, 2009, and Dec 2, 2010. Adult patients (aged 18 years or older) undergoing successful stent implantation in one or more native coronary artery and discharged on DAPT were eligible for enrolment. Patients were followed up at months 1, 6, 12, and 24 after implantation. Prespecified categories for DAPT cessation included physician-recommended discontinuation, brief interruption (for surgery), or disruption (non-compliance or because of bleeding). All adverse events and episodes of DAPT cessation were independently adjudicated. Using Cox models with time-varying covariates, we examined the effect of DAPT cessation on major adverse events (MACE [composite of cardiac death, definite or probable stent thrombosis, myocardial infarction, or target-lesion revascularisation]). Incidence rates for DAPT cessation and adverse events were calculated as Kaplan-Meier estimates of time to the first event. This study is registered with ClinicalTrials.gov, number NCT00998127. FINDINGS: We enrolled 5031 patients undergoing PCI, including 5018 in the final study population. Over 2 years, the overall incidence of any DAPT cessation was 57·3%. Rate of any discontinuation was 40·8%, of interruption was 10·5%, and of disruption was 14·4%. The corresponding overall 2 year MACE rate was 11·5%, most of which (74%) occurred while patients were taking DAPT. Compared with those on DAPT, the adjusted hazard ratio (HR) for MACE due to interruption was 1·41 (95% CI 0·94-2·12; p=0·10) and to disruption was 1·50 (1·14-1.97; p=0·004). Within 7 days, 8-30 days, and more than 30 days after disruption, adjusted HRs were 7·04 (3·31-14·95), 2·17 (0·97-4·88), and 1·3 (0·97-1·76), respectively. By contrast with patients who remained on DAPT, those who discontinued had lower MACE risk (0·63 [0·46-0·86]). Results were similar after excluding patients receiving bare metal stents and using an alternative MACE definition that did not include target lesion revascularisation. INTERPRETATION: In a real-world setting, for patients undergoing PCI and discharged on DAPT, cardiac events after DAPT cessation depend on the clinical circumstance and reason for cessation and attenuates over time. While most events after PCI occur in patients on DAPT, early risk for events due to disruption is substantial irrespective of stent type. FUNDING: Bristol-Myers Squibb and Sanofi-Aventis.

Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction.

BACKGROUND: The combination of glycoprotein IIb/IIIa inhibitors and heparin has not been compared with bivalirudin in studies specifically involving patients with non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). We compared the two treatments in this patient population. METHODS: Immediately before PCI, we randomly assigned, in a double-blind manner, 1721 patients with acute non-ST-segment elevation myocardial infarction to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study tested the hypothesis that abciximab and heparin would be superior to bivalirudin with respect to the primary composite end point of death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. Secondary end points included the composite of death, any recurrent myocardial infarction, or urgent target-vessel revascularization (efficacy end point) and major bleeding (safety end point) within 30 days. RESULTS: The primary end point occurred in 10.9% of the patients in the abciximab group (94 patients) and in 11.0% in the bivalirudin group (95 patients) (relative risk with abciximab, 0.99; 95% confidence interval [CI], 0.74 to 1.32; P=0.94). Death, any recurrent myocardial infarction, or urgent target-vessel revascularization occurred in 12.8% of the patients in the abciximab group (110 patients) and in 13.4% in the bivalirudin group (115 patients) (relative risk, 0.96; 95% CI, 0.74 to 1.25; P=0.76). Major bleeding occurred in 4.6% of the patients in the abciximab group (40 patients) as compared with 2.6% in the bivalirudin group (22 patients) (relative risk, 1.84; 95% CI, 1.10 to 3.07; P=0.02). CONCLUSIONS: Abciximab and unfractionated heparin, as compared with bivalirudin, failed to reduce the rate of the primary end point and increased the risk of bleeding among patients with non-ST-segment elevation myocardial infarction who were undergoing PCI. (Funded by Nycomed Pharma and others; ISAR-REACT 4 ClinicalTrials.gov number, NCT00373451.).

Safety of coronary angiography and percutaneous coronary intervention via the radial versus femoral route in patients on uninterrupted oral anticoagulation with warfarin.

OBJECTIVE: To evaluate access site and other bleeding complications associated with radial versus femoral access in patients receiving oral anticoagulation (OAC) with warfarin. BACKGROUND: Patients receiving OAC with warfarin undergoing coronary angiography and percutaneous coronary intervention (PCI) may have OAC continued despite the risk of bleeding. To what extent arterial access site impacts bleeding in such patients is not well studied. METHODS: Over 6 years, we identified 255 consecutive patients in whom warfarin was continued who underwent coronary angiography with an international normalized ratio >1.8. A total of 97 patients also underwent PCI at the same setting (27% femoral vs 73% radial). The primary outcome was Bleeding Academic Research Consortium bleeds; a secondary end point was frequency of access site complications in the 72 hours post-PCI. Complications were evaluated based on the initial access site attempted. RESULTS: Minimal baseline clinical characteristics differences existed between the groups. International normalized ratio was significantly higher in the radial group (2.42 ± 0.67 vs 2.24 ± 0.49, P = .02). Bivalirudin use was greater during radial PCI than femoral (76% vs 42%, P < .05), whereas unfractionated heparin alone was greater during femoral PCI than radial (46% vs 18%, P < .05). No significant difference was seen in the primary end point between femoral (2.8%) and radial (1.6%, P = .54) during coronary angiography alone. However, PCI via the femoral artery had significantly more Bleeding Academic Research Consortium bleeding (19.2% vs 1.4%, P = .005) and transfusions (15% vs 0%, P = .004) than via the radial artery. Patients who underwent PCI using radial access were less likely to have any vascular or bleeding complications (1% vs 23%, P = .001). CONCLUSIONS: Patients who underwent coronary angiography during uninterrupted OAC had similar bleeding rates regardless of access site. However, when PCI was performed, radial access was associated with fewer bleeding and vascular complications than the femoral approach. CONDENSED ABSTRACT: We retrospectively identified 255 consecutive patients on warfarin who underwent coronary angiography, 97 of whom underwent a percutaneous coronary intervention. The data reveal a reduction in Bleeding Academic Research Consortium bleeds (1.6% vs 8.1%, P = .02) with radial versus femoral access. The radial approach was associated with an overall lower rate of any vascular or bleeding complication than the femoral approach during percutaneous coronary intervention (1% vs 23%, P = .001).

Would tirofiban have been shown non-inferior to abciximab had the TENACITY trial not been terminated for financial reasons?

OBJECTIVES: To investigate whether tirofiban would have been non-inferior to abciximab had the trial completed enrollment and place the termination of this trial in a broader research ethics context. BACKGROUND: TENACITY was terminated by the sponsor for financial reasons. At the time, event rates for the 2 treatment arms were unknown. METHODS: TENACITY was designed to compare tirofiban with abciximab in approximately 8,000 patients; however, enrollment was terminated after 383 (4.8%) patients. The primary end-point was a composite of 30-day death, myocardial infarction, and urgent target vessel revascularization. Non-inferiority was defined as the likelihood that tirofiban would preserve at least 50% of the ability of abciximab to reduce the primary end-point at 30 days, based on abciximab's demonstrated ability to reduce such events by 43% (relative risk, 0.573; 95% confidence interval [CI], 0.507-0.648; P < 0.001). To determine the probability of non-inferiority given the patients already enrolled, a Bayesian approach was used. RESULTS: The primary composite end-point occurred in 8.8% of patients randomized to abciximab versus 6.9% receiving high-bolus-dose tirofiban (odds ratio, 0.77; 95% CI, 0.37-1.64). The estimated conditional power for the test that tirofiban would be non-inferior to abciximab if all patients been enrolled is 93.7%. Using the estimated predictive power method, the likelihood was 84.8%. CONCLUSIONS: TENACITY was well powered to identify non-inferiority with tirofiban versus abciximab, and the patients enrolled strengthened the probability that this would have been the outcome had the trial been completed. When a clinical trial is terminated solely for financial reasons, it is incumbent upon the sponsor to provide proper patient follow-up and publication of the findings.

Collagen plug vascular closure devices and reduced risk of bleeding with bivalirudin versus heparin plus abciximab in patients undergoing percutaneous coronary intervention for non st-segment elevation myocardial infarction.

INTRODUCTION: In ISAR-REACT-4 (abciximab and heparin vs. bivalirudin for non-ST-elevation myocardial infarction [NSTEMI]), bivalirudin reduced the risk of bleeding after percutaneous coronary intervention (PCI) compared with unfractionated heparin plus abciximab (UFH + abciximab). Vascular closure devices (VCDs) may also prevent bleeding complications, and thus attenuate the benefit of bivalirudin. This analysis examined whether there exists an interaction on bleeding between VCDs and bivalirudin versus UFH + abciximab after PCI. METHODS: Patients with NSTEMI were randomly assigned to either receive UFH + abciximab or bivalirudin for PCI. The use of a VCD after femoral access was left to the operator's discretion. The effect of randomized treatment in patients who received a VCD was compared to that in patients with manual compression of the femoral access site. The primary end-point of this analysis was the 30-day incidence of ISAR-REACT-4 major bleeding. RESULTS: A total of 1,711 patients were enrolled in this analysis. Among the 365 (21.3%) patients receiving a VCD, 188 (51.5%) were treated with UFH + abciximab and 177 (48.5%) with bivalirudin. ISAR- REACT-4 major bleeding was higher with UFH + abciximab than with bivalirudin, independent of whether a VCD was used (4.8% vs. 2.3% with VCD and 4.6% vs. 2.7% without VCD, Pint = 0.76). There were also no interactions between randomized treatment and VCDs with respect to any of the ischemic end-points or net clinical outcome (Pint > 0.56). CONCLUSIONS: In patients undergoing PCI for NSTEMI, the reduction of major bleeding by bivalirudin compared with UFH + abciximab was not affected whether a VCD was used.