Nonemergent Percutaneous Coronary Intervention Research Articles

Effects of pretreatment with clopidogrel on nonemergent percutaneous coronary intervention after fibrinolytic administration for ST-segment elevation myocardial infarction: A Clopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis in Myocardial Infarction (CLARITY-TIMI) 28 study

The use of routine nonemergent percutaneous coronary intervention (PCI) among patients with ST-segment elevation myocardial infarction (STEMI) after fibrinolytic therapy is unknown. We sought to evaluate the effect of nonemergent PCI on mortality among patients with STEMI treated with fibrinolytic administration and the consequence of clopidogrel pretreatment on this effect. CLARITY-TIMI 28 randomized 3491 patients with STEMI treated with fibrinolytic administration and aspirin to clopidogrel or placebo. All patients were to undergo angiography 48 to 192 hours after randomization. Percutaneous coronary intervention was performed at the discretion of the treating physician. Nonemergent PCI, which was defined as PCI that was not precipitated by recurrent myocardial infarction, was performed in 1781 patients (55.7%). Nonemergent PCI did not affect 30-day mortality (2.0% vs 2.3% among patients who did not undergo PCI). However, nonemergent PCI was associated with lower mortality among patients randomized to clopidogrel (1.3% vs 2.8%, P = .04) but not among those randomized to placebo (2.6% vs 1.7%, P = .25; interaction P = .025). In multivariate modeling, PCI remained associated with lower mortality among patients randomized to clopidogrel (OR 0.34, 95% CI 0.13-0.92, P = .034) but not placebo (OR 1.41, 95% CI 0.63-3.19, P = .40, interaction P = .028). Among patients with STEMI treated with fibrinolytic administration and aspirin, nonemergent PCI was associated with lower mortality among patients pretreated with clopidogrel. These results suggest that routine nonemergent PCI is beneficial among such patients, although further confirmatory randomized studies are needed.

Abstract 3472: The Prediction of Ischemic Events After Percutaneous Coronary Intervention by Platelet Reactivity to Adenosine Diphosphate: First Evidence for an Oral Antiplatelet Therapeutic Target Determined by an Ex Vivo Test of Platelet Function.

Background: High on-treatment platelet reactivity to adenosine diphosphate (HPR-ADP) may be a risk factor for ischemic events after percutaneous coronary intervention (PCI). We determined whether a cutpoint of HPR-ADP, similar to the INR used to guide anticoagulant therapy, could predict ischemic event occurrence after PCI. Methods : Post-procedural platelet reactivity to ADP was measured by conventional aggregometry in 352 consecutive patients undergoing non-emergent PCI followed for up to 2 years for post-discharge ischemic events. All patients had received clopidogrel and aspirin therapy at the time of aggregation measurements. Results: Eighty-two patients (23%) suffered ischemic events and had higher 5 and 20 μM ADP-induced aggregation compared to patients without ischemic events (46 ± 14% and 60 ± 13% versus 30 ± 17% and 43 ± 19%, respectively, p<0.0001 for both measurements). Using a combined receiver operator curve analysis, HPR-ADP cutpoints of 46% aggregation following 5μM ADP stimulation and 59% aggregation following 20μM ADP stimulation were associated with 63% and 74% of ischemic events, respectively. Multivariate Cox regression demonstrated significance between events and post-procedural HPR-ADP cutpoints (20μM ADP, OR=8.6, p<0.0001; and 5μM ADP, OR=2.9, p=0.01). Conclusions: High on-treatment platelet reactivity to ADP is an independent risk factor for ischemic events within 2 years of non-emergent PCI. These data are the first to support a therapeutic target for antiplatelet therapy based on an ex vivo platelet function test, similar to the INR used for anticoagulant therapy. The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy.

Increased Risk in Patients With High Platelet Aggregation Receiving Chronic Clopidogrel Therapy Undergoing Percutaneous Coronary Intervention: Is the Current Antiplatelet Therapy Adequate?

We sought to determine whether patients receiving chronic clopidogrel therapy undergoing nonemergent stenting who display high on-treatment preprocedural platelet aggregation measured by standard light transmittance aggregometry and thrombelastography (TEG) will be at increased risk for poststenting ischemic events. Patients exhibiting heightened platelet reactivity to adenosine diphosphate (ADP) might be at increased risk for recurrent ischemic events after coronary stenting. A total of 100 consecutive patients receiving chronic antiplatelet therapy consisting of aspirin (325 mg qd) and clopidogrel (75 mg qd) were studied before undergoing nonemergent stenting. Patients were followed for 1 year after coronary stenting for the occurrence of death, myocardial infarction, stent thrombosis, stroke, or ischemia requiring a hospital stay. All patients were aspirin responsive. Patients with ischemic events (23 of 100, 23%) within 1 year had greater on-treatment prestent ADP-induced platelet aggregation than patients without ischemic events by aggregometry and TEG (p < 0.001 for both measurements). Of patients with an ischemic event, 70% and 87% displayed high on-treatment platelet reactivity at baseline by aggregometry and TEG, respectively. High on-treatment platelet reactivity as measured by aggregometry and TEG were the only variables significantly related to ischemic events (p < 0.001 for both assays). The administration of eptifibatide reduced periprocedural elevation in platelet reactivity, with no significant differences in bleeding events. Patients receiving chronic clopidogrel therapy undergoing nonemergent percutaneous coronary intervention who exhibit high on-treatment ADP-induced platelet aggregation are at increased risk for postprocedural ischemic events. These findings might have implications for the alteration in clopidogrel maintenance dose and use of glycoprotein IIb/IIIa inhibitors in selected patients.

Nonemergent percutaneous coronary interventions in a veterans affairs medical center without onsite cardiac surgery

Percutaneous coronary intervention (PCI) performed in centers without onsite cardiac surgery remains controversial. Advances in PCI techniques and medical therapy have markedly decreased postprocedural complications. Our aim was to assess the efficacy and safety of performing PCI in the Veterans Affairs patient population in a hospital without onsite cardiac surgery. We prospectively evaluated 401 consecutive patients who underwent elective PCI or PCI after admission for acute coronary syndrome. Patients who had ST-elevation myocardial infarction or were hemodynamically unstable were classified as emergent and had their PCI performed elsewhere and were therefore excluded from our analysis. Our cardiac surgery backup was a community hospital 8 miles away. The patient's mean age was 65.6 +/- 10 years, and most were men (99.5%). Patients had high-risk clinical and angiographic profiles, with diabetes mellitus in 44%, prior myocardial infarction in 41%, comorbid conditions in 45% and type B or C angiographic lesions in 83%. Of 401 patients, 338 (84%) received a stent, and 86 (21%), a drug eluting stent. Percutaneous coronary intervention success rate was 97%. There were no periprocedural or inhospital deaths, and no patients required emergency transfer for cardiac surgery. At 1 and 6 months of follow-up, total mortality was 1.5% and 3.5%, respectively; target vessel revascularization rate was 0% and 1.7%. Nonemergent PCI can be performed effectively and safely in patients with higher clinical and angiographic risk without onsite backup cardiac surgery. This has significant implications for most hospitals that have an invasive but not an interventional program.

Isolated Elevation in Troponin T After Percutaneous Coronary Intervention Is Associated With Higher Long-Term Mortality

The aim of this study was to evaluate whether, in patients with normal post-procedure CK-MB, an isolated elevation in cardiac troponin T (cTnT) predicts long-term survival. Cardiac troponin T is a sensitive and specific marker of myonecrosis. There is little known about the incidence and prognostic significance of an isolated elevation of cTnT without a rise in creatine kinase (CK)-MB following PCI. We evaluated the outcomes of 1,949 patients from the Mayo Clinic registry who had normal pre-procedure cTnT and CK-MB, required nonemergency percutaneous coronary intervention (PCI), and had normal CK-MB after the procedure. An elevation in cTnT (cTnT+) was observed in 383 patients (19.6%) (median 0.04 ng/ml, interquartile range 0.03 to 0.06 ng/ml). The TnT+ status was associated with adverse clinical and angiographic characteristics, and multivessel PCI. Over the median follow-up duration of 26 months, mortality (p < 0.001) and the combined rate of death and myocardial infarction (p = 0.004) were significantly higher in cTnT+ patients. Estimated 3-year survival for those with and without cTnT elevation was 86.9% and 93.2%, respectively. By multivariate analysis, an elevation in cTnT after PCI was an independent predictor of increased long-term mortality. A doubling in the post-PCI cTnT was associated with a partial hazard ratio of 1.20 (95% confidence interval 1.02 to 1.40; p = 0.023). An isolated minor elevation in cTnT after PCI provides long-term prognostic information regarding mortality and myocardial infarction.

Changes in health-related quality of life following percutaneous coronary intervention: A longitudinal study

Background Coronary artery disease (CAD) is a major cause of mortality and morbidity in developed countries. The percutaneous coronary intervention (PCI) is a frequently used treatment for CAD. In order to manage the disease more effectively and to promote the health-related quality of life (HRQoL) of these patients, understanding the current status of HRQoL before and after PCI procedure is essential. Objectives This study was to examine the changes of HRQoL from before PCI to the first 3 months after PCI on Hong Kong Chinese. Design A longitudinal, one-group observational design was used. Setting Data collected from cardiac patients admitted into a regional public hospital at Hong Kong Island for PCI. Participants Between August 2003 and February 2004, all patients admitted for non-emergency PCI at the study site and met the inclusion criteria were invited to take part in the study. Seventy-eight out of 85 eligible patients agreed to participate. However, 13 patients dropped out during data collection period. Methods HRQoL data using the Medical Outcomes Study 36-Item Short Form 36 (SF-36) and Seattle Angina Questionnaire (SAQ) were collected before PCI, 1 and 3 months after PCI. Results Sixty-five patents completed the study. All domains in SF-36 and SAQ improved at 1 month but the improvements did not continue in all domains at 3 months. The HRQoL measured by SF-36 improved significantly over time ( p<0.05) for six out of the eight domains. Scores of all domains of SF-36 improved at 3 months when compared with baseline. Moreover, all five domains of SAQ changed significantly over time ( p<0.05); however, the score of angina stability at the third month was lower than that at baseline. Conclusions The results of this study quantify the benefits of PCI procedure on HRQoL of patients. Although PCI improved the HRQoL 1 month after PCI, the effect did not last long. Nursing interventions are needed to maintain and further enhance the HRQoL of these patients and the interventions should be introduced immediately post-PCI.

Clopidogrel Treatment Prior to Percutaneous Coronary Intervention

WORLDWIDE, MORE THAN 2 MILLION PATIENTS WILL be treated with a percutaneous coronary intervention (PCI) this year, with approximately half of these performed in the United States. For almost three fourths of these patients, the diagnosis necessitating the procedure will be an acute coronary syndrome (ACS)—eitherunstableanginaoramyocardial infarction(MI). Inhibitors of platelet function are a critical component of peri-PCI pharmacological therapy. Aspirin, although initially viewed as a weak agent with minimal potential to prevent acute thrombotic events, has been shown in a placebocontrolled trial to decrease the incidence of Q-wave MIs by 75% compared with heparin alone during coronary angioplasty. However, with aspirin alone, thrombotic complications following PCI remained unacceptably high. To address this, the platelet glycoprotein (Gp) IIb/IIIa antagonists were developed as a means to effectively prevent platelet aggregation and its associated complications. Abciximab, eptifibatide, and tirofiban were studied in several placebocontrolled trials involving nearly 17 000 patients undergoing nonemergent PCI. In the Evaluation of Platelet IIb/IIIa Inhibitor for Stenting (EPISTENT) and Enhanced Suppression of the Platelet IIb/IIIa Receptor with Integrilin Therapy (ESPRIT) trials, randomization of stented patients to receive either abciximab or eptifibatide was found to decrease rates of 30-day death, MI, or urgent target vessel revascularization by 52% and 35%, respectively, compared with placebo. Importantly, this relative risk reduction was similar for patients diagnosed with stable angina or an ACS. Since no other antiplatelet agents were available clinically that prevented platelet aggregation as completely and as quickly as the Gp IIb/IIIa antagonists, it was assumed that no other antiplatelet regimen would be as effective in preventing periPCI thrombotic events. But soon after long-term post-PCI treatment with thienopyridines—initially ticlopidine and then clopidogrel—became standard care in patients receiving stents, limited reports began to emerge suggesting that pretreatment with these agents might also protect patients from periprocedural events. Although a subsequent randomized, placebo-controlled trial failed toconfirmthis benefit, retrospective analysis suggested that adequate durations of pretreatment achieved an approximately 50% relative risk reduction in the incidence of 28-day death, MI, or urgent target vessel revascularization. This level of benefit for clopidogrel pretreatment was consistent with that found in subset analyses in both the PCI-Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY) and PCI-Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trials. These highly suggestive but nondefinitive results regarding the clinical benefit of clopidogrel pretreatment set the stage for a series of influential studies by the Intracoronary Stenting and Antithrombotic Regimen (ISAR) group to establish the optimal antiplatelet regimen in a broad range of patients undergoing PCI. Using a 600-mg clopidogrel loading dose given at least 2 hours prior to a PCI in all patients, the investigators systematically studied the additional benefit of adjunctive abciximab in lowto intermediate-risk patients undergoing PCI, in patients undergoing revascularization of small-diameter ( 2.5 mm) vessels, and in patients with diabetes. In all of these trials, abciximab was not found to provide even a trend toward additional benefit when given in addition to adequate pretreatment with clopidogrel. However, a large and critically important subgroup of patients was excluded from these studies—those presenting with an ACS. Not only do these patients represent the majority of patients treated with a PCI, but they are also a group of patients that most data suggest may derive the greatest benefit from adjunctive therapy with Gp IIb/IIIa antagonists. In this issue of JAMA, the ISAR investigators close this remaining gap. The ISAR-REACT 2 trial is similar in design to the previous ISAR trial, but it enrolled only patients with objective evidence of an ACS as manifest by anginal symptoms at rest or with minimal exertion accompanied by an elevated level of troponin T or by a new ST-segment deviation or bundle-branch block. Just more than half of the 2022 patients enrolled had elevated troponin levels. In contrast to previous ISAR studies, randomization to abciximab was associated with a significant 25% relative risk reduction in the 30-day combined end point of death, MI, or urgent target vessel revascularization. Interestingly, all of this benefit was con-

Prepercutaneous Coronary Intervention Plasma Homocysteine Concentration Is a Useful Predictor of Angioplasty-Induced Myocardial Damage

Plasma homocysteine is a modifiable cardiovascular risk factor related to the extent of both coronary and carotid atherosclerosis (1)(2)(3)(4). Plasma homocysteine has been shown to predict the occurrence of cardiac events and mortality in patients with coronary atherosclerosis (5)(6)(7). The predictive value of homocysteine on restenosis after percutaneous coronary intervention (PCI) has been debated (8)(9)(10). Recent evidence, however, indicated that the pre-PCI homocysteine plasma concentration was an independent predictor of death, nonfatal myocardial infarction (MI), and target lesion revascularization (11). Cardiac troponins provide prognostic information in patients with acute coronary syndrome (ACS) (12). Several studies have demonstrated that PCI induces MI as assessed by increases in cardiac troponins, particularly in the case of ACS (13)(14)(15). Furthermore, increased cardiac troponin concentrations after PCI are associated with poor clinical outcome (16)(17)(18)(19). We therefore hypothesized that the pre-PCI plasma homocysteine concentration could be related to the occurrence of MI after PCI, as assessed by changes in plasma cardiac troponin I (cTnI) concentration. Consecutive admissions for nonemergency PCI were studied prospectively. All patients had a stenosis >70% in 1 or more coronary arteries. Two groups were examined: patients with stable angina (SA) pain and those with ACS. The SA pain group had myocardial ischemia during exercise stress testing (n = 29). The ACS group included patients admitted with unstable angina without a subsequent increase in troponin concentrations (n = 28) and those with a definite MI with a documented cTnI increase and electrocardiogram changes that had occurred 7–14 days previously (n = 39). Patients with inflammatory diseases, as well as those being treated with corticosteroids or nonsteroidal antiinflammatory or immunosuppressive drugs, were excluded to minimize potential bias. This study complies …

Nonemergent Percutaneous Coronary Intervention With Off-Site Surgery Backup

Nonemergent primary coronary intervention (PCI) at hospitals with off-site cardiac surgery backup is currently given a "Class III" indication by the American College of Cardiology/American Heart Association (ACC/AHA) PCI Guidelines on the basis of "consensus opinion of experts," not on trials or studies (Level of Evidence C). Yet the evidence is mounting, both in the US and abroad, that urgent and elective PCI can be performed safely and effectively at qualified nonsurgical hospitals in controlled circumstances. As the need for PCI grows, especially in the large population with high-risk acute coronary syndromes (ACS), the lack of local access to and underutilization of timely PCI can demonstrably result in inferior outcomes. The multiple clinical, performance, and economic advantages of the broader availability of PCI are discussed extensively in this paper. Removing the requirement for on-site cardiac surgery from nonemergent PCI can also increase procedural volumes at the growing numbers of primary angioplasty programs at hospitals with off-site backup, while also reducing the pressure to build new low-volume cardiac surgery programs merely to support PCI programs. The many US hospitals that are already participating in this growing movement to provide PCI with off-site backup are encouraged to enroll in the ACC National Cardiovascular Data Registry to assure that this strategy is fairly assessed and monitored on a national level. We anticipate that state regulations and national guidelines will continue to evolve and keep pace with this growing movement and with the already-evolving guidelines from abroad.

Safety of coronary stenting with eptifibatide and ultra-low-dose heparin

With the advent of multiple potent antiplatelet and anticoagulation agents in percutaneous coronary intervention (PCI), the risk of bleeding complications has increased. The optimal dose of unfractionated heparin in this setting is unclear. This study was designed to determine the feasibility and safety of PCI with an ultra-low-dose weight-adjusted unfractionated heparin regimen (30 IU/kg bolus, maximum 3,000 IU) in combination with aspirin, clopidogrel, and eptifibatide. We enrolled 83 patients who underwent nonemergency PCI of native coronary arteries. At 30 days, all patients were free of the primary clinical outcomes defined as a composite of death, myocardial infarction, or repeat target vessel revascularization, and there were no major bleeding complications.

Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for percutaneous coronary interventionResults from the REPLACE-2 trial

The purpose of this study was to compare the cost of percutaneous coronary intervention (PCI) using bivalirudin with provisional platelet glycoprotein (GP) IIb/IIIa inhibition with that of heparin + routine GP IIb/IIIa inhibition. Although GP IIb/IIIa inhibition has been shown to reduce ischemic complications in a broad range of patients undergoing PCI, many patients currently do not receive such therapy because of concerns about bleeding complications or cost. Recently, bivalirudin with provisional GP IIb/IIIa inhibition has been validated as an alternative to heparin + routine GP IIb/IIIa inhibition for patients undergoing PCI. However, the cost-effectiveness of this novel strategy is unknown. In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, 4,651 U.S. patients undergoing non-emergent PCI were randomized to receive bivalirudin with provisional GP IIb/IIIa (n = 2,319) versus heparin + routine GP IIb/IIIa (n = 2,332). Resource utilization data were collected prospectively through 30-day follow-up on all U.S. patients. Medical care costs were estimated using standard methods including bottom-up accounting (for procedural costs), the Medicare fee schedule (for physician services), hospital billing data (for 2,821 of 4,862 admissions), and regression-based approaches for the remaining hospitalizations. Among the bivalirudin group, 7.7% required provisional GP IIb/IIIa. Thirty-day ischemic outcomes including death or myocardial infarction were similar for the bivalirudin and GP IIb/IIIa groups, but bivalirudin resulted in lower rates of major bleeding (2.8% vs. 4.5%, p = 0.002) and minor bleeding (15.1% vs. 28.1%, p &lt; 0.001). Compared with routine GP IIb/IIIa, in-hospital and 30-day costs were reduced by $405 (95% confidence interval [CI] $37 to $773) and $374 (95% CI $61 to $688) per patient with bivalirudin (p &lt; 0.001 for both). Regression modeling demonstrated that, in addition to the costs of the anticoagulants themselves, hospital savings were due primarily to reductions in major bleeding (cost savings = $107/patient), minor bleeding ($52/patient), and thrombocytopenia ($47/patient). Compared with heparin + routine GP IIb/IIIa inhibition, bivalirudin + provisional GP IIb/IIIa inhibition resulted in similar acute ischemic events and cost savings of $375 to $400/patient depending on the analytic perspective.

Economic evaluation of bivalirudin with provisional glycoprotein IIB/IIIA inhibition versus heparin with routine glycoprotein IIB/IIIA inhibition for percutaneous coronary intervention: Results from the REPLACE-2 trial

The purpose of this study was to compare the cost of percutaneous coronary intervention (PCI) using bivalirudin with provisional platelet glycoprotein (GP) IIb/IIIa inhibition with that of heparin + routine GP IIb/IIIa inhibition. Although GP IIb/IIIa inhibition has been shown to reduce ischemic complications in a broad range of patients undergoing PCI, many patients currently do not receive such therapy because of concerns about bleeding complications or cost. Recently, bivalirudin with provisional GP IIb/IIIa inhibition has been validated as an alternative to heparin + routine GP IIb/IIIa inhibition for patients undergoing PCI. However, the cost-effectiveness of this novel strategy is unknown. In the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE)-2 trial, 4,651 U.S. patients undergoing non-emergent PCI were randomized to receive bivalirudin with provisional GP IIb/IIIa (n = 2,319) versus heparin + routine GP IIb/IIIa (n = 2,332). Resource utilization data were collected prospectively through 30-day follow-up on all U.S. patients. Medical care costs were estimated using standard methods including bottom-up accounting (for procedural costs), the Medicare fee schedule (for physician services), hospital billing data (for 2,821 of 4,862 admissions), and regression-based approaches for the remaining hospitalizations. Among the bivalirudin group, 7.7% required provisional GP IIb/IIIa. Thirty-day ischemic outcomes including death or myocardial infarction were similar for the bivalirudin and GP IIb/IIIa groups, but bivalirudin resulted in lower rates of major bleeding (2.8% vs. 4.5%, p = 0.002) and minor bleeding (15.1% vs. 28.1%, p < 0.001). Compared with routine GP IIb/IIIa, in-hospital and 30-day costs were reduced by $405 (95% confidence interval [CI] $37 to $773) and $374 (95% CI $61 to $688) per patient with bivalirudin (p < 0.001 for both). Regression modeling demonstrated that, in addition to the costs of the anticoagulants themselves, hospital savings were due primarily to reductions in major bleeding (cost savings = $107/patient), minor bleeding ($52/patient), and thrombocytopenia ($47/patient). Compared with heparin + routine GP IIb/IIIa inhibition, bivalirudin + provisional GP IIb/IIIa inhibition resulted in similar acute ischemic events and cost savings of $375 to $400/patient depending on the analytic perspective.

Coronary flow velocity reserve does not correlate with TIMI frame count in patients undergoing non-emergency percutaneous coronary intervention

The purpose of this research was to compare the Thrombolysis In Myocardial Infarction (TIMI) frame count (CTFC) with coronary flow velocity reserve (CFVR) in patients undergoing percutaneous coronary intervention (PCI). The relationship between CTFC and CFVR has not been adequately assessed in patients with coronary artery disease. We studied 62 patients who underwent successful non-emergent PCI. All patients had Doppler evaluation of CFVR, CTFC, and quantitative coronary angiography. In an additional 17 patients, a frame count reserve was calculated as baseline CTFC/CTFC at peak hyperemia, induced by intracoronary adenosine after PCI. The CTFC decreased from 27 +/- 13 to 18 +/- 8, and CFVR increased from 1.5 +/- 0.4 to 2.6 +/- 0.7 (both p < 0.0001). The pre-PCI CTFC and the CFVR were closely related to minimal lumen diameter (p < 0.0001). After PCI, there was no correlation between CFVR and CTFC. In addition, no relationship was observed between CFVR and the frame count reserve. There was no significant correlation between CFVR and CTFC in patients undergoing coronary intervention. The relative utility of these measures in predicting outcomes in this setting requires further evaluation, but CTFC (or frame count reserve) does not appear to be an adequate surrogate measure of Doppler-derived CFVR.

Predictors of repeat revascularization after nonemergent, first percutaneous coronary intervention in the community

BackgroundWe sought to determine the incidence of and risk factors for repeat revascularization after nonemergent, first percutaneous coronary intervention (PCI) performed in contemporary community practice. MethodsWe analyzed a prospective registry of consecutive patients undergoing isolated PCI in the state of Washington. Multivariate Cox regression analysis was used to determine predictors of repeat revascularization (by PCI or bypass surgery) within 1 year after first PCI. ResultsBetween January 1, 1999, and December 31, 1999, there were 3571 nonemergent first PCIs, 87.7% of which involved stent placement. Repeat revascularization occurred in 577 (16.2%) patients. Repeat revascularization was predicted by multivessel disease (hazard ratio [HR] 1.36, 95% CI 1.12–1.66), stable versus no angina (HR 1.27, 95% CI 1.03–1.57), and maximum stent length used (per 1 mm longer: HR 1.01, 95% CI 1.002–1.02), while prior myocardial infarction (HR 0.77, 95% CI 0.62–0.96) and creatinine >1.2 mg/dL (HR 0.74, 95% CI 0.56–0.98) were associated with lower risk of repeat revascularization. Diabetes was a significant predictor only when the outcome was limited to revascularization by coronary artery bypass surgery (HR 1.52, 95% CI 1.03–2.23). Although glycoprotein IIb/IIIa inhibitor use was a significant univariate predictor of freedom from early repeat revascularization (within 60 days after first PCI), after controlling for potential confounders, it was no longer significant. ConclusionsIn this contemporary, community-based registry of patients undergoing nonemergent first PCI, clinical practice and outcomes are consistent with evidence from clinical trials and previous controlled studies. Results from controlled studies may reasonably be extrapolated to such a community setting.

A prospective, nonrandomized, open-labeled pilot study investigating the use of magnesium in patients undergoing nonacute percutaneous coronary intervention with stent implantation.

Magnesium has recently been shown to inhibit acute stent thrombosis in animal models. This study tested the feasibility of magnesium administration in patients undergoing nonacute percutaneous coronary intervention with stent implantation. Twenty-one patients undergoing nonemergent percutaneous coronary intervention were enrolled and received intravenous magnesium sulfate (2-g bolus over 20 minutes prepercutaneous coronary intervention, followed by 14 g over 12 hours infusion). safety outcomes--hypotension, bradycardia, bleeding complications and heart block within first 24 hours; angiographic outcomes--acute thrombotic occlusion and need for platelet glycoprotein IIb/IIIa inhibitor bailout; and clinical outcomes--death, myocardial infarction, recurrent ischemia, and need for urgent revascularization at 48 hours and 30 days. No significant effects on heart rate or blood pressure, major bleeding complication, or new electrocardiographic changes were observed. Angiographic thrombus was visualized in two cases, and coronary artery dissection in one case poststent deployment. None of these cases required the use of glycoprotein inhibitors for bailout. Death, myocardial infarction, recurrent ischemia, and need for urgent revascularization were not observed. The serum magnesium level increased from 2.1 +/- 0.3 mg/dL at baseline to 3.5 +/- 0.8 mg/dL at the end of the infusion (P <.0001). Platelet activation was significantly inhibited at the end of the magnesium sulfate infusion. Intravenous magnesium sulfate has been demonstrated as a feasible and safe agent in patients undergoing nonacute percutaneous coronary intervention with stent implantation. A randomized clinical trial comparing magnesium with glycoprotein inhibitors during percutaneous coronary intervention is warranted.

Correlation of Point-of-Care ecarin clotting time versus activated clotting time with bivalirudin concentrations

To rapidly and specifically monitor the anticoagulant effect of direct thrombin inhibitors, a thrombin inhibitor management (TIM) point-of-care test was developed (PharmaNetics, Inc., Morrisville, North Carolina), based upon the ecarin clotting time (ECT). This method utilizes the enzyme ecarin (from the venom of Echis carinatus) to convert prothrombin to meizothrombin. Meizothrombin catalyzes the conversion of fibrinogen to fibrin and is rapidly inhibited by direct thrombin inhibitors, such as bivalirudin. This assay has the particular advantage of being relatively specific for the effect of direct thrombin inhibitors, because heparins are poor inhibitors of meizothrombin. 1,2 The TIM-ECT test card may provide a more accurate measurement of direct thrombin inhibitor activity than current point-of-care assays. The purpose of this study was to compare the TIM-ECT test and 2 available activated clotting time (ACT) methods with a central laboratory anti-Factor IIa assay for monitoring bivalirudin-mediated anticoagulation. ••• Consecutive patients who underwent non-emergency percutaneous coronary intervention (PCI) with bivalirudin at The Cleveland Clinic Foundation were enrolled into the study. The protocol was approved by the institutional review board, and all patients gave written informed consent. Patients were not allowed to receive lepirudin, argatroban, abciximab, epti fibatide, or tirofiban 72 hours before PCI. All unfractionated heparin was discontinued 12 hours before PCI and all fractionated heparins 24 hours before PCI. All patients received preprocedural aspirin. Information regarding patient demographics, laboratory data, procedural details, and serial postprocedural creatine kinase (CK, CK-MB) was prospectively collected. Clinical outcomes were assessed to 30-day follow-up. Arterial blood samples were collected at baseline (sample 1), after bivalirudin bolus and infusion initiation (sample 2), after glycoprotein IIb/IIIa inhibitor bolus and infusion initiation (sample 3), during the procedure (sample 4), and before sheath removal (sample 5). Samples were procured from a nonheparinized arterial sheath and were placed into a noncitrated tube (3 ml) and a 3.2% sodium citrate tube (2.7 ml). Immediately at collection, the noncitrated whole blood samples were tested with the Hemochron ACT (International Technidyne, Edison, New Jersey), CoaguChek Pro/DM ACT (Roche Diagnostics, Indianapolis, Indiana), and the TIM-ECT. After this, the citrated whole blood was tested with the TIM-ECT. The remaining citrated blood was promptly centrifuged, and the plasma was aliquoted into cryovials and frozen at 70°C for the bivalirudin concentration assay. The ACT measures the time for whole blood to clot in the presence of an activating substance. 3,4 The Hemochron tube-based system uses a magnet in a rotating glass specimen tube that contains diatomaceous earth.5 As the blood clots, the magnet is displaced from the tube’ s bottom, thereby activating a proximity switch. Hemochron ACT values were truncated at a maximum of 999 seconds. The Pro/DM ACT is a cartridge-based system that uses tissue factor and sulfatides as activating substances. 6 The blood sample is drawn by capillary action into the reagent chamber, where it mixes with the chemical activators. The time from application of blood to cessation of flow within the chamber is detected by an optical system and converted to an ACT equivalent. Pro/DM clotting times were truncated at a maximum of 500 seconds.