Bivalirudin versus heparin during coronary angioplasty for unstable or postinfarction angina: Final report reanalysis of the Bivalirudin Angioplasty Study.

BACKGROUND: This study was a reanalysis of the Bivalirudin Angioplasty Study, which compared bivalirudin with high-dose heparin during coronary angioplasty for unstable angina. METHODS: Differences in rates of death, myocardial infarction, or repeat revascularization were compared at 7, 90, and 180 days after angioplasty with intention-to-treat analysis. RESULTS: The combined end point occurred in 135 of 2161 patients (6.2%) in the bivalirudin group and in 169 of 2151 patients (7.9%) in the heparin group at 7 days (P =.039). Differences persisted between the groups at 90 days (P =.012) and 180 days (P =.153). Bleeding occurred in 76 patients (3.5%) in the bivalirudin group versus 199 (9.3%) in the heparin group (P <.001). CONCLUSIONS: This analysis supports the hypothesis that bivalirudin reduces ischemic complications and bleeding after angioplasty. Further trials are needed to evaluate bivalirudin versus heparin in conjunction with platelet-glycoprotein IIb/IIIa inhibitors and for coronary stenting.

Clinical outcomes of bivalirudin for ischemic heart disease.

BACKGROUND: Current treatment strategies for percutaneous coronary revascularization and acute coronary syndromes incorporate thrombin inhibition with either unfractionated or fractionated heparin. The peptide bivalirudin (Hirulog) is a direct thrombin inhibitor whose pharmacological properties differ from those of heparin. We conducted a systematic overview (meta-analysis) to assess the effect of bivalirudin on 4 end points: death, myocardial infarction, major hemorrhage, and the composite of death or infarction. METHODS AND RESULTS: Six trials (5674 patients) represent the randomized, controlled bivalirudin experience, including 4603 patients undergoing elective percutaneous coronary revascularization and 1071 patients with acute coronary syndromes. ORs for the 4 clinical end points were calculated for each trial. Four trials (4973 patients) that compared bivalirudin with heparin were combined with the use of a random-effects model. In these trials, bivalirudin was associated with a significant reduction in the composite of death or infarction (OR 0.73, 95% CI 0.57 to 0.95; P=0.02) at 30 to 50 days, or 14 fewer events per 1000 patients so treated. There also was a significant reduction in major hemorrhage for the same trials (OR 0.41, 95% CI 0. 32 to 0.52; P<0.001, or 58 fewer events per 1000 patients so treated). A similar analysis combined 2 dose-ranging trials (701 patients) that compared therapeutic (activated partial thromboplastin time more than twice the control time) with subtherapeutic bivalirudin anticoagulation (activated partial thromboplastin time less than twice the control time). CONCLUSIONS: Bivalirudin is at least as effective as heparin, with clearly superior safety. Thus, it provides an unprecedented net clinical benefit over heparin in patients with ischemic heart disease.

No-touch technique for reducing aortic wall trauma during renal artery stenting.

Cholesterol embolism, a serious but infrequent complication of renal artery stenting, may be avoided by minimizing contact between the guide catheter and the atherosclerotic aorta. In this report, we illustrate the "no-touch" technique for stenting renal arteries. By placing a second 0.035-inch J-wire within the guide catheter during cannulation of the renal artery to prevent the tip of the guide from rubbing the aortic wall, we minimize the contact between the guide catheter and atherosclerotic plaques and reduce the potential for intimal disruption and cholesterol embolization.

Effect of transient abrupt vessel closure during otherwise successful angioplasty for unstable angina on clinical outcome at six months. Hirulog Angioplasty Study Investigators.

OBJECTIVES: The objective of this study was to identify predictors of major adverse cardiac events after successful coronary angioplasty. BACKGROUND: The acute complications of angioplasty are related to baseline clinical and angiographic variables, and early complications adversely affect long-term outcome. However, the predictors of enduring success after uncomplicated angioplasty are less well defined. METHODS: Of 4,098 patients undergoing angioplasty in the Hirulog Angioplasty Study, 3,899 (95%) had a successful procedure without in-hospital death, emergent bypass surgery or clinical evidence of myocardial infarction. Baseline and procedural variables for these 3,899 patients were examined. RESULTS: Major adverse cardiac events occurred in 22% of the patients with initially successful procedures at 6 months: death in 1%, myocardial infarction in 2% and repeat revascularization in 21%. Univariable predictors of increased events included successful salvage from abrupt vessel closure (p < 0.001), emergency stenting (p < 0.001), multilesion angioplasty (p < 0.001), diabetes (p=0.02), target lesion in the left anterior descending artery (p=0.02), unstable angina (p=0.03) and smaller final luminal diameter (p=0.04). There was a trend toward increased events among patients with prior angioplasty (p=0.08), but asymptomatic elevation of the creatine kinase was not predictive (p=0.5). In a multivariable model, abrupt vessel closure was the strongest independent predictor of major adverse cardiac events at 6 months (p < 0.001; odds ratio [95% confidence interval]=3.6 [2.5 to 5.1]), while multivessel angioplasty, target lesion in the left anterior descending artery and diabetes also remained independent predictors (all p < or = 0.02). CONCLUSIONS: This analysis suggests that "uncomplicated" abrupt vessel closure is a powerful predictor of adverse clinical outcome following successful angioplasty. Improved techniques to reduce abrupt closure during angioplasty are thus urgently needed, and patients who experience "uncomplicated" closure require closer surveillance during follow-up.

A randomized comparison of bivalirudin and heparin in patients undergoing coronary angioplasty for postinfarction angina. Hirulog Angioplasty Study Investigators.

The outcome of coronary angioplasty performed for unstable angina is determined, in part, by the acuteness and severity of the clinical presentation. The risk of abrupt vessel closure is increased in patients with postinfarction angina. The Hirulog Angioplasty Study compared the efficacy and safety of bivalirudin with weight-adjusted heparin in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) for unstable or postinfarction angina. We report the results of the intent-to-treat analysis using adjudicated data for the prespecified group of 741 patients who underwent angioplasty within 2 weeks of documented myocardial infarction. Patients received either bivalirudin or heparin immediately before angioplasty. The primary efficacy endpoint was procedural failure defined as abrupt vessel closure, death, myocardial infarction, or revascularization during hospitalization. Bivalirudin significantly (p = 0.004) decreased the incidence of procedural failure compared with heparin (5.1% vs 10.8%, odds ratio 0.45; 95% CI 0.25-0.79). The improved efficacy of bivalirudin was replicated for each individual clinical endpoint. The incidence of major bleeding was significantly (p = 0.001) lower in bivalirudin-treated patients compared with heparin-treated patients (2.4% vs 11.8%, respectively). The benefits observed with bivalirudin are of similar magnitude as those reported for platelet glycoprotein (GP) IIb/IIIa inhibitors, such as abciximab. Bivalirudin may be a more effective foundation anticoagulant than heparin in patients undergoing coronary angioplasty for postinfarction angina.

Relation between abrupt vessel closure and the anticoagulant response to heparin or bivalirudin during coronary angioplasty.

The dosing of anticoagulants during coronary angioplasty is commonly guided by measurements of activated clotting time (ACT), but the usefulness of these measurements remains uncertain. The Hirulog Angioplasty Study was a randomized, double-blind comparison of heparin versus bivalirudin in 4,312 patients undergoing angioplasty for unstable or postinfarction angina. In 4,098 of the patients randomized, the balloon was inflated. All patients had ACT measurements 5 minutes after a weight-adjusted bolus of heparin or bivalirudin, and patients undergoing complicated or prolonged angioplasty procedures lasting >45 minutes had additional ACT measurements to guide further anticoagulant therapy. The analysis presented in this article evaluated the relation between the initial or maximum ACT measurements and the risk of abrupt vessel closure during heparin or bivalirudin therapy. Abrupt vessel closure occurred in 189 of 2,039 patients (9.3%) treated with heparin, and in 189 of 2,059 patients (9.2%) treated with bivalirudin (p = not significant). An inverse relation between the risk of abrupt closure and initial ACT measurements was observed in heparin-treated patients: the probability of abrupt vessel closure decreased by 1.3% for every 10-second increase in the initial ACT response to heparin therapy (p = 0.02). Among 903 of 2,039 heparin-treated patients (44%) who received additional heparin for prolonged or complicated procedures, the likelihood of abrupt vessel closure also decreased by 1.1% for every 10-second increase in ACT (p = 0.04). In 2,059 patients treated with bivalirudin, however, no relation between the probability of abrupt vessel closure and the initial ACT measurement was observed (p = 0.88). From the results it was concluded that when heparin is used during coronary angioplasty, the risk of abrupt vessel closure is related to patient responsiveness to anticoagulation therapy. Heparin-resistant patients are more likely to experience abrupt vessel closure than patients who have high ACT values in response to initial therapy. In contrast, when bivalirudin is used during coronary angioplasty, a flat relation between the risk of abrupt vessel closure and ACT values is seen. This suggests that the direct thrombin inhibitor, bivalirudin, provides more even levels of anticoagulation and more predictable levels of risk of abrupt closure than heparin. Measurements of ACT may not be necessary when bivalirudin is used during coronary angioplasty.

Effect of direct thrombin inhibition with Bivalirudin (Hirulog) on restenosis after coronary angioplasty.

The direct antithrombin, bivalirudin, did not reduce angiographic restenosis measured either as the dichotomous restenosis rate of 62% for bivalirudin and 58% for heparin (p = 0.70), or as the late loss in lumen diameter of 0.44 +/- 0.47 mm for bivalirudin and 0.39 +/- 0.53 mm for heparin (p = 0.62). Direct thrombin inhibition with bivalirudin neither reduces angiographic restenosis nor alters the impact of several established risk factors for restenosis.

Laser wire for crossing chronic total occlusions: "learning phase" results from the U.S. TOTAL trial. Total Occlusion Trial With Angioplasty by Using a Laser Wire.

The Prima laser guidewire system (Spectranectics Corp., Colorado Springs, CO) consists of an 0.018" hypotube containing a bundle of 45-microm optical fibers coupled to a pulsed excimer laser operating at a tip fluence of 60 ml/mm2 and a repetition rate ranging from 25-40 Hz. This laser guidewire was specifically designed to cross total occlusions refractory to passage with conventional wires. The Prima wire was evaluated in a feasibility study at 15 U.S. centers. Following failure to cross a total occlusion with approved guidewires, the Prima wire was utilized in 179 patients. Average age of subjects was 61 yr. Lesion locations included left anterior descending (36%), right (45%), and circumflex (19%) coronary arteries. Mean angiographic age of total occlusions was 70 wk (range, 2-1,020 wk, median, 14 wk). The use of the Prima wire either solely or in combination with conventional guidewires resulted in successful crossing in 61% of these previously impenetrable occlusions. Failure of the device was commonly related to length of the occlusion and tortuosity along the occluded pathway. Major complications included myocardial infarction in 7 patients (3.9%), tamponade in 3 (1.7%), and death in 2 (1.1%). This "learning phase" pilot study confirmed the feasibility of a laser guidewire in chronic total occlusions that are resistant to passage of conventional guidewires. An extended registry at these investigative sites is planned.

Myonecrosis after revascularization procedures.

The detection of elevated cardiac enzyme levels and the occurrence of electrocardiographic (ECG) abnormalities after revascularization procedures have been the subject of recent controversy. This report represents an effort to achieve a consensus among a group of researchers with data on this subject. Creatine kinase (CK) or CK-MB isoenzyme (CK-MB) elevations occur in 5% to 30% of patients after a percutaneous intervention and commonly during coronary artery bypass graft surgery (CABG). Although Q wave formation is rare, other ECG changes are common. The rate of detection is highly dependent on the intensity of enzyme and ECG measurement. Because most events occur without the development of a Q wave, the ECG will not definitively diagnose them; even the ECG criteria for Q wave formation signifying an important clinical event have been variable. At least 10 studies evaluating > 10,000 patients undergoing percutaneous intervention have demonstrated that elevation of CK or CK-MB is associated not only with a higher mortality, but also with a higher risk of subsequent cardiac events and higher cost. Efforts to identify a specific cutoff value below which the prognosis is not impaired have not been successful. Rather, the risk of adverse outcomes increases with any elevation of CK or CK-MB and increases further in proportion to the level of intervention. This information complements similar previous data on CABG. Obtaining preprocedural and postprocedural ECGs and measurement of serial cardiac enzymes after revascularization are recommended. Patients with enzyme levels elevated more than threefold above the upper limit of normal or with ECG changes diagnostic for Q wave myocardial infarction (MI) should be treated as patients with an MI. Patients with more modest elevations should be observed carefully. Clinical trials should ensure systematic evaluation for myocardial necrosis, with attention paid to multivariable analysis of risk factors for poor long-term outcome, to determine the extent to which enzyme elevation is an independent risk factor after considering clinical history, coronary anatomy, left ventricular function and clinical evidence of ischemia. In addition, tracking of enzyme levels in clinical trials is needed to determine whether interventions that reduce periprocedural enzyme elevation also improve mortality.

Excimer laser coronary angioplasty: the New Approaches to Coronary Intervention (NACI) experience.

In the New Approaches to Coronary Intervention (NACI) registry, 887 patients were electively treated with excimer laser coronary angioplasty (ELCA) for coronary artery disease. The Advanced Interventional System (AIS) system was used in 487 cases; the Spectranetics system, in 400. The mean age was 63.4 years. Most patients had unstable angina (60.3%); 43.7% had a prior myocardial infarction; and 18.6% were high risk or inoperable patients. Mean ejection fraction was 55.4%. A total of 1,000 lesions were treated in the 887 patients. Of the 1,000 lesions treated with ELCA in the 887 patients, 36% were in the right coronary artery; 33%, left anterior descending; 13%, circumflex; 3%, left main; and 16.6%, vein graft. By angiographic core laboratory analysis available for 752 (85%) patients with 839 lesions, lesions were 12.76 mm long. The minimum lumen diameter increased to 1.29 mm after the laser and finally to 1.95 mm after adjunctive percutaneous transluminal coronary angioplasty (PTCA) (which was performed in 93% of all lesions), with a final residual stenosis of 32.1% and Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in 95%. Dissections of grades B, C, or D were seen after 22.0% of initial laser attempts, and postlaser perforations were noted in 2.6%. Additional such dissections accumulated after adjunctive PTCA but the perforation rate remained low. Procedural success was achieved in 84% of patients, but 1.2% died, 0.7% experienced Q-wave myocardial infarction (MI), and 2.7% required emergency bypass surgery. Multiple logistic regression analysis could not identify any independent predictors of these in-hospital complications. One-year mortality was 5.7% and the cumulative incidence of Q-wave MI was 1.5%. Coronary artery bypass graft (CABG) surgery was performed in 15.0% of patients whereas 25.5% required repeat percutaneous intervention with a target lesion revascularization rate of 31%. Independent predictors of death, Q-wave MI, or target lesion revascularization (which, combined, occurred in 35.6% of patients) were the absence of prior MI, ELCA in the circumflex, perforation after the procedure, and small (<2 mm) final minimal lumen diameter. Considering the large number of patients with high-risk lesions, laser angioplasty was performed with excellent procedural success rates and a reasonable incidence of major complications.