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Patients undergoing percutaneous coronary intervention (PCI) have a significant risk of hemorrhagic complications. Predictors of major hemorrhage and its relation to mortality in PCI are not well defined. Baseline and periprocedural predictors of major hemorrhage and its impact on mortality in patients undergoing elective or urgent PCI randomly assigned to heparin plus planned glycoprotein IIb/IIIa inhibitor (GPI) versus bivalirudin plus provisional GPIs in the REPLACE-2 Trial were determined. Of 6,001 patients, 3.2% experienced a major hemorrhage. Independent baseline predictors of major hemorrhage included advanced age, female gender, impaired creatinine clearance, and anemia. Independent periprocedural predictors of major hemorrhage included treatment with heparin plus GPI, increased procedural duration, provisional use of GPI, increased time to sheath removal, length of intensive care unit stay, and use of an intra-aortic balloon pump (all p <0.05). Mortality rates were higher in patients with than without major hemorrhage at 30 days (5.1% vs 0.2%), 6 months (6.7% vs 1.0%), and 1 year (8.7% vs 1.9%; p <0.001 for all). Furthermore, major hemorrhage was an independent predictor of 1-year mortality (odds ratio 2.66, 95% confidence interval 1.44 to 4.92, p = 0.002). In conclusion, in patients undergoing elective or urgent PCI, major hemorrhage was an independent predictor of 1-year mortality. A number of baseline and periprocedural factors independently predicted major hemorrhage, including treatment with heparin plus GPI.

To assess the efficacy of the direct thrombin inhibitor bivalirudin relative to heparin during contemporary coronary intervention, 1,056 patients who underwent elective or urgent revascularization were randomized in a large-scale pilot study to receive heparin (70 U/kg initial bolus) or bivalirudin (0.75 mg/kg bolus, 1.75 mg/kg/hour infusion during the procedure). All patients received aspirin; pretreatment with clopidogrel was encouraged, and glycoprotein (GP) IIb/IIIa blockade was at the physician's discretion. Stents were placed in 85% of patients; 72% received a GP IIb/IIIa inhibitor, and 56% were pretreated with clopidogrel. Activated clotting times were higher among patients randomized to bivalirudin than among those given heparin before device activation (median 359 vs 293 seconds, p <0.001). The composite efficacy end point of death, myocardial infarction, or repeat revascularization before hospital discharge or within 48 hours occurred in 5.6% and 6.9% of patients in the bivalirudin and heparin groups, respectively (p = 0.40). Major bleeding occurred in 2.1% versus 2.7% of patients randomized to bivalirudin or heparin, respectively (p = 0.52). This trial represents the largest prospective dataset of bivalirudin administered concomitantly with planned GP IIb/IIIa blockade and provides evidence of the safety and efficacy of this combined antithrombotic approach.

Chronic kidney disease is associated with an increased risk of ischemic and bleeding events after percutaneous coronary intervention (PCI). The direct thrombin inhibitor bivalirudin reduces these combined events. We sought to assess whether this benefit was influenced by renal function. A meta-analysis of 3 randomized trials (n = 5,035) comparing bivalirudin with heparin during PCI, stratified by estimated creatinine clearance using the Cockcroft-Gault equation (>90 [n = 1,578], 90 to 60 [n = 2,163], 59 to 30 [n = 1,255], and <30 ml/min [n = 39]), was conducted. The composite end points of death, myocardial infarction or revascularization, hemorrhage, and combined ischemic or bleeding events were assessed. A common odds ratio for each creatinine clearance strata was estimated with a random-effects model. The interaction between renal impairment and benefit from bivalirudin was assessed. Adverse ischemic and bleeding events increased with decreasing renal function. The relative benefit of bivalirudin with respect to ischemic and bleeding events was maintained within each stratum. The absolute benefit in terms of ischemic and bleeding complications increased with decreasing creatinine clearance (normal 2.2%, mild 5.8%, moderate 7.7%, severe 14.4%; p trend <0.001, interaction p = 0.044). Renal dysfunction remains a prevalent risk factor for ischemic and bleeding events in patients who undergo PCI. Bivalirudin provides greater absolute benefit in patients with impaired renal function.

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.

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.

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.

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.

Calcified and fibrotic coronary artery lesions cannot always be dilated with conventional balloon angioplasty even at high pressures. This study examines the success of excimer laser facilitated angioplasty in 38 lesions in 37 patients with lesions that failed balloon angioplasty alone.

A total of 495 patients underwent treatment with excimer laser angioplasty for 545 saphenous vein graft stenoses. Clinical success was achieved in 455 of 495 patients (92%), as indicated by < or = 50% residual stenosis at every target lesion and no complication during hospitalization. At least 1 in-hospital complication occurred in 30 of 495 patients (6.1%): death (1.0%), bypass surgery (0.6%), and Q-wave (2.4%) or non-Q-wave (2.2%) myocardial infarction. Relative risk analysis showed that ostial lesions (n = 65) tended to have higher clinical success (success rate = 95%, adjusted odds ratio [OR] = 2.1 [95% confidence interval (CI) 0.62, 6.88]; p = 0.24) and lower complications (complication rate = 0%, OR = 0.10 [CI 0.01, 0.79]; p = 0.03) than lesions in the body of the vein graft. Lesions > 10 mm (n = 131) had lower success (success rate = 84%, OR = 0.30 [CI 0.16, 0.56]; p = 0.001) and higher complications (complication rate = 12%, OR = 3.3 [CI 1.6, 6.6]; p = 0.004) than discrete lesions. Lesions in small vein grafts < 3.0 mm (n = 76) tended to have increased success (success rate = 94%, OR = 1.55 [CI 0.70, 3.44]; p = 0.39) and lower complications (complication rate = 2.2%, OR = 0.31 [CI 0.10, 0.94]; p = 0.03). Thus, excimer laser-facilitated angioplasty has the most favorable outcome for discrete lesions located at the ostium of all grafts and in the body of smaller saphenous vein grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Several studies have shown that diabetes mellitus increases the risk of restenosis after coronary intervention, but the role of insulin in restenosis has not been defined. The relation between fasting insulin levels and restenosis was evaluated prospectively at 6-month angiographic follow-up in 70 patients undergoing excimer laser coronary angioplasty of 75 lesions. Restenosis (> 50% diameter narrowing on quantitative angiography) was observed at 37 of 75 treated sites (49%). Although patients with glucose intolerance and noninsulin-dependent diabetes mellitus showed a trend toward increased restenosis (restenosis rate 69%; odds ratio for restenosis 2.7 [95% confidence interval 0.76, 9.82]; p = 0.124), those with increased fasting insulin levels > 15 muU/ml had reduced restenosis (restenosis rate 24%; odds ratio 0.22 [0.07, 0.67]; p = 0.008). Other factors including fasting serum glucose, glycated hemoglobin and lipoprotein fraction were not predictive of restenosis. The relation between insulin levels and restenosis after excimer laser angioplasty may provide insights into the biology of vascular injury and repair after coronary intervention.

The diagnosis of unstable angina encompasses a broad spectrum of patients with myocardial ischemia, varying widely in cause, prognosis and responsiveness to therapy. A new clinical classification of unstable angina is based on the following 2 components: severity, and the clinical setting in which unstable angina develops. The hypothesis that this clinical classification correlates with the underlying coronary artery anatomy was tested. In 238 consecutive patients, an unstable angina score ranging from 2 to 6 was determined by adding the scores for severity (1 = unstable angina without pain at rest; 2 = pain at rest > 48 hours before angiography; and 3 = pain at rest < or = 48 hours before angiographic evaluation) and the clinical setting of unstable angina (1 = unstable angina secondary to a noncardiac condition; 2 = primary unstable angina; and 3 = early postinfarction unstable angina). Fifty concurrently studied consecutive patients with stable angina were assigned a score of 0. Patients with unstable angina averaged 63 +/- 11 years of age, and 165 were men (69%). Pain at rest occurred in 202 of 238 patients (85%), and angiography was performed < or = 48 hours in 139 of these patients (69%). Among patients with unstable angina, 5 (2%) had secondary unstable angina, 143 (60%) had primary unstable angina, and 90 (38%) had postinfarction unstable angina. Multivariable regression analysis identified the unstable angina score as the most important predictor of intracoronary thrombus (p = 0.011) and lesion complexity (p = 0.004) in the ischemia-related artery.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of excimer laser angioplasty in treating complex coronary artery disease remains uncertain. A randomized trial comparing this new technology with balloon angioplasty cannot be designed until systematic analysis identifies the lesion types that are likely to benefit from treatment with excimer laser angioplasty. In a cohort of 764 patients who had 858 coronary stenoses treated with excimer laser-facilitated angioplasty, relative risk analysis was used to examine acute success, complications and restenosis rates, and the results were compared with those of balloon angioplasty to identify the lesion types that show the greatest benefit with the new treatment. Clinical success was achieved in 657 patients (86%), as indicated by < or = 50% residual stenosis and no in-hospital complication. A major in-hospital complication (death, bypass surgery, or Q-wave or non-Q-wave myocardial infarction) occurred in 58 patients (7.6%). Follow-up angiography was obtained in 70% of eligible patients. Combining angiographic and noninvasive restenosis rates yielded an overall restenosis rate of 46%. Relative risk analysis showed that major complications occurred frequently in lesions at an arterial bifurcation (odds ratio [OR] 5.96 [2.76, 12.6]; p = 0.001). However, certain complex lesions that are difficult to treat with balloon angioplasty (saphenous vein graft lesions, lesions > 10 mm, ostial lesions, calcified stenoses, total occlusions and unsuccessful balloon dilatations), analyzed together as a group, had lower complication rates by univariate (OR 0.59 [0.35, 1.00]; p = 0.051) and multivariate logistic regression (p = 0.006) analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Estimation of mitral valve area (MVA) in the cardiac catheterization laboratory is prone to pitfalls because of the time required for calculations and inaccuracies in the measurement of cardiac output. Because the rate of decrease in the mitral gradient directly correlates with the severity of mitral stenosis, an on-line estimate of MVA at the time of catheterization may be possible with regression analysis of digitized pressure recordings. A total of 61 comparisons of mitral gradient measurements and MVA were obtained in 37 patients at diagnostic catheterization and in 24 patients after balloon mitral valvotomy. Linear and nonlinear regression parameters yielded pressure half-time values and empiric constants similar to those used in Doppler echocardiography for estimation of MVA. The correlations derived from linear analysis were as good as those obtained from nonlinear analysis: from linear analysis, MVAregression = 0.79.MVAGorlin -0.03; r2 = 0.64, p = 0.0001; and from double exponential analysis, MVAregression = 0.86.MVAGorlin -0.07; r2 = 0.74; p = 0.0001. The correlations were not significantly affected by the presence of mild to moderate mitral regurgitation or whether they were obtained after balloon valvotomy. In summary, linear regression analysis yields accurate estimates of MVA despite the theoretical superiority of nonlinear methods. On-line digital analysis of mitral gradient tracings may thus be useful at the time of diagnostic cardiac catheterization or balloon mitral valvotomy to assess the severity of mitral stenosis and the response to interventions.

The response of left ventricular (LV) geometry to altered loading conditions after mitral valvuloplasty has been incompletely described. Therefore, 15 patients with rheumatic mitral stenosis were studied using quantitative 2-dimensional echocardiography a mean of 1 +/- 2 months before and 11 +/- 5 months after percutaneous balloon mitral valvuloplasty. Mitral valve area (Gorlin) increased in all patients, from 1.0 +/- 0.3 to 1.9 +/- 0.5 cm2 (p less than 0.01). Mitral regurgitation (1+/4+) developed in 3 patients, and increased by 1 grade in 1 patient as a consequence of mitral valvuloplasty. After valvuloplasty, there were significant increases in LV end-diastolic volume (69 +/- 22 to 82 +/- 26 ml, p less than 0.01), stroke volume (34 +/- 13 to 46 +/- 19 ml, p less than 0.05) and mass (181 +/- 46 to 200 +/- 42 ml, p less than 0.005). LV end-systolic volume and ejection fraction did not change significantly. LV mass-to-volume ratio was unchanged (5.6 +/- 1.5 to 5.8 +/- 1.4 g/ml, p = not significant). Quantitatively similar results were obtained when these changes were indexed to body surface area. Thus, successful mitral valvuloplasty was associated with significant increases in LV end-diastolic volume and mass. These findings suggest that increased preload may be a stimulus to myocardial growth.