Comparison of abciximab with "high-dose" tirofiban in patients undergoing percutaneous coronary intervention

BACKGROUND: The TARGET study has been criticised for sub-optimal platelet inhibition with tirofiban. We aimed to compare a high-dose bolus regimen of tirofiban (hd-tirofiban) to standard dose of abciximab for patients undergoing percutaneous coronary intervention (PCI). METHODS: We assessed consecutive patients who received either hd-tirofiban (25 mcg/kg bolus followed by 0.15 mcg/kg/min infusion for 18 h) or standard dose abciximab. In-hospital and 6-month outcomes were obtained in all cases. RESULTS: Over an 18-month period, 109 patients who received hd-tirofiban were compared with 110 patients who received abciximab. Both hd-tirofiban and abciximab groups had acute coronary syndromes in 86% and 80% and diabetes in 10% and 13% respectively. Most patients had coronary stent implantation (96% vs. 98%). Thrombocytopenia (platelet count< 100,000) developed in 0.9% of patients receiving hd-tirofiban and 2% of patients receiving abciximab (p = 0.566). Bleeding requiring transfusion occurred in 7.3% and 3% of patients respectively (p = 0.118). Peri-procedural troponin rise was 0.9% in patients receiving hd-tirofiban and 5.5% in patients receiving abciximab (p = 0.07). MACE (Myocardial infarction, Stroke, Revascularisation and Death) at 6 months was 23% in the hd-tirofiban group and 20% in the abciximab group (p = 0.711). The pharmaceutical costs were AUD 322 for hd-tirofiban (one ampoule) and AUD 1,350 for abciximab (3 ampoules). CONCLUSION: There was a small increase in bleeding requiring transfusion and a lower rate of peri-procedural troponin rise in the hd-tirofiban group however, the overall 6-month MACE rates were similar in both groups. There was a considerable cost-saving with the use of hd-tirofiban. A prospective randomised trial of hd-tirofiban vs. abciximab is warranted.     

Long-term mortality benefit with abciximab in patients undergoing percutaneous coronary intervention

OBJECTIVES

The goal of this study was to test: 1) if platelet glycoprotein IIb/IIIa (GP IIb/IIIa) blockade with abciximab bolus plus 12-h infusion reduces mortality after percutaneous coronary intervention (PCI); 2) if prevention of early myocardial infarction (MI) after PCI is a mechanism for reducing mortality; and 3) for risk factors for mortality after PCI.

BACKGROUND

Studies of PCI suggest that MI after intervention is predictive of mortality. Abciximab, a platelet GP IIb/IIIa receptor inhibitor, has consistently reduced the incidence of MI among PCI patients in several trials. The presumed mechanism is prevention of platelet thrombus associated with vessel wall injury and downstream embolization into the microcirculation.

METHODS

In eight trials, 5,154 patients were randomized to a regimen comprising conventional therapy plus a bolus of abciximab within 1 h before PCI followed by a 12-h infusion; 4,136 controls were randomized to conventional therapy alone. Patient follow-up from six months to three years was available. Survival differences are examined using proportional hazards regression and survival curves.

RESULTS

A hazard ratio of 0.71 (95% confidence interval 0.57 to 0.89; P = 0.003) suggests a mortality benefit with abciximab. The absolute reduction in mortality was estimated to be 0.5% through 30 days, 0.7% through six months, 0.9% through one year and 1.8% through three years. Early MI explained 18% of the observed mortality benefit at one year. Multivariate regression suggests that patients with advanced cardiovascular disease may derive the greatest mortality benefit from abciximab.

CONCLUSIONS

The evidence from 9,290 randomized PCI patients shows a mortality benefit provided by abciximab bolus plus 12-h infusion.     

Follow-up clinical results in patients undergoing percutaneous transluminal coronary angioplasty

Complete follow-up data were obtained from 229 consecutive patients who underwent percutaneous transluminal coronary angioplasty (PTCA) between 1979 and 1982 (mean follow-up 14 months, range 6 to 37). Single-vessel disease was present in 143 and multivessel disease in 86. PTCA was successful in 153 patients (67%). Failure was followed initially by bypass surgery in 59 and by continued medical therapy in 17. After successful PTCA, 90% of patients were improved subjectively and 74% were asymptomatic at follow-up. After unsuccessful PTCA but prompt bypass, 90% were improved subjectively and 85% were asymptomatic. Among the 229 patients, 39 (17%) required an additional intervention because of angina during follow-up; 15 of these had repeat PTCA and 18 had bypass surgery. Among patients with successful PTCA, revascularization was complete in 77% and partial in 23%. The completeness of revascularization with PTCA had a significant impact on follow-up. The follow-up data of patients with successful single-vessel PTCA and of those with multivessel disease with complete revascularization were similar. When the patients with complete revascularization were compared with those with multivessel disease but incomplete revascularization, the follow-up data were characterized by a higher incidence of angina or need for bypass surgery in the latter group (63%) than in the former group (29%); those with incomplete revascularization also had a significantly reduced event-free survival.     

Early and late clinical outcomes following coronary perforation in patients undergoing percutaneous coronary intervention.

Coronary perforation is a rare but serious complication that occurs during percutaneous coronary intervention (PCI). This study examines the frequency of coronary perforation during PCI, evaluates the management strategies used to treat perforations, and describes the long-term prognosis of patients who have developed coronary perforation during PCI. Coronary perforations were found in 69 (0.93%) of 7,443 consecutive PCI procedures, occurring more often after use of a new device (0.86%) than after use of balloon angioplasty (0.41%) (p<0.05). Coronary perforation was attributable solely to the coronary guidewire in 27 (0.36%) cases. Coronary perforations were divided into 2 types: (1) Those with epicardial staining without ajet of contrast extravasation (type I, n=51), and (2) those with a jet of contrast extravasation (type II, n= 18). Patients with type I and type II perforations were managed by observation only (35% and 0%, respectively), reversal of anticoagulation (57% and 94%), pericardiocentesis and drainage (27% and 61%), and prolonged perfusion balloon angioplasty (16% and 100%). Two patients with type II perforations required emergency coronary artery bypass surgery. There were no in-hospital deaths. Late pseudoaneurysms developed in 18 (28.6%) patients during the 13.4 +/- 11.3 months' follow-up period, and were more common in patients with type II perforations (72.2% vs 11.1% with type I perforations; p<0.001). During the follow-up period, no patient had evidence of coronary rupture. The results suggest that coronary perforation is uncommon after PCI, and can be managed without cardiac surgery in the majority of cases. Late pseudoaneurysms developed in some patients, particularly in patients with type II perforations, but there were no late consequences of coronary perforation after PCI.     

Circulating immunoreactive endothelin in patients undergoing percutaneous transluminal coronary angioplasty

Circulating immunoreactive endothelin (ir-ET) in the coronary sinus (CS) and the femoral artery (Ao) was measured in patients who underwent percutaneous transluminal coronary angioplasty (PTCA). Plasma ir-ET level in the CS was significantly increased from 1.6 +/- 0.8 pg/mL to 2.0 +/- 1.0 pg/mL after PTCA (P less than .05). Plasma ir-ET level in the Ao tended to increase after PTCA, but it was not significant. Plasma ir-ET level in the CS was not related to the plasma thromboglobulin level, plasma thrombin-antithrombin complex level, mean blood pressure, or heart rate. These results suggest that the increase of plasma ir-ET level in the CS may be associated with the coronary endothelial injury by PTCA.     

Long-term angiographic follow-up results in patients undergoing percutaneous transluminal coronary angioplasty

Long-term effects following percutaneous transluminal coronary angioplasty (PTCA) were examined using follow-up coronary angiography (CAG) in 49 lesions in cases in which the procedure was considered to be successful. Follow-up CAG was performed 2-5 times (average, 2.7 times) per patient during a period of 1 year to 3 years and 7 months (average, 1 year and 10 months). The luminal diameter of the PTCA sites was expressed as the percentage of the value immediately after the procedure. Narrowing by 10% or more was observed in 17 lesions 3-8 months after PTCA but in only 4 lesions on the final CAG. The luminal diameter of the PTCA site was significantly greater (p less than 0.05) 2 years after PTCA in comparison to the findings after 1 year. These results suggest excellent long-term effects at the PTCA site.     

Percutaneous cardiopulmonary bypass support in high-risk patients undergoing percutaneous transluminal coronary angioplasty

Fifty-one consecutive patients in whom percutaneous cardiopulmonary bypass support was instituted to enhance the safety of high-risk elective coronary angioplasty were studied. All patients had a low ejection fraction, a large amount of viable myocardium perfused by the target artery(s) or both. Thirty-five men and 16 women, mean age 63 years, with Canadian Cardiovascular Society class III angina (23 patients) or class IV (28 patients) were studied. There was a history of myocardial infarction in 45 (88%), bypass surgery in 14 (27%) and congestive heart failure in 17 (33%). Forty-six (90%) had impaired left ventricular function. Twenty (39%) had an ejection fraction of less than or equal to 25%. Left main stenosis was present in 9 (18%), 3-vessel disease in 48 (94%) and 2-vessel disease in 2 (4%). Twenty (39%) were considered at a prohibitive risk for bypass surgery (14 were turned down for surgery). Bypass was instituted percutaneously with flows ranging from 2 to 5 liters/min (mean 3.6). Angioplasty was successful in 115 of the 117 lesions attempted with the culprit vessel dilated in all. Dilatation of the only remaining vessel was performed in 14 (27%). Inflation times up to 10 minutes were well tolerated. Bypass was discontinued after a mean bypass time of 37 minutes. Hemostasis was achieved by external clamp compression in 50. There were 3 hospital deaths unrelated to bypass. Patient follow-up at 2 to 8 months (mean 4.9) disclosed 1 late death, 31 (66%) asymptomatic patients, 12 (26%) patients in class I and 4 patients (9%) in class II. Thus, this study demonstrates the safety and efficacy of percutaneous bypass support in selected patients undergoing high-risk coronary angioplasty.     

Clinical efficacy and safety of intracoronary vs. intravenous abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention: a meta-analysis of randomized trials

Adjunctive therapy with abciximab has been proven to reduce mortality and reinfarction in patients with ST-elevation myocardial infarction (STEMI) referred to invasive management. Standard abciximab regimen consists of an intravenous (IV) bolus followed by a 12-h IV infusion. Experimental studies and small clinical trials suggest the superiority of intracoronary (IC) injection of abciximab over the IV route. We aimed to perform a meta-analysis of randomized controlled trials to assess the clinical efficacy and safety of IC vs. IV abciximab administration in STEMI patients undergoing primary percutaneous coronary intervention (PPCI). The primary endpoint was mortality, while recurrent myocardial infarction and target vessel revascularization (TVR) were selected as secondary endpoints. The safety endpoint was the risk of major bleeding complications. A total of six randomized trials were finally included in the meta-analysis, enrolling a total of 1246 patients. Compared to IV route, IC abciximab was associated with a significant reduction in mortality (odds ratio, OR [95% confidence interval (CI)]?=0.43 [0.20-0.94], p=0.03), and TVR (OR [95% CI]?=0.53 [0.29-0.99], p=0.05). No differences in terms of recurrent myocardial infarction (OR [95% CI]?=0.54 [0.23-1.28], p=0.17) or major bleeding complications (OR [95% CI]?=0.91 [0.46-1.79], p=0.79) were observed between the two strategies. The present meta-analysis showed that IC administration of abciximab is associated with significant benefits in mortality at short-term follow-up compared to IV abciximab administration, without any excess of major bleeding in STEMI patients undergoing PPCI. However, further trials are warranted to establish the optimal strategy of abciximab treatment in this setting.     

Safety of abciximab in patients with chronic renal insufficiency who are undergoing percutaneous coronary interventions

Background

Patients with chronic renal insufficiency (CRI) have worse outcomes during and after percutaneous coronary interventions (PCI). Abciximab reduces complications, but may cause excessive bleeding in patients with CRI. Therefore, we sought to determine the safety of abciximab in patients with CRI.

Methods

Patients (n = 4158) undergoing PCI at the Mayo Clinic since abciximab became available were analyzed according to their estimated creatinine clearance (≥70, 50-69, or <50 mL/min) or need for dialysis. Major bleeding was defined as a cerebrovascular bleed or a decrease in the hematocrit level >15%. Minor bleeding was defined as a decrease in the hematocrit level of 10% to 15% with an identifiable site of bleeding.

Results

CRI was associated with increased bleeding in patients who received abciximab and patients who did not. However, there was only a trend toward an interaction between creatinine clearance and major bleeding with abciximab (odds ratio [OR], 1.18; P = .06) and no interaction with minor bleeding (OR, 1.01; P = .94) or any bleeding (OR, 1.10; P = .15).

Conclusion

CRI is associated with an increased risk of bleeding complications after PCI. Although abciximab increases the risk of bleeding in all patients, the increase in relative risk is not significantly greater in patients with CRI. Thus, abciximab may be given safely in patients with CRI who are undergoing PCI.     

Effect of coronary endothelial function on outcomes in patients undergoing percutaneous coronary intervention

Numerous studies have documented the association between endothelial dysfunction and adverse cardiovascular events. For example, coronary artery disease is associated with functional and structural changes of the coronary arteries, resulting in ischemia or plaque rupture, and is highly associated with endothelial dysfunction. Recent data suggest that implantation of drug-eluting stents (DES) can induce coronary artery endothelial dysfunction at follow-up when compared with bare-metal stents (BMS) and that this endothelial dysfunction may be associated with late stent thrombosis. Indeed, despite the superiority of DES in preventing restenosis, the incidence of death and myocardial infarction is similar when comparing DES with BMS. Medical treatment, such as statins, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers, can improve endothelial dysfunction. Thus, administration of these drugs along with percutaneous coronary intervention (PCI) may be a low-risk strategy to provide therapeutic benefit by stabilizing unstable plaque or by suppressing new lesion formation in patients undergoing PCI.     

"High-risk" percutaneous transluminal coronary angioplasty

Of 6,500 percutaneous transluminal coronary angioplasty procedures performed between June 1980 and June 1987, 3,501 (1,604 single lesion and 1,897 multiple lesion) were performed in "low-risk" patients with a procedure-related mortality of 0.2 to 0.3%. In comparison, several clinical variables were identified that increased procedural risk by up to 50-fold. These factors include left main dilatation (n = 103, mortality 3.9%), left main equivalent dilatation (n = 77, mortality 2.6%), ejection fraction less than or equal to 40% (n = 664, mortality 2.7%), age greater than or equal to 70 years (n = 1,038, mortality 1.4%), dilatation of all 3 vessels (n = 305, mortality 1.3%), combined diagnostic catheterization and angioplasty for unstable angina (n = 193, mortality 1.5%), and percutaneous transluminal coronary angioplasty for acute myocardial infarction (n = 446, mortality 8.5%). Important considerations in the selection and management of these high-risk patients are discussed.     

The role of intra-aortic balloon counterpulsation in patients undergoing percutaneous transluminal coronary angioplasty

Between June, 1979, and July, 1982, 14 patients required an IABP in conjunction with PTCA. The clinical indications for balloon counterpulsation, in the performance of PTCA were (1) clinically unstable situations where PTCA might otherwise be contraindicated, e.g., left main stem disease, multivessel coronary artery disease, unstable anginal syndromes, and cardiogenic shock; (2) preoperative insertion of an IABP for added safety following unsuccessful angioplasty; (3) abrupt vessel closure during a PTCA procedure in which the patient becomes hemodynamically unstable; and (4) late vessel closure following an initially successful angioplasty resulting in hemodynamic compromise. Of the 14 cases requiring balloon counterpulsation, 13 survived hospitalization and were alive at the time this report was submitted. We conclude that IABP is a useful adjunct to PTCA in a variety of clinical circumstances.     

Septic endarteritis following percutaneous transluminal coronary angioplasty

We report a case of bacterial arteritis of the external iliac artery complicated by mycotic aneurysm following coronary angioplasty. To our knowledge, this is the first reported instance of arterial wall infection caused by coronary angioplasty at a distance from the insertion site equal to the length of the sheath.     

Impact of "off-label" utilization of drug-eluting stents on clinical outcomes in patients undergoing percutaneous coronary intervention

The utilization of drug-eluting stents (DES) in "real world" practice has deviated from Food and Drug Administration-approved indications. Safety concerns have arisen from recent reports that suggested increased mortality and nonfatal myocardial infarction (MI) with DES usage. Little is known about the clinical outcomes of patients undergoing intracoronary DES implantation for unapproved indications as a group compared with outcomes after bare metal stent (BMS) placement. The clinical outcomes of 546 patients undergoing DES implantation for >or=1 non-Food and Drug Administration-approved ("off label") indication since the approval of the device were assessed. The group was then matched by propensity score with 546 patients receiving BMSs prior to DES approval for the same indications. The primary endpoint was major adverse cardiac events (cardiac death, nonfatal Q-wave myocardial infarction [MI], and target vessel revascularization) at 12 months. Baseline clinical and angiographic characteristics were well matched between BMS and DES groups. The use of debulking devices was higher in the BMS group. Patients in the BMS group were more likely to be treated with larger diameter and shorter stents. There was no significant difference in the rate of in-hospital and 30-day adverse cardiac events. At 12 months, the primary endpoint of major adverse cardiac events was significantly reduced in the DES group (23.6% vs 16.7%, p=0.004), driven by reductions in the need for repeat revascularization (target lesion revascularization: 16.4% vs 7.8%, p<0.001; target vessel revascularization: 20.2% vs 13.1%, p=0.003). There was no significant difference in freedom from cardiac death or nonfatal Q-wave MI between groups (p=0.27). In conclusion, the utilization of DES for non-Food and Drug Administration-approved indications proved to be efficacious and safe when compared with a BMS cohort matched by propensity score. The advantage for DES was driven by reductions in repeat revascularization. "Off-label" DES use was not associated with increased rates of cardiac death and nonfatal MI at 12 months.