Drug-eluting stents for acute myocardial infarction.

This is a review of the literature comparing the efficacy and safety of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with acute myocardial infarction (MI). The present article reviews whether DES are beneficial in the setting of primary percutaneous coronary intervention (PCI), and this has been the subject of many recent publications and debate among clinicians. To the best of our knowledge there are limited registries and randomized trials about DES for acute MI in the English literature. Bare-metal stents have a higher incidence of instent restenosis whereas DES might have a slightly higher late thrombosis risk. With the current data DES might still have an advantage over BMS in the treatment of ST-segment elevation MI (STEMI) patients with the vastly improved target vessel revascularization rates. Despite the lack of well-designed head-to-head long-term prospective clinical trials, DES may not be effective in patients who are on short-term dual antiplatelet therapy owing to an increased risk of late stent thrombosis. In conclusion, DES use in STEMI patients continuing long-term dual antiplatelet therapy is safe and effective.

Combined cutting balloon angioplasty and intracoronary beta radiation for treatment of in-stent restenosis: clinical outcomes and effect of pullback radiation for long lesions.

Intracoronary beta (beta) radiation decreases the incidence of target lesion revascularization after percutaneous intervention (PCI) for in-stent restenosis (ISR). Cutting balloon (CB) angioplasty may also be superior to other percutaneous techniques for the treatment of ISR. We sought to study the outcomes of patients with ISR who underwent both CB angioplasty and intracoronay beta radiation and compare them to patients with ISR who underwent other PCI techniques without concomitant radiation. We also sought to evaluate the safety and efficacy of pullback intracoronary beta radiation for the treatment of long ISR lesions. Between January 2001 and November 2001, 102 patients (mean age = 55 +/- 13 years) with ISR underwent both CB angioplasty and intracoronay beta radiation. beta radiation was delivered using the Beta Cath (Novoste) 30 mm system, and pullback radiation was performed in 41 patients. A comparison group included a total of 393 patients with ISR who underwent other PCI techniques without concomitant intracoronary radiation therapy. Follow-up was obtained in 99 patients (97%) in the CB angioplasty with intracoronary radiation group and 377 patients (96%) in the comparison group. At follow-up, both target vessel revascularization (TVR) and major adverse cardiovascular events (MACE) occurred significantly less in the CB angioplasty with intracoronary radiation group than in the comparison group (7% vs. 18% for TVR, and 14% vs. 24% for MACE; P < 0.05 for both). In the pullback radiation group, TVR was performed in five patients (12%), and MACE occurred in eight patients (20%). A combination of CB angioplasty and intracoronay beta radiation for ISR seems to yield low rates of subsequent target vessel revascularization and adverse cardiac events. In addition, pullback beta radiation using the Beta Cath (Novoste) 30 mm system is safe and can be used to treat long ISR lesions effectively. Further randomized trials are needed to confirm these findings.

Risk assessment of slow or no-reflow phenomenon in aortocoronary vein graft percutaneous intervention.

Slow or no-reflow phenomenon (SNR) complicates 10%-15% of cases of percutaneous intervention (PCI) in aortocoronary saphenous vein grafts (SVG). At present, there are no uniform, effective strategies to predict or prevent this common and potentially serious complication. The purpose of our study was to characterize variables correlated with the risk of SNR in SVG PCI in the era of stenting and glycoprotein IIb/IIIa receptor inhibitors. We identified 2,898 consecutive patients who had PCI, of whom 163 underwent PCI of at least one SVG. The clinical and angiographic characteristics of patients who developed SNR (SNR group) were compared with those who did not (no-SNR group). A total of 23 patients experienced SNR and 140 did not. Using a stepwise multivariate logistic regression analysis, four independent predictors for SNR were detected: probable thrombus (OR 6.9; 95% CI, 2.1-23.9; P = 0.001), acute coronary syndromes (OR 6.4; 95% CI, 2.0-25.3; P = 0.003), degenerated vein graft (OR 5.2; 95% CI, 1.7-16.6; P = 0.003), and ulcer (OR 3.4; 95% CI, 0.99-11.6; P = 0.04). The risk of developing SNR could be estimated according to the number of predictors found: low-grade risk (1%-10%) if < or = one variable was present, moderate risk (20%-40%) if two variables were present, and high risk (60%-90%) if three or more variables were present. We identified and quantified current risk factors for SNR and concluded that the risk of developing SNR during PCI in SVG can be predicted by simple clinical and angiographic variables obtained before PCI. This information may be useful when the risk of PCI has to be balanced against alternative strategies such as medical therapy or redo-bypass surgery or in the selection of those patients that will most benefit from the use of protection devices during PCI.

Platelet inhibition reduces cyclic flow variations and neointimal proliferation in normal and hypercholesterolemic-atherosclerotic canine coronary arteries.

BACKGROUND: Platelet-derived growth factors help stimulate the neointimal proliferation of restenosis after coronary interventions. Reducing platelet accumulation at treated sites may attenuate restenosis. We tested this hypothesis by inducing repetitive platelet aggregation at coronary angioplasty sites in dogs and measuring subsequent neointima formation. METHODS AND RESULTS: Cholesterol-sensitive dogs (n=74) received either 4% cholesterol-enriched diets for >8 months (n=29), creating visible atheromas, or normal canine diets (n=45). A coronary balloon angioplasty cyclic flow variation (CFV) model was used. One group of control dogs (group 1, n=8) had angioplasty with no arterial constriction applied and no drug treatment. Three other groups had arterial constrictors applied to provoke CFVs: group 2 (n=28) received no drug therapy, group 3 (n=18) received oral aspirin alone, and group 4 (n=20) received 3 oral antiplatelet agents: ridogrel, ketanserin, and clopidogrel (R+K+C) to simultaneously inhibit the thromboxane A(2), serotonin, and ADP pathways of platelet aggregation, respectively. Bleeding times were moderately prolonged in the aspirin-treated group (124+/-9 seconds after 3 weeks versus 76+/-6 seconds at baseline, P<0.01) and greatly prolonged on R+K+C (>600 versus 104+/-5 seconds, P<0.001). The frequency and severity of CFVs were inversely related to the degree of platelet inhibition and prolongation of bleeding times, as was sudden death due to acute thrombotic coronary occlusion. Quantitative histology at 8 weeks revealed increased intima-to-media ratio with CFVs: 0.89+/-0.14 in the untreated group 2 versus 0.11+/-0.04 in the control group (P<0.001). Intima-to-media ratio was significantly reduced with antiplatelet treatment (0.27+/-0.05 with aspirin treatment and 0.20+/-0.05 with R+K+C treatment, respectively, P<0.001). Cholesterol feeding did not appear to influence results. CONCLUSIONS: Repetitive platelet accumulation at coronary angioplasty sites caused enhanced neointimal proliferation by 8 weeks. Oral inhibitors of platelet aggregation attenuated platelet function, prolonged bleeding times, reduced or prevented cyclic flows and abrupt thrombotic occlusions, and thereby inhibited neointimal proliferation. Platelet inhibition should continue to receive attention in efforts to reduce restenosis after coronary interventions.

Randomized comparison of a novel anticoagulant, vasoflux, and heparin as adjunctive therapy to streptokinase for acute myocardial infarction: results of the VITAL study (Vasoflux International Trial for Acute Myocardial Infarction Lysis).

BACKGROUND: Vasoflux is a low-molecular-weight heparin derivative that inhibits factor IXa activation of factor X and catalyzes fibrin-bound thrombin inactivation by heparin cofactor II. We studied whether vasoflux improves the results of thrombolysis with streptokinase for acute myocardial infarction. METHODS AND RESULTS: We randomized 277 patients with acute myocardial infarction to standard intravenous unfractionated heparin (UFH) or intravenous vasoflux 1, 4, 8, or 16 mg/kg as a bolus followed by 1, 4, 8, or 16 mg/kg per hour infusion, on top of streptokinase and aspirin, until angiography at 90 minutes. Patency and corrected Thrombolysis in Myocardial Infarction (TIMI) frame count were studied at 60 and 90 minutes. Rates of TIMI grade 3 flow with vasoflux at any dose (35% to 42%) were not different from UFH (41%) at either time point, nor was the corrected TIMI frame count. However, there was an excess of bleeding in the patients randomized to vasoflux 8 or 16 mg/kg: 78% and 71%, compared with 53% for UFH (P =.004 and.043, respectively). Major bleeding was observed in 13% and 28% at these vasoflux doses compared with 8% with UFH (P =.558 and.01, respectively). CONCLUSION: At doses that increase the risk of bleeding, the addition of vasoflux to streptokinase and aspirin did not lead to improved patency rates compared with UFH. Targeting factor IXa and heparin cofactor II may not be a useful adjunct to thrombolysis.

Percutaneous and surgical interventions for in-stent restenosis: long-term outcomes and effect of diabetes mellitus.

OBJECTIVE: We examined long-term outcomes of patients with in-stent restenosis (ISR) who underwent different percutaneous interventions at the discretion of individual operators: balloon angioplasty (BA), repeat stent or rotational atherectomy (RA). We also examined long-term outcomes of patients with ISR who underwent coronary artery bypass surgery (CABG). BACKGROUND: In-stent restenosis remains a challenging problem, and its optimal management is still unknown. METHODS: Symptomatic patients (n = 510) with ISR were identified using cardiac catheterization laboratory data. Management for ISR included BA (169 patients), repeat stenting (117 patients), RA (107 patients) or CABG (117 patients). Clinical outcome events of interest included death, myocardial infarction, target vessel revascularization (TVR) and a combined end point of these major adverse cardiovascular events (MACE). Mean follow-up was 19+/-12 months (range = 6 to 61 months). RESULTS: Patients with ISR treated with repeat stent had significantly larger average post-procedure minimal lumen diameter compared with BA or RA (3.3+/-0.4 mm vs. 3.0+/-0.4 vs. 2.9+/-0.5, respectively, p < 0.05). Incidence of TVR and MACE were similar in the BA, stent and RA groups (39%, 40%, 33% for TVR and 43%, 40%, 33% for MACE, p = NS). Patients with diabetes who underwent RA had similar outcomes as patients without diabetes, while patients with diabetes who underwent BA or stent had worse outcomes than patients without diabetes. Patients who underwent CABG for ISR, mainly because of the presence of multivessel disease, had significantly better outcomes than any percutaneous treatment (8% for TVR and 23% for MACE). CONCLUSIONS: In this large cohort of patients with ISR and in the subset of patients without diabetes, long-term outcomes were similar in the BA, repeat stent and RA groups. Tissue debulking with RA yielded better results only in diabetic patients. Bypass surgery for patients with multivessel disease and ISR provided the best outcomes.

Percutaneous intervention in saphenous venous grafts: in-stent restenosis lesions are safer than de novo lesions.

BACKGROUND: The histological appearance of stenosis in de novo saphenous venous grafts (DNSVG) consists of diffuse atherosclerosis that contains blood elements, necrotic debris and limited fibrocollagenous tissue. The friable nature of these lesions complicates percutaneous intervention (PCI) procedures. On the other hand, in-stent restenosis (ISR) of SVG is due primarily to atherosclerotic plaque or fibromuscular hyperplasia, with thrombus formation playing a secondary role. The purpose of this study is to compare the results of PCI in these two types of SVG lesions. METHODS: We reviewed our institutional interventional database from March 1996 through February 2000 and identified all consecutive patients who underwent PCI of at least one SVG. One hundred and ten patients were identified: 89 undergoing DNSVG intervention and 21 patients with ISR lesions. RESULTS: Acute coronary syndromes, degenerated and thrombus-containing lesions were more common in the DNSVG group. "Slow-, no-reflow" complicated 20% of the DNSVG lesions compared to none of the ISR lesions (p = 0.02). Post-procedural myocardial infarction was higher in the DNSVG group (13.5% versus 0%; p = 0.1) and correlated significantly with the occurrence of "slow-, no-reflow" (r = 0.43; p = 0.0001). Utilizing statistical modeling to adjust for baseline differences between the groups, ISR lesions were associated with a low risk of procedural complications (r = 0.22; p = 0.03). CONCLUSION: This study demonstrates that in this relatively high-risk population, PCI is safer in ISR lesions than in de novo SVG lesions.

"Hot" unstable angina--is it worse than subacute unstable angina? Results from the GUARANTEE Registry.

BACKGROUND AND METHODS: Because time to presentation to the hospital affects time to treatment and is known to be important in acute myocardial infarction, we evaluated this variable in patients with unstable angina/non-ST segment elevation myocardial infarction (UA/NSTEMI). Among 2909 consecutive patients with UA/NSTEMI admitted to 35 hospitals in 6 geographic regions of the United States, we compared patients with acute (onset of pain <12 hours before admission) and subacute (onset >12 hours) unstable angina. RESULTS: Patients with "hot" (acute) unstable angina presented more often to the emergency department and were subsequently admitted more often to an intensive care unit. Hospital administration of medications did not differ between the two groups, with the exception of heparin, which was paradoxically used more often in subacute patients (p<0.001). All cardiac invasive procedures were undertaken less often in the acute patients (catheterization, 41.4% vs. 58.7%, p=0.001; percutaneous coronary intervention, 11.3% vs. 21.1%, p=0.001; coronary artery bypass grafting, 5.6% vs. 12.0%, p=0.001). A greater percentage of acute patients were found to have no significant coronary artery disease at cardiac catheterization (20.1% vs. 15.0%, p=0.006). Mortality did not differ between the two groups; however, the composite endpoint of death and MI favored the acute patients (1.3% vs. 2.2%, p=0.032). CONCLUSIONS: Contrary to our initial hypothesis, "hot" UA patients tended to be at lower risk than patients with subacute presentation, highlighting the fact that patients with UA/NSTEMI remain at high risk even after the initial 12-hour period.

Adenosine use during aortocoronary vein graft interventions reverses but does not prevent the slow-no reflow phenomenon.

Slow or no reflow (SNR) complicates 10-15% of cases of percutaneous intervention (PI) in saphenous vein bypass graft (SVG). To date there have been limited options for the prevention and treatment of this common and potentially serious complication. We evaluated the procedural outcome of 143 consecutive SVG interventions. We compared patients who received pre-intervention intra-graft adenosine boluses with those who did not. In addition we examined the efficacy of adenosine boluses to reverse slow-no reflow events. Angiograms were reviewed and flow graded (TIMI grade) by film readers blinded to the use of any intraprocedural drug or clinical history. Seventy patients received intragraft adenosine boluses before percutaneous intervention (APPI), 73 received no preintervention adenosine (NoAPPI). There were no significant angiographic differences between the two groups at baseline. A total of 20 patients experienced SNR. The incidence of SNR was similar in the two groups (APPI = 14.2% vs. NoAPPI = 13.6%, P = 0.9). SNR was treated with repeated, rapid boluses (24 microg each) of intra-graft adenosine. Reversal of SNR was observed in 10 of 11 patients (91%) who received high doses of adenosine (>/=5 boluses, mean 7.7 +/- 2.6) and in 3 of 9 (33%) of those who received low doses (<5 boluses, mean 1.5 +/- 1.2). Final TIMI flow was significantly better in the high dose than in the low dose group (final TIMI 2.7 +/- 0.6 vs. 2 +/- 0.8, P = 0.04). No significant untoward complications were observed during adenosine infusion. These findings suggest that SNR after PI in SVG is not prevented by pre-intervention adenosine, but it can be safely and effectively reversed by delivery of multiple, rapid and repeated boluses of 24 microg of intra-graft adenosine.

Causes of early reintervention after successful coronary artery stenting.

Acute reintervention was performed in 26 of 1,620 patients after coronary stenting (1.6%). Half of the patients had stent thrombosis and the other half residual anatomic problems. The mean time for reintervention was shorter in patients with stent thrombosis. All patients with stent thrombosis had a sudden recurrence of chest pain. Electrocardiographic changes were more common with stent thrombosis. Composite end point occurred in 10 patients (77%) with stent thrombosis versus 5 (39%) in the other group (p = 0.04).