Optimal treatment of ACS patients: issues and considerations for upstream antiplatelet therapy.

Acute coronary syndromes (ACS) caused by atherosclerotic plaque rupture are clinically manifested as an ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, or unstable angina. Regardless of the management strategy chosen, antithrombotic therapy is necessary to optimize patient outcomes. The American College of Cardiology/American Heart Association guidelines provide a degree of flexibility in the use of antithrombotic and antiplatelet therapies; although this is largely influenced by the clinical severity of the ACS presentation, it can still be difficult for clinicians to decide which antiplatelet therapy regimen should be used. In this article, current recommendations for the use of antiplatelet therapy in the management of ACS are reviewed, along with an overview of the timing of upstream treatment and the decision points involved in choosing the appropriate antiplatelet regimen.

In-stent restenosis and remote coronary lesion progression are coupled in cardiac transplant vasculopathy but not in native coronary artery disease.

OBJECTIVES: The purpose of this study was to describe the clinical, angiographic, and histological features of concomitant in-stent restenosis (ISR) and cardiac allograft vasculopathy (CAV) progression. BACKGROUND: Cardiac allograft vasculopathy is a major challenge to long-term success of heart transplantation. Coronary stenting for CAV is hampered by ISR. METHODS: Quantitative coronary angiography compared late lumen loss (LL) at stented and reference, non-stented segments during 1-year follow-up in post-heart transplant and control atherosclerosis patients. Stented and non-stented arteries with CAV were also obtained post-mortem for immunohistochemical analysis. RESULTS: In 37 stented lesions (25 patients), 1-year binary restenosis occurred in 37.8%. Patients with ISR had higher long-term cardiac death/myocardial infarction rates than patients without ISR (53.8% vs. 9.1%, p = 0.03). In the same 25 patients, 34 CAV lesions with non-significant obstructions were identified as reference controls. After 1 year, patients who developed ISR also had more control lesion LL (0.78 +/- 0.38 mm vs. 0.39 +/- 0.27 mm, p < 0.006) compared to patients without ISR. In the post-transplant patients, in-stent LL was closely coupled to control segment LL (R(2) = 0.63, p < 0.05). Conversely, in native atherosclerosis patients, ISR and remote disease progression were not correlated. Histological staining of stented and control arteries from CAV patients revealed similar pathologies common to ISR and non-intervened CAV segments. CONCLUSIONS: Progression of CAV at non-intervened segments and ISR correlate strongly and share common histopathology. Optimized treatment for patients with aggressive CAV needs to address the widespread nature of this disease, even when it presents as an initially focal lesion.

Effect of tirofiban before primary angioplasty on initial coronary flow and early ST-segment resolution in patients with acute myocardial infarction.

Sixty-one patients with ST elevation acute myocardial infarction were randomized to receive open-label tirofiban in the emergency room before primary angioplasty versus glycoprotein IIb/IIIa inhibitors administered after initial coronary angiography. Early administration of tirofiban before primary angioplasty resulted in nonsignificant improvement in initial coronary flow (Thrombolysis In Myocardial Infarction trial grade 2 or 3 flow, 39% vs 27%, p >0.20). Patients receiving early tirofiban treatment were more likely to achieve complete (>70%) ST-segment resolution at 90 minutes (69% vs 44%, p = 0.07).

Effects of ischemia on repolarization in patients with single and multivessel coronary disease.

To evaluate if QT dispersion (QTd) may be affected by the number of obstructed coronary arteries (CAs) in patients with acute myocardial infarction (MI) and undergoing angioplasty, and to evaluate if QTd may be affected by ejection function of the heart. The infarct related CA was identified by coronary angiography in 141 patients (97 men, mean age 61.6 +/- 12.9 years) with acute MI undergoing percutaneous angioplasty. Successful reperfusion was defined as TIMI III flow with < 20% residual stenosis. QTd, calculated by subtracting the shortest from the longest QT interval on 12-lead electrocardiograms, was examined immediately before and after angioplasty, at 24 hours, and 3 days after angioplasty. Successful reperfusion was achieved in 98 (69.5%) patients. Prolonged QTd at baseline was found in all patients with ischemia. A trend toward a decrease in QTd was observed immediately after angioplasty and at 24 hours, and a significant decrease at 3 days in patients with successful reperfusion regardless of the number of occluded CAs. There was no change in QTd found in patients with no reperfusion. An increase in QTd was observed in patients with acute ischemia due to single or multivessel disease.

The immediate and short-term effect of successful percutaneous coronary intervention on repolarization in acute myocardial infarction patients.

OBJECTIVES: The primary objective was to assess the immediate and short-term impact of successful percutaneous coronary intervention (PCI) on QT dispersion (QT disp) and corrected QT dispersion (QTc disp). Secondarily, the impact of PCI on QT and QTc disp within different infarct-related arteries and the impact of successful PCI in these different arteries were evaluated. METHODS: Patients (n = 140, age 61.6 +/- 12.9, 69% male) undergoing direct primary PCI for acute MI were evaluated. Twelve-lead ECGs were obtained before (baseline), immediately after (0 h), 24hours after, and 3 days after PCI. The QT and QTc interval in each of the 12-leads were measured and the shortest interval was subtracted from the longest to derive the QT disp and QTc disp, respectively. RESULTS: Angiography showed blockages in the left anterior descending, right coronary artery, and circumflex in 37.1, 48.9, and 15.0% of patients, respectively. Overall, 97 patients achieved successful reflow. QT and QTc disp were significantly improved in the group with successful reflow at each follow-up time after PCI versus baseline and corresponding values in the unsuccessful reflow group. QT disp was improved among patients with successful reflow irrespective of which infarct artery was responsible for the acute myocardial infarction. CONCLUSIONS: Successful reflow with PCI is associated with a rapid reduction in QT disp and QTc disp that is maintained for at least 3 days after the event. Conversely, unsuccessful reflow was not associated with significant reductions in QT or QTc disp.

A comparison of two individual amiodarone regimens to placebo in open heart surgery patients.

BACKGROUND: This study compares the ability of two oral amiodarone regimens to reduce the risk of atrial fibrillation (AF) as compared with the placebo among elderly open heart surgery (OHS) patients receiving beta blockade. METHODS: This is a randomized, double-blinded, placebo-controlled trial of 220 patients undergoing OHS. Patients (average age, 73 years) received 7 g of oral amiodarone more than 10 days starting 5 days before OHS (slow load; n = 56), a 6 g oral amiodarone regimen more than 6 days starting 1 day before OHS (fast load; n = 64), or matching placebo in one of the two previously mentioned regimens (n = 100). RESULTS: Patients receiving the slow load amiodarone regimen had a significant reduction in the risk of AF (48.4%; p = 0.013), AF lasting more than 24 hours (76.5%; p = 0.003), symptomatic AF (90.0%; p = 0.002), and recurrent AF (64.5%; p = 0.025) as compared with the placebo. Patients receiving the fast load amiodarone regimen had significant reductions in the risk of AF lasting more than 24 hours (52.6%; p = 0.038) and symptomatic AF (65.0%; p = 0.024), but the incidence of any AF or any recurrence of AF only showed a trend toward significance (34.0% and 45.5%; p = 0.054 and 0.09, respectively). CONCLUSIONS: Oral amiodarone in a slow loading regimen provides significant suppression of all AF factors and can be used when a patient has started it at least 5 days before OHS. If a patient has less than 5 days before OHS, the fast loading regimen is an efficacious alternative as it provides significant benefits in preventing AF from lasting more than 24 hours and for preventing symptomatic AF. Both regimens were well tolerated and safe in elderly patients receiving beta blockade according to the hospital's standard protocol.

The effects of hydroxy-methyl-glutaryl co-enzyme A reductase inhibitors on platelet thrombus formation.

BACKGROUND: Hydroxy-methyl-glutaryl co-enzyme A reductase inhibitors (HMG CoA RIs) markedly improve the lipid profile of patients with hypercholesterolemia, but the magnitude and time course of the effect of these drugs on other risk factors for atherosclerosis are not well defined. METHODS: We employed a random assignment, double-blind design to compare the effect of 8 weeks of HMG CoA RI therapy with either pravastatin (40 mg QD; n=12) or simvastatin (20 mg QD; n=12) with placebo (n=13) on serum lipids, platelet thrombus formation (PTF), and markers of inflammation and thrombosis in patients with coronary artery disease. PTF was measured using a validated ex vivo perfusion chamber system. RESULTS: Total and LDL cholesterol decreased 20.3 +/- 12.7% and 31.4 +/- 16.5% in the HMG CoA RI group and were unchanged with placebo (P<0.01). Triglycerides also decreased 15.3 +/- 22.5% with HMG CoA RI therapy, but increased 8.4 +/- 30.0% with placebo (P=0.01). PTF increased 54.1 +/- 89.0% with placebo and decreased 8.0 +/- 46.82% with HMG CoA RI treatment (P<0.01). CONCLUSIONS: HMG CoA RI therapy with pravastatin or simvastatin reduces PTF after only 8 weeks of therapy. Such lipid effects may contribute to the prompt reduction in cardiovascular events noted in some clinical trials.

Impact of diabetes on the risk stratification using stress single-photon emission computed tomography myocardial perfusion imaging in patients with symptoms suggestive of coronary artery disease.

BACKGROUND: Coronary artery disease can develop prematurely and is the leading cause of death among diabetics, making noninvasive risk stratification desirable. METHODS AND RESULTS: Patients with symptoms of coronary artery disease who were undergoing stress myocardial perfusion imaging (MPI) from 5 centers were prospectively followed (2.5+/-1.5 years) for the subsequent occurrence of cardiac death, myocardial infarction (MI), and revascularization. Stress MPI results were categorized as normal or abnormal (fixed or ischemic defects and 1, 2, or 3 vessel distribution). Of 4755 patients, 929 (19.5%) were diabetic. Patients with diabetes, despite an increased revascularization rate, had 80 cardiac events (8.6%; 39 deaths and 41 MIs) compared with 172 cardiac events (4.5%; 69 deaths and 103 MIs) in the nondiabetic cohort (P<0.0001). Abnormal stress MPI was an independent predictor of cardiac death and MI in both populations. Diabetics with ischemic defects had an increased number of cardiac events (P<0.001), with the highest MI rates (17.1%) observed with 3-vessel ischemia. Similarly, a multivessel fixed defect was associated with the highest rate of cardiac death (13.6%) among diabetics. The unadjusted cardiac survival rate was lower for diabetic patients (91% versus 97%, P<0.001), but it became comparable once adjusted for the pretest clinical risk and stress MPI results. In multivariable Cox analysis, both ischemic and fixed MPI defects independently predicted cardiac death alone or cardiac death/MI. Diabetic women had the worst outcome for any given extent of myocardial ischemia. CONCLUSIONS: In this large cohort of diabetics undergoing stress MPI, the presence and the extent of abnormal stress MPI independently predicted subsequent cardiac events. Using stress MPI in conjunction with clinical information can provide risk stratification of diabetic patients.

An economic analysis of amiodarone versus placebo for the prevention of atrial fibrillation after open heart surgery.

STUDY OBJECTIVE: To determine if the additional costs of oral amiodarone in patients undergoing open heart surgery would be offset by reductions in the frequency of atrial fibrillation. DESIGN: Piggyback cost analysis of the data from a randomized, double-blind, placebo-controlled trial. SETTING: Urban academic hospital. PATIENTS: Two hundred twenty elderly patients (> or = 60 yrs old) undergoing open heart surgery. INTERVENTION: Hospital costs of open heart surgery in patients given amiodarone for the prevention of atrial fibrillation and in prespecified subgroups were compared with those for patients given placebo (i.e., standard care with beta-blockers alone). MEASUREMENTS AND MAIN RESULTS: Total hospital costs incurred were $15,565 +/- $9832 and $16,126 +/- $8043 in the amiodarone and placebo groups, respectively (p=0.12). General ward, intensive care unit, operating room, pharmacy, and costs in all other departments were similar between the groups (p>0.05 for all comparisons). Because costs were similar but amiodarone was more effective than placebo, amiodarone was cost-effective compared with placebo. Amiodarone remained cost-effective compared with placebo regardless of the following subgroup characteristics: rapid or slow loading strategy, no history of atrial fibrillation or heart failure, age older than 70 years, and no tolerance to preoperative beta-blockers. Moreover, in the one-way sensitivity analysis, the findings remained robust to changes in effectiveness and cost of amiodarone. CONCLUSION: Routine prophylaxis with amiodarone is cost-effective compared with placebo. Future studies should examine the cost-effectiveness of selective prophylaxis, and primary cost-effectiveness studies should be conducted to validate these findings.

Results of primary percutaneous transluminal coronary angioplasty plus abciximab with or without stenting for acute myocardial infarction complicated by cardiogenic shock.

This study examines the effects of abciximab as adjunctive therapy in primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction (AMI) complicated by cardiogenic shock. Abciximab improves the outcome of primary PTCA for AMI, but its efficacy in cardiogenic shock remains unknown. Case report forms were completed in-hospital and follow-up was obtained by telephone, outpatient visit, and review of hospital readmission records. A total of 113 patients with cardiogenic shock from AMI were included. All underwent emergency PTCA during which abciximab was administered to 54 patients (48%). The 2 groups of patients who received and did not receive abciximab were similar at baseline. Coronary stents were implanted slightly more often in the abciximab group (59% vs 42%; p = 0.1). A significantly improved final TIMI flow, less no-reflow, and a decrease in vessel residual diameter stenosis occurred in the abciximab group. At 30-day follow-up, the composite event rate of death, myocardial reinfarction, and target vessel revascularization was better in the abciximab group (31% vs 63%; p = 0.002). The combination of abciximab and stents was synergistic and resulted in improvement of all components of the composite end point beyond that seen with each therapy alone. Thus, abciximab therapy improves the 30-day outcome of primary PTCA in cardiogenic shock, especially when combined with coronary stenting.

Clinical and angiographic outcome in the laser angioplasty for restenotic stents (LARS) multicenter registry

In-stent restenosis (ISR) when treated with balloon angioplasty (PTCA) alone, has a angiogrphic recurrence rate of 30%-85%. Ablating the hypertrophic neointimal tissue prior to PTCA is an attractive alternative, yet the late outcomes of such treatment have not been fully determined. This multicenter case control study assessed the angiographic and clinical outcomes of 157 consecutive procedures in 146 patients with ISR at nine institutions treated with either the PTCA alone (n=64)o excrimer laser assisted coronary angioplasty (ELCA, n=93) for ISR. Demographics were similar except more unstable angina at presentation in ELCA-treated patients (74.5% vs 63.5$; P=0.141). Lesions selected for ELCA were longer (16.8 +_ 11.2mm vs. 11.2+_ 8.6 mm;P < 0.001), more complex (ACC/AHA type C:35.1% vs. 13.6%;P<0.00001)...