Prognostic impact of blood transfusion after primary angioplasty for acute myocardial infarction: analysis from the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) Trial.

OBJECTIVES: We sought to determine the relationship between red blood cell (RBC) transfusion and clinical outcomes in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). BACKGROUND: The implications of RBC transfusion in patients undergoing primary PCI for AMI have not been evaluated. METHODS: Clinical outcomes of patients from the prospective, randomized CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) trial were analyzed by administration of in-hospital RBC transfusion not related to coronary artery bypass surgery. RESULTS: Of 2,060 randomized patients, 82 (3.98%) received RBC transfusion during the index hospitalization, including 33 (1.60%) with moderate/severe bleeding and 49 (2.38%) without overt major bleeding. Transfusion was independently associated with baseline anemia (odds ratio [95% confidence interval]: 4.44 [2.60 to 7.58], p < 0.0001), older age (1.03 [1.01 to 1.06], p = 0.002), triple-vessel disease (2.54 [1.47 to 4.38], p = 0.0008), and female sex (1.04 [1.02 to 1.06], p = 0.0008). Patients transfused versus not transfused had significantly higher rates of 1-year mortality (23.9% vs. 3.4%), disabling stroke (2.5% vs. 0.5%), reinfarction (7.0% vs. 2.2%), and composite major adverse cardiac events (41.0% vs. 16.6%) (all p values < 0.01). After multivariable adjustment for potential confounders including transfusion propensity, RBC transfusion was independently associated with mortality at 30 days (hazards ratio: 4.71, p = 0.0005) and 1 year (hazards ratio: 3.16, p = 0.0005). CONCLUSIONS: An RBC transfusion after primary PCI in AMI may be harmful, which is consistent with the findings from other studies after PCI in the noninfarct setting. Alternatively, RBC transfusion may be a marker of markedly increased risk. Randomized studies are warranted to determine the optimal threshold for RBC transfusion in patients with AMI undergoing mechanical reperfusion therapy.

Impact of thienopyridine administration prior to primary stenting in acute myocardial infarction.

The impact of thienopyridine administration prior to primary stenting in acute myocardial infarction (AMI) has not been well studied. We therefore examined the database from the prospective, multicenter, controlled CADILLAC trial in which 1,036 patients were randomized to bare metal stenting with or without abciximab to determine whether patients who received a thienopyridine prior to bare metal stenting in AMI had superior clinical outcomes. Per operator discretion, 659 patients (63.6%; Th+) received either a 500 mg ticlopidine loading dose (n = 623) or a 300 mg clopidogrel loading dose (n = 40), while 377 patients (36.4%; Th-) received no thienopyridine prior to stent implantation. Baseline and procedural characteristics of the two groups, including abciximab use (52.5% vs 52.8%, P = 0.93) were well matched. Th+ compared to Th- patients had lower rates of core lab assessed TIMI 0/1 flow postprocedure (0.8% vs 2.7%, P = 0.01). Th+ compared to Th- patients also had significantly reduced in-hospital and 30-day rates of ischemic target vessel revascularization (TVR) (1.1% vs 3.2%, P = 0.01 and 1.5% vs 3.8%, P = 0.02, respectively) and major adverse cardiovascular events (MACE) (2.7% vs 5.8%, P = 0.01 and 4.0% vs 6.9%, P = 0.03, respectively), results that remained significant after covariate adjustment. In conclusion, in this large prospective, controlled trial, patients receiving a thienopyridine prior to primary stenting in AMI were less likely to have TIMI 0/1 flow postprocedure and experienced reduced in-hospital and 30-day rates of ischemic TVR and MACE compared to those not administered a thienopyridine prior to stent implantation.

Predictors of infarct size after primary coronary angioplasty in acute myocardial infarction from pooled analysis from four contemporary trials.

Determinates of infarct size in patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) have been incompletely characterized, in part because of the limited sample size of previous studies. Databases therefore were pooled from 4 contemporary trials of primary or rescue PCI (EMERALD, COOL-MI, AMIHOT, and ICE-IT), in which the primary end point was infarct size assessed using technetium-99m sestamibi single-photon emission computed tomographic imaging, measured at the same core laboratory. Of 1,355 patients, infarct size was determined using technetium-99m sestamibi imaging in 1,199 patients (88.5%), at a mean time of 23 +/- 15 days. Median infarct size of the study population was 10% (interquartile range 0% to 23%; mean 14.9 +/- 16.1%). Using multiple linear regression analysis of 18 variables, left anterior descending infarct artery, baseline Thrombolysis In Myocardial Infarction grade 0/1 flow, male gender, and prolonged door-to-balloon time were powerful independent predictors of infarct size (all p <0.0001). Other independent correlates of infarct size were final Thrombolysis In Myocardial Infarction grade <3 flow (p = 0.0001), previous AMI (p = 0.005), symptom-onset-to-door time (p = 0.021), and rescue angioplasty (p = 0.026). In conclusion, anterior infarction, time to reperfusion, epicardial infarct artery patency before and after reperfusion, male gender, previous AMI, and failed thrombolytic therapy were important predictors of infarct size after angioplasty in patients with AMI assessed using technetium-99m sestamibi imaging and should be considered when planning future trials of investigational drugs or devices designed to enhance myocardial recovery.

Usefulness of routine unfractionated heparin infusion following primary percutaneous coronary intervention for acute myocardial infarction in patients not receiving glycoprotein IIb/IIIa inhibitors.

We evaluated the utility of a routine postprocedure course of unfractionated heparin after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) in patients not receiving glycoprotein IIb/IIIa inhibitors. In the CADILLAC study, 2,082 patients with AMI who underwent primary PCI were randomized to receive stents versus percutaneous transluminal coronary angioplasty (PTCA), each with or without abciximab. In a subset of 976 patients who did not receive abciximab, we compared outcomes of patients who received postprocedural heparin (n = 758; 78%; median duration 2 days) with those who did not. In 421 patients treated with PTCA, postprocedural heparin use was associated with lower in-hospital major adverse cardiac events (MACEs; 5.3% vs 11.4%, p = 0.069), 1-year MACEs (22% vs 31%, p = 0.08), and decreased in-hospital moderate/severe bleeding (2.3% vs 8.9%, p = 0.01). By multivariate analyses, heparin use correlated with freedom from in-hospital and 1-year MACEs in patients after PTCA. In contrast, in 555 patients who underwent stenting, postprocedural heparin use was associated with increased bleeding and hospitalization costs without a decrease in early or late MACEs. In conclusion, in patients with AMI treated with coronary stenting without glycoprotein IIb/IIIa inhibitors, routine postprocedural heparin was not associated with any significant benefits and may be safely omitted. However, in a subset of patients treated with PTCA, postprocedural heparin use was independently associated with fewer in-hospital and 1-year MACEs.

Comparative early and late outcomes after primary percutaneous coronary intervention in ST-segment elevation and non-ST-segment elevation acute myocardial infarction (from the CADILLAC trial).

We determined the outcomes of patients with acute ST-segment elevation (STE) myocardial infarction (STEMI) and non-STEMI (NSTEMI) after primary percutaneous coronary intervention (PCI). The prognosis after primary PCI in STEMI has been extensively studied and defined. Outcomes of patients who undergo primary PCI for NSTEMI are less well established. In total, 2,082 patients with ongoing chest pain for > 30 minutes consistent with acute MI were randomized to balloon angioplasty versus stenting, each with/without abciximab. Of 1,964 patients, STEMI was present in 1,725 (87.8%) and NSTEMI in 239 (12.2%). Compared with STEMI, those with NSTEMI were more likely to have delayed time-to-hospital arrival (2.4 vs 1.8 hours, p = 0.0002) and increased door-to-balloon time (3.2 vs 1.9 hours, p < 0.0001). Patients with NSTEMI were more likely to have Thrombolysis In Myocardial Infarction grade 3 flow at baseline (37.3% vs 19.4%, p < 0.0001) and higher ejection fraction (58.7% vs 55.8%, p = 0.001), but similar rates of postprocedural Thrombolysis In Myocardial Infarction grade 3 flow. At 1 year, patients with NTEMI had similar mortality (3.4% vs 4.4%, p = 0.40) but higher rates of major adverse cardiac events (24.0% vs 16.6%, p = 0.007) that was driven by more frequent ischemic target vessel revascularization (21.8% vs 11.9%, p <0.0001). In conclusion, patients with acute MI without STE who are treated with primary PCI have marked delays to treatment, similar late mortality, and increased rates of ischemic target vessel revascularization compared with patients with STEMI, despite more favorable angiographic features at presentation and similar reperfusion success. The adverse prognosis of patients with NSTEMI should be recognized and efforts made to decrease reperfusion times.

Impact of body mass index on outcomes after primary angioplasty in acute myocardial infarction.

BACKGROUND: The prognostic importance of obesity after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) is unknown. We therefore sought to investigate the impact of body mass index (BMI) in patients with AMI undergoing primary PCI. METHODS: In the CADILLAC trial, 2082 patients of any age with AMI within 12 hours onset undergoing primary PCI were randomized to balloon angioplasty versus stenting, each +/-abciximab. Outcomes were stratified by baseline BMI. RESULTS: Baseline BMI was measured in 2035 (98%) randomized patients; 552 (27%) patients have normal weight (BMI < 25 kg/m2), 915 (45%) were overweight (> or = 25 to < 30 kg/m2), and 568 (28%) were obese (> or = 30 kg/m2). Compared with normal-weight patients, obese patients were younger and more frequently had diabetes, hyperlipidemia, hypertension, non-anterior myocardial infarction, and higher creatinine clearance. Obese patients were less likely to develop thrombocytopenia (1.8% vs 4.2%), moderate hemorrhagic complications (1.4% vs 3.3%), or required blood product transfusions (3.2% vs 6.3%) (all P < or = .04). Obese compared with normal-weight patients had lower inhospital mortality (0.9% vs 2.7%, P = .03) at 30 days (1.1% vs 3.8%, P = .02) and 1 year (1.8% vs 7.5%, P < .0001). Independent predictors of 30-day and 1-year mortality included lower ejection fraction, advanced age, 3-vessel disease, anterior AMI, and lower creatinine clearance, but not BMI. CONCLUSIONS: Obese patients with AMI have an improved prognosis after primary PCI compared with normal-weight patients, a finding attributable to AMI onset at younger age, with better renal function and less anterior infarction.

Outcomes of patients consented but not randomized in a trial of primary percutaneous coronary intervention in acute myocardial infarction (the CADILLAC registry).

Baseline features, management, and outcomes of patients who had acute myocardial infarction (AMI) and were excluded from randomized trials of primary percutaneous coronary intervention (PCI) have not been well described. We examined the baseline features and outcomes of patients who had AMI and were excluded due to angiographic ineligibility from a randomized trial of primary PCI. The CADILLAC trial evaluated 4 primary PCI strategies in patients who had AMI without cardiogenic shock. Of 2,681 patients who consented, 599 (22.3%) were subsequently excluded from randomization due to protocol-specified angiographic findings. These patients were enrolled in a formal in-hospital registry and were treated at the discretion of attending physicians. Registry versus randomized patients were older (median age 61.9 vs 59.0 years, p = 0.002), more frequently had 3-vessel disease (52.4% vs 15.6%, p = 0.0001), and more frequently had lower left ventricular ejection fraction (45% vs 50%, p = 0.002). Registry patients were treated with PCI (n = 234), coronary artery bypass grafting (n = 136), or medically only (n = 226). In-hospital mortality rate among all patients who consented was 2.2% and was higher among registry than among randomized patients (4.0% vs 1.6%, relative risk 2.45, p = 0.001). Within the registry, covariate-adjusted risk of mortality was lower among patients who were treated by PCI compared with those who were treated medically (odds ratio 0.21, p=0.03). In conclusion, angiographic ineligibility for randomization in a large, prospective, primary PCI trial was associated with numerous high-risk demographic characteristics and higher short-term mortality. Nonetheless, the overall survival of patients who were referred for primary PCI was excellent, and performance of primary PCI versus medical therapy was associated with increased survival among excluded patients.

Impact of smoking status on outcomes of primary coronary intervention for acute myocardial infarction--the smoker's paradox revisited.

OBJECTIVES: We sought to determine the relationship between cigarette smoking and outcomes after mechanical reperfusion therapy in acute myocardial infarction (AMI). BACKGROUND: Prior studies have found that smokers with AMI have lower mortality rates and a more favorable response to fibrinolytic therapy than nonsmokers. The impact of cigarette smoking in patients undergoing primary percutaneous coronary intervention has not been examined. METHODS: In the CADILLAC trial, 2082 patients with AMI were randomized to percutaneous transluminal coronary angioplasty +/- abciximab versus stenting +/- abciximab. Data on smoking status were prospectively collected and follow-up continued for 1 year. RESULTS: At the time of presentation, 638 (31%) patients had never smoked, 546 (26%) were former smokers, and 898 (45%) were currently smoking. In comparison to nonsmokers, current smokers were younger, more often men, and less frequently had diabetes, hypertension, prior AMI, and triple-vessel coronary disease. Procedural success rates were unrelated to smoking status. Mortality was lowest in current smokers, intermediate in former smokers, and highest in nonsmokers at 30 days (1.3% vs 1.7% vs 3.5%, respectively, P = .02) and 1 year (2.9% vs 3.7% vs 6.6%, P = .0008). After multivariate correction for differences in baseline variables, however, current smoking status was no longer protective from late mortality (hazard ratio 0.96, 95% CI 0.52-1.76, P = .89). CONCLUSIONS: The "smoker's paradox" extends to patients undergoing primary PCI for AMI, with increased survival seen in current smokers, an effect entirely explained by differences in baseline risk and not smoking status per se. The deleterious effects of smoking are expressed in the occurrence of AMI nearly a decade earlier than in nonsmokers, with similar age-adjusted risk, mandating intensive primary and secondary cigarette-cessation efforts.

Impact of in-hospital acquired thrombocytopenia in patients undergoing primary angioplasty for acute myocardial infarction.

Thrombocytopenia that develops after percutaneous coronary intervention (PCI) may result in hemorrhagic complications, requirement for blood product transfusions, and potentially thrombotic or ischemic complications. The incidence and prognostic significance of thrombocytopenia, in patients with acute myocardial infarction (AMI) who undergo primary PCI have not been evaluated. In the CADILLAC trial 2,082 patients who had AMI within 12 hours of onset without shock were prospectively randomized to receive balloon angioplasty with or without abciximab versus stenting with or without abciximab. Acquired thrombocytopenia, defined as a nadir platelet count <100 x 10(9)/L in patients who did not have baseline thrombocytopenia, developed in 50 of 1,975 qualifying patients (2.5%) after primary PCI. By multivariate analysis, acquired thrombocytopenia developed more frequently in patients who had non-insulin-requiring diabetes mellitus (odds ratio 3.88 [OR], p = 0.0002), previous statin administration (OR 3.28, p = 0.002), and use of abciximab (OR 2.06, p = 0.02) and less frequently in patients who had previous aspirin use (OR 0.26, p = 0.002), a higher baseline platelet count (OR 1.20, p < 0.0001), and greater body mass index (OR 0.90, p = 0.006). Patients who developed thrombocytopenia versus those who did not had higher in-hospital rates of major hemorrhagic complications (10.0% vs 2.7%, p = 0.01), greater requirement for blood transfusions (10.0% vs 3.9%, p = 0.05), longer hospital stay (median 4.8 vs 3.6 days, p = 0.008), and increased costs (median dollar 14,466 vs dollar 11,629, p = 0.001). All-cause mortality was markedly increased at 30 days (8.0% vs 1.6%, p = 0.0008) and at 1 year (10.0% vs 3.9%, p = 0.03) in patients who developed thrombocytopenia. In conclusion, thrombocytopenia that develops after primary PCI for AMI, although uncommon, is associated with increased hemorrhagic complications and decreased survival.

Impact of stenting and abciximab in patients with diabetes mellitus undergoing primary angioplasty in acute myocardial infarction (the CADILLAC trial).

We sought to determine the benefits of stent implantation and abciximab in patients with diabetes mellitus and acute myocardial infarction (AMI) who underwent primary angioplasty. In a 2-by-2 factorial design, 2,082 patients with AMI were randomly assigned to balloon angioplasty versus stenting, with or without abciximab. Diabetes was present in 346 patients (16.6%). The primary end point was the composite incidence of death, disabling stroke, reinfarction, and ischemic target vessel revascularization (TVR). The primary end point at 1 year occurred significantly more frequently in diabetic than nondiabetic patients (21.9% vs 16.8%, p <0.02), driven by increased rates of death (6.1% vs 3.9%, p = 0.04) and TVR (16.4% vs 12.7%, p = 0.07). Among patients with diabetes, TVR at 1 year was significantly reduced with routine stenting compared with balloon angioplasty (10.3% vs 22.4%, p = 0.004), with no differences in death, reinfarction, or stroke. Angiographic restenosis was also greatly reduced in diabetics randomized to stenting (21.1% vs 47.6%, p = 0.009). No beneficial effects were apparent with abciximab in diabetic patients at 1 year. Despite the improved outcomes with stenting in patients with diabetes, 1-year mortality remained increased in diabetic patients who received stents compared with nondiabetics (8.2% vs 3.6%, p = 0.005). Thus, routine stent implantation in diabetic patients with AMI significantly reduces restenosis and enhances survival free from TVR, independent of abciximab use, although survival remains reduced compared with survival in nondiabetic patients regardless of reperfusion modality.

Predictors of and outcomes of early thrombosis following balloon angioplasty versus primary stenting in acute myocardial infarction and usefulness of abciximab (the CADILLAC trial).

We sought to identify the predictors and clinical outcomes of early thrombosis after primary angioplasty and stenting for acute myocardial infarction (AMI). Little is known about the correlates and prognosis of acute and subacute thromboses after percutaneous coronary intervention (PCI) for AMI. We therefore studied the frequency, clinical determinants, and implications of early thrombosis in a large trial of patients who had primary PCI. In the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications trial, 2,082 patients who had AMI were randomized in a 2 x 2 factorial design to primary stenting or to balloon angioplasty, each with and without abciximab. Early thrombosis occurred in 19 patients (0.9%) at a median of 2 days (range 0 to 23). Maximal balloon diameter was smaller, and aneurysmal and bifurcation lesions were more prevalent in the group with early thrombosis. Early thrombosis occurred in 0.4% of patients who had been randomized to receive abciximab versus 1.5% of control patients (p <0.01) and in 0.5% of patients who had been randomized to undergo stenting versus 1.4% of those who underwent balloon angioplasty (p = 0.04). By multivariate analysis, abciximab use was an independent predictor of no thrombosis (hazard ratio 0.27, 95% confidence interval 0.09 to 0.86, p = 0.026). Within 30 days, 5.3% of patients who had early thrombosis died, 32.9% developed reinfarction, and 89.5% required repeat target vessel revascularization (including bypass surgery in 11.1%). As a result, patients who had versus those who did not have early thrombosis had markedly higher rates of major adverse cardiac events at 30 days (94.7% vs 5.0%, p <0.0001) and at 1 year (94.7% vs 16.9%, p <0.0001). Patients who develop early thrombosis after primary PCI have a very high rate of major adverse cardiac events, including death and reinfarction, and usually require repeat coronary angioplasty or surgery for management. Complex baseline angiographic morphology and smaller maximal balloon diameter are predictors of early thrombosis after primary PCI for AMI. The incidence of early thrombosis after primary angioplasty and stenting is decreased by abciximab use.

Influence of admission and discharge aspirin use on survival after primary coronary angioplasty for acute myocardial infarction.

We examined the effect of aspirin use at the time of admission and discharge from a large-scale, prospective multicenter trial of patients who had been treated with primary percutaneous coronary intervention in acute myocardial infarction.

Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: analysis from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial.

OBJECTIVES: We sought to investigate the impact of anemia in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI). BACKGROUND: The prognostic importance of anemia on primary PCI outcomes is unknown. METHODS: In the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial, 2,082 patients of any age with AMI within 12 h onset undergoing primary PCI were randomized to balloon angioplasty versus stenting, each +/- abciximab. Outcomes were stratified by the presence of anemia at baseline, as defined by World Health Organization criteria (hematocrit <39% for men and <36% for women). RESULTS: Anemia was present in 260 (12.8%) of 2,027 randomized patients with baseline laboratory values. Patients with versus without baseline anemia more frequently developed in-hospital hemorrhagic complications (6.2% vs. 2.4%, p = 0.002), had higher rates of blood product transfusions (13.1% vs. 3.1%, p < 0.0001), and had a prolonged (median 4.1 vs. 3.5 days, p < 0.0001) and more expensive (median costs $12,434 vs. $11,603, p = 0.002) index hospitalization. Patients with versus without anemia had strikingly higher mortality during hospitalization (4.6% vs. 1.1%, p = 0.0003), at 30 days (5.8% vs. 1.5%, p < 0.0001), and at 1 year (9.4% vs. 3.5%, p < 0.0001). The rates of disabling stroke at 30 days (0.8% vs. 0.1%, p = 0.005) and at 1 year (2.1% vs. 0.4%, p = 0.0007) were also significantly higher in patients with anemia. By multivariate analysis, anemia was an independent predictor of in-hospital mortality (hazard ratio, 3.26; p = 0.048) and one-year mortality (hazard ratio, 2.38; p = 0.016). CONCLUSIONS: Anemia at baseline in patients with AMI undergoing primary PCI is common, and is strongly associated with adverse outcomes and increased mortality.

Magnitude and impact of treatment delays on weeknights and weekends in patients undergoing primary angioplasty for acute myocardial infarction (the cadillac trial).

In 2,082 patients in the CADILLAC trial, the outcomes of patients presenting during peak hours were compared with those presenting during peak hours (Monday to Friday 8a.m. to 8 p.m., n = 1,047, 51%) were compared with those of patients presenting during off-peak hours (weeknights from 8 p.m. to 8 a.m. and weekends, n = 989, 49%). Although treatment times to percutaneous coronary intervention (PCI) were delayed approximately 21 minutes, in patients with acute myocardial infarctions occurring on weeknights and weekends, this modest delay did not adversely affect procedural success, myocardial recovery, or survival after PCI.

Outcome in elderly patients undergoing primary coronary intervention for acute myocardial infarction: results from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.

BACKGROUND: Biological age is a strong determinant of prognosis in patients with acute myocardial infarction (AMI). We sought to examine the impact of age after primary percutaneous coronary intervention in AMI and to determine whether routine coronary stent implantation and/or platelet glycoprotein IIb/IIIa inhibitors improve clinical outcomes in elderly patients after primary angioplasty. METHODS AND RESULTS: In the CADILLAC trial, 2082 patients with AMI were randomized to balloon angioplasty, angioplasty plus abciximab, stenting alone, or stenting plus abciximab. No patient was excluded on the basis of advanced age; patients ranging from 21 to 95 years of age were enrolled. One-year mortality increased for each decile of age, exponentially after 65 years of age (1.6% for patients <55 years, 2.1% for 55 to 65 years, 7.1% for 65 to 75 years, 11.1% for patients >75 years; P<0.0001). Elderly patients also had increased rates of stroke and major bleeding compared with their younger counterparts. Among elderly patients (> or =65 years), 1-year rates of ischemic target revascularization (7.0% versus 17.6%; P<0.0001) and subacute or late thrombosis (0% versus 2.2%; P=0.005) were reduced with stenting compared with balloon angioplasty. Routine abciximab administration, although safe, was not of definite benefit in elderly patients. Rates of mortality, reinfarction, disabling stroke, and major bleeding in the elderly were independent of reperfusion modality. CONCLUSIONS: Despite contemporary mechanical reperfusion strategies, mortality, major bleeding, and stroke rates remain high in elderly patients undergoing primary percutaneous coronary intervention, outcomes that are not affected by stents or glycoprotein IIb/IIIa inhibitors. By reducing restenosis, however, stent implantation improves clinical outcomes in elderly patients with AMI.

Frequency, correlates, and clinical implications of myocardial perfusion after primary angioplasty and stenting, with and without glycoprotein IIb/IIIa inhibition, in acute myocardial infarction.

OBJECTIVES: We sought to determine the prognostic importance of myocardial reperfusion after various contemporary interventional strategies in patients with acute myocardial infarction (AMI). BACKGROUND: The frequency, correlates, and clinical implications of myocardial perfusion after primary angioplasty in AMI have not been examined in a large-scale prospective study. Similarly, whether glycoprotein (GP) IIb/IIIa inhibitors and/or stents improve myocardial perfusion beyond balloon angioplasty has not been investigated. METHODS: Tissue-level perfusion assessed by the myocardial blush grade was evaluated in 1,301 patients with AMI randomized to balloon angioplasty versus stenting, each with or without abciximab. RESULTS: Despite Thrombolysis In Myocardial Infarction flow grade 3 restoration in 96.1% of patients, myocardial perfusion was normal in only 17.4% of patients, reduced in 33.9%, and absent in 48.7%. Myocardial perfusion status post-coronary intervention stratified patients into three distinct risk categories, with 1-year mortality rates of 1.4% (normal blush), 4.1% (reduced blush), and 6.2% (absent blush) (p = 0.01). Among patients randomized to angioplasty, angioplasty + abciximab, stenting, and stenting + abciximab, normal myocardial perfusion was restored in 17.7%, 17.0%, 17.5%, and 17.6%, respectively (p = 0.95), which was associated with similar 1-year rates of mortality in patients randomized to stenting versus angioplasty (4.5% vs. 4.8%, p = 0.91) and abciximab versus no abciximab (4.3% vs. 5.0%, p = 0.63). CONCLUSIONS: Restoration of normal tissue-level perfusion is a powerful determinate of survival after primary PCI in AMI and is achieved in a minority of patients. Neither stents nor GP IIb/IIIa inhibitors significantly enhance myocardial perfusion compared to balloon angioplasty alone, underlying the similar long-term mortality with these different mechanical reperfusion strategies.

Impact of intravenous beta-blockade before primary angioplasty on survival in patients undergoing mechanical reperfusion therapy for acute myocardial infarction.

OBJECTIVES: We sought to examine the effect of intravenous beta-blockers administered before primary percutaneous coronary intervention (PCI) on survival and myocardial recovery after acute myocardial infarction (AMI). BACKGROUND: Studies of primary PCI but not thrombolysis have suggested that beta-blocker administration before reperfusion may enhance survival. Whether oral beta-blocker use before admission modulates this effect is unknown. METHODS: The Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial randomized 2082 AMI patients to either stenting or balloon angioplasty, each +/- abciximab. In accordance with the protocol, intravenous beta-blockers were administered before PCI in the absence of contraindications. RESULTS: A total of 1136 patients (54.5%, BB+ group) received beta-blockers before PCI, whereas 946 (45.5%, BB- group) did not. The 30-day mortality was significantly lower in the BB+ group than in the BB- group (1.5% vs. 2.8%, p = 0.03), an effect entirely limited to patients who had not been receiving beta-blockers before admission (1.2% vs. 2.9%, p = 0.007). In contrast, no survival benefit with pre-procedural beta-blockers was observed in patients receiving beta-blockers at home (3.3% vs. 1.9%, respectively, p = 0.47). By multivariate analysis, pre-procedural beta-blocker use was an independent predictor of lower 30-day mortality among patients without previous beta-blocker therapy (relative risk = 0.38 [95% confidence interval 0.17 to 0.87], p = 0.02). The improvement in left ventricular ejection fraction from baseline to seven months was also greater after intravenous beta-blockers (3.8% vs. 1.3%, p = 0.01), an effect limited to patients not receiving oral beta-blockers before admission. CONCLUSIONS: In patients with AMI undergoing primary PCI, myocardial recovery is enhanced and 30-day mortality is reduced with pre-procedural intravenous beta-blockade, effects confined to patients untreated with oral beta-blocker medication before admission.

Importance of mitral regurgitation inpatients undergoing percutaneous coronary intervention for acute myocardial infarction: the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.

OBJECTIVES: We sought to determine the prognostic importance of mitral regurgitation (MR) in patients undergoing percutaneous coronary intervention for acute myocardial infarction (AMI). BACKGROUND: Mitral regurgitation has been associated with a poor prognosis in patients treated with thrombolytic therapy for AMI. The prognostic significance of MR in patients undergoing mechanical reperfusion therapy for AMI is unknown. METHODS: Left ventriculography was performed during the index procedure in 1,976 (95%) of 2,082 non-shock patients enrolled in a prospective, multicenter, randomized trial of mechanical reperfusion strategies in AMI. The severity of operator-assessed MR was divided into four strata: none (n = 1,726), mild (n = 192), and moderate/severe (n = 58). RESULTS: Patients with progressively more severe MR were older (p < 0.0001), were more often women (p < 0.0001), and had higher Killip class (p = 0.0007). More severe grades of MR correlated with triple-vessel disease (p < 0.0001) and lower left ventricular ejection fraction (LVEF) as measured during the index procedure (p = 0.0004). Increasingly severe MR was strongly associated with a higher mortality at 30 days (1.4% vs. 3.7% vs. 8.6%, respectively; p < 0.0001) and at one year (2.9%, 8.5%, 20.8%, respectively; p < 0.0001). By multivariate analysis, the presence of even mild MR was an independent predictor of long-term mortality (mild MR, relative risk [RR] = 2.40, p = 0.005; moderate/severe MR, RR = 2.82, p = 0.006). CONCLUSIONS: Mitral regurgitation of any degree present on the baseline left ventriculogram during the index procedure is a powerful, independent predictor of mortality in patients undergoing mechanical reperfusion therapy for AMI. The presence of MR identifies high-risk patients in whom close out-patient follow-up is warranted, and who may benefit from aggressive adjunctive medical or surgical therapies.

Impact of renal insufficiency in patients undergoing primary angioplasty for acute myocardial infarction.

BACKGROUND: The prognostic importance of renal insufficiency (RI) in patients undergoing primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) has not been well characterized. METHODS AND RESULTS: PCI was performed in 2082 AMI patients without shock presenting within 12 hours of symptom onset in a prospective, multicenter randomized trial. RI was defined as a calculated (Cockroft-Gault) creatinine clearance (CrCl) < or =60 mL/min. RI at baseline was present in 18% of patients. Compared with patients without RI, patients with RI were older and were more likely to be female; to have hypertension, peripheral vascular disease, or cerebrovascular disease; and to present in heart failure. Mortality was markedly increased in patients with versus without baseline RI both at 30 days (7.5% versus 0.8%, P<0.0001) and at 1 year (12.7% versus 2.4%, P<0.0001). Mortality rates increased incrementally for every 10-mL/min decrease in baseline CrCl. By multivariate analysis, reduced baseline CrCl was a powerful independent predictor of 30-day mortality (hazard ratio, 5.77; P<0.0001) and remained associated with reduced survival at 1 year (hazard ratio, 1.98; P=0.08). Hemorrhagic complications and transfusion requirements were also increased more than 2-fold in patients with RI, as were severe restenosis (diameter stenosis > or =70%; 20.6% versus 11.8%, P=0.024) and infarct artery reocclusion (14.7% versus 7.3%, P=0.02). CONCLUSIONS: Baseline RI in patients with AMI undergoing primary PCI is associated with a markedly increased risk of mortality, as well as bleeding and restenosis. Novel approaches are needed to improve the otherwise poor prognosis of patients with RI and AMI.