Judith Boura

Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials.

BACKGROUND Many trials have been done to compare primary percutaneous transluminal coronary angioplasty (PTCA) with thrombolytic therapy for acute ST-segment elevation myocardial infarction (AMI). Our aim was to look at the combined results of these trials and to ascertain which reperfusion therapy is most effective. METHODS We did a search of published work and identified 23 trials, which together randomly assigned 7739 thrombolytic-eligible patients with ST-segment elevation AMI to primary PTCA (n=3872) or thrombolytic therapy (n=3867). Streptokinase was used in eight trials (n=1837), and fibrin-specific agents in 15 (n=5902). Most patients who received thrombolytic therapy (76%, n=2939) received a fibrin-specific agent. Stents were used in 12 trials, and platelet glycoprotein IIb/IIIa inhibitors were used in eight. We identified short-term and long-term clinical outcomes of death, non-fatal reinfarction, and stroke, and did subgroup analyses to assess the effect of type of thrombolytic agent used and the strategy of emergent hospital transfer for primary PTCA. All analyses were done with and without inclusion of the SHOCK trial data. FINDINGS Primary PTCA was better than thrombolytic therapy at reducing overall short-term death (7% [n=270] vs 9% [360]; p=0.0002), death excluding the SHOCK trial data (5% [199] vs 7% [276]; p=0.0003), non-fatal reinfarction (3% [80] vs 7% [222]; p<0.0001), stroke (1% [30] vs 2% [64]; p=0.0004), and the combined endpoint of death, non-fatal reinfarction, and stroke (8% [253] vs 14% [442]; p<0.0001). The results seen with primary PTCA remained better than those seen with thrombolytic therapy during long-term follow-up, and were independent of both the type of thrombolytic agent used, and whether or not the patient was transferred for primary PTCA. INTERPRETATION Primary PTCA is more effective than thrombolytic therapy for the treatment of ST-segment elevation AMI.

Comparison of primary and facilitated percutaneous coronary interventions for ST-elevation myocardial infarction: quantitative review of randomised trials.

BACKGROUND Facilitated percutaneous coronary intervention for ST-segment-elevation myocardial infarction (STEMI) is defined as the use of pharmacological substances before a planned immediate intervention, to improve coronary patency. We undertook a meta-analysis of randomised controlled trials (published and unpublished) to compare facilitated and primary percutaneous coronary intervention. METHODS We identified 17 trials of patients with STEMI assigned to facilitated (n=2237) or primary (n=2267) percutaneous coronary intervention. We identified short-term outcomes (up to 42 days) of death, stroke, non-fatal reinfarction, urgent target vessel revascularisation, and major bleeding. Grade 3 flow rates for prethrombolysis and post-thrombolysis in myocardial infarction (TIMI) were also analysed. FINDINGS The facilitated approach resulted in a greater than two-fold increase in the number of patients with initial TIMI grade 3 flow, compared with the primary approach (832 patients [37%] vs 342 [15%], odds ratio 3.18, 95% CI 2.22-4.55); however, final rates did not differ (1706 [89%] vs 1803 [88%]; 1.19, 0.86-1.64). Significantly more patients assigned to the facilitated approach than those assigned to the primary approach died (106 [5%] vs 78 [3%]; 1.38, 1.01-1.87), had higher non-fatal reinfarction rates (74 [3%] vs 41 [2%]; 1.71, 1.16-2.51), and had higher urgent target vessel revascularisation rates (66 [4%] vs 21 [1%]; 2.39, 1.23-4.66); the increased rates of adverse events seen with the facilitated approach were mainly seen in thrombolytic-therapy-based regimens. Facilitated intervention was associated with higher rates of major bleeding than primary intervention (159 [7%] vs 108 [5%]; 1.51, 1.10-2.08). Haemorrhagic stroke and total stroke rates were higher in thrombolytic-therapy-containing facilitated regimens than in primary intervention (haemorrhagic stroke 15 [0.7%] vs two [0.1%], p=0.0014; total stroke 24 [1.1%] vs six [0.3%], p=0.0008). INTERPRETATION Facilitated percutaneous coronary intervention offers no benefit over primary percutaneous coronary intervention in STEMI treatment and should not be used outside the context of randomised controlled trials. Furthermore, facilitated interventions with thrombolytic-based regimens should be avoided.

A randomized trial of transfer for primary angioplasty versus on-site thrombolysis in patients with high-risk myocardial infarction: The air primary angioplasty in myocardial infarction study

OBJECTIVES The Air Primary Angioplasty in Myocardial Infarction (PAMI) study was designed to determine the best reperfusion strategy for patients with high-risk acute myocardial infarction (AMI) at hospitals without percutaneous transluminal coronary angioplasty (PTCA) capability. BACKGROUND Previous studies have suggested that high-risk patients have better outcomes with primary PTCA than with thrombolytic therapy. It is unknown whether this advantage would be lost if the patient had to be transferred for PTCA, and reperfusion was delayed. METHODS Patients with high-risk AMI (age >70 years, anterior MI, Killip class II/III, heart rate >100 beats/min or systolic BP <100 mm Hg) who were eligible for thrombolytic therapy were randomized to either transfer for primary PTCA or on-site thrombolysis. RESULTS One hundred thirty-eight patients were randomized before the study ended (71 to transfer for PTCA and 67 to thrombolysis). The time from arrival to treatment was delayed in the transfer group (155 vs. 51 min, p < 0.0001), largely due to the initiation of transfer (43 min) and transport time (26 min). Patients randomized to transfer had a reduced hospital stay (6.1 +/- 4.3 vs. 7.5 +/- 4.3 days, p = 0.015) and less ischemia (12.7% vs. 31.8%, p = 0.007). At 30 days, a 38% reduction in major adverse cardiac events was observed for the transfer group; however, because of the inability to recruit the necessary sample size, this did not achieve statistical significance (8.4% vs. 13.6%, p = 0.331). CONCLUSIONS Patients with high-risk AMI at hospitals without a catheterization laboratory may have an improved outcome when transferred for primary PTCA versus on-site thrombolysis; however, this will require further study. The marked delay in the transfer process suggests a role for triaging patients directly to specialized heart-attack centers.

Angiographic and clinical characteristics associated with increased in-hospital mortality in elderly patients with acute myocardial infarction undergoing percutaneous intervention (a pooled analysis of the primary angioplasty in myocardial infarction trials).

Advanced age is associated with increased mortality in acute myocardial infarction (AMI) but the mechanism remains unclear. We performed a pooled analysis of 3,032 patients from the Primary Angioplasty in Myocardial Infarction (PAMI)-2, Stent-PAMI, and PAMI-No Surgery On Site trials to determine which clinical, hemodynamic, and angiographic characteristics in the elderly were associated with in-hospital death. There were 452 patients aged >/=75 years and 2,580 patients aged <75 years. Older patients had a lower number of risk factors for coronary artery disease but more comorbidities. Acute catheterization demonstrated more 3-vessel disease, higher left ventricular (LV) end-diastolic pressure, lower LV ejection fraction, and higher initial rates of Thrombolysis In Myocardial Infarction (TIMI) trial 2 or 3 flow. Elderly patients were equally likely to undergo percutaneous intervention but had a lower procedural success rate and lower rates of final TIMI 3 flow, and older patients were more likely to have post-AMI complications. In-hospital mortality was 10.2% and 1.8%, respectively (p = 0.001). Cardiac and noncardiac mortality was higher in elderly patients, and no significant differences in causes of death were identified. Multivariate analysis revealed that the strongest predictors of death were age >/=75 years, lower LV ejection fraction, lower final TIMI flow, higher Killip class, need for an intra-aortic balloon pump (IABP), and post-AMI stroke/transient ischemic attack, or significant arrhythmia. Despite avoiding thrombolysis, elderly patients remain at increased risk of bleeding, stroke, and other post-AMI complications, and death. Cardiac risk factor analysis and acute catheterization offer prognostic information but do not completely explain the mechanism of increased in-hospital mortality in the elderly.

Importance of time to reperfusion on outcomes with primary coronary angioplasty for acute myocardial infarction (results from the Stent Primary Angioplasty in Myocardial Infarction Trial).

The mortality benefit of thrombolytic therapy for acute myocardial infarction (AMI) is strongly dependent on time to treatment. Recent observations suggest that time to treatment may be less important with primary percutaneous transluminal coronary angioplasty (PTCA). Patients with AMI of <12 hours duration, without cardiogenic shock, who were treated with primary PTCA from the Stent PAMI Trial (n = 1,232) were evaluated to assess the effect of time to reperfusion on outcomes. Thrombolysis In Myocardial Infarction grade 3 flow was achieved in a high proportion of patients regardless of time to treatment. Improvement in ejection fraction from baseline to 6 months was substantial with reperfusion at <2 hours but was modest and relatively independent of time to reperfusion after 2 hours (<2 hours, 12.3% vs > or =2 hours, 4.2%, p = 0.004). There were no differences in 1- or 6-month mortality by time to reperfusion (6-month mortality: <2 hours [5.5%], 2 to <4 hours [4.6%], 4 to <6 hours [4.5%], >6 hours [4.2%], p = 0.97). There were also no differences in other clinical outcomes by time to reperfusion, except that reinfarction and infarct artery reocclusion at 6 months were more frequent with later reperfusion. The lack of correlation between time to treatment and mortality in patients without cardiogenic shock suggests that the survival benefit of primary PTCA may be related principally to factors other than myocardial salvage. These data may also have implications regarding the triage of patients with AMI for primary PTCA.

Chronic pudendal neuromodulation: Expanding available treatment options for refractory urologic symptoms†

Chronic pudendal nerve stimulation (CPNS) is a logical alternative particularly in those who fail sacral stimulation. We evaluated symptoms, complications, and satisfaction after CPNS.

Impact of angina class on inhibition of platelet aggregation following clopidogrel loading in patients undergoing coronary intervention: Do we need more aggressive dosing regimens in unstable angina?

Pretreatment with thienopyridines has been shown to improve clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We determine the impact of angina class on inhibition of platelet aggregation (IPA) following clopidogrel loading. Seventy‐two patients (mean age, 64 ± 11 years; 76% male) were pretreated with 450 mg of clopidogrel at least 3 hr prior to PCI. All patients received ASA 325 mg prior to the procedure. Patients were classified into two groups according to angina class: group 1 = stable angina or Braunwald class 1 unstable angina (UA; n = 33); group 2 = Braunwald class 2 or 3 UA (n = 39). IPA was measured prior to PCI, with the Ichor point‐of‐care platelet analyzer (Helena Laboratories, Beaumont, TX), using 20 μM of ADP. Group 2 patients were more likely to have prior MI (54% vs. 27%; P = 0.023), prior CABG (33% vs. 5%; P = 0.046), and received IV heparin (64% vs. 27%; P = 0.0018). Mean IPA was significantly lower in group 2 compared to group 1 (19% ± 22% vs. 32% ± 22%; P = 0.004). In multivariate analysis, higher angina class was independently associated with lower IPA (P = 0.018). Patients with UA undergoing PCI have a lower IPA following clopidogrel loading with 450 mg. This may indicate the possibility of clopidogrel resistance in such patients. Cathet Cardiovasc Intervent 2003;59:21–25.

Predictive value of the Killip classification in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction.

The predictive value of Killip classification of acute myocardial infarction (AMI) in patients undergoing percutaneous coronary intervention (PCI) is not well established. We performed a pooled analysis of 2,654 patients with AMI enrolled in 3 primary angioplasty trials. Of these, 2,305 patients were class I, 302 were class II, and 47 were class III (class IV patients were excluded). Univariate and multivariate analyses were performed to determine if Killip class at admission was a predictor of in-hospital and 6-month mortality. Higher Killip classification was associated with greater in-hospital (2.4%, 7%, and 19% for class I, II, and III, respectively) and 6-month mortality (4%, 10%, and 28% for class I, II, and III, respectively). Higher Killip class was associated with increased age (p <0.001), history of diabetes (p <0.02), lower systolic blood pressure and higher heart rate at presentation (p <0.0001 for both), more 3-vessel disease (p <0.001), lower left ventricular ejection fraction (p <0.0001), and higher peak creatine phosphokinase (p <0.0001). With each increasing Killip class, there was an increased need for an intra-aortic balloon counterpulsation (p <0.001) and greater incidence of renal failure (p <0.001), major arrhythmia (p <0.001), and major bleeding (p <0.001). After controlling for potential confounding variables, Killip classification remained a multivariate predictor of mortality at both time end points. Killip classification at hospital admission remains a simple and useful independent predictor of in-hospital and 6-month mortality in patients with AMI who are undergoing primary PCI.

Clinical and angiographic outcomes in patients with previous coronary artery bypass graft surgery treated with primary balloon angioplasty for acute myocardial infarction

OBJECTIVES We sought to characterize the presenting characteristics of patients with previous coronary artery bypass graft surgery (CABG) and acute myocardial infarction (AMI) and to determine the angiographic success rate and clinical outcomes of a primary percutaneous transluminal coronary angioplasty (PTCA) strategy. BACKGROUND Patients who have had previous CABG and AMI comprise a high risk group with decreased reperfusion success and increased mortality after thrombolytic therapy. Little is known about the efficacy of primary PTCA in AMI. METHODS Early cardiac catheterization was performed in 1,100 patients within 12 h of onset of AMI at 34 centers in the prospective, controlled Second Primary Angioplasty in Myocardial Infarction trial (PAMI-2), followed by primary PTCA when appropriate. Data were collected by independent study monitors, end points were adjudicated and films were read at an independent core laboratory. RESULTS Of 1,100 patients with AMI, 58 (5.3%) had undergone previous CABG. The infarct-related vessel in these patients was a bypass graft in 32 patients (55%) and a native coronary artery in 26 patients. Compared with patients without previous CABG, patients with previous CABG were older and more frequently had a previous myocardial infarction and triple-vessel disease. Coronary angioplasty was less likely to be performed when the infarct-related vessel was a bypass graft rather than a native coronary artery (71.9% vs. 89.8%, p = 0.001); Thrombolysis in Myocardial Infarction trial (TIMI) flow grade 3 was less frequently achieved (70.2% vs. 94.3%, p < 0.0001); and in-hospital mortality was increased (9.4% vs. 2.6%, p = 0.02). As a result, mortality at six months was 14.3% versus 4.1% in patients with versus without previous CABG (p = 0.001). By multivariate analysis, independent determinants of late mortality in the entire study group were advanced age, triple-vessel disease, Killip class and post-PTCA TIMI flow grade <3. CONCLUSIONS Reperfusion success of a primary PTCA strategy in patients with previous CABG, although favorable with respect to historic control studies, is reduced as compared with that in patients without previous CABG. New approaches are required to treat patients with previous CABG and AMI, especially when the infarct-related vessel is a diseased saphenous vein graft.

Role of cardiac surgery in the hospital phase management of patients treated with primary angioplasty for acute myocardial infarction.

Although cardiac surgery is performed in approximately 10% of acute myocardial infarction (AMI) patients undergoing a primary percutaneous transluminal coronary angioplasty (PTCA) reperfusion strategy before discharge, the indications for and timing of operative revascularization, and the short- and long-term outcomes after surgery have not been characterized. In the prospective, controlled Primary Angioplasty in Myocardial Infarction-2 trial, cardiac catheterization was performed in 1,100 patients within 12 hours of onset of AMI at 34 centers, followed by primary PTCA when appropriate. Cardiac surgery was performed before hospital discharge in 120 patients (10.9%), electively in 42.6%, and on an urgent or emergent basis in 57.4%. Surgery was performed in 6.1% of 982 patients after primary PTCA (although emergently for failed PTCA in only 4 cases [0.4%]), and in 53 of 118 patients (44.9%) not undergoing primary PTCA. Patients requiring surgery were older, and more frequently had diabetes and 3-vessel disease than those managed nonoperatively. Internal mammary artery grafts were placed in only 31% of patients. In-hospital mortality was 6.4% in patients undergoing urgent/emergent surgery, 2.0% after elective surgery, and 2.6% in patients not undergoing surgery (p = NS). After multivariate correction for baseline risk factors, early and late survival free of reinfarction were similar in patients undergoing versus not undergoing in-hospital cardiac surgery. Thus, the appropriate use of coronary artery bypass graft surgery in the peri-infarction period is an integral component of the primary PTCA approach, and is frequently used to optimize the prognosis of a high-risk AMI cohort with unfavorable baseline features. The implications for the performance of primary PTCA in AMI at centers without on-site surgical facilities are discussed.