Ticagrelor vs Clopidogrel for Complex Percutaneous Coronary Intervention in Chronic Coronary Syndrome.

BACKGROUND: Whether ticagrelor in chronic coronary syndrome patients undergoing complex percutaneous coronary intervention (PCI) can prevent cardiovascular events is unknown. OBJECTIVES: The authors sought to evaluate outcomes of complex PCI and the efficacy of ticagrelor vs clopidogrel in stable patients randomized in the ALPHEUS (Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting) trial. METHODS: All PCI procedures were blindly reviewed and classified as complex if they had at least 1 of the following criteria: stent length >60 mm, 2-stent bifurcation, left main, bypass graft, chronic total occlusion, use of atherectomy or guiding catheter extensions, multiwire technique, multiple stents. The primary endpoint was a composite of type 4a or b myocardial infarction (MI) and major myocardial injury during the 48 hours after PCI. We compared the event rates according to the presence or not of complex PCI criteria and evaluated the interaction with ticagrelor or clopidogrel. RESULTS: Among the 1,866 patients randomized, 910 PCI (48.3%) were classified as complex PCI. The primary endpoint was more frequent in complex PCI (45.6% vs 26.6%; P < 0.001) driven by higher rates of type 4 MI and angiographic complications (12.2% vs 4.8 %; P < 0.001 and 19.3% vs 8.6%; P < 0.05, respectively). The composite of death, MI, and stroke at 48 hours (12.7% vs 5.1 %; P < 0.05) and at 30 days (13.4% vs 5.3%; P < 0.05) was more frequent in complex PCI. No interaction was found between PCI complexity and the randomized treatment for the primary endpoint (Pinteraction = 0.47) nor the secondary endpoints. CONCLUSIONS: In chronic coronary syndrome, patients undergoing a complex PCI have higher rates of periprocedural and cardiovascular events that are not reduced by ticagrelor as compared with clopidogrel.

P2Y12 Inhibitor Loading Time Before Elective PCI and the Prevention of Myocardial Necrosis.

BACKGROUND: There are dated and conflicting data about the optimal timing of initiation of P2Y12 inhibitors in elective percutaneous coronary intervention (PCI). Peri-PCI myocardial necrosis is associated with poor outcomes. We aimed to assess the impact of the P2Y12 inhibitor loading time on periprocedural myocardial necrosis in the population of the randomized Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting (ALPHEUS) trial, which compared ticagrelor with clopidogrel in high-risk patients who received elective PCI. METHODS: The ALPHEUS trial divided 1809 patients into quartiles of loading time. The ALPHEUS primary outcome was used (type 4 [a or b] myocardial infarction or major myocardial injury) as well as the main secondary outcome (type 4 [a or b] myocardial infarction or any type of myocardial injury). RESULTS: Patients in the first quartile group (Q1) presented higher rates of the primary outcome (P = 0.01). When compared with Q1, incidences of the primary outcome decreased in patients with longer loading times (adjusted odds ratio [adjOR], 0.70 [0.52.-0.95]; P = 0.02 for Q2; adjOR 0.65 [0.48-0.88]; P < 0.01 for Q3; adjOR 0.66 [0.49-0.89]; P < 0.01 for Q4). Concordant results were found for the main secondary outcome. There was no interaction with the study drug allocated by randomization (clopidogrel or ticagrelor). Bleeding complications (any bleeding ranging between 4.9% and 7.3% and only 1 major bleeding at 48 hours) and clinical ischemic events were rare and did not differ among groups. CONCLUSIONS: In elective PCI, administration of the oral P2Y12 inhibitor at the time of PCI could be associated with more frequent periprocedural myocardial necrosis than an earlier administration. The long-term clinical consequences remain unknown.

ßeta blocker interruption after uncomplicated myocardial infarction: rationale and design of the randomized ABYSS trial.

BACKGROUND: The long-term use of ß-blocker after myocardial infarction (MI) when global left ventricular ejection fraction (LVEF) is preserved has not been studied in the era of modern myocardial reperfusion and secondary prevention therapies. It is unknown whether ß-blockers are useful in stable post-MI patients without reduced LVEF and without heart failure. METHODS: The Assessment of ß-blocker interruption 1 Year after an uncomplicated myocardial infarction on Safety and Symptomatic cardiac events requiring hospitalization (ABYSS) Trial enrolled in 49 centers in France, 3,700 patients with a prior (>6 months) history of MI and a LVEF >40%, chronically treated with a ß-blocker and without any major cardiovascular event (MACE) in the past 6 months. These patients were randomized to interruption or continuation of their ß-blocker therapy. The primary objective is to demonstrate the noninferiority of interruption vs continuation of the ß-blocker therapy on the primary composite endpoint of all-cause death, stroke, MI, hospitalization for any cardiovascular reason at the end of follow-up (accrual follow-up) with a one-year minimum follow-up for the last randomized patient. Secondary objectives will focus on patient reported outcomes with the evaluation of the quality of life before and after randomization with the EQ5D-5L questionnaire. Enrolment has been completed. CONCLUSION: The ABYSS trial evaluates the cardiovascular safety of ß-blocker interruption in stabilized post-MI patients without heart failure nor reduced LVEF. ABYSS trial is a reappraisal of ß-blockers life-long therapy in stable post-MI patients without reduced LVEF. CLINICAL TRIAL REGISTRATION: NCT03498066 (clinicaltrials.gov).

Ticagrelor versus clopidogrel in elective percutaneous coronary intervention (ALPHEUS): a randomised, open-label, phase 3b trial.

BACKGROUND: Percutaneous coronary intervention (PCI)-related myonecrosis is frequent and can affect the long-term prognosis of patients. To our knowledge, ticagrelor has not been evaluated in elective PCI and could reduce periprocedural ischaemic complications compared with clopidogrel, the currently recommended treatment. The aim of the ALPHEUS study was to examine if ticagrelor was superior to clopidogrel in reducing periprocedural myocardial necrosis in stable coronary patients undergoing high-risk elective PCI. METHODS: The ALPHEUS study, a phase 3b, randomised, open-label trial, was done at 49 hospitals in France and Czech Republic. Patients with stable coronary artery disease were eligible for the study if they had an indication for PCI and at least one high-risk characteristic. Eligible patients were randomly assigned (1:1) to either ticagrelor (180 mg loading dose, 90 mg twice daily thereafter for 30 days) or clopidogrel (300-600 mg loading dose, 75 mg daily thereafter for 30 days) by use of an interactive web response system, and stratified by centre. The primary outcome was a composite of PCI-related type 4 (a or b) myocardial infarction or major myocardial injury and the primary safety outcome was major bleeding, both of which were evaluated within 48 h of PCI (or at hospital discharge if earlier). The primary analysis was based on all events that occurred in the intention-to-treat population. The trial was registered with ClinicalTrials.gov, NCT02617290. FINDINGS: Between Jan 9, 2017, and May 28, 2020, 1910 patients were randomly assigned at 49 sites, 956 to the ticagrelor group and 954 to the clopidogrel group. 15 patients were excluded from the ticagrelor group and 12 from the clopidogrel group. At 48 h, the primary outcome was observed in 334 (35%) of 941 patients in the ticagrelor group and 341 (36%) of 942 patients in the clopidogrel group (odds ratio [OR] 0·97, 95% CI 0·80-1·17; p=0·75). The primary safety outcome did not differ between the two groups, but minor bleeding events were more frequently observed with ticagrelor than clopidogrel at 30 days (105 [11%] of 941 patients in the ticagrelor group vs 71 [8%] of 942 patients in the clopidogrel group; OR 1·54, 95% CI 1·12-2·11; p=0·0070). INTERPRETATION: Ticagrelor was not superior to clopidogrel in reducing periprocedural myocardial necrosis after elective PCI and did not cause an increase in major bleeding, but did increase the rate of minor bleeding at 30 days. These results support the use of clopidogrel as the standard of care for elective PCI. FUNDING: ACTION Study Group and AstraZeneca.

Blunting periprocedural myocardial necrosis: Rationale and design of the randomized ALPHEUS study.

BACKGROUND: Clopidogrel associated with aspirin is the recommended treatment for patients undergoing elective percutaneous coronary intervention (PCI). Although severe PCI-related events are rare, evidence suggests that PCI-related myocardial infarction and myocardial injury are frequent complications that can impact the clinical prognosis of the patients. Antiplatelet therapy with a potent P2Y12 receptor inhibitor such as ticagrelor may reduce periprocedural ischemic complications while maintaining a similar safety profile as compared with conventional dual antiplatelet therapy by aspirin and clopidogrel in this setting. METHODS: Assessment of Loading with the P2Y12 inhibitor ticagrelor or clopidogrel to Halt ischemic Events in patients Undergoing elective coronary Stenting (ALPHEUS) (NCT02617290) is an international, multicenter, randomized, parallel-group, open-label study in patients with stable coronary artery disease who are planned for an elective PCI. In total, 1,900 patients will be randomized before a planned PCI to a loading dose of ticagrelor 180 mg or a loading dose of clopidogrel (300 or 600 mg) in addition to aspirin. Patients will then receive a dual antiplatelet therapy with aspirin and ticagrelor 90 mg twice daily or clopidogrel 75 mg once daily for 30 days. The primary ischemic end point is PCI-related myocardial infarction (myocardial infarction type 4a or 4b) or major myocardial injury within 48 hours (or at hospital discharge if earlier) after elective PCI/stent. Safety will be evaluated by major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 48 hours (or discharge if it occurs earlier). CONCLUSION: ALPHEUS is the first properly sized trial comparing ticagrelor to clopidogrel in the setting of elective PCI and is especially designed to show a reduction in periprocedural events, a surrogate end point for mortality.

Early exercise training feasibility after aortic valve repair: A multicentre prospective French survey on behalf of the Aortic Valve repair International Registry (AVIATOR).

BACKGROUND: Standardization of aortic valve repair by the external ring annuloplasty approach is an alternative to valve replacement to avoid prosthetic valve-related events. Although the benefit of exercise training to improve postoperative exercise tolerance has been demonstrated in many conditions after cardiac surgery, it has never been described after aortic valve repair. OBJECTIVES: To evaluate the feasibility of an early exercise training programme after aortic valve repair. METHODS: Consecutive patients were prospectively included in 13 postoperative centres. Patients underwent an exercise training programme for approximately 3-5 weeks. Transthoracic echocardiography and a cardiopulmonary exercise test were performed before and after the exercise training programme. RESULTS: Fifty patients (mean±standard deviation [SD] age: 50±13 years) were included a mean of 13.6±12.0 days after aortic valve repair. The preoperative degree of aortic insufficiency was moderate to severe in 35 patients (70%) and the aortic valve was bicuspid in 24 patients (48%). Valve-sparing root replacement and isolated aortic valve repair (including 10% supracoronary aorta replacement) were performed in 64% and 36% of patients, respectively. We found no aortic insufficiency occurrence or worsening and no adverse clinical events after the exercise training programme. Mean left ventricular ejection fraction increased significantly (from 54%±8% to 57%±9%; P=0.0007). Mean peak oxygen consumption and first ventilatory threshold increased from 17.0±5.3 to 22.5±7.8mL/kg/min (32% increase) and from 12.0±3.9 to 14.3±5.2mL/kg/min (19% increase), respectively (both P<0.05). CONCLUSION: Exercise training early after aortic valve repair is safe and seems to significantly improve exercise capacity.

Incidence, diagnostic methods, and evolution of left ventricular thrombus in patients with anterior myocardial infarction and low left ventricular ejection fraction: a prospective multicenter study.

BACKGROUND AND OBJECTIVES: We aimed to assess the incidence and evolution of left ventricular (LV) thrombi in a high-risk population of patients with LV systolic dysfunction after anterior myocardial infarction (ant-MI). We also compared the accuracy of transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging with contrast-delayed enhancement (CMR-DE) in detecting LV thrombi. METHODS: We prospectively included 100 consecutive patients with LV ejection fraction (LVEF) <45% at the first TTE performed <7 days after ant-MI. A second evaluation with TTE and CMR-DE (by blinded examiners) was performed at 30 days. A third TTE and assessment of clinical status were performed between 6 and 12 months after ant-MI. RESULTS: Patients (males 71%; mean age 59.1 ± 12.1 years; mean LVEF 33.5% ± 6.0%) were included at a median of 5.5 days (interquartile range 25th-75th percentile 4.25-6.0 days) after ant-MI. Thrombi were detected among 26 (26%) patients at a median of 12.0 days after ant-MI (7 patients at 1-7 days after MI; 15 at 8-30 days; and 4 after day 30). Sensitivity and specificity for LV thrombi detection were 94.7% and 98.5%, respectively, for TTE as compared with CMR-DE. Most thrombi (n = 24; 92.3%) disappeared after triple antithrombotic therapy (vitamin K antagonist in addition to dual antiplatelet therapy). CONCLUSION: Left ventricular thrombus is a frequent complication after ant-MI with systolic dysfunction. When a search for thrombus is prespecified, the accuracy of TTE is high as compared with CMR-DE. The best antithrombotic strategy is not known.

Greater prognostic value of peak VO2 after exercise training program completion in heart failure patients.

BACKGROUND: Exercise capacity, best reflected by peak exercise oxygen consumption (peak VO(2)), is a powerful prognostic factor in patients with chronic heart failure (CHF). However, the optimal time to assess exercise capacity for prognosis remains unclear and whether an exercise training program (ETP) to improve exercise capacity alters the prognostic value of cardiopulmonary exercise (CPX) testing variables in CHF is unknown. METHODS AND RESULTS: CHF patients who underwent an ETP in two cardiac rehabilitation centers between 2004 and 2009 were prospectively included, and CPX testing was performed before and after ETP completion. We included 285 consecutive patients who underwent an ETP (19.4 ± 8.7 training sessions in 4 to 10 weeks), including segmental gymnastics and cycling sessions. During follow-up (12 months), 14 patients died, 6 underwent cardiac transplantation and 15 were hospitalized for acute heart failure. Univariate analysis and receiver operating characteristic (ROC) curve analysis showed that CPX variables, especially peak oxygen consumption and circulatory power (product of peak VO(2) × peak systolic blood pressure) before and after ETP completion predicted prognosis. However, CPX data obtained after ETP completion had the best prognostic value (area under the ROC curve = 0.79 ± 0.03 for peak VO(2) after ETP completion vs 0.64 ± 0.04 before ETP completion, p < 0.0001). The results did not change even when considering only deaths. CONCLUSION: In patients with stable CHF who can exercise, the prognostic value of CPX data seems greater after versus before completion of a hospital-based ETP. Therefore, CPX capacity for prognostic purposes should at best be assessed after cardiac rehabilitation.

Renal function, atherothrombosis extent, and outcomes in high-risk patients.

BACKGROUND: Although prior data showed an association between chronic kidney disease (CKD) and atherothrombotic events, little is known about the risk profile and specific outcomes of atherothrombotic outpatients with CKD. METHODS: More than 69,000 outpatients at risk of atherothrombotic events were enrolled in the REACH Registry. Creatinine clearance (CrCl) was available for 51,208 patients divided into 4 groups: normal (CrCl > or =90 mL/min, n = 13,949), mild (60-89 mL/min, n = 19,474), moderate (30-59 mL/min, n = 15,883), and severe CKD (CrCl <30 mL/min, n = 1902). Baseline characteristics, number of arterial beds overtly affected, medications, overall mortality, cardiovascular death, myocardial infarction, stroke, congestive heart failure, peripheral arterial events, and bleeding events were assessed according to renal function. RESULTS: The number of arterial beds affected increased with severity of CKD. However, patients with severe CKD were less likely to receive medications of proven benefit. Severe CKD was an independent correlate of all-cause mortality, cardiovascular mortality, myocardial infarction, congestive heart failure, peripheral arterial revascularization, or amputation. CONCLUSION: One third of outpatients at risk for atherothrombotic events have moderate to severe CKD. They are less likely to receive beneficial therapies despite a higher atherothrombotic burden and worse outcomes.

Intravenous low-molecular-weight heparins compared with unfractionated heparin in percutaneous coronary intervention: quantitative review of randomized trials.

BACKGROUND: Despite its limitations, unfractionated heparin (UFH) is the recommended anticoagulant during percutaneous coronary intervention (PCI). Few randomized trials have compared low-molecular-weight heparin (LMWH) and UFH, and most lacked the power to detect a difference between the 2 anticoagulants in terms of safety or efficacy. Our objective was to perform a meta-analysis of randomized trials comparing the efficacy and safety of LMWH vs UFH as anticoagulants in the setting of PCI. METHODS: We used MEDLINE, randomized trials presented at major cardiology conferences, and journal article bibliographies from January 1998 and September 2006. Two reviewers independently identified randomized studies comparing the intravenous administration of LMWH vs UFH among patients undergoing PCI. Data on sample size, baseline characteristics, and outcomes of interest were independently extracted and analyzed. RESULTS: Thirteen trials including 7318 patients met the inclusion criteria. A total of 4201 patients (57.4%) received LMWH, and 3117 patients (42.6%) received UFH. Intravenous LMWH use was associated with a significant reduction in the risk of major bleeding compared with UFH (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.40-0.82; P = .002). A trend toward a reduction in minor bleeding was also observed among LMWH-treated patients (OR, 0.75; 95% CI, 0.47-1.20; P = .24). Similar efficacy was observed between LMWH and UFH regarding the double end point of death or myocardial infarction (OR, 0.99; 95% CI, 0.79-1.24; P = .93). There were no significant differences in death, myocardial infarction, and urgent revascularization between patients receiving LMWH and those receiving UFH. CONCLUSION: The use of intravenous LMWH during PCI is associated with a significant reduction in major bleeding events compared with UFH, without compromising outcomes on hard ischemic end points.

High plasma aldosterone levels on admission are associated with death in patients presenting with acute ST-elevation myocardial infarction.

BACKGROUND: Aldosterone, the final mediator of the renin-angiotensin-aldosterone pathway, is at its highest plasma levels at presentation for ST-elevation myocardial infarction (STEMI). Whether aldosterone level at presentation for STEMI is associated with adverse outcome remains unknown. METHODS AND RESULTS: Plasma aldosterone levels were measured at presentation in consecutive patients referred for primary percutaneous coronary intervention for STEMI. We assessed the association between aldosterone levels and in-hospital events and mortality during a 6-month follow-up. Of 356 STEMI patients, 23 and 36 died during the hospital stay and 6-month follow-up period, respectively. Nine other patients survived in-hospital cardiac arrest. High aldosterone levels were associated with an almost stepwise increase in rates of in-hospital death (P=0.01), cardiovascular death (P=0.03), heart failure (P=0.005), ventricular fibrillation (P=0.02), and resuscitated cardiac arrest (P=0.01). After adjustment for age, Killip class, and reperfusion status, compared with patients in the first aldosterone quartile group, those in the highest quartile were at higher risk of death (hazard ratio 3.28, 95% CI 1.09 to 9.89, P=0.035) and death or resuscitated cardiac arrest (hazard ratio 3.74, 95% CI 1.40 to 9.98, P=0.008) during the follow-up. CONCLUSIONS: Plasma aldosterone levels on admission among patients referred for primary percutaneous coronary intervention for STEMI are associated with early and late adverse clinical outcomes, including mortality. The association between high aldosterone levels and late mortality is independent of age, heart failure, and reperfusion status. Such results underline the pivotal role of aldosterone and justify a randomized trial to assess the early administration of aldosterone antagonists in the setting of STEMI.

Association of a history of systemic hypertension with mortality, thrombotic, and bleeding complications following non-ST-segment elevation acute coronary syndrome.

Chronic hypertension is a well established risk factor for the development of cardiovascular disease; however, its prognostic significance after a non-ST-segment elevation acute coronary syndrome remains to be established. Data from 15,414 patients included in six randomized Thrombolysis in Myocardial Infarction (TIMI) trials (TIMI 3B, TIMI 11A, TIMI 11B, TIMI 12, the Orbofiban in Patients With Unstable Coronary Syndromes [OPUS]-TIMI 16, and the Treat Angina With Aggrastat and Determine Cost of Therapy With an Invasive or Conservative Strategy [TACTICS]-TIMI 18) were analyzed. A history of hypertension was present in 10,998 (71.35%) patients; comorbidities and higher TIMI risk scores were more likely in these patients. However, positive troponin and ST-segment deviations were less frequent among hypertensive patients. After multivariate analysis, the history of hypertension was associated with more adverse outcomes, specifically the composite end point of death/myocardial infarction at 30 days and 1 year (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.31-1.81; p<0.001 at 1 year) than in patients without this history. An independent relationship was also observed with mortality (OR 1.70, 95% CI 1.34-2.16; p<0.001 at 1 year), myocardial infarction (OR 1.50, 95% CI 1.23-1.82; p<0.001 at 1 year), recurrent ischemia (OR 1.24, 95% CI 1.11-1.38; p<0.001 at 1 year), and major bleeding (OR 1.45, 95% CI 1.03-2.06; p=0.036 at 30 days). It was concluded that chronic hypertension remains an independent marker for major short- and long-term cardiac adverse outcomes after non-ST-segment elevation acute coronary syndrome.

Prognostic significance of renal insufficiency in patients presenting with acute coronary syndrome (the Prospective Multicenter SYCOMORE study).

This prospective, multicenter, observational study was designed to assess the in-hospital prognostic importance of renal insufficiency among patients presenting with acute coronary syndrome (ACS). One third of patients with ACS presented with renal insufficiency. After adjustment for potential confounders, decreasing renal function was independently associated with in-hospital death, bleeding, and contrast-induced nephropathy.

Association of glomerular filtration rate on presentation with subsequent mortality in non-ST-segment elevation acute coronary syndrome; observations in 13,307 patients in five TIMI trials.

AIMS: To determine the association of glomerular filtration rate (GFR) with clinical outcomes in the setting of non-ST-segment elevation acute coronary syndromes (NSTE-ACS). METHODS AND RESULTS: Data were pooled from five NSTE-ACS TIMI trials (TIMI 11A and B, TIMI 12, OPUS-TIMI 16 and TACTICS-TIMI 18) and were available in 13 307 patients. GFR was assessed as a continuous and a categorical variable (normal: > or = 90 mL/min/1.73 m2, n=4952; mildly decreased: 60-89 mL/min/1.73 m2, n=6262; and moderately to severely decreased GFR: <60 mL/min/1.73 m2, n=2093). There was an independent association between decreasing GFR and mortality at 30 days (OR 1.19, 95% CI 1.12-1.27, p<0.001) and at 6 months (OR 1.16, 95% CI 1.11-1.22, p<0.001). The combination of TIMI risk score (TRS) and decreasing GFR provided further mortality risk stratification with highest 30-day and 6-month mortality rates among patients with the lowest GFR who also had a TRS > or = 5 (9.1% and 15.4%, respectively). Decreasing GFR was also independently associated with stroke and recurrent ischaemia at 30-days as well as with major bleeding (p<0.001). CONCLUSION: In the setting of NSTE-ACS, impaired GFR is associated with higher mortality as well as higher rates of thrombotic and major bleeding events, independent of TRS.

Enoxaparin in unstable angina patients who would have been excluded from randomized pivotal trials.

OBJECTIVES: In the present study, we describe the characteristics and examine the anticoagulation levels and safety of subcutaneous enoxaparin in unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI) patients who would not have been eligible in the Efficacy Safety Subcutaneous Enoxaparin in Non-Q-wave Coronary Events (ESSENCE) and Thrombolysis In Myocardial Infarction (TIMI)-11B trials. BACKGROUND: It is not known whether the benefit shown with enoxaparin in the selected population of pivotal trials can be extended to the real world. METHODS: In our center, all patients with UA/NSTEMI are anticoagulated with subcutaneous enoxaparin adjusted to creatinine clearance. Among 515 consecutive patients, we identified 174 who would not have been eligible for ESSENCE or TIMI-11B ("EP" group for excluded patients). We evaluated cardiovascular death or non-fatal myocardial infarction (MI), as well as major and minor bleeding events, at 30 days in the EP group and in patients without any of the exclusion criteria ("NEP" group for non-excluded patients). RESULTS: This EP group was older, had a higher female/male ratio, and more frequently had a history of MI or a diagnosis of non-Q MI on admission than the NEP group. The distribution of the anti-Xa activity was similar in both groups. The bleeding rates (major and minor) at 30 days were similar in the EP and NEP groups (2.3% vs. 2.9%, respectively, P = NS). On multivariate analysis, the use of glycoprotein IIb/IIIa inhibitors and the presence of hypertension were the only independent predictors of bleeding found in the whole population. Compared with the NEP group, the EP group had a fourfold increased rate of death or MI at 30 days (15.5% vs. 4.1%, p < 0.01). On multivariate analysis, the independent predictors of death or MI at 30 days were NSTEMI on admission, creatinine clearance, and heart failure. CONCLUSIONS: Patients who do not fit the enrollment criteria of ESSENCE/TIMI-11B have higher risk baseline characteristics for both bleeding and ischemic events. In these patients, enoxaparin with dose adjustment to creatinine clearance provides adequate anti-Xa levels and no excess of bleeding.

Myocardial reperfusion: its assessment and its relation to clinical outcomes.

It has become increasingly apparent that epicardial blood flow restoration is necessary, but not sufficient, to achieve optimal clinical outcomes in the setting of acute coronary syndromes. Indeed, clinical outcomes are strongly associated with myocardial perfusion. The diagnostic tools available to assess myocardial perfusion following acute myocardial infarction and their association with clinical outcomes are reviewed here. Many simple angiographic markers--the Thrombolysis in Myocardial Infarction (TIMI) count frame, TIMI myocardial perfusion grade, pulsatile flow--are all readily available measures and are strongly related to clinical outcomes. Other tools, while accurate, remain limited by their high cost, low availability, and complexity for routine use.