Faculty Bibliography

BACKGROUND: Higher levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with a higher risk of cardiovascular events and may play a causal role in atherogenesis. Darapladib inhibits Lp-PLA(2) activity in plasma and in arterial plaques and may confer clinical benefit in preventing cardiovascular events. STUDY DESIGN: The SOLID-TIMI 52 trial is a randomized, double-blind, placebo-controlled, multicenter, event-driven trial. Approximately 13,000 subjects are being randomized to darapladib (160 mg enteric-coated tablet daily) or matching placebo within 30 days of hospitalization with an acute coronary syndrome. The primary end point is the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Secondary end points include major and total coronary events, individual components of the primary end point, and all-cause mortality. The study will continue until approximately 1,500 primary end point events have occurred to achieve 90% power to detect a 15.5% reduction in the primary end point. The median treatment duration is anticipated to be approximately 3 years, with a total study duration of approximately 4.1 years. CONCLUSIONS: The SOLID-TIMI 52 trial will determine the clinical benefit of direct inhibition of Lp-PLA(2) activity with darapladib in patients after an acute coronary syndrome.

BACKGROUND: . Unique identifier: NCT00798122

BACKGROUND: In patients with cardiogenic shock (CS) complicating an acute myocardial infarction, a strategy of early revascularization (ERV) versus initial medical stabilization (IMS) improves survival. Intra-aortic balloon counterpulsation (IABC) provides hemodynamic support and facilitates coronary angiography and revascularization in CS patients. METHODS AND RESULTS: We evaluated 499 patients with record of systemic hypoperfusion status as an early response to IABC from the SHOCK trial (n = 185) and registry (n = 314) to determine the association between rapid complete reversal of systemic hypoperfusion (CRH) after 30 minutes of IABC and in-hospital, 30-day and 1-year mortality. Rapid complete reversal of systemic hypoperfusion was highly associated with lower in-hospital mortality (29% versus 65%, P < .001) in all patients. In the SHOCK trial, among patients assigned to ERV versus IMS, 30-day mortality was 26% versus 29%, respectively, with CRH and 61% versus 81%, respectively, without CRH after commencing IABC. The corresponding 1-year mortality rates were 35% versus 52% for ERV and 69% versus 87% for IMS (interaction P >/= .25 at both time points). After adjusting for important correlates of outcome (left ventricular ejection fraction, age, and randomization to ERV), a significant association remained between CRH and registry and trial in-hospital mortality (odds ratio 0.23, 95% CI 0.14-0.39, P < .001) and trial 1-year mortality (odds ratio .28, 95% CI 0.12-0.67, P < .001). CONCLUSIONS: In CS patients, CRH after commencing IABC was independently associated with improved in-hospital, 30-day and 1-year survival regardless of early revascularization. In CS patients, CRH with IABC is an important early prognostic feature

BACKGROUND: Mortality after ST-elevation myocardial infarction (STEMI) has reduced with reperfusion by primary percutaneous coronary intervention (PCI), which may have impacted on the adverse outcomes of cardiogenic shock (CS) and congestive heart failure (CHF). METHODS AND RESULTS: In the APEX-AMI trial, 5,745 patients with STEMI and planned primary PCI were randomly assigned pexelizumab or matching placebo. Post-randomization CS or CHF was adjudicated by a clinical endpoints committee. Treatment assignment to pexelizumab did not influence either endpoint or mortality rates. Cardiogenic shock developed in 196 patients (3.4%) at a median of 6.0 hours (interquartile range 3.9-28.3) post-randomization, and mortality at 90 days was 54.6%. Congestive heart failure occurred in 254 of patients (4.4%) at a median of 2.6 days (IQR 1.0-16.6), and mortality through 90 days was 10.2%; mortality among those with neither endpoint was 2.1%. Patients with CS or CHF were older, were more often female, and had more hypertension and diabetes, but smoked less compared with non-CS/CHF patients (all P < .05). Independent mortality predictors among those with CS or CHF were hyperlipidemia and a history of angina (interaction P = .011 and .008, respectively); procedural predictors among survivors to PCI were pre-PCI Thrombolysis In Myocardial Infarction (TIMI) flow 0-1 and post-PCI TIMI flow <3 (P = .013 and <.0001, respectively). CONCLUSIONS: Survival after CS remains poor despite aggressive reperfusion. Both CS and CHF remain the major causes of death among STEMI patients undergoing primary PCI. Future studies should examine treatments that aim to reduce mortality in these highest risk patients

OBJECTIVE: The study aims to evaluate sex differences in extent and severity of coronary artery disease (CAD) and myocardial findings at autopsy among young people with fatal ischemic heart disease (IHD). BACKGROUND: Women with acute coronary syndrome are less likely than men to display obstructive CAD at angiography. This suggests unique mechanisms of acute coronary syndrome exist in women or may reflect prehospital death of women with the most severe CAD. METHODS: Reports of autopsies by the Office of the Chief Medical Examiner of New York City on people aged 21 to 54 years who died between January 1, 2006, and December 31, 2008, were reviewed. A total of 639 cases of death due to atherosclerotic or arteriosclerotic cardiovascular disease according to the medical examiner were analyzed. Significant CAD was defined as >/=75% cross-sectional area stenosis in an epicardial vessel or >/=50% left main. RESULTS: Women were less likely to have obstructive CAD (63% vs 77% of men, P = .002). There was pathologic evidence of myocardial infarction (MI) in 43% of cases, 17% of which had nonobstructive CAD. Frequency of MI did not vary by sex overall (38% of women vs 45% of men, P = .18) or among those without significant CAD (23% vs 29%, P = .45). CONCLUSIONS: Among young people determined at autopsy to have died of IHD, fewer women had obstructive CAD, consistent with angiographic data in other IHD syndromes. Pathologic evidence of MI may exist in the absence of obstructive CAD