Faculty Bibliography

BACKGROUND: Left ventricular end-diastolic pressure (LVEDP) is frequently measured during primary percutaneous coronary intervention (PCI). However, little is known of this measurement's utility in predicting outcomes or informing treatment decisions. We sought to determine the prognostic value of LVEDP measured during primary PCI for ST-segment elevation myocardial infarction (STEMI). METHODS: We studied 1,909 (33.2%) of 5,745 STEMI patients in whom LVEDP was measured during primary PCI in the APEX-AMI trial. Cox regression analysis was used to evaluate whether LVEDP was an independent predictor of mortality and the composite of death, cardiogenic shock, or congestive heart failure (CHF) at 90 days. RESULTS: The median (25th, 75th percentiles) LVEDP level was 22 mm Hg (16, 29); compared with patients with LVEDP 22 mm Hg had higher rates of CHF (7.3% vs 3.1%, P < .001), cardiogenic shock (4.6% vs 1.7%, P < .001), and death (4.1% vs 2.2%, P = .014) at 90 days. After multivariable adjustment, LVEDP was associated with increased risk of mortality through 90 days (adjusted hazard ratio 1.22, 95% CI 1.02-1.46, per 5-mmHg increase, P = .044) and the composite of death, cardiogenic shock, or CHF within the first 2 days (adjusted hazard ratio 1.40, 95% CI 1.23-1.59, per 5-mm Hg increase, P < .001), but not from day 3 to 90 (P = .25). CONCLUSIONS: Left ventricular end-diastolic pressure measured during primary PCI for STEMI is an independent predictor of inhospital and longer term cardiovascular outcomes. Measuring LVEDP may be useful to stratify patient risk and guide postinfarct treatment.

BACKGROUND: Female sex is an established risk factor for bleeding, which is an important safety end point in patients presenting with non-ST-segment elevation acute coronary syndromes (NSTE ACS). However, it is unknown whether the association between bleeding and mortality is modulated by sex in this patient population. METHODS: We examined the interaction between sex and bleeding and 30-day mortality outcomes among 2,975 women and 6,431 men with high-risk NSTE ACS enrolled in the EARLY ACS trial. The Global Utilization of Strategies to Open Occluded Arteries (GUSTO) criteria were used to identify moderate or severe bleeds. RESULTS: Women were older and had more comorbid disease compared with men. Bleeding rates were higher among women (8.2%) than among men (5.5%; P < .01). However, the association of bleeding and 30-day mortality was stronger among men (odds ratio 5.8, 95% CI 3.9-8.8) than among women (odds ratio 1.5, 95% CI 0.8-2.9; sex * bleeding interaction P < .01). Sex differences in the association of bleeding and mortality persisted in a landmark analysis of 120-hour survivors. CONCLUSIONS: In a contemporary high-risk NSTE ACS cohort, women had higher bleeding rates than did men. Paradoxically, the association between bleeding and mortality was worse among men than among women.

BACKGROUND: Dual antiplatelet therapy in older versus younger patients with acute coronary syndromes is understudied. Low-dose prasugrel (5 mg/d) is recommended for younger, lower-body-weight patients and elderly patients with acute coronary syndromes to mitigate the bleeding risk of standard-dose prasugrel (10 mg/d). METHODS AND RESULTS: A total of 9326 medically managed patients with acute coronary syndromes from the Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY ACS) trial (<75 years of age, n=7243; >/=75 years of age, n=2083) were randomized to prasugrel (10 mg/d; 5 mg/d for those >/=75 or <75 years of age and <60 kg in weight) or clopidogrel (75 mg/d) plus aspirin for /=75 years of age (25% of total elderly population) had serial platelet reactivity unit measurements in a platelet-function substudy. Cumulative risks of the primary end point (cardiovascular death/myocardial infarction/stroke) and Thrombolysis in Myocardial Infarction (TIMI) major bleeding increased progressively with age and were >/=2-fold higher in older participants. Among those >/=75 years of age, TIMI major bleeding (4.1% versus 3.4%; hazard ratio, 1.09; 95% confidence interval, 0.57-2.08) and the primary end point rates were similar with reduced-dose prasugrel and clopidogrel. Despite a correlation between lower 30-day on-treatment platelet reactivity unit values and lower weight only in the prasugrel group, there was a nonsignificant treatment-by-weight interaction for platelet reactivity unit values among participants >/=75 years of age in the platelet-function substudy (P=0.06). No differences in weight were seen in all participants >/=75 years of age with versus without TIMI major/minor bleeding in both treatment groups. CONCLUSIONS: Older age is associated with substantially increased long-term cardiovascular risk and bleeding among patients with medically managed acute coronary syndromes, with no differences in ischemic or bleeding outcomes with reduced-dose prasugrel compared with clopidogrel in elderly patients. No significant interactions among weight, pharmacodynamic response, and bleeding risk were observed between reduced-dose prasugrel and clopidogrel in elderly patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov/ct2/home. Unique identifier: NCT0069999.

BACKGROUND: Cardiogenic shock complicating acute myocardial infarction (MI) in older patients is associated with a high risk of inhospital mortality; however, the long-term prognosis among these patients who survive the index hospitalization is uncertain. METHODS: We evaluated 42,656 patients 65 years or older with non-ST-segment elevation MI from the CRUSADE Registry treated at 448 hospitals in the United States from 2003 to 2006 and linked to Medicare longitudinal claims data. Among patients who survived to hospital discharge, Cox proportional hazards modeling was used to compare survival between patients with and without inhospital shock. The secondary outcome of "percent days alive and out of hospital" (%DAOH) was also compared between the 2 groups. RESULTS: Overall, 2,001 (4.7%) patients had shock on presentation and/or developed shock during the index hospitalization. Inhospital mortality rates among those with and without shock were 39.1% versus 4.5% (P < .001). Among the 40,036 index hospital survivors, postdischarge survival curves diverged early with lower survival (48.1% [95% CI 45.0-51.2] vs 56.5% [95% CI 56.0-57.1], P < .001) and lower %DAOH (65.5% +/- 40.6% and 73.4% +/- 36.8 %, P < .001) among patients with shock through 4 years. Based on the observation of parallel survival curves starting 6 months postdischarge, we performed landmark analyses and found no difference in mortality (hazard ratio 1.02, 95% CI 0.91-1.14) or %DAOH (79.7% +/- 32.0% vs 81.3% +/- 31.0%, P = .17) beyond 6 months between those with and without shock. CONCLUSIONS: Our results highlight the time-dependent hazard of risk during the early postdischarge period for older patients with non-ST-segment elevation MI and cardiogenic shock that appears to be mitigated after 6 months, thereby lending support for the examination of new therapies designed to ameliorate this early risk.