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Context: At 30-day follow-up, patients with moderate- and high-risk acute coronary syndromes (ACS) undergoing early invasive treatment in the ACUITY trial with bivalirudin monotherapy vs heparin plus glycoprotein (GP) IIb/IIIa inhibitors had noninferior rates of adverse ischemic events with reduced rates of major bleeding. Deferred upstream use of GP IIb/IIIa inhibitors for selective administration to patients undergoing percutaneous coronary intervention (PCI) resulted in a significant reduction in major bleeding, although a small increase in composite ischemia could not be excluded.Objective: To determine 1-year ischemic outcomes for patients in the ACUITY trial.Design, Setting, and Patients: A prospective, randomized, open-label trial with 1-year clinical follow-up at 450 academic and community-based institutions in 17 countries. A total of 13,819 patients with moderate- and high-risk ACS undergoing invasive treatment were enrolled between August 23, 2003, and December 5, 2005.Interventions: Patients were assigned to heparin plus GP IIb/IIIa inhibitors (n = 4603), bivalirudin plus GP IIb/IIIa inhibitors (n = 4604), or bivalirudin monotherapy (n = 4612). Of these patients, 4605 were assigned to routine upstream GP IIb/IIIa administration and 4602 were deferred to selective GP IIb/IIIa inhibitor administration.Main Outcome Measure: Composite ischemia (death, myocardial infarction, or unplanned revascularization for ischemia) at 1 year.Results: Composite ischemia at 1 year occurred in 15.4% of patients assigned to heparin plus GP IIb/IIIa inhibitors and 16.0% assigned to bivalirudin plus GP IIb/IIIa inhibitors (compared with heparin plus GP IIb/IIIa inhibitors, HR, 1.05; 95% CI, 0.95-1.16; P = .35), and 16.2% assigned to bivalirudin monotherapy (HR, 1.06; 95% CI, 0.95-1.17; P = .29). Mortality at 1 year occurred in an estimated 3.9% of patients assigned to heparin plus GP IIb/IIIa inhibitors, 3.9% assigned to bivalirudin plus GP IIb/IIIa inhibitors (HR, 0.99; 95% CI, 0.80-1.22; P = .92), and 3.8% assigned to bivalirudin monotherapy (HR, 0.96; 95% CI, 0.77-1.18; P = .67). Composite ischemia occurred in 16.3% of patients assigned to deferred use compared with 15.2% of patients assigned to upstream administration (HR, 1.08; 95% CI, 0.97-1.20; P = .15).Conclusions: At 1 year, no statistically significant difference in rates of composite ischemia or mortality among patients with moderate- and high-risk ACS undergoing invasive treatment with the 3 therapies was found. There was no statistically significant difference in the rates of composite ischemia between patients receiving routine upstream administration of GP IIb/IIIa inhibitors vs deferring their use for patients undergoing PCI.Trial Registration: clinicaltrials.gov Identifier: NCT00093158. [ABSTRACT FROM AUTHOR]

Context: In patients with moderate- and high-risk acute coronary syndromes (ACS) who undergo an early, invasive treatment strategy, current guidelines recommend administration of platelet glycoprotein IIb/IIIa (Gp IIb/IIIa) inhibitors, either upstream to all patients prior to angiography or deferred for selective use in the catheterization laboratory just prior to angioplasty. The preferred approach is undetermined.Objective: To determine the optimal strategy for the use of Gp IIb/IIIa inhibitors in patients with moderate- and high-risk ACS undergoing an early, invasive treatment strategy.Design: Prospective, randomized, open-label trial with 30-day clinical follow-up.Setting: Four hundred fifty academic and community-based institutions in 17 countries.Patients: A total of 9207 patients with moderate- and high-risk ACS undergoing an invasive treatment strategy.Interventions: Patients were randomly assigned to receive either routine upstream (n=4605) or deferred selective (n=4602) Gp IIb/IIIa inhibitor administration, respectively.Main Outcome Measures: The primary outcome was assessment of noninferiority of deferred Gp IIb/IIIa inhibitor use compared with upstream administration for the prevention of composite ischemic events (death, myocardial infarction, or unplanned revascularization for ischemia) at 30 days, using a 1-sided alpha level of .025. Major secondary end points included noninferiority or superiority of major bleeding and net clinical outcomes (composite ischemia or major bleeding).Results: Glycoprotein IIb/IIIa inhibitors were used more frequently (98.3% vs 55.7%, respectively) and for a significantly longer duration (median, 18.3 vs 13.1 hours; P<.001) in patients in the upstream group compared with the deferred group. Composite ischemia at 30 days occurred in 7.9% of patients assigned to deferred use compared with 7.1% of patients assigned to upstream administration (relative risk, 1.12; 95% confidence interval, 0.97-1.29; P = .044 for noninferiority; P = .13 for superiority); as such, the criterion for noninferiority was not met. Deferred use compared with upstream use resulted in reduced 30-day rates of major bleeding (4.9% vs 6.1%, respectively; P<.001 for noninferiority; P = .009 for superiority) and similar rates of net clinical outcomes (11.7% vs 11.7%; P<.001 for noninferiority; P = .93 for superiority).Conclusions: Among patients with moderate- and high-risk ACS undergoing an invasive treatment strategy, deferring the routine upstream use of Gp IIb/IIIa inhibitors for selective administration in the cardiac catheterization laboratory only to patients undergoing percutaneous coronary intervention resulted in a numerical increase in composite ischemia that, while not statistically significant, did not meet the criterion for noninferiority. This finding was offset by a significant reduction in major bleeding.Trial Registration: ClinicalTrials.gov Identifier: NCT00093158. [ABSTRACT FROM AUTHOR]

Context: Physical activity may help maintain cognitive function in older adults., Objective: To examine the relation of long-term regular physical activity, including walking, to cognitive function., Design: Women reported participation in leisure-time physical activities on biennial mailed questionnaires beginning in 1986. We assessed long-term activity by averaging energy expenditures from questionnaires in 1986 through participants' baseline cognitive assessments (1995 to 2001). We used linear regression to estimate adjusted mean differences in baseline cognitive performance and cognitive decline over 2 years, across levels of physical activity and walking., Setting and Participants: Nurses' Health Study, including 18 766 US women aged 70 to 81 years., Main Outcome Measure: Validated telephone assessments of cognition administered twice approximately 2 years apart (1995 to 2001 and 1997 to 2003), including tests of general cognition, verbal memory, category fluency, and attention., Results: Higher levels of activity were associated with better cognitive performance. On a global score combining results of all 6 tests, women in the second through fifth quintiles of energy expenditure scored an average of 0.06, 0.06, 0.09, and 0.10 standard units higher than women in the lowest quintile (P for trend <.001). Compared with women in the lowest physical activity quintile, we found a 20% lower risk of cognitive impairment for women in the highest quintile of activity. Among women performing the equivalent of walking at an easy pace for at least 1.5 h/wk, mean global scores were 0.06 to 0.07 units higher compared with walking less than 40 min/wk (P< or =.003). We also observed less cognitive decline among women who were more active, especially those in the 2 highest quintiles of energy expenditure. Women in the fourth and fifth quintiles had mean changes in global scores that were 0.04 (95% confidence interval, 0.02-0.10) and 0.06 (95% confidence interval, 0.02-0.11) standard units better than those in the lowest quintile., Conclusion: Long-term regular physical activity, including walking, is associated with significantly better cognitive function and less cognitive decline in older women.