Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.
Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.
De-Escalating Antibiotics in Sepsis
Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?
Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.
Study design: Prospective observational study.
Setting: Academic hospital ICU in Spain.
Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.
The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.
This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.
Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.
Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.
Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.
New Oral Anticoagulants Increase GI Bleed Risk
Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?
Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.
Study design: Systematic review and meta-analysis.
Setting: Data from MEDLINE, Embase, and the Cochrane Library.
Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Post-surgical patients had the lowest risk.
This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%-40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.