Highlights from #AAST2014 - Beta-blockers and Statins in Sepsis

Is the combination of Beta-blockers and Statins helpful in sepsis?  This retrospective study seems to suggest that.

TWO ARE BETTER THAN ONE: SYNERGY OF BETA-BLOCKADE AND STATIN THERAPY ON SURVIVAL IN SEPSIS

Irada Ibrahim-zada MD,Ph.D., Peter Rhee* MD,MPH, John Santoro Jr., Irina Maskaykina BS, Lynn Gries MD, Terence O'Keeffe* MD, Randall Friese* MD, University of Arizona - Tucson

Invited Discussant: Carl Hauser, MD

Introduction:Current evidence suggests the importance of immunomodulatory therapy in sepsis. Recent clinical trials have demonstrated survival benefits of statins and beta-blocker therapies in sepsis via anti-inflammatory mechanisms. The aim of the study is to evaluate the effect of synchronous administration of beta-blockade and statin therapy in sepsis. We hypothesize that combined administration is associated with increased survival in patients with sepsis.

Methods: This is a single-institution retrospective cohort study on patients with sepsis hospitalized in the ICU at our urban tertiary referral center from 1/1/2008 through 3/31/2011. Records were cross-referenced with pharmacy database to identify patients on beta-blockers (BB), statins (ST), both (BB+ST), and none. Primary outcome is in-hospital 28-day mortality. Kaplan-Meier and Cox-regression analyses were utilized to identify survival benefits adjusted by gender and APACHE II scores.

Results: 304 patients were identified in our database. 101(33%) patients received BB only, 14(5%) received ST only, and 36(12%) patients had BB+ST. Mean APACHE II score was 19.45±7.5 with no difference between groups(p=0.5). Mean survival was 15, 18, 20 and 22 days in groups with none, ST, BB, and BB+ST, respectively. Cox-regression analysis showed that synchronous administration of BB and ST during ICU stay improved in-hospital survival in patients (HR=0.35, 95%CI 0.18 to 0.67, p=0.002) compared to patients without therapy whereas BB only group had HR of 0.51 (p=0.001).

Therapy	p value	HR	95%CI
None	1.0 (REFERENCE)
Statins	.488	.72	0.29; 1.80
Beta-blockers	.001	.51	0.35; 0.76
Statins+beta-blockers	.002	.35	0.18; 0.67
APACHE II	.000	1.11	1.08; 1.14
Gender	.027	.67	0.47; 0.96

Conclusion:Beta-blockade combined with statin therapy during ICU stay has additive effect and is associated with a further 1.5-fold reduction in mortality in septic patients. Randomized clinical trials are warranted to evaluate their synergistic benefits on survival and explore immunomodulatory mechanisms.