Impact of Previous Statin and Angiotensin II Receptor Blocker Use
Impact of Previous Statin and Angiotensin II Receptor Blocker Use
Study Objective. To examine the effect of previous outpatient use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and/or angiotensin II receptor blockers (ARBs) on 30-day mortality in patients hospitalized with sepsis.
Design. Retrospective national cohort study.
Data Source. Department of Veterans Affairs (VA) national patient care and pharmacy databases.
Patients. A total of 3018 patients who were hospitalized with sepsis in fiscal year 2000, had at least 1 year of previous VA outpatient care, and had at least one active and filled VA prescription within 90 days of admission.
Measurements and Main Results. The primary outcome was 30-day mortality. The primary analysis was a multilevel model with hospital as a random effect and control variables that included comorbid conditions, demographics, and other drugs. Among the 3018 patients hospitalized with sepsis, mean age was 74.4 years, 2975 (98.6%) were male, and 811 (26.9%) died within 30 days of admission. Regarding prescription drug use, 480 patients (15.9%) were taking statins and 107 (3.5%) were taking ARBs. After adjusting for potential confounders, statin use (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.36–0.64) and ARB use (OR 0.42, 95% CI 0.24–0.76) were significantly associated with decreased 30-day mortality.
Conclusions. Use of statins and/or ARBs before admission was associated with decreased mortality in patients hospitalized with sepsis. Further research is needed to determine if these drugs might be started on admission for those with sepsis.
Sepsis is the 10th leading cause of death in the United States and has a mortality rate of up to 70%. Inpatients with sepsis have a 26-fold increased risk for death compared with patients without sepsis who are in the intensive care unit.3 New drugs are urgently needed to prevent or treat sepsis since only a few new classes of antibiotics have been added to the available drugs in the past 10 years, and only one new class of drug specifically targeting sepsis (drotrecogin alfa) has been added.
Recently, several classes of drugs including 3- hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and angiotensin II receptor blockers (ARBs) have been found to attenuate the systemic inflammatory response. Statins have been demonstrated to have protective endothelial effects and have also been proposed to influence the balance between endothelial nitric oxide and inducible nitric oxide to promote hemodynamic stability. Several epidemiologic studies have demonstrated that patients receiving statins who were hospitalized with bacteremia and community-acquired pneumonia had improved clinical outcomes or decreased frequency of sepsis; however, we found no studies that examined the effect of ARB use on infectious disease–related outcomes. Further research is needed to clarify the roles and importance of these drugs in the treatment of patients with sepsis.
Thus, the objective of this study was to assess the effect of outpatient use of statins and ARBs on 30-day mortality in patients hospitalized with sepsis, after adjusting for other potential confounders.
Abstract and Introduction
Abstract
Study Objective. To examine the effect of previous outpatient use of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and/or angiotensin II receptor blockers (ARBs) on 30-day mortality in patients hospitalized with sepsis.
Design. Retrospective national cohort study.
Data Source. Department of Veterans Affairs (VA) national patient care and pharmacy databases.
Patients. A total of 3018 patients who were hospitalized with sepsis in fiscal year 2000, had at least 1 year of previous VA outpatient care, and had at least one active and filled VA prescription within 90 days of admission.
Measurements and Main Results. The primary outcome was 30-day mortality. The primary analysis was a multilevel model with hospital as a random effect and control variables that included comorbid conditions, demographics, and other drugs. Among the 3018 patients hospitalized with sepsis, mean age was 74.4 years, 2975 (98.6%) were male, and 811 (26.9%) died within 30 days of admission. Regarding prescription drug use, 480 patients (15.9%) were taking statins and 107 (3.5%) were taking ARBs. After adjusting for potential confounders, statin use (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.36–0.64) and ARB use (OR 0.42, 95% CI 0.24–0.76) were significantly associated with decreased 30-day mortality.
Conclusions. Use of statins and/or ARBs before admission was associated with decreased mortality in patients hospitalized with sepsis. Further research is needed to determine if these drugs might be started on admission for those with sepsis.
Introduction
Sepsis is the 10th leading cause of death in the United States and has a mortality rate of up to 70%. Inpatients with sepsis have a 26-fold increased risk for death compared with patients without sepsis who are in the intensive care unit.3 New drugs are urgently needed to prevent or treat sepsis since only a few new classes of antibiotics have been added to the available drugs in the past 10 years, and only one new class of drug specifically targeting sepsis (drotrecogin alfa) has been added.
Recently, several classes of drugs including 3- hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and angiotensin II receptor blockers (ARBs) have been found to attenuate the systemic inflammatory response. Statins have been demonstrated to have protective endothelial effects and have also been proposed to influence the balance between endothelial nitric oxide and inducible nitric oxide to promote hemodynamic stability. Several epidemiologic studies have demonstrated that patients receiving statins who were hospitalized with bacteremia and community-acquired pneumonia had improved clinical outcomes or decreased frequency of sepsis; however, we found no studies that examined the effect of ARB use on infectious disease–related outcomes. Further research is needed to clarify the roles and importance of these drugs in the treatment of patients with sepsis.
Thus, the objective of this study was to assess the effect of outpatient use of statins and ARBs on 30-day mortality in patients hospitalized with sepsis, after adjusting for other potential confounders.
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