Prehospital Statin Use Research Articles

Impact of in-hospital statin use on mortality in COVID-19 patients from a majority African American population

BackgroundThe COVID-19 pandemic has claimed over 6.4 million lives globally. Finding effective medications to reduce mortality in hospitalized COVID-19 patients remains critical. No previous study has been published on the effects of statin use in a majority African American COVID-19 patient population. ObjectiveThis study aims to assess the relationship between in-hospital statin use and mortality in this population. MethodsA retrospective chart review of patients diagnosed with COVID-19 from March 2020 to June 2020 admitted to the Phoebe Putney Health System in Albany, Georgia, an early epicenter of the COVID-19 pandemic, was conducted. The outcomes of 735 hospitalized COVID-19 positive patients from over 40 counties in Georgia were analyzed. The primary outcome of interest was all-cause mortality, with secondary outcomes of interest of ICU care, length of ICU stay, need for mechanical ventilator, duration of intubation, and need for dialysis. Multivariate logistic regression and Cox proportional hazards analysis were conducted to examine the effect of in-hospital statin use and mortality. Results186 of 735 total patients were prescribed statins in-hospital. 83.8% were African American. Multivariate logistic regression found in-hospital statin use was not significantly associated with the primary outcome – all-cause mortality (p=0.23). Similar findings were seen in need for ICU care, length of ICU stay, need for mechanical ventilator, duration of intubation, and need for dialysis (p>0.05). Additionally, results from a Cox proportional hazards model found in-hospital statin use was not associated with survival time. Sensitivity analysis conducted on only African American patients validated that in-hospital statin use was not associated with all-cause mortality in these patients. Of note, immunosuppression and severe disease presentation were associated with a six-fold increase in risk of mortality and the largest decreases in survival time. ConclusionIt is possible statins have no mortality benefit for this patient population, but further research beyond this association study would need to be conducted to determine this conclusively. From this study, the best clinical recommendation would be to continue statins for COVID-19 patients with pre-hospital statin use and to launch a randomized clinical trial to definitively determine the efficacy of statins in the treatment of hospitalized COVID-19 patients.

Admission Neutrophil to Lymphocyte Ratio for Predicting Outcome in Subarachnoid Hemorrhage

PurposeWe sought to evaluate the relationship between admission neutrophil-to-lymphocyte ratio (NLR) and functional outcome in aneurysmal subarachnoid hemorrhage (aSAH) patients. Material and methodsConsecutive patients with aSAH were treated at two tertiary stroke centers during a five-year period. Functional outcome was defined as discharge modified Rankin score dichotomized at scores 0-2 (good) vs. 3-6 (poor). Results474 aSAH patients were evaluated with a mean NLR 8.6 (SD 8.3). In multivariable logistic regression analysis, poor functional outcome was independently associated with higher NLR, older age, poorer clinical status on admission, prehospital statin use, and vasospasm. Increasing NLR analyzed as a continuous variable was independently associated with higher odds of poor functional outcome (OR 1.03, 95%CI 1.00-1.07, p=0.05) after adjustment for potential confounders. When dichotomized using ROC curve analysis, a threshold NLR value of greater than 6.48 was independently associated with higher odds of poor functional outcome (OR 1.71, 95%CI 1.07-2.74, p=0.03) after adjustment for potential confounders. ConclusionsHigher admission NLR is an independent predictor for poor functional outcome at discharge in aSAH patients. The evaluation of anti-inflammatory targets in the future may allow for improved functional outcome after aSAH.

Statin use and low-density lipoprotein cholesterol levels in patients aged 75 years and older with acute coronary syndrome in China

Objective: To assess the use of statins and low-density lipoprotein cholesterol (LDL-C) levels at admission in hospitalized patients aged 75 years and older with acute coronary syndrome (ACS) in China. Methods: Data used in this study derived from the Improving Care for Cardiovascular Disease in China (CCC)-ACS project, a nationwide registry with 150 tertiary hospitals reporting details of clinical information of ACS patients. This study enrolled patients 75 years and older with ACS in CCC-ACS project from November 2014 to June 2017. Patients were divided into two groups according to the history of atherosclerotic cardiovascular disease (ASCVD). Pre-hospital statin use, LDL-C levels at admission and prescription of statins at discharge were reported. Results: A total of 10 899 patients 75 years and older with ACS were enrolled. The median age was 79 years and 58.7% (6 397 cases) were male. Among patients with history of ASCVD, 33.9% (1 028 cases) of them received statins before hospitalization. Among patients without history of ASCVD, 12.7% (996/7 871) received statins before hospitalization. The mean level of LDL-C was (2.4±0.9) mmol/L and LDL-C was <1.8 mmol/L in 24.7% (747 cases) of patients with history of ASCVD. The mean level of LDL-C was (2.6±0.9) mmol/L and LDL-C was <2.6 mmol/L in 51.7% (4 072 cases) of patients without history of ASCVD. At discharge, 91.2% (9 524/10 488) of patients were prescribed with statins in patients without contraindications for statin. Conclusion: In elderly patients with recurrent ASCVD, there was an inadequate statin use before hospitalization and most patients did not reach the LDL-C target level when they had the recurrent events. In the elderly ACS patients without history of ASCVD, more than half of the patients had an ideal LDL-C level. It seems that ideal LDL-C level for primary prevention of ACS in elderly people needs to be reevaluated with further studies.

Lipid profile and statin use in critical care setting: implications for kidney outcome.

ABSTRACTObjective:To determine whether pre-hospital statin use is associated with lower renal replacement therapy requirement and/or death during intensive care unit stay.Methods:Prospective cohort analysis. We analyzed 670 patients consecutively admitted to the intensive care unit of an academic tertiary-care hospital. Patients with ages ranging from 18 to 80 years admitted to the intensive care unit within the last 48 hours were included in the study.Results:Mean age was 66±16.1 years old, mean body mass index 26.6±4/9kg/m2 and mean abdominal circumference was of 97±22cm. The statin group comprised 18.2% of patients and had lower renal replacement therapy requirement and/or mortality (OR: 0.41; 95%CI: 0.18-0.93; p=0.03). The statin group also had lower risk of developing sepsis during intensive care unit stay (OR: 0.42; 95%CI: 0.22-0.77; p=0.006) and had a reduction in hospital length-of-stay (14.7±17.5 days versus 22.3±48 days; p=0.006). Statin therapy was associated with a protective role in critical care setting independently of confounding variables, such as gender, age, C-reactive protein, need of mechanical ventilation, use of pressor agents and presence of diabetes and/or coronary disease.Conclusion:Statin therapy prior to hospital admission was associated with lower mortality, lower renal replacement therapy requirement and sepsis rates.

Prehospital statin use and low-density lipoprotein cholesterol levels at admission in acute coronary syndrome patients with history of myocardial infarction or revascularization: Findings from the Improving Care for Cardiovascular Disease in China (CCC) project

Lowering low-density lipoprotein cholesterol (LDL-C) by statins is a key strategy for secondary prevention of acute coronary syndrome (ACS). However, few studies have examined prehospital statin use and admission LDL-C levels in ACS patients with history of myocardial infarction (MI) or revascularization. This study aimed to assess use of prehospital statins and LDL-C levels at admission in ACS patients with history of MI or revascularization. Improving Care for Cardiovascular Disease in China project was a nationwide registry, with 192 participating hospitals reporting details of clinical information of ACS patients from November 2014. By May 2018, 80,282 patients with ACS were included. LDL-C levels were obtained from the initial admission lipid testing. Of the 80,282 ACS patients, 6,523 with a history of MI or revascularization were enrolled. Among them, 50.8% were receiving lipid-lowering therapy before hospitalization (statin monotherapy in 98.4%, combination in 1.2%). A total of 30.1% of patients had LDL-C < 70 mg/dL at admission. In patients receiving prehospital statins, 36.1% had LDL-C < 70 mg/dL compared to 24.0% without prehospital statins (P < .001). At discharge, 91.8% of patients were treated with statin monotherapy, 90.7% at moderate doses irrespective of prehospital statin use and LDL-C levels at admission. Among ACS patients with history of MI or revascularization, half were not being treated with statin therapy prior to admission, and most had not attained LDL-C < 70 mg/dL despite prehospital statin use. There is an important opportunity to provide intensive statin or combination lipid-lowering therapy to these very high risk patients.

Higher low-density lipoprotein cholesterol levels are associated with decreased mortality in patients with intracerebral hemorrhage

Background and aimsThe relationship between lipoprotein levels, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and clinical outcome after intracerebral hemorrhage (ICH) remains controversial. We sought to evaluate the association of lipoprotein cholesterol levels and statin dosage with clinical and neuroimaging outcomes in patients with ICH. MethodsData on consecutive patients hospitalized with spontaneous acute ICH was prospectively collected over a 5-year period and retrospectively analyzed. Demographic characteristics, clinical severity documented by NIHSS-score and ICH-score, neuroimaging parameters, pre-hospital statin use and doses, and LDL-C and HDL-C levels were recorded. Outcome events characterized were hematoma volume, hematoma expansion, in-hospital functional outcome, and in-hospital mortality. ResultsA total of 672 patients with acute ICH [(mean age 61.6 ± 14.0 years, 43.6% women, median ICH score 1 (IQR: 0–2)] were evaluated. Statin pretreatment was not associated with neuroimaging or clinical outcomes. Higher LDL-C levels were associated with several markers of poor clinical outcome and in-hospital mortality. LDL-C levels were independently and negatively associated with the cubed root of hematoma volume (linear regression coefficient −0.021, 95% CI: −0.042−-0.001; p = 0.049) on multiple linear regression models. Higher admission LDL-C (OR 0.88, 95% CI 0.77–0.99; p = 0.048) was also an independent predictor for decreased hematoma expansion. Higher admission LDL-C levels were independently (p < 0.001) associated with lower likelihood of in-hospital mortality (OR per 10 mg/dL increase 0.68, 95% CI: 0.57–0.80) in multivariable logistic regression models. ConclusionsHigher LDL-C levels at hospital admission were an independent predictor for lower likelihood of hematoma expansion and decreased in-hospital mortality in patients with acute spontaneous ICH. This association requires independent confirmation.

Statins and delirium during critical illness: a multicenter, prospective cohort study.

Since statins have pleiotropic effects on inflammation and coagulation that may interrupt delirium pathogenesis, we tested the hypotheses that statin exposure is associated with reduced delirium during critical illness, whereas discontinuation of statin therapy is associated with increased delirium. Multicenter, prospective cohort study. Medical and surgical ICUs in two large tertiary care hospitals in the United States. Patients with acute respiratory failure or shock. None. We measured statin exposure prior to hospitalization and daily during the ICU stay, and we assessed patients for delirium twice daily using the Confusion Assessment Method for the ICU. Of 763 patients included, whose median (interquartile range) age was 61 years (51-70 yr) and Acute Physiology and Chronic Health Evaluation II was 25 (19-31), 257 (34%) were prehospital statin users and 197 (26%) were ICU statin users. Overall, delirium developed in 588 patients (77%). After adjusting for covariates, ICU statin use was associated with reduced delirium (p < 0.01). This association was modified by sepsis and study day; for example, statin use was associated with reduced delirium among patients with sepsis on study day 1 (odds ratio, 0.22; 95% CI, 0.10-0.49) but not among patients without sepsis on day 1 (odds ratio, 0.92; 95% CI, 0.46-1.84) or among those with sepsis later, for example, on day 13 (odds ratio, 0.70; 95% CI, 0.35-1.41). Prehospital statin use was not associated with delirium (odds ratio, 0.86; 95% CI, 0.44-1.66; p = 0.18), yet the longer a prehospital statin user's statin was held in the ICU, the higher the odds of delirium (overall p < 0.001 with the odds ratio depending on sepsis status and study day due to significant interactions). In critically ill patients, ICU statin use was associated with reduced delirium, especially early during sepsis; discontinuation of a previously used statin was associated with increased delirium.

Association Between Endothelial Dysfunction and Acute Brain Dysfunction During Critical Illness

Background Acute brain dysfunction (delirium and coma) during critical illness is prevalent and costly, but the pathophysiology remains unclear. The relationship of acute brain dysfunction with endothelial function, which is impaired in critical illness and may contribute to alterations in cerebral blood flow and blood-brain barrier permeability, has not been studied. This study sought to determine whether systemic endothelial dysfunction is associated with acute brain dysfunction during critical illness. Methods In this prospective cohort study, adult medical/surgical intensive care unit patients in shock and/or respiratory failure were enrolled. Endothelial function was assessed at enrollment using peripheral artery tonometry to calculate the reactive hyperemia index, with lower reactive hyperemia index indicative of worse endothelial function. Patients were assessed for coma and delirium with the Richmond Agitation-Sedation Scale and Confusion Assessment Method for the Intensive Care Unit. Multivariable linear regression was used to analyze the association between reactive hyperemia index and (1) delirium/coma-free days among all patients and (2) delirium duration among survivors, both over a 14-day period. Results One hundred forty-seven patients with median age of 57 yr and median Acute Physiology and Chronic Health Evaluation II score of 26 were enrolled. After adjusting for age, severity of illness, severe sepsis, preexisting cognitive function, medical versus surgical intensive care unit admission, and prehospital statin use, lower reactive hyperemia index (worse systemic endothelial function) was associated with fewer delirium/coma-free days (P = 0.02) and more delirium days (P = 0.05). Conclusions In this study, critically ill patients with lower vascular reactivity indicative of worse systemic endothelial function had increased duration of acute brain dysfunction.

Association between Endothelial Dysfunction and Acute Brain Dysfunction during Critical Illness

Acute brain dysfunction (delirium and coma) during critical illness is prevalent and costly, but the pathophysiology remains unclear. The relationship of acute brain dysfunction with endothelial function, which is impaired in critical illness and may contribute to alterations in cerebral blood flow and blood-brain barrier permeability, has not been studied. This study sought to determine whether systemic endothelial dysfunction is associated with acute brain dysfunction during critical illness. In this prospective cohort study, adult medical/surgical intensive care unit patients in shock and/or respiratory failure were enrolled. Endothelial function was assessed at enrollment using peripheral artery tonometry to calculate the reactive hyperemia index, with lower reactive hyperemia index indicative of worse endothelial function. Patients were assessed for coma and delirium with the Richmond Agitation-Sedation Scale and Confusion Assessment Method for the Intensive Care Unit. Multivariable linear regression was used to analyze the association between reactive hyperemia index and (1) delirium/coma-free days among all patients and (2) delirium duration among survivors, both over a 14-day period. One hundred forty-seven patients with median age of 57 yr and median Acute Physiology and Chronic Health Evaluation II score of 26 were enrolled. After adjusting for age, severity of illness, severe sepsis, preexisting cognitive function, medical versus surgical intensive care unit admission, and prehospital statin use, lower reactive hyperemia index (worse systemic endothelial function) was associated with fewer delirium/coma-free days (P = 0.02) and more delirium days (P = 0.05). In this study, critically ill patients with lower vascular reactivity indicative of worse systemic endothelial function had increased duration of acute brain dysfunction.

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Prehospital HMG Co-A reductase inhibitor use and reduced mortality in hemorrhagic shock due to trauma

3-Hydroxy-3-methyl-glutaryl Co-A reductase inhibitors (HMG Co-A reductase inhibitors, statins) are commonly used medications for the control of serum cholesterol. Recent data suggests that these medications also modify the inflammatory pathways in sepsis, septic shock, and hemorrhagic shock due to ruptured abdominal aortic aneurysms. Statin use in hemorrhagic shock due to trauma, however, has conflicting data, with one study showing improvement, but only in certain subsets of patients. We retrospectively reviewed the medical records of patients from our institution's trauma registry database from January 2000 to December 2008. We included patients with an age greater than 45years and an Injury Severity Score (ISS) greater than 15 with evidence of shock as follows: hypotension, elevated serum lactate, base deficit, metabolic acidosis, or objective evidence of end-organ malperfusion. We excluded patients with devastating head injury, patients with pre-existing advance directives directing against life-sustaining measures, patients for whom family or health care proxies withdrew support in 24h or less, and patients who succumbed to their injuries in the first 24h in the hospital. We compared age, gender, mortality, statin use, aspirin use, and Sequential Organ Failure Assessment (SOFA) scores. Mortality in the group without prehospital statin use was 38.1% (95% confidence interval [CI]: 28.4-48.8%) and mortality in the group with prehospital statin use was 8.3% (95% CI: 2.13-22.5%, P=0.0009). The absolute risk reduction was 29.8% and the relative risk reduction was 78.1%. Survivors were statistically significantly younger than nonsurvivors in the group without prehospital statin use, but not in the group with documented prehospital statin use. There was no similar benefit to aspirin use. There were no significant differences in the SOFA scores, hospital length of stay (HLOS), or intensive care unit length of stay (ICU LOS) between statin users and nonusers. Prehospital HMG Co-A reductase use was associated with improved survival in a population with severe trauma and evidence of ongoing hemorrhagic shock.

Prehospital statin and aspirin use and the prevalence of severe sepsis and acute lung injury/acute respiratory distress syndrome*

To determine whether prehospital statin use is associated with a lower risk of sepsis, acute lung injury/acute respiratory distress syndrome, and mortality in critically ill patients. We also investigated the effect of combined prehospital use of both statins and aspirin. Cross-sectional analysis of a prospective cohort. A total of 575 critically ill patients admitted to the medical or surgical intensive care unit of an academic tertiary-care hospital. None. Of 575 patients, 149 (26%) were on statin therapy before hospitalization. A multivariable analysis including age, gender, current tobacco use, prehospital aspirin use, race, and Acute Physiology and Chronic Health Evaluation II score revealed that patients on statin therapy before hospitalization were less likely to have or develop severe sepsis (odds ratio 0.62, 95% confidence interval 0.40-0.96) or acute lung injury/acute respiratory distress syndrome (odds ratio 0.60, 95% confidence interval 0.36-0.99) during the first four intensive care unit days. In-hospital mortalities for patients with and without prehospital statin use (odds ratio 1.06, 95% confidence interval 0.62-1.83) were similar. Patients who had prehospital use of both statins and aspirin had the lowest rates of severe sepsis, acute lung injury/acute respiratory distress syndrome, and mortality. Prehospital use of statins may be protective against sepsis and acute lung injury. This effect may be potentiated by prehospital aspirin use.

Temporal Change in Pre-hospital Statin Use and Total Cholesterol Levels in Patients Presenting with Acute Coronary Syndromes

Background: We assessed if patients presenting with acute coronary syndromes (ACS) were better treated with statins prior to hospitalisation and the effect on total cholesterol (TC) with time. Method: Australian patients with discharge diagnosis of ACS enrolled in the Global Registry of Acute Coronary Events (GRACE, 1999–2007, n= 4069) and The Cooperative National Registry of Acute Coronary Care Guideline Adherence and Clinical Events (CONCORDANCE, 2009–2010, n= 777) were included. Yearly change in initial admission TC and statin use prior to hospitalisation were assessed and adjusted for temporal change in demographic characteristics, background cardiac history 140 The FHWA Program: Nurse-led Cascade Screening for Familial Hypercholesterolaemia (FH)

Prehospital HMG Co-A Reductase Inhibitor Use and Reduced Mortality in Ruptured Abdominal Aortic Aneurysm

Conclusion: In patients with ruptured abdominal aortic aneurysms prehospital statin use appears to be associated with increased survival. Summary: One of the pleotrophic effects of statins appears to be reduction of inflammatory mediators. These mediators include heat shock proteins, tumor necrosis factor α, multiple interleukins, nuclear factor κ b, as well as nitric oxide. Statins likely have free radical scavenger activity. Statins also appear to exert anti-inflammatory and antioxidant affects that improve mortality in septic shock populations and patients with severe sepsis who were taking statins appear to develop septic shock less frequently. Theoretically, similar shock mechanisms could be active in the setting of a ruptured abdominal aortic aneurysm (rAAA). The authors performed a retrospective review of their patients with rAAAs from January 2000 to December 2008. They compared hospital and ICU lengths of stay, cardiac morbidity, and number of cardiac events per patient between survivor groups with and without pre hospital statin use. Mortality, cardiac morbidity, and gender were also compared. The Physiologic Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) was also calculated for all patients analyzed. There are 121 records screened with 40 patients excluded due to the presence of active cancer, chronic immune suppression or living wills or advanced directives against live sustaining treatment,. There were no statistically significant differences between statin users and non-users with respect to age, gender and POSSUM scores. Mortality in the group without pre hospital statin use was 63.8%. In the group with pre hospital statin use mortality was 34.8% (p=0.018, odds ratio 0.30 to 0.11). Hospital and ICU lengths of stay, cardiac morbidity, and number of cardiac events per patient were not statistically different among survivors. Comment: This study provides further evidence for the ever-widening pleotrophic effects of statin medications. It does have several limitations including its small sample size and the fact that endovascular repair of ruptured aneurysms and the use of statins increased over the study period. Patients were included in this study if they used any statin at any dose for any period of time up to their time of admission for rAAA. What is now needed is prospective studies on dose related response and time delays in the generation of the pleotrophic effects of statin medications.

Prehospital HMG Co-A Reductase Inhibitor Use and Reduced Mortality in Ruptured Abdominal Aortic Aneurysm

The compounds 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (HMG Co-A reductase inhibitors, statins) are popular medications for the control of elevated serum cholesterol. Recent evidence has demonstrated a survival benefit to patients who take statins in the premorbid period with severe sepsis, septic shock, or severe trauma. We hypothesized that a similar benefit would be seen in patients with ruptured abdominal aortic aneurysm. We completed a retrospective review of patients with ruptured abdominal aortic aneurysm in our institution from January 2000 to December 2008. We compared age, gender, mortality rates, and Physiologic and Operative Severity Score for the enumeration of Mortality and Morbidity (POSSUM) scores for all patients who met inclusion and exclusion criteria. We compared hospital and ICU lengths of stay, cardiac morbidity, and number of cardiac events per patient between survivor groups with and without prehospital statin use. We compared mortality, cardiac morbidity, and gender using the Pearson chi-square test, Physiologic and Operative Severity Score for the enumeration of Mortality and Morbidity scores and age using the Student's t-test and lengths of stay using the Mann Whitney-U test. Mortality in the group without prehospital statin use was 63.8%, and in the group with prehospital statin use was 34.8% (p=0.018, odds ratio 0.30 to 0.11). Physiologic and Operative Severity Score for the enumeration of Mortality and Morbidity scores were similar between survivor groups with and without statin use and nonsurvivor groups with and without statin use. Hospital and ICU lengths of stay, cardiac morbidity, and number of cardiac events per patient were not statistically different among survivors. Prehospital statin use appears to be associated with a significant survival benefit in the ruptured abdominal aortic aneurysm population.