Mayo Clinic Proceedings Home

Pre-admission and In-Hospital Statin Use is Associated With Reduced Short Term Mortality in Infective Endocarditis

Published:September 13, 2022DOI:



      To investigate for potential protective effects of statin use among patients with infective endocarditis (IE) with consideration for underlying diseases and bacterial culture — variables which have prognostic implications and show considerable geographic variation yet are unappreciated in previous pharmacoepidemiological studies.

      Patients and Methods

      Patients diagnosed with IE between January 1, 1996, and December 31, 2019, were identified. We estimated the effect on mortality of pre-admission statin use (≥90 cumulative days of use before index date) and in-hospital use (use beginning within 2 days of admission), compared with nonusers and discontinued users, respectively, through propensity score analytics.


      Of 6700 IE patients (mean age, 58.0 years; 63.3% male [n=4251]), 776 patients had pre-admission statin use, with 626 continuing statin use following admission (in-hospital users). Pre-admission statin users had a 31% lower risk of 1-year mortality (HR, 0.69; 95% CI, 0.58 to 0.82) compared with nonusers. In-hospital users had a 48% lower risk of 1-year mortality (HR, 0.52; 95% CI, 0.34 to 0.78) compared with discontinued users. Subgroup analyses showed significant protective effects of statin use for patients with varying causative agents, underlying diseases, and with or without prosthetic valves. Results were consistent across different statins, and were dose-dependent.


      In patients with IE, pre-admission and in-hospital use of statin, when compared with statin nonusers and discontinued users, respectively, were associated with a lower risk of 1-year mortality.

      Abbreviations and Acronyms:

      CBPS (covariate balancing propensity score), CDARS (Clinical Data Analysis Reporting System), DDD (daily defined dose), IE (infective endocarditis), IPTW (inverse probability of treatment weighting)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Mayo Clinic Proceedings
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Habib G.
        • Erba P.A.
        • Iung B.
        • et al.
        Clinical presentation, aetiology and outcome of infective endocarditis. Results of the ESC-EORP EURO-ENDO (European infective endocarditis) registry: a prospective cohort study.
        Eur Heart J. 2019; 40: 3222-3232
        • Hoen B.
        • Alla F.
        • Selton-Suty C.
        • et al.
        Changing profile of infective endocarditis results of a 1-year survey in France.
        JAMA. 2002; 288: 75-81
        • Shah A.S.V.
        • McAllister D.A.
        • Gallacher P.
        • et al.
        Incidence, microbiology, and outcomes in patients hospitalized with infective endocarditis.
        Circulation. 2020; 141: 2067-2077
        • Olmos C.
        • Vilacosta I.
        • Fernández-Pérez C.
        • et al.
        The evolving nature of infective endocarditis in Spain: a population-based study (2003 to 2014).
        J Am Coll Cardiol. 2017; 70: 2795-2804
        • Habib G.
        • Lancellotti P.
        • Antunes M.J.
        • et al.
        2015 ESC guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European Society of Cardiology (ESC) endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM).
        Eur Heart J. 2015; 36: 3075-3128
        • Smit J.
        • López-Cortés L.E.
        • Thomsen R.W.
        • et al.
        Statin use and risk of community-acquired Staphylococcus aureus bacteremia: a population-based case-control study.
        Mayo Clin Proc. 2017; 92: 1469-1478
        • Hackam D.G.
        • Mamdani M.
        • Li P.
        • Redelmeier D.A.
        Statins and sepsis in patients with cardiovascular disease: a population-based cohort analysis.
        Lancet. 2006; 367: 413-418
        • Thomsen R.W.
        • Riis A.
        • Kornum J.B.
        • Christensen S.
        • Johnsen S.P.
        • Sørensen H.T.
        Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients.
        Arch Intern Med. 2008; 168: 2081-2087
        • Mortensen E.M.
        • Nakashima B.
        • Cornell J.
        • et al.
        Population-based study of statins, angiotensin II receptor blockers, and angiotensin-converting enzyme inhibitors on pneumonia-related outcomes.
        Clin Infect Dis. 2012; 55: 1466-1473
        • Anavekar N.S.
        • Schultz J.C.
        • De Sa D.D.C.
        • et al.
        Modifiers of symptomatic embolic risk in infective endocarditis.
        Mayo Clin Proc. 2011; 86: 1068-1074
        • Yang T.F.
        • Chu H.
        • Ou S.M.
        • et al.
        Effect of statin therapy on mortality in patients with infective endocarditis.
        Am J Cardiol. 2014; 114: 94-99
        • Sapey E.
        • Patel J.M.
        • Greenwood H.
        • et al.
        Simvastatin improves neutrophil function and clinical outcomes in pneumonia. A pilot randomized controlled clinical trial.
        Am J Respir Crit Care Med. 2019; 200: 1282-1293
        • Calfee C.S.
        • Delucchi K.L.
        • Sinha P.
        • et al.
        Acute respiratory distress syndrome subphenotypes and differential response to simvastatin: secondary analysis of a randomised controlled trial.
        Lancet Respir Med. 2018; 6: 691-698
        • Sunder S.
        • Grammatico-Guillon L.
        • Baron S.
        • et al.
        Clinical and economic outcomes of infective endocarditis.
        Infect Dis (Lond). 2015; 47: 80-87
      1. The Hospital Authority. Hospital authority statistical report 2016-2017. Accessed 15 March 2021.

        • Cheung K.S.
        • Chan E.W.
        • Wong A.Y.S.
        • Chen L.
        • Wong I.C.K.
        • Leung W.K.
        Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study.
        Gut. 2018; 67: 28-35
        • Cheung K.S.
        • Chen L.
        • Chan E.W.
        • Seto W.K.
        • Wong I.C.K.
        • Leung W.K.
        Statins reduce the progression of non-advanced adenomas to colorectal cancer: a postcolonoscopy study in 187,897 patients.
        Gut. 2019; 68: 1979-1985
        • Leung W.K.
        • Wong I.O.L.
        • Cheung K.S.
        • et al.
        Effects of Helicobacter pylori treatment on incidence of gastric cancer in older individuals.
        Gastroenterology. 2018; 155: 67-75
        • Cheung K.S.
        • Chan E.W.
        • Wong A.Y.S.
        • et al.
        Metformin use and gastric cancer risk in diabetic patients after Helicobacter pylori eradication.
        J Natl Cancer Inst. 2019; 111: 484-489
        • Lau W.C.Y.
        • Chan E.W.
        • Cheung C.-L.
        • et al.
        Association between dabigatran vs warfarin and risk of osteoporotic fractures among patients with nonvalvular atrial fibrillation.
        JAMA. 2017; 317: 1151-1158
        • Schneeweiss S.
        • Robicsek A.
        • Scranton R.
        • Zuckerman D.
        • Solomon D.H.
        Veteran's affairs hospital discharge databases coded serious bacterial infections accurately.
        J Clin Epidemiol. 2007; 60: 397-409
        • Toyoda N.
        • Chikwe J.
        • Itagaki S.
        • Gelijns A.C.
        • Adams D.H.
        • Egorova N.N.
        Trends in infective endocarditis in California and New York State, 1998-2013.
        JAMA. 2017; 317: 1652-1660
        • Wiese A.D.
        • Griffin M.R.
        • Stein C.M.
        • et al.
        Validation of discharge diagnosis codes to identify serious infections among middle age and older adults.
        BMJ Open. 2018; 8e020857
        • Havers F.
        • Bramley A.M.
        • Finelli L.
        • et al.
        Statin use and hospital length of stay among adults hospitalized with community-acquired pneumonia.
        Clin Infect Dis. 2016; 62: 1471-1478
        • Imai K.
        • Ratkovic M.
        Covariate balancing propensity score.
        J Royal Stat Soc Series B (Stat Methodol). 2014; 76: 243-263
        • Verma A.A.
        • Khuu W.
        • Tadrous M.
        • Gomes T.
        • Mamdani M.M.
        Fixed-dose combination antihypertensive medications, adherence, and clinical outcomes: a population-based retrospective cohort study.
        PLoS Med. 2018; 15e1002584
        • Austin P.C.
        • Stuart E.A.
        Moving towards best practice when using inverse probability of treatment weighting (IPTW) using the propensity score to estimate causal treatment effects in observational studies.
        Stat Med. 2015; 34: 3661-3679
        • Funk M.J.
        • Westreich D.
        • Wiesen C.
        • Stürmer T.
        • Brookhart M.A.
        • Davidian M.
        Doubly robust estimation of causal effects.
        Am J Epidemiol. 2011; 173: 761-767
        • Schoenfeld D.
        Partial residuals for the proportional hazards regression model.
        Biometrika. 1982; 69: 239-241
      2. WHO Collaborating Center for Drugs Statistics Methoodlogy.
        (Accessed 15 March 2021.)
        • Therneau T.M.
        • Grambsch P.M.
        Modeling Survival Data: Extending the Cox Model.
        Springer, 2013
        • Therneau T.M.
        • Grambsch P.M.
        • Fleming T.R.
        Martingale-based residuals for survival models.
        Biometrika. 1990; 77: 147-160
        • VanderWeele T.J.
        • Ding P.
        Sensitivity analysis in observational research: introducing the E-value.
        Ann Intern Med. 2017; 167: 268-274
        • Lee C.C.
        • Lee M.G.
        • Hsu T.C.
        • et al.
        A population-based cohort study on the drug-specific effect of statins on sepsis outcome.
        Chest. 2018; 153: 805-815
        • Siegman-Igra Y.
        • Koifman B.
        • Porat R.
        • Porat D.
        • Giladi M.
        Healthcare associated infective endocarditis: a distinct entity.
        Scand J Infect Dis. 2008; 40: 474-480
        • Tleyjeh I.M.
        • Abdel-Latif A.
        • Rahbi H.
        • et al.
        A systematic review of population-based studies of infective endocarditis.
        Chest. 2007; 132: 1025-1035
        • Emilsson L.
        • García-Albéniz X.
        • Logan R.W.
        • Caniglia E.C.
        • Kalager M.
        • Hernán M.A.
        Examining bias in studies of statin treatment and survival in patients with cancer.
        JAMA Oncol. 2018; 4: 63-70
        • Kruger P.S.
        • Harward M.L.
        • Jones M.A.
        • et al.
        Continuation of statin therapy in patients with presumed infection: a randomized controlled trial.
        Am J Respir Crit Care Med. 2011; 183: 774-781
        • Kruger P.
        • Bailey M.
        • Bellomo R.
        • et al.
        A multicenter randomized trial of atorvastatin therapy in intensive care patients with severe sepsis.
        Am J Respir Crit Care Med. 2013; 187: 743-750
        • Leutner M.
        • Matzhold C.
        • Bellach L.
        • et al.
        Diagnosis of osteoporosis in statin-treated patients is dose-dependent.
        Ann Rheum Dis. 2019; 78: 1706-1711
        • Ko M.J.
        • Jo A.J.
        • Kim Y.J.
        • et al.
        Time- and dose-dependent association of statin use with risk of clinically relevant new-onset diabetes mellitus in primary prevention: a nationwide observational cohort study.
        J Am Heart Assoc. 2019; 8e011320
        • Patel J.M.
        • Thickett D.R.
        • Gao F.
        • Sapey E.
        Statins for sepsis: distinguishing signal from the noise when designing clinical trials.
        Am J Respir Crit Care Med. 2013; 188: 874
        • Loppnow H.
        • Zhang L.
        • Buerke M.
        • et al.
        Statins potently reduce the cytokine-mediated IL-6 release in SMC/MNC cocultures.
        J Cell Mol Med. 2011; 15: 994-1004
        • van der Meij E.
        • Koning G.G.
        • Vriens P.W.
        • et al.
        A clinical evaluation of statin pleiotropy: statins selectively and dose-dependently reduce vascular inflammation.
        PLoS ONE. 2013; 8e53882
        • Harbarth S.
        • Holeckova K.
        • Froidevaux C.
        • et al.
        Diagnostic value of procalcitonin, interleukin-6, and interleukin-8 in critically ill patients admitted with suspected sepsis.
        Am J Respir Crit Care Med. 2001; 164: 396-402
        • Siciliano R.F.
        • Gualandro D.M.
        • Bittencourt M.S.
        • et al.
        Biomarkers for prediction of mortality in left-sided infective endocarditis.
        Int J Infect Dis. 2020; 96: 25-30
        • Baddour L.M.
        • Wilson W.R.
        • Bayer A.S.
        • et al.
        Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association.
        Circulation. 2015; 132: 1435-1486
        • Kadri A.N.
        • Wilner B.
        • Hernandez A.V.
        • et al.
        Geographic trends, patient characteristics, and outcomes of infective endocarditis associated with drug abuse in the United States from 2002 to 2016.
        J Am Heart Assoc. 2019; 8e012969