The influence of early statin administration on in-hospital and 1-year mortality after acute coronary syndrome: experience from the Croatian branch of the ISACS-CT registry

    Authors

    Abstract

    **Background and Aim:** The relevance of statin therapy in acute coronary syndrome (ACS) is well-established, but little is known about the optimal timing of statin administration, particularly within the first 24 hours following ACS. (1, 2) The aim of the study was to gather data on early and late outcomes of ACS patients (pts) through the Croatian branch of the ISACS-CT (International Registry of Acute Coronary Syndromes in Transitional Countries) registry. **Patients and Methods:** The data was gathered retrospectively from January 2012 to October 2017. The study population included 1898 ACS pts: 46.4% (n=881) with ST-segment elevation myocardial infarction (STEMI), 36.1% (n=685) with non-ST-segment elevation myocardial infarction (NSTEMI) and 17.5% (n=332) with unstable angina pectoris (UA). Follow-up was performed on 33% (n=630) of the cohort, 43.7% (n=275) with STEMI, 34.4% (n=217) NSTEMI and 21.9% (n=138) with UA. **Results:** In the first 24 hours following ACS, statins were administered in 1734 (93%) pts (for 24 pts the data is missing), while the pts who received them later or not at all were the control group. The two groups did not differ regarding age, gender, body mass index, left ventricular ejection fraction (LVEF) during initial hospitalization, smoking status, history of diabetes, chronic heart failure or arterial hypertension at initial hospitalization nor at 1-year follow-up (**Table 1**). The overall in-hospital mortality rate was 4%, similar to that in pts treated with statins within the first 24 hours (3%), while in pts without early statin treatment, in-hospital mortality rate was 18% (p<0.001). The risk of in-hospital death was significantly higher in pts without early statin therapy (odds ratio [OR] 7.32, 95% confidence interval [CI] 4.371-12.27, p<0.001), while the risk of primary outcome at 1-year follow-up was not significantly different between groups in univariate regression analysis. Older age (OR 1.1, 95% CI 1.06-1.20, p< 0.001), higher creatinine level (OR 1.0, 95% CI 1.005-1.012, p<0.001), lower LVEF (OR 0.90, 95%CI 0.86-0.94, p<0.001) and lack of early statin treatment (OR 3.6, 95% CI 1.0-13.10, p=0.05) were positively associated with increased odds for early primary outcome in multivariable regression model (**Table 2**). ### TABLE 1: Baseline characteristics and the comparison of patients with acute coronary syndrome with and without early statin therapy. | | **Statin group** **(n=1734)** | **Non-statin group** **(n=140)** | **p value** | **Statin group 1y** **(n=566)** | **Non-statin group** **1y (n=63)** | **p value 1y** | | --- | --- | --- | --- | --- | --- | --- | | Age (IQR) | 65 (57, 75) | 67 (55, 78) | 0.293 | 65 (57, 74) | 65 (52, 74) | 0.402 | | Male sex, n (%) | 1202 (69) | 89 (64) | 0.184 | 397 (70) | 45 (71) | 0.885 | | DM, n (%) | 472 (27 | 37 (27) | 0.921 | 161 (28) | 18 (29) | 0.543 | | HTN, n (%) | 1324 (77) | 103 (76) | 0.912 | 441 (78) | 51 (81) | 0.240 | | Smoking, n (%) | 809 (47) | 70 (50) | 0.527 | 274 (48) | 38 (60) | 0.257 | | CHF, n (%) | 69 (4) | 7 (5) | 0.143 | 16 (3) | 4 (6) | 0.194 | | HR median (IQR) | 77 (67, 90) | 80 (69, 90) | 0.182 | - | - | - | | SBP median (IQR) | 138 (120, 150) | 130 (118, 149) | **0.038** | - | - | - | | STEMI n (%) | 807 (47) | 60 (43) | **0.031** | 252 (45) | 23 (37) | 0.134 | | NSTEMI n (%) | 633(37) | 44 (31) | 196 (35) | 20 (32) | | | | UA n (%) | 294 (17) | 36 (26) | 118 (22) | 20 (32) | | | | Hemoglobin (IQR) | 140 (129, 150) | 138 (123, 150) | 0.144 | - | - | - | | Creatinine (IQR) | 94 (80, 112) | 97 (78, 115) | 0.819 | - | - | - | | hsTnT max median (IQR) | 1600 (240, 5292) | 1145 (242, 4245) | 0.113 | - | - | - | | CRP median (IQR) | 4 (2, 16) | 10 (3, 98) | 0.205 | - | - | - | | LVEF median (IQR) | 52 (45, 60) | 50 (40, 60) | 0.442 | 47 ± 12 | 44 ± 16 | 0.708 | | In-hospital mortality / 1y mortality, n (%) | 50 (3) | 25 (18) | **<0.001** | 28 (5) | 6 (10) | 0.238 | [†] IQR - Interquartile range; y - year; DM – Diabetes mellitus; HTN – Arterial hypertension; CHF – Chronic heart failure; HR – Heart rate; SBP – Systolic blood pressure; STEMI – ST-segment elevation myocardial infarction; NSTEMI - Non-ST-segment elevation myocardial infarction; UA – Unstable angina; hsTnT - High-sensitive troponin T; CRP – C reactive protein; LVEF – Left ventricular ejection fraction. ### TABLE 2: Univariable and multivariable binary regression analysis for early statin therapy with in-hospital and 1-year death as primary outcome. | | **Initial hospitalization (n=1898)** | **Initial hospitalization (n=1898)** | **Initial hospitalization (n=1898)** | **1 year follow-up (n=629)** | **1 year follow-up (n=629)** | **1 year follow-up (n=629)** | | --- | --- | --- | --- | --- | --- | --- | | | **HR** | **95% CI** | **p value** | **HR** | **95% CI** | **p value** | | **Univariable regression** | 7.32 | 4.371-12.27 | <0.001 | 2.02 | 0.80-5.09 | 0.135 | | **Multivariable regression*** | 3.61 | 0.99-13.10 | 0.051 | - | - | - | [†] * Adjusted for age, sex, DM2, BMI, creatinine, LVEF during initial hospitalization, ACS type. DM – Diabetes mellitus; BMI – Body mass index; LVEF – Left ventricular ejection fraction; HR – Hazard ratio; CI - confidence interval. **Conclusion:** Initiation of statin therapy within the first 24 hours following ACS is associated with a significant reduction in in-hospital mortality, although the positive effect of early statin therapy did not reach statistical significance at 1-year follow-up.

    Keywords

    acute coronary syndrome, statins, mortality

    DOI

    https://doi.org/10.15836/ccar2018.301

    Literature

    1. Schwartz GG, Fayyad R, Szarek M, DeMicco D, Olsson AG. Early, intensive statin treatment reduces ‘hard’ cardiovascular outcomes after acute coronary syndrome. Eur J Prev Cardiol. 2017 Aug;24(12):1294–6. https://doi.org/10.1177/2047487317708677
    2. Navarese EP, Kowalewski M, Andreotti F, van Wely M, Camaro C, et al. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol. 2014 May 15;113(10):1753–64. https://doi.org/10.1016/j.amjcard.2014.02.034
    Cardiologia Croatica
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    The influence of early statin administration on in-hospital and 1-year mortality after acute coronary syndrome: experience from the Croatian branch of the ISACS-CT registry

    Extended Abstract
    Issue11-12
    Published
    Pages301-302
    PDF via DOIhttps://doi.org/10.15836/ccar2018.301
    acute coronary syndrome
    statins
    mortality

    Authors

    Dora Fabijanović*ORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Nina JakušORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Filip LončarićORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Petra MjehovićORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Dorja SabljakORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Antonija MiškovićORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Dominik OrozORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Ines VinkovićORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Vedrana VlahovićORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Grgur SalaiORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Saša PavasovićORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Maja ČikešORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska
    Davor MiličićORCIDMedicinski fakultet Sveučilišta u Zagrebu, Klinički bolnički centar Zagreb, Zagreb, Hrvatska

    *Correspondence email: dora.fabijanovic@gmail.com

    Abstract

    **Background and Aim:** The relevance of statin therapy in acute coronary syndrome (ACS) is well-established, but little is known about the optimal timing of statin administration, particularly within the first 24 hours following ACS. (1, 2) The aim of the study was to gather data on early and late outcomes of ACS patients (pts) through the Croatian branch of the ISACS-CT (International Registry of Acute Coronary Syndromes in Transitional Countries) registry. **Patients and Methods:** The data was gathered retrospectively from January 2012 to October 2017. The study population included 1898 ACS pts: 46.4% (n=881) with ST-segment elevation myocardial infarction (STEMI), 36.1% (n=685) with non-ST-segment elevation myocardial infarction (NSTEMI) and 17.5% (n=332) with unstable angina pectoris (UA). Follow-up was performed on 33% (n=630) of the cohort, 43.7% (n=275) with STEMI, 34.4% (n=217) NSTEMI and 21.9% (n=138) with UA. **Results:** In the first 24 hours following ACS, statins were administered in 1734 (93%) pts (for 24 pts the data is missing), while the pts who received them later or not at all were the control group. The two groups did not differ regarding age, gender, body mass index, left ventricular ejection fraction (LVEF) during initial hospitalization, smoking status, history of diabetes, chronic heart failure or arterial hypertension at initial hospitalization nor at 1-year follow-up (**Table 1**). The overall in-hospital mortality rate was 4%, similar to that in pts treated with statins within the first 24 hours (3%), while in pts without early statin treatment, in-hospital mortality rate was 18% (p<0.001). The risk of in-hospital death was significantly higher in pts without early statin therapy (odds ratio [OR] 7.32, 95% confidence interval [CI] 4.371-12.27, p<0.001), while the risk of primary outcome at 1-year follow-up was not significantly different between groups in univariate regression analysis. Older age (OR 1.1, 95% CI 1.06-1.20, p< 0.001), higher creatinine level (OR 1.0, 95% CI 1.005-1.012, p<0.001), lower LVEF (OR 0.90, 95%CI 0.86-0.94, p<0.001) and lack of early statin treatment (OR 3.6, 95% CI 1.0-13.10, p=0.05) were positively associated with increased odds for early primary outcome in multivariable regression model (**Table 2**). ### TABLE 1: Baseline characteristics and the comparison of patients with acute coronary syndrome with and without early statin therapy. | | **Statin group** **(n=1734)** | **Non-statin group** **(n=140)** | **p value** | **Statin group 1y** **(n=566)** | **Non-statin group** **1y (n=63)** | **p value 1y** | | --- | --- | --- | --- | --- | --- | --- | | Age (IQR) | 65 (57, 75) | 67 (55, 78) | 0.293 | 65 (57, 74) | 65 (52, 74) | 0.402 | | Male sex, n (%) | 1202 (69) | 89 (64) | 0.184 | 397 (70) | 45 (71) | 0.885 | | DM, n (%) | 472 (27 | 37 (27) | 0.921 | 161 (28) | 18 (29) | 0.543 | | HTN, n (%) | 1324 (77) | 103 (76) | 0.912 | 441 (78) | 51 (81) | 0.240 | | Smoking, n (%) | 809 (47) | 70 (50) | 0.527 | 274 (48) | 38 (60) | 0.257 | | CHF, n (%) | 69 (4) | 7 (5) | 0.143 | 16 (3) | 4 (6) | 0.194 | | HR median (IQR) | 77 (67, 90) | 80 (69, 90) | 0.182 | - | - | - | | SBP median (IQR) | 138 (120, 150) | 130 (118, 149) | **0.038** | - | - | - | | STEMI n (%) | 807 (47) | 60 (43) | **0.031** | 252 (45) | 23 (37) | 0.134 | | NSTEMI n (%) | 633(37) | 44 (31) | 196 (35) | 20 (32) | | | | UA n (%) | 294 (17) | 36 (26) | 118 (22) | 20 (32) | | | | Hemoglobin (IQR) | 140 (129, 150) | 138 (123, 150) | 0.144 | - | - | - | | Creatinine (IQR) | 94 (80, 112) | 97 (78, 115) | 0.819 | - | - | - | | hsTnT max median (IQR) | 1600 (240, 5292) | 1145 (242, 4245) | 0.113 | - | - | - | | CRP median (IQR) | 4 (2, 16) | 10 (3, 98) | 0.205 | - | - | - | | LVEF median (IQR) | 52 (45, 60) | 50 (40, 60) | 0.442 | 47 ± 12 | 44 ± 16 | 0.708 | | In-hospital mortality / 1y mortality, n (%) | 50 (3) | 25 (18) | **<0.001** | 28 (5) | 6 (10) | 0.238 | [†] IQR - Interquartile range; y - year; DM – Diabetes mellitus; HTN – Arterial hypertension; CHF – Chronic heart failure; HR – Heart rate; SBP – Systolic blood pressure; STEMI – ST-segment elevation myocardial infarction; NSTEMI - Non-ST-segment elevation myocardial infarction; UA – Unstable angina; hsTnT - High-sensitive troponin T; CRP – C reactive protein; LVEF – Left ventricular ejection fraction. ### TABLE 2: Univariable and multivariable binary regression analysis for early statin therapy with in-hospital and 1-year death as primary outcome. | | **Initial hospitalization (n=1898)** | **Initial hospitalization (n=1898)** | **Initial hospitalization (n=1898)** | **1 year follow-up (n=629)** | **1 year follow-up (n=629)** | **1 year follow-up (n=629)** | | --- | --- | --- | --- | --- | --- | --- | | | **HR** | **95% CI** | **p value** | **HR** | **95% CI** | **p value** | | **Univariable regression** | 7.32 | 4.371-12.27 | <0.001 | 2.02 | 0.80-5.09 | 0.135 | | **Multivariable regression*** | 3.61 | 0.99-13.10 | 0.051 | - | - | - | [†] * Adjusted for age, sex, DM2, BMI, creatinine, LVEF during initial hospitalization, ACS type. DM – Diabetes mellitus; BMI – Body mass index; LVEF – Left ventricular ejection fraction; HR – Hazard ratio; CI - confidence interval. **Conclusion:** Initiation of statin therapy within the first 24 hours following ACS is associated with a significant reduction in in-hospital mortality, although the positive effect of early statin therapy did not reach statistical significance at 1-year follow-up.

    Literature

    1. 1.
      Schwartz GG, Fayyad R, Szarek M, DeMicco D, Olsson AG. Early, intensive statin treatment reduces ‘hard’ cardiovascular outcomes after acute coronary syndrome. Eur J Prev Cardiol. 2017 Aug;24(12):1294–6.DOI
    2. 2.
      Navarese EP, Kowalewski M, Andreotti F, van Wely M, Camaro C, et al. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention. Am J Cardiol. 2014 May 15;113(10):1753–64.DOI