Enhanced-Dose Statins for ST-Segment Elevation Myocardial Infarction Patients after Emergency Percutaneous Coronary Intervention

Chen, Wenzhong; Fan, Zhiwen; Huang, Canhui; Han, Zhiyuan; Liu, Junying

doi:https://doi.org/10.1155/2022/2751750

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Abstract Introduction Materials and Methods Results Discussion Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

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Research Article | Open Access

Volume 2022 | Article ID 2751750 | https://doi.org/10.1155/2022/2751750

Enhanced-Dose Statins for ST-Segment Elevation Myocardial Infarction Patients after Emergency Percutaneous Coronary Intervention

Wenzhong Chen,¹Zhiwen Fan,²Canhui Huang,¹Zhiyuan Han,¹and Junying Liu³

Academic Editor: Zhongjie Shi

Received02 Apr 2022

Accepted04 Jun 2022

Published28 Jun 2022

Abstract

Background. Acute ST-segment elevation myocardial infarction (STEMI) is a serious multiple acute cardiovascular disease. This study investigated the effect of statins on the efficacy and prognosis of STEMI patients after emergency PCI. Methods. From October 2019 to January 2021, 98 patients with STEMI in our hospital were selected and divided into study group and control group. The study group took atorvastatin 40 mg 2 hours before surgery, 40 mg/day after surgery, and 20 mg/day 1 week later. The control group received 20 mg of atorvastatin every night after admission. The cardiac output, left ventricular ejection fraction, blood flow classification, vagus nerve function, heart rate deceleration force and chemoreflex sensitivity were compared between the two groups, and recorded the incidence of adverse reactions before and after treatment and 3 months after treatment. The number of major adverse cardiac events (MACEs) was also recorded. Results. Before treatment, there were no differences in CO, CI, and LVEF between the study and control groups. After treatment, CO, CI, and LVEF in the study group were significantly higher than those in the control group. Before treatment, there was no significant difference in TIMI blood flow classification among the groups, and after treatment, the study group was better than the control group. DC and ChRS were significantly higher in the study group than in the control group. There was no difference in the incidence of adverse reactions between the study group and the control group. However, the incidence of MACE in the study group was lower than that in the control group. Conclusion. Enhanced-dose atorvastatin for STEMI patients improved PCI treatment effect, cardiac function, and vagus nerve function and reduced the incidence of adverse cardiac events. Thus, statins are safe and worth considering.

1. Introduction

Acute ST-segment elevation myocardial infarction (STEMI) is a serious and multiple acute cardiovascular disease. The occurrence of STEMI is mainly due to the rupture, excessive activation, and accumulation of unstable plaques in the coronary arteries, forming clots that block the coronary arteries, leading to myocardial ischemia and irreversible damage to myocardial cells. STEMI poses a serious threat to the lives of patients [1–3]. In recent years, the incidence of STEMI has continuously increased as the population ages and poor lifestyle habits increase. Therefore, the safe and effective treatment of STEMI is crucial [4].

Percutaneous coronary intervention (PCI) can be used to treat STEMI by rebuilding the blood supply and opening the blocked vessels to save ischemic-damaged myocardium [5]. However, some STEMI patients still have abnormal myocardial perfusion, and the damaged myocardium remains unprotected after PCI. Statins have antioxidant effects, reduce inflammation, improve endothelial function, and improve plaque stability. Therefore, the use of statins during treatment can improve the therapeutic effect of PCI. However, the appropriate dose and safety need to be further confirmed [6, 7]. Previous study indicated that atorvastatin therapy increases heart rate variability, decreases QT variability, and shortens QTc interval duration in patients with advanced chronic heart failure [8].

Myocardial reperfusion and vagal function are important clinical indicators to evaluate the clinical treatment and prognosis of patients with cardiovascular disease. However, there are few systematic studies on how booster-dose statins affect vagal function after emergency PCI in STEMI patients [9, 10]. Therefore, we investigated the efficacy of enhanced-dose statins in this patient population following a randomized controlled protocol.

2. Materials and Methods

2.1. Baseline Data

The protocol of study was approved by the ethics committee of Guangzhou First People’s Hospital. From October 2019 to January 2021, 98 patients with STEMI in our hospital were selected and divided into study and control groups using a simple randomized method (49 patients per group). Gender, age, smoking and alcohol consumption, body mass index, and the Killip classification of cardiac function and basic diseases were recorded for comparison between the two groups (Table 1).

2.2. Selection Criteria

2.2.1. Inclusion Criteria

Patients were included if they met the STEMI diagnostic criteria [11], serum myocardial necrosis markers increased ≥2 times, there was ST elevation in at least two adjacent leads, a mV or a pathological Q wave, or a mV, or they had persistent min. Further, all patients received PCI treatment, were confirmed by electrocardiogram, were treated at the first onset, had cardiac function classified as Killip classes I-III, and gave informed consent.

2.2.2. Exclusion Criteria

Patients with other cardiovascular and cerebrovascular diseases, immune system diseases, infectious diseases, renal and hepatic insufficiency who cannot tolerate PCI and drug therapy, received antioxidant or lipid-lowering drug therapy within 1 month before the study, or have allergies were excluded.

2.3. Intervention

After admission, both groups received clopidogrel 300-600 mg and aspirin 300 mg. The study group was given atorvastatin 40 mg 2 h before surgery, 40 mg/d after surgery, and 20 mg/d 1 week later [12]. The control group received 20 mg of atorvastatin every night after admission. PCI was performed using the right femoral artery and radial artery puncture, and only the infarct-related vessels were treated. The patient received intravenous heparin (70-100 IU/kg) intraoperatively. 20–25 mL of a platelet glycoprotein II B/III A receptor antagonist or intraventricular injection of 200 μg of sodium nitroso was also administered, and an aortic balloon pulsatile catheter was inserted. Three to 5 days after operation, low molecular weight heparin (4100 U) was subcutaneously injected every 12 h, and long-term oral aspirin (100 mg/d) and clopidogrel (75 mg/d) were administered once.

2.4. Observation Indices

Cardiac output (CO), cardiac index (CI), left ventricular ejection fraction (LVEF), and other cardiac function indexes were measured by color Doppler ultrasound (Minrui DC-N2S) before and after treatment in the two groups. The blood flow classification (TIMI) of the two groups before and after treatment was statistically analyzed, and the forward perfusion of the distal occluded vessels was 0. Anterior perfusion of vessels distal to the lesion, but difficulty in filling distal vessels, is grade 1. After at least three cardiac cycles, the distal vessels of the lesion were filled. Contrast can completely fill the distal vessel within three cardiac cycles of grade 3. Vagus nerve function, including heart rate deceleration power (DC) and chemoreflex sensitivity (ChRS), was measured by 24-hour Holter. For ChRS measurements, the patient was in a supine position at rest and inhaled oxygen through a mask for 5 minutes (5 L/min). Venous blood was drawn before and after oxygen inhalation, and venous partial pressure of oxygen (PVO2) was measured. 10 consecutive normal RR intervals were recorded continuously, and the average RR interval was calculated (). The incidence of adverse reactions in the two groups and the incidence of major adverse cardiac events (MACEs) after 3 months were analyzed.

2.5. Statistical Method

SPSS 22.0 (IBM Corp., Armonk, N.Y., USA) was used for data analysis. Measurement data were analyzed by -tests and expressed as . Enumeration data were analyzed by test and expressed as (%). values < 0.05 indicated statistical significance.

3. Results

3.1. Cardiac Function Index Comparisons

Before treatment, CO, CI, and LVEF did not differ between the groups (CO: vs. L/min, CI: vs. L·min^-1·m^-2, and LVEF: vs. %; ). After treatment, CO, CI, and LVEF were significantly higher in the study group than in the control group (CO: vs. L/min, CI: vs. L·min^-1·m^-2, and LVEF: vs. %; ; Table 2).

3.2. TIMI Blood Flow Grading Comparison

TIMI blood flow grading did not differ between the two groups before treatment (). However, it was significantly better in the study group than in the control group after treatment (; Table 3).

3.3. Vagus Nerve Function Indicator Comparisons

DC and ChRS were significantly higher in the study group than in the control group (DC: vs. ms and ChRS: vs. ms/mm Hg; ; Table 4).

3.4. Comparison of Incidence of Adverse Reactions

The rate of incidence of adverse reactions did not differ between the study group (10.20%) and the control group (6.12%) (; Table 5).

3.5. Comparison of Incidence of MACEs

The rate of incidence of MACEs was significantly lower in the study group (6.12%) than in the control group (20.41%) (; Table 6).

4. Discussion

Emergency PCI is an important STEMI treatment as it can completely, quickly, and permanently restore coronary artery blood flow, reduce disease mortality, relieve clinical symptoms, and prolong patients’ lives [13]. However, mechanical damage can occur during PCI treatment, resulting in a vascular endothelial tear. Thus, a large amount of subcutaneous tissue is exposed to blood, which can trigger an inflammatory response, damage myocardial cells, activate coagulation functions, and increase the risk of MACE [14, 15]. Previously, dual antiplatelet and antithrombotic interventions mainly focused on perioperative PCI. However, clinical studies indicate that atorvastatin administration before and after an emergency or elective PCI helped reduce the risk of perioperative and postoperative MACE for patients with myocardial infarction [16, 17].

The dose of atorvastatin was controversial, and previous studies indicated that a high-dose loading of statins (80 mg/day) before PCI in patients with ACS reduces MACCE and reduces the risk of MI with no impact on mortality at 30 days [18]. But high-dose atorvastatin pretreatment does not seem to prevent CIN in patients receiving primary angioplasty [19]. In addition, High-dose atorvastatin may produce an optimal result for STEMI patients undergoing PCI by improving microvascular myocardial perfusion [20]. This study investigated the value of atorvastatin as an adjuvant therapy at different doses during PCI treatment for STEMI patients. We found that CO, CI, and LVEF were higher, the TIMI blood grade was better, and the MACE incidence was lower in the study group than in the control group (). The incidence of adverse reactions did not differ between the two groups, suggesting that, compared with routine dosing of atorvastatin, increasing the atorvastatin dosage improved the therapeutic effect of PCI in STEMI patients, restored cardiac function and blood flow grading, and helped reduce the risk of MACE. These results are noteworthy as they suggest a good disease outcome without an increased risk of adverse reactions, and that the treatment is safe. This may be because atorvastatin has a unique chemical structure, namely, aromatic groups, which form hydroxyl-activated metabolites that prolong the half-life of atorvastatin to improve vascular endothelial function, reduce cholesterol, and inhibit platelet aggregation, oxidation, and inflammation. They also increase other cardiovascular protective functions and regulate lipids, which can be further improved by enhanced-dose application [21, 22]. For example, an enhanced atorvastatin dose reduces platelet aggregation and activation. Further, there are different degrees of inflammatory responses in STEMI patients that cause myocardial injury, elicit an immune response, and increase the risk of ventricular muscle remodeling, which worsens cardiac function. Enhanced doses of atorvastatin can minimize these reactions through a potent anti-inflammatory effect [23].

In the early stage of STEMI, cardiac autonomic nerve necrosis, injury, and remodeling occur, mainly manifesting as sympathetic nerve remodeling and vagus nerve function decline. The stability of myocardial cell electrical activity decreases, and the myocardial metabolism is abnormal, leading to poor phenomena such as pleomorphism, persistent ventricular tachycardia, ventricular fibrillation, and eventually sudden cardiac death. Foreign studies indicate that abnormal vagus nerve function and sympathetic nerve remodeling are the main causes of myocardial excitability enhancement and abnormal conduction and are important electrophysiological mechanisms for the occurrence and maintenance of malignant arrhythmias. Autonomic nerve function, especially the vagus nerve state, can predict the occurrence of adverse cardiovascular events. DC has been an important part of Holter electrocardiogram research in recent years. By analyzing the overall 24 h heart rate trend and measuring the deceleration ability, the vagal tone can be quantitatively assessed, allowing for a new noninvasive electrocardiogram technology for screening and warning high-risk MACE patients. ChRS is also a noninvasive indicator reflecting autonomic nerve function and is an independent predictor of adverse cardiovascular events after PCI in STEMI patients. It is better than ventricular arrhythmia, ventricular late potential, and LVEF and can accurately reflect the stability of myocardial electrical activity [24, 25]. However, in our study, DC and ChRS were higher in the study group than in the control group after treatment (), further verifying that the enhanced atorvastatin dose is advantageous for PCI in STEMI patients and improves the therapeutic effect and disease prognosis.

In conclusion, intervention with an enhanced atorvastatin dose for STEMI patients improved PCI treatment effect, cardiac function, and vagus nerve function and reduced the incidences of adverse cardiac events. Thus, enhanced statin treatment is safe and worth considering. However, in our study, we did not investigate the long-term living conditions of patients. Therefore, the effect of an enhanced atorvastatin dose on the long-term prognosis of STEMI patients after PCI requires further investigation.

Data Availability

All data was provided in the manuscript.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgments

This study was supported by the scientific research project of Traditional Chinese Medicine Bureau of Guangdong Province (20201254).

References

A. Firouzi, A. K. Moussavi, A. Mohebbi et al., “Comparison between rosuvastatin and atorvastatin for the prevention of contrast-induced nephropathy in patients with STEMI undergoing primary percutaneous coronary intervention,” Journal of Cardiovascular and Thoracic Research, vol. 10, no. 3, pp. 149–152, 2018.
View at: Publisher Site | Google Scholar
A. S. Elserafy, N. M. Farag, A. I. El Desoky, and K. A. Eletriby, “Effect of high-intensity statin preloading on TIMI flow in patients presenting with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention,” The Egyptian Heart Journal, vol. 72, no. 1, pp. 40–46, 2020.
View at: Publisher Site | Google Scholar
M. Shehata, A. Samir, and M. Dardiri, “Prognostic impact of intensive statin therapy on N‐terminal pro‐BNP level in non-ST-segment elevation acute myocardial infarction patients,” Journal of interventional cardiology, vol. 30, no. 6, pp. 514–521, 2017.
View at: Publisher Site | Google Scholar
V. E. Oleynikov, E. V. Dushina, Y. A. Barmenkova, M. V. Lukyanova, and L. I. Salyamova, “The impact of effective therapy with atorvastatin on the dynamics of parameters of electrical instability in patients with ST-elevation myocardial infarction,” Kardiologiia, vol. 17, no. 8, pp. 18–24, 2018.
View at: Publisher Site | Google Scholar
X. R. Xu, K. B. Li, P. Wang et al., “The impact of different doses of atorvastatin on plasma endothelin and platelet function in acute ST-segment elevation myocardial infarction after emergency percutaneous coronary intervention,” Zhonghua nei ke za zhi, vol. 55, no. 12, pp. 932–936, 2016.
View at: Publisher Site | Google Scholar
A. Rahhal, F. Khir, A. H. Aljundi et al., “Clinical outcomes of high‐intensity doses of atorvastatin in patients with acute coronary syndrome: A retrospective cohort study using real‐world data,” British Journal of Clinical Pharmacology, vol. 87, no. 4, pp. 2043–2052, 2021.
View at: Publisher Site | Google Scholar
X. Xu, Y. Liu, K. Li et al., “Intensive atorvastatin improves endothelial function and decreases ADP-induced platelet aggregation in patients with STEMI undergoing primary PCI: a single-center randomized controlled trial,” International Journal of Cardiology, vol. 222, pp. 467–472, 2016.
View at: Publisher Site | Google Scholar
B. Vrtovec, R. Okrajsek, A. Golicnik, M. Ferjan, V. Starc, and B. Radovancevic, “Atorvastatin therapy increases heart rate variability, decreases QT variability, and shortens QTc interval duration in patients with advanced chronic heart failure,” Journal of cardiac failure, vol. 11, no. 9, pp. 684–690, 2005.
View at: Publisher Site | Google Scholar
R. D. Lopes, P. G. M. de Barros e Silva, I. de Andrade Jesuíno et al., “Timing of loading dose of atorvastatin in patients undergoing percutaneous coronary intervention for acute coronary syndromes: insights from the SECURE-PCI randomized clinical trial,” JAMA cardiology, vol. 3, no. 11, pp. 1113–1118, 2018.
View at: Publisher Site | Google Scholar
O. Gruzdeva, E. Uchasova, Y. Dyleva, O. Akbasheva, V. Karetnikova, and O. Barbarash, “Early effects of treatment low-dose atorvastatin on markers of insulin resistance and inflammation in patients with myocardial infarction,” Frontiers in pharmacology, vol. 7, p. 324, 2016.
View at: Publisher Site | Google Scholar
Y. Ozaki, H. Hara, Y. Onuma et al., “CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) update 2022,” Cardiovascular intervention and therapeutics, pp. 1–34, 2022.
View at: Publisher Site | Google Scholar
T. R. Pedersen, N. B. Cater, O. Faergeman et al., “Comparison of atorvastatin 80 mg/day versus simvastatin 20 to 40 mg/day on frequency of cardiovascular events late (five years) after acute myocardial infarction (from the Incremental Decrease in End Points through Aggressive Lipid Lowering [IDEAL] trial),” The American journal of cardiology, vol. 106, no. 3, pp. 354–359, 2010.
View at: Publisher Site | Google Scholar
O. Berwanger, E. V. Santucci, I. de Andrade Jesuíno et al., “Effect of loading dose of atorvastatin prior to planned percutaneous coronary intervention on major adverse cardiovascular events in acute coronary syndrome: the SECURE-PCI randomized clinical trial,” Jama, vol. 319, no. 13, pp. 1331–1340, 2018.
View at: Publisher Site | Google Scholar
M. Ma, L. Bu, L. Shi et al., “Effect of loading dose of atorvastatin therapy prior to percutaneous coronary intervention in patients with acute coronary syndrome: a meta-analysis of six randomized controlled trials,” Drug Design, Development and Therapy, vol. 13, p. 1233, 2019.
View at: Publisher Site | Google Scholar
W. Liu, Z. Zou, H. Jiang et al., “Clinical effect of preoperative high-dose atorvastatin against no-reflow after PCI,” Experimental and therapeutic medicine, vol. 13, no. 1, pp. 97–102, 2017.
View at: Publisher Site | Google Scholar
M. Hougaard, H. S. Hansen, P. Thayssen et al., “Influence of ezetimibe in addition to high-dose atorvastatin therapy on plaque composition in patients with ST-segment elevation myocardial infarction assessed by serial: intravascular ultrasound with iMap: the OCTIVUS trial,” Cardiovascular Revascularization Medicine, vol. 18, no. 2, pp. 110–117, 2017.
View at: Publisher Site | Google Scholar
R. C. García-Méndez, E. Almeida-Gutierrez, L. Serrano-Cuevas et al., “Reduction of no reflow with a loading dose of atorvastatin before primary angioplasty in patients with acute ST myocardial infarction,” Archives of Medical Research, vol. 49, no. 8, pp. 620–629, 2018.
View at: Publisher Site | Google Scholar
J. A. Borovac, M. Leth-Olsen, M. Kumric et al., “Efficacy of high-dose atorvastatin or rosuvastatin loading in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a meta-analysis of randomized controlled trials with GRADE qualification of available evidence,” European Journal of Clinical Pharmacology, pp. 1–16, 2021.
View at: Publisher Site | Google Scholar
S. H. Jo, J. Y. Hahn, S. Y. Lee et al., “High-dose atorvastatin for preventing contrast-induced nephropathy in primary percutaneous coronary intervention,” Journal of Cardiovascular Medicine, vol. 16, no. 3, pp. 213–219, 2015.
View at: Publisher Site | Google Scholar
J. S. Kim, J. Kim, D. Choi et al., “Efficacy of high-dose atorvastatin loading before primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: the STATIN STEMI trial,” JACC: Cardiovascular Interventions, vol. 3, no. 3, pp. 332–339, 2010.
View at: Publisher Site | Google Scholar
W. He, M. Cao, and Z. Li, “Effects of different doses of atorvastatin, rosuvastatin, and simvastatin on elderly patients with ST‐elevation acute myocardial infarction (AMI) after percutaneous coronary intervention (PCI),” Drug Development Research, vol. 81, no. 5, pp. 551–556, 2020.
View at: Publisher Site | Google Scholar
Q. Liu, Y. Wang, and X. Cheng, “The functional effect of atorvastatin dose-dependent via inflammation factors on acute ST segment elevation myocardial infarction after emergency percutaneous coronary intervention,” Journal of Cardiovascular Medicine, vol. 20, no. 4, pp. 215–219, 2019.
View at: Publisher Site | Google Scholar
M. Gavazzoni, E. Gorga, G. Derosa, P. Maffioli, M. Metra, and R. Raddino, “High-dose atorvastatin versus moderate dose on early vascular protection after ST-elevation myocardial infarction,” Drug design, development and therapy, vol. 11, p. 3425, 2017.
View at: Publisher Site | Google Scholar
K. Priti, A. Agrawal, and B. L. Ranwa, “High versus low dose statin therapy in Indian patients with acute ST-segment elevation myocardial infarction undergoing thrombolysis,” Indian Heart Journal, vol. 69, no. 4, pp. 453–457, 2017.
View at: Publisher Site | Google Scholar
Q. Li, Y. G. Zhao, Z. Wang, H. P. Jiang, W. B. Liu, and B. F. Cao, “Effects of first high-dose atorvastatin loading in patients with ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention,” American Journal of Therapeutics, vol. 25, no. 3, pp. e291–e298, 2018.
View at: Publisher Site | Google Scholar

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Copyright © 2022 Wenzhong Chen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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