Effect of Upstream Treatment With High Intensity Statin on the Outcomes of STMI Patients Treated With PPCI

Effect of Upstream Treatment With High Intensity Statin on the Outcomes of ST Segment Elevation Myocardial Infarction Patients Treated With Primary Percutaneous Coronary Intervention

Effect of upstream treatment with high intensity statin on the outcome of ST segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention

Study Overview

• Status: Unknown
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Drug: Atorvastatin; Drug: Aspirin

Detailed Description

Inflammation plays a key role in the occurrence and development of atherosclerosis(.T lymphocytes are among the earliest cells to be recruited into the atherosclerotic plaque.The combination of macrophages and lymphocytes in vulnerable plaque is associated with the secretion of cytokines and lytic enzymes that result in thinning of the fibrous cap, predisposing a lesion to rupture.The neutrophil to lymphocyte ratio (NLR) is an indicator of systemic inflammation and a prognostic marker in patients undergoing percutaneous coronary intervention (PCI).In previous studies, the NLR has been demonstrated to be related to in-hospital cardiovascular mortality and long-term mortality in patients with ST segment elevation myocardial infarction (STEMI).

In addition to its beneficial lipid modulation effects, statins exert a variety of pleiotropic actions such as inflammatory inhibition, antiventricular remodeling, improving vascular endothelial function, and antioxidant effects. Because ofitsmultiple functions, atorvastatin therapy was associated with a significant reduction in cardiovascular morbidity and mortality both in primary and secondary prevention. The Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL)study demonstrated thatatorvastatin 80 mg which was given during the first days after an ACS decreased the rate of major adverse cardiovascular events (MACE). This effect was observed as early as 6 weeks after randomization and was significant at 16 weeks. Atorvastatin for Reduction of MYocardial Damage during Angioplasty (ARMYDA) trial demonstrated a reduction in peri-procedural myocardial infarction (MI) in patients with stable CAD undergoing PCI preloaded by high potency statins atorvastatin 80 mg. The ARMYDARECAPTURE study showed a reduction in 30 days MACE in patients with stable angina or with non-ST elevation MI who were previously treated with statins and were reloaded with high potency statins.

The prompt effect that was observed with high-potency statins is one of the cornerstones of the plaque stabilization hypothesis, in which a clinical effect is demonstrated well before the low levels of low density lipoprotein-cholesterol (LDL-c) can affect plaque progression.

The effect of high vs. low potency statins in ACS was examined by the Pravastatin or Atorvastatin. ThePCI PROVE IT, a sub-study of the PROVE IT-TIMI 22 trial, demonstrated that patients pretreated with high potency statins before PCI had a significantly lower rate of target vessel revascularization. TheIn-vitro models showed that statins given prior to PCI decrease distal embolization and increase circulating endothelial progenitor cells, thus potentially increase endothelial healing following the injury caused by PCI. In addition, patients undergoing elective PCI, which were pre-treated with statins, had less microcirculatory resistance compared to placebo.

Conversely, the STATIN STEMI Trial did not show a significant reduction of MACEs in patients preloaded with high-dose (80 mg) versus low-dose (10 mg) atorvastatin before primary PCI (5.8% versus 0.6%, p=0.26) but showed improved immediate coronary flow after primary PCI.

Furthermore, in the SECURE-PCI trial, the periprocedural loading doses of atorvastatin did not reduce the rate of MACE at 30 days in ACS patients.However, the subgroup analysis showed a significant reduction of MACE in STEMI patients preloaded with atorvastatin compared with the placebo (P=0.01), still not all patients were treated with primary PCI.

• Study Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 3

Contacts and Locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• STEMI patients eligible for primary PCI presented to Assiut university heart hospital.

Exclusion Criteria:

• Previous (within 3 months) or current treatment with statins
• Patients with contraindications to statins.
• Patients with cardiogenic shock.
• Patients with acute STEMI not eligible for Primary.
• Patients with other factors affecting leucocytic count such as active infection or leukemia.
• Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: group for loading with statin before PPCI; All patients will receive the routine guidelines advised management before and after primary PCI. Patients will be randomly assigned (1:1) to receive two 80-mg loading doses of atorvastatin, the first loading dose will be administered in the Emergency Room before transfer to Cath Lab, the second dose of 80-mg atorvastatin will be administered 24 hours afterthe first dose.	Drug: Atorvastatin; preloading with high dose statins (atorvastatin 80mg) with loading dose of dual antiplatelet( asprine 300 mg and ticagrelor 180 mg) pre-primary PCI; Other Names: aspirin; ticagrelor
PLACEBO_COMPARATOR: group receive the routine guidelines management before PPCI; All patients will receive the routine guidelines advised management before and after primary PCI. Patients will be randomly assigned (1:1) to receive only the routine management.	Drug: Aspirin; Loading dose of dual antiplatelet (asprine 300 mg and ticagrelor 180 mg); Other Names: ticagrelor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
laboratory investigation	Follow up the change in inflammatory marker: C reactive protein during hospital admission, after 24 hours, 1 month then after 3 months	up to 3 months after primary PCI
laboratory investigation	Follow up the change in inflammatory marker: Neutrophil lymphocyte ratio during hospital admission, after 24 hours, 1 month then after 3 months	up to 3 months after primary PCI
laboratory investigation	Follow up the change in inflammatory marker: total leukocytic count during hospital admission, after 24 hours, 1 month then after 3 months	up to 3 months after primary PCI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TIMI flow during PCI	-During PCI: TIMI flow of the culprit vessel	During primary PCI
corrected TIMI frame count	-During PCI: corrected TIMI frame count of the culprit vessel	During primary PCI
Myocardial blush grade during PCI	-During PCI: myocardial blush grade of the culprit vessel	During primary PCI
MACE within 1 month and 3 months after primary PCI	-MACE(major adverse cardiovascular events) within 1 month and 3 months after primary PCI	up to 3 months after primary PCI

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: Nagwa Ahmed Abdelrahman, Lecturer, Nagwaabdelrahman@yahoo.com

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): February 20, 2021
• Primary Completion (ANTICIPATED): March 1, 2021
• Study Completion (ANTICIPATED): March 1, 2021

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: February 12, 2021
• First Posted (ACTUAL): February 15, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 12, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: PPCI
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Aspirin; Ticagrelor; Atorvastatin
• Other Study ID Numbers: High dose statin pre PPCI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes