Comparison of High and Moderate Intensity Statins in Achieving the Target LDL-C Level After Acute Coronary Syndrome

Comparison of High and Moderate Intensity Statins in Achieving the Target LDL-C Level After Acute Coronary Syndrome: Randomized Controlled Trial

This study evaluates the effectiveness of high- and moderate-intensity statins in achieving target low-density lipoprotein cholesterol (LDL-C) levels in patients with acute coronary syndrome (ACS). The study aims to determine whether moderate-intensity statins can provide comparable benefits to high-intensity statins, particularly for patients at higher risk of adverse effects from higher doses. The findings may inform treatment decisions and reduce financial and clinical burdens on patients.

Study Overview

• Status: Completed
• Conditions: Acute Coronary Syndrome
• Intervention / Treatment: Drug: Moderate-Intensity Statins; Drug: High-Intensity Statins

Detailed Description

Statins are the cornerstone of therapy for reducing cardiovascular events in patients with atherosclerotic cardiovascular disease. Current guidelines recommend high-intensity statins for patients with ACS to lower LDL-C levels by 50% or more. However, emerging evidence suggests that the benefits of lowering LDL-C may be independent of the statin dose and type.

This randomized controlled trial investigates the effectiveness of moderate-intensity statins compared to high-intensity statins in reducing LDL-C levels among local populations. The study also explores whether moderate-intensity statins can mitigate adverse effects, such as myopathy or liver dysfunction, commonly associated with high-intensity statin therapy, particularly in populations with lower baseline LDL-C levels and high statin responsiveness.

Participants will be randomly assigned to receive either high-intensity or moderate-intensity statin therapy. The primary outcome measure is the percentage of participants achieving an LDL-C reduction of ≥50% after three months of treatment. Secondary outcomes include the frequency of adverse effects, adherence to therapy, and changes in liver function tests (LFTs) and creatine phosphokinase (CPK) levels.

The study will contribute to understanding the role of moderate-intensity statins in managing LDL-C levels and guide future clinical practices for patient subgroups at risk of adverse effects from high-intensity therapy.

• Study Type: Interventional
• Enrollment (Actual): 190
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • Khyber Pakhtunkhwa
    • Peshawar, Khyber Pakhtunkhwa, Pakistan, 25000
      • MTI-KTH (Medical Teaching Institution-Khyber Teaching Hospital), Peshawar-Pakistan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants aged between 25 and 85 years.
• Both males and females.
• Diagnosed with acute coronary syndrome as defined in the operational definitions.

Exclusion Criteria:

• History of adverse reactions to statins (e.g., hypersensitivity, myopathy, acute renal failure).
• Current acute liver disease.
• Pregnant or breastfeeding women.
• Participants already on statin therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Moderate-Intensity Statin Group; Participants in this group will receive moderate-intensity statins (Atorvastatin 20 mg, Rosuvastatin 10 mg). The dosage will be in the tablet form, which will be Dosage Form: Tablet Frequency: Once daily Duration: 3 months	Drug: Moderate-Intensity Statins; Participants will be administered statins based on moderate intensity. This group will receive oral tablets once daily for 3 months. The intervention includes Atorvastatin 20 mg and rosuvastatin 10 mg.; Other Names: Lipitor (brand name for Atorvastatin), Crestor (brand name for Rosuvastatin)
Active Comparator: High-Intensity Statin Group; Participants in this group will receive high-intensity statins. Interventions include Atorvastatin 40 mg, or Rosuvastatin 20 mg which will be taken in tablet form. Frequency: Once daily Duration: 3 months	Drug: High-Intensity Statins; Participants will be administered statins based on high intensity. This group will receive oral tablets once daily for 3 months. The intervention includes Atorvastatin 40 mg and rosuvastatin 20 mg.; Other Names: Lipitor (brand name for Atorvastatin), Crestor (brand name for Rosuvastatin)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in Low-Density Lipoprotein Cholesterol Level	The primary outcome is the percentage of participants achieving a reduction of ≥50% in LDL-C levels from baseline after 3 months of treatment with either moderate-intensity or high-intensity statins. LDL-C levels will be measured using lipid profiles obtained at baseline (upon admission) and at the end of the study (3 months post-treatment).	3 months after the start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Myopathy	The number of participants who develop myopathy as an adverse effect of statins, determined through clinical symptoms and laboratory tests.	Throughout the 3-month treatment duration
Frequency of Elevated Liver Enzymes	The number of participants with elevated liver enzyme levels (AST and ALT) as an adverse effect of statin therapy, determined through laboratory tests.	Throughout the 3-month treatment duration
Frequency of Elevated Creatine Phosphokinase (CPK) Levels	The number of participants with elevated CPK levels as an adverse effect of statin therapy, determined through laboratory tests.	Throughout the 3-month
Severity of Adverse Effects	The severity of adverse effects, such as myopathy, elevated liver enzymes, and elevated CPK levels, categorized using predefined clinical severity scales.	Throughout the 3-month treatment duration
Compliance with Statin Therapy	Evaluation of participant adherence to prescribed statin therapy, defined as the proportion of days with medication taken as prescribed over the 3-month period. Compliance will be assessed through patient questionnaires and medication logs.	At 3 months
Reduction in Symptom Severity	Reduction in the severity and frequency of symptoms, such as chest pain and fatigue, associated with acute coronary syndrome (ACS). Symptom severity will be measured using the Visual Analogue Scale (VAS) and patient-reported questionnaires. VAS scores for symptom severity: 1-3 Mild pain; 2-6 Moderate pain; 7-10 Severe pain	Baseline and at 3 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Lipid Profile Changes During Follow-Up	Changes in LDL-C levels as measured through laboratory investigations at 1 month and 3 months. Unit of Measure: LDL-C levels (mg/dL)	1 month and 3 months
Liver Function Test (LFT) Results During Follow-Up	Changes in liver enzyme levels (AST and ALT) as measured through laboratory investigations at 1 month and 3 months. Unit of Measure: LFT levels (U/L)	1 month and 3 months
Creatine Phosphokinase (CPK) Levels During Follow-Up	Changes in CPK levels as measured through laboratory investigations at 1 month and 3 months. Unit of Measure: CPK levels (U/L)	1 month and 3 months

Collaborators and Investigators

• Sponsor: Khyber Medical University Peshawar
• Collaborators: Khyber Teaching Hospital
• Investigators: Principal Investigator: Dr Shafeeq Mehmood, MBBS, Khyber Teaching Hospital; Principal Investigator: Muhammad Faheem Mehmood, MBBS, Khyber Teaching Hospital; Principal Investigator: Syed Muhammad Shabbir Ali Naqvi, Clinical Trial Unit, Khyber Medical University Peshawar

Publications and helpful links

General Publications

• LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, Gotto AM, Greten H, Kastelein JJ, Shepherd J, Wenger NK; Treating to New Targets (TNT) Investigators. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005 Apr 7;352(14):1425-35. doi: 10.1056/NEJMoa050461. Epub 2005 Mar 8.
• Cholesterol Treatment Trialists' (CTT) Collaboration; Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010 Nov 13;376(9753):1670-81. doi: 10.1016/S0140-6736(10)61350-5. Epub 2010 Nov 8.
• Reiner Z. Statins in the primary prevention of cardiovascular disease. Nat Rev Cardiol. 2013 Aug;10(8):453-64. doi: 10.1038/nrcardio.2013.80. Epub 2013 Jun 4.
• Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, Joyal SV, Hill KA, Pfeffer MA, Skene AM; Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 Investigators. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004 Apr 8;350(15):1495-504. doi: 10.1056/NEJMoa040583. Epub 2004 Mar 8.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Actual): July 30, 2025
• Study Completion (Actual): August 25, 2025

Study Registration Dates

• First Submitted: January 9, 2025
• First Submitted That Met QC Criteria: January 16, 2025
• First Posted (Actual): January 17, 2025

Study Record Updates

• Last Update Posted (Actual): January 8, 2026
• Last Update Submitted That Met QC Criteria: January 6, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Cardiovascular Diseases; Acute Coronary Syndrome; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Low-Density Lipoprotein Cholesterol
• Additional Relevant MeSH Terms: Vascular Diseases; Heart Diseases; Myocardial Ischemia; Cardiovascular Diseases; Acute Coronary Syndrome; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fatty Acids; Lipids; Azoles; Hydrocarbons; Amides; Pyrimidines; Hydrocarbons, Halogenated; Pyrroles; Heptanoic Acids; Sulfonamides; Sulfones; Fluorobenzenes; Hydrocarbons, Fluorinated; Atorvastatin; Rosuvastatin Calcium
• Other Study ID Numbers: KMU/DIR/CTU/2024/013

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) collected during the study will be made available to other researchers upon reasonable request. The shared data will include de-identified participant data such as baseline demographic details, laboratory results, and follow-up outcomes related to LDL-C levels.
• IPD Sharing Time Frame: The data will be made available starting six months after the publication of the study results and will remain accessible for a period of five years.
• IPD Sharing Access Criteria: Access to the data will be granted upon approval of a written proposal outlining the purpose of the data request and intended use. Researchers must provide a signed data access agreement to ensure data confidentiality and compliance with ethical standards.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No