Comparison of Effects of Atorvastatin Versus Rosuvastatin on Cardiac Function in Heart Failure Patients (ASTRO-CHF)

Comparison of Effects of Atorvastatin Versus Rosuvastatin Treatment on Cardiac Function and Inflammation in Patients With Chronic Heart Failure With Reduced Ejection Fraction: A Randomised, Double Blind Clinical Study

Statins have a protective effect in patients with established heart failure because of their lipid-lowering and pleiotropic effects. There is no randomized controlled trial comparing lipophilic versus hydrophilic statins in these patients (head to head comparison). The best evidence so far is from a meta-analysis in which the authors did an adjusted indirect comparison between lipophilic statins and rosuvastatin and found that lipophilic statins were associated with significantly lower incidence of all-cause mortality, cardiovascular mortality, and hospitalization for worsening heart failure compared to rosuvastatin (hydrophilic statin) among patients with heart failure. So, the investigators plan to conduct a randomized controlled trial comparing the effects of atorvastatin and rosuvastatin on cardiac function in patients with heart failure with reduced ejection fraction.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Drug: Atorvastatin Oral Tablet; Drug: Rosuvastatin Oral Tablet

Detailed Description

HMG CoA reductase inhibitors or Statins have been widely used for primary prevention and secondary prevention of atherosclerotic cardiovascular disease. Also, the protective effect of statins has been observed in patients with established heart failure because of their lipid-lowering and pleiotropic effects.

Various randomized and non-randomized clinical trials have evaluated statins like Atorvastatin, Rosuvastatin, Simvastatin, Pitavastatin and reported improved clinical outcomes in patients with heart failure with reduced ejection fraction as well as heart failure with preserved ejection fraction. Similar benefits on improved cardiac function, reduced inflammation, and improved mortality have been seen in small randomized controlled trials (RCTs) with Atorvastatin. The two large RCTs - Controlled Rosuvastatin Multinational Study in Heart Failure (CORONA) and Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiac (GISSI-HF) - which compared Rosuvastatin versus placebo, failed to show statistically significant benefits in mortality outcomes in heart failure patients compared to placebo, although CORONA trial did show a significant reduction in hospital admissions but not on mortality.

However, these two large trials only compared one statin i.e rosuvastatin versus placebo; which is a hydrophilic statin. Statin is not a uniform class of drugs. They differ in their pleiotropic effects based on lipophilic nature. There is evidence that lipophilic statins enter cells via passive diffusion and are widely distributed to various tissues including cardiac tissues where it exerts pleiotropic actions whereas uptake of hydrophilic statins is via carrier-mediated mechanisms and is restricted to the liver, thus reduced the capacity of non-lipid effects on extra-hepatic tissues.

Currently, there is no RCT comparing lipophilic statin versus hydrophilic statin (head to head comparison). The best evidence so far is from a meta-analysis which is an adjusted indirect comparison between lipophilic statins and rosuvastatin. They found that lipophilic statins were associated with a significantly lower incidence of all-cause mortality, cardiovascular mortality, and hospitalization for worsening heart failure compared to rosuvastatin (hydrophilic statin) among patients with heart failure. So, the investigators plan to conduct a randomized controlled trial comparing the effects of atorvastatin and rosuvastatin on cardiac function and inflammation in patients with heart failure with reduced ejection fraction.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Ashish kakkar, MD, DM; Phone Number: 91-172-2755297; Email: drashishkakkar@gmail.com
• Study Contact Backup: Name: Rachna Rohilla, MD; Email: rachna.rohilla20@gmail.com

Study Locations

• India
  • Chandigarh, India, 160012
    • Recruiting
    • Postgraduate Institute of Medical Education and Research, Chandigarh
    • Contact: Ashish kakkar, MD, DM; Phone Number: 91-172-2755297; Email: drashishkakkar@gmail.com
    • Contact: Rachna Rohilla, MD; Email: rachna.rohilla20@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Either gender,18-65 years of age
2. Left ventricular ejection fraction <40% as assessed by 2D echocardiography
3. NYHA class II-III
4. CHF patients currently optimized on standard treatment for at least 1 month before enrolment and on an OPD basis treatment
5. Ready to give written informed consent
6. Willing to comply with the study protocol

Exclusion Criteria:

1. Known hypersensitivity to statins
2. NYHA class IV patient
3. Serum creatinine >3 mg/dl
4. Significant liver disease: SGOT/SGPT >3 times the upper limit of normal (ULN) or >2.5 times the ULN in symptomatic patients
5. Patient on an enzyme inducer or inhibitor currently
6. Any malignancy or patient on chemotherapeutic agents
7. Pregnant or lactating females
8. Patients who have participated in another trial within the past 3 months
9. Patient with uncontrolled diabetes mellitus (HbA1c >7 g%)/ uncontrolled hypertension (BP >140/90 mmHg despite in ≥3 antihypertensive drugs)
10. Patient with HIV/ HBV / HCV infection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Atorvastatin arm; Tablet Atorvastatin 40mg once daily at bed-time given for 6 months	Drug: Atorvastatin Oral Tablet; Atorvastatin 40 mg
ACTIVE_COMPARATOR: Rosuvastatin arm; Tablet Rosuvastatin 20mg once daily at bed-time given for 6 months	Drug: Rosuvastatin Oral Tablet; Rosuvastatin 20 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the effect of atorvastatin and rosuvastatin on LVEF	Change from baseline in Left ventricular ejection fraction (LVEF) measured by 2D Echocardiography after atorvastatin or rosuvastatin treatment	Measurements at enrolment (baseline), 3 month and 6 months
To compare the effect of atorvastatin and rosuvastatin on NT-ProBNP	Change from baseline in NT-ProBNP (cardiac marker) after atorvastatin or rosuvastatin treatment.	Measurements at enrolment (baseline), 3 months and 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To compare the effect of atorvastatin and rosuvastatin on IL-6	Change from baseline in IL-6 levels after atorvastatin or rosuvastatin treatment	Measurements at enrolment (baseline) and 6 months
To compare the effect of atorvastatin and rosuvastatin on hsCRP	Change from baseline in hsCRP levels after atorvastatin or rosuvastatin treatment.	Measurements at enrolment (baseline), 3 month and 6 months
To compare the effect of atorvastatin and rosuvastatin on Minnesota living with heart failure questionnaire (MLHFQ)	Change from baseline in Minnesota living with heart failure questionnaire (MLHFQ) after atorvastatin or rosuvastatin treatment. MLHFQ consists of 21 questions and each question has a score from 0 to 5. The total score ranges from 0 to 105, with higher scores indicating greater impairment in health related quality of life.	Measurements at enrolment (baseline), 3 month and 6 months
To compare the effect of atorvastatin and rosuvastatin on 6-minute walk test (6MWT)	Change from baseline in 6-minute walk test (6MWT) after atorvastatin or rosuvastatin treatment.	Measurements at enrolment (baseline), 3 month and 6 months
Compare incidence of hospitalization for worsening of heart failure at 6 months in atorvastatin and rosuvastatin group	Incidence of hospitalization due to worsening of heart failure in 6 months in both groups	Analysis at 6 months
Compare incidence of adverse events and major adverse events including all-cause mortality, non-fatal MI, stroke in atorvastatin and rosuvastatin group.	Incidence of adverse events including serious adverse events in 6 months in both groups	Analysis at 6 months

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Collaborators: Indian Council of Medical Research
• Investigators: Principal Investigator: Ashish K Kakkar, Postgraduate Institute of Medical Education and Research

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 16, 2019
• Primary Completion (ANTICIPATED): June 30, 2022
• Study Completion (ANTICIPATED): August 31, 2022

Study Registration Dates

• First Submitted: September 28, 2021
• First Submitted That Met QC Criteria: September 28, 2021
• First Posted (ACTUAL): October 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): October 19, 2021
• Last Update Submitted That Met QC Criteria: October 11, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Heart failure; Atorvastatin; Rosuvastatin
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin; Rosuvastatin Calcium
• Other Study ID Numbers: PGIMER-CV-2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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