Clinical trial NCT05072054: Comparison of Effects of Atorvastatin Versus Rosuvastatin on Cardiac Function in Heart Failure Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: Atorvastatin
Rosuvastatin
Heart failure
Lead sponsor: PGIMER
Sponsor class: UNKNOWN
Collaborators: name: Indian Council of Medical Research
First posted: 2021-10-08
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind clinical study
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: To compare the effect of atorvastatin and rosuvastatin on LVEF
timeFrame: Measurements at enrolment (baseline), 3 month and 6 months
measure: To compare the effect of atorvastatin and rosuvastatin on NT-ProBNP
timeFrame: Measurements at enrolment (baseline), 3 months and 6 months
Secondary outcomes:
measure: To compare the effect of atorvastatin and rosuvastatin on IL-6
timeFrame: Measurements at enrolment (baseline) and 6 months
measure: To compare the effect of atorvastatin and rosuvastatin on hsCRP
timeFrame: Measurements at enrolment (baseline), 3 month and 6 months
measure: To compare the effect of atorvastatin and rosuvastatin on Minnesota living with heart failure questionnaire (MLHFQ)
timeFrame: Measurements at enrolment (baseline), 3 month and 6 months
measure: To compare the effect of atorvastatin and rosuvastatin on 6-minute walk test (6MWT)
timeFrame: Measurements at enrolment (baseline), 3 month and 6 months
measure: Compare incidence of hospitalization for worsening of heart failure at 6 months in atorvastatin and rosuvastatin group
timeFrame: Analysis at 6 months
measure: Compare incidence of adverse events and major adverse events including all-cause mortality, non-fatal MI, stroke in atorvastatin and rosuvastatin group.
timeFrame: Analysis at 6 months
Other outcomes:
Locations:
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research, Chandigarh
Study officials:
affiliation: Post Graduate Institute of Medical Education and Research, Chandigarh
name: Ashish K Kakkar
role: PRINCIPAL_INVESTIGATOR
References: