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.

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.

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

Patients will be randomized to two arms in ratio 1:1 using computer-generated random list. Patients, investigator and care provider will be blinded to the treatment group.