Impact of lipophilic vs hydrophilic statins on the clinical outcome and biomarkers of remodelling in heart failure patients: A prospective comparative randomized study

Abstract

Aims There are insufficient direct comparative studies addressing the impact of the type of statin on their respective efficacy in heart failure (HF). The aim of the current study was to compare the effects of lipophilic (atorvastatin) vs hydrophilic (rosuvastatin) on left ventricular function, inflammatory and fibrosis biomarkers in patients with chronic HF. Methods This was a prospective, randomized, comparative, parallel study. A total of 85 patients with chronic HF optimized on guideline directed therapy were randomized to receive either atorvastatin 40 mg (n = 42) or rosuvastatin 20 mg (n = 43) for 6 months. Baseline and follow‐up assessment included 2D echocardiography, measurement of N‐terminal pro‐brain natriuretic peptide, interleukin‐6 and soluble suppression of tumorigenicity 2 (sST2) levels, liver enzymes and lipid profile. Results The increase in left ventricular ejection fraction was significantly higher in the atorvastatin group compared to the rosuvastatin group (6.5% [3–11] vs 4% [2–5], P = .006). The reduction in left ventricular end diastolic and end systolic volume was comparable between the 2 groups. The decrease in sST2 levels in pg/mL was significantly higher in the atorvastatin compared to the rosuvastatin group (−255 [−383 to −109.8 vs − 151 [−216 to −69], P = .003). There was a significant reduction in N‐terminal pro‐brain natriuretic peptide and interleukin‐6 levels in both groups, yet the reduction was comparable in both groups. Conclusion The study results suggest that lipophilic atorvastatin is superior to hydrophilic rosuvastatin in increasing left ventricular ejection fraction and reducing fibrosis marker sST2 in HF patients. Trial registration ID: NCT03255044, registered on 21 August 2017.

Investigation of mesalazine as an antifibrotic drug following myocardial infarction in male mice

“…The reason why mesalazine affected perivascular fibrosis in particular might be due to the pharmacological distribution of the hydrophilic compound. For the use of statins after MI, it has been demonstrated that the lipophilic atorvastatin offered advantages such as increasing left ventricular EF and reducing fibrosis marker expression over the hydrophilic rosuvastatin (El Said et al, 2021 ). The authors attribute this observation to increased extrahepatic tissue penetration of the lipophilic agent (El Said et al, 2021 ).…”

“…For the use of statins after MI, it has been demonstrated that the lipophilic atorvastatin offered advantages such as increasing left ventricular EF and reducing fibrosis marker expression over the hydrophilic rosuvastatin (El Said et al, 2021 ). The authors attribute this observation to increased extrahepatic tissue penetration of the lipophilic agent (El Said et al, 2021 ). Similar observations were made in the treatment of tuberculosis, in which lipophilic antibiotics displayed higher anti‐tuberculosis activity (Piccaro et al, 2015 ).…”

Cognition, Statins, and Cholesterol in Elderly Ischemic Stroke Patients: A Neurologist’s Perspective

“…In support of the direct influence of the lipophilic statins on the brain cholesterol come the findings of more frequent associations of cognitive impairments with the recent use of atorvastatin and simvastatin [76,77], which are lipophilic statins, as well as the findings of Rojas-Fernandez and colleagues, who showed that switching from a lipophilic to a hydrophilic statin might resolve the cognitive impairment [78]. The differences between the two classes of statins in cardiac outcomes are also not settled: while a meta-analysis showed similar effects of the two types of statins in coronary artery disease [79], the lipophylic atorvastatin in 40 mg daily dose was superior in increasing left ventricular ejection fraction and in reducing markers of fibrosis in patients with heart failure as compared to the hydrophilic rosuvastatin in daily doses of 20 mg over 6 months [80].…”

Hydrophilic or Lipophilic Statins?

“…A recent study comparing the effects of atorvastatin vs. rosuvastatin on left ventricular function, inflammatory and fibrosis biomarkers in patients with chronic HF, published by El Said et al ( 47 ) suggested that the impact of lipophilic atorvastatin was greater than that of hydrophilic rosuvastatin in HF patients with regards to the improvement in left ventricular ejection fraction and soluble suppression of tumorigenicity reduction, a novel fibrosis marker.…”