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 w… Show more
“…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 ).…”
Section: Discussionmentioning
confidence: 99%
“…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 ).…”
ObjectivesMyocardial infarction (MI) initiates a complex reparative response during which damaged cardiac muscle is replaced by connective tissue. While the initial repair is essential for survival, excessive fibrosis post‐MI is a primary contributor to progressive cardiac dysfunction, and ultimately heart failure. Currently, there are no approved drugs for the prevention or the reversal of cardiac fibrosis. Therefore, we tested the therapeutic potential of repurposed mesalazine as a post‐MI therapy, as distinct antifibrotic effects have recently been demonstrated.MethodsAt 8 weeks of age, MI was induced in male C57BL/6J mice by LAD ligation. Mesalazine was administered orally at a dose of 100 μg/g body weight in drinking water. Fluid intake, weight development, and cardiac function were monitored for 28 days post intervention. Fibrosis parameters were assessed histologically and via qPCR.ResultsCompared to controls, mesalazine treatment offered no survival benefit. However, no adverse effects on heart and kidney function and weight development were observed, either. While total cardiac fibrosis remained largely unaffected by mesalazine treatment, we found a distinct reduction of perivascular fibrosis alongside reduced cardiac collagen expression.ConclusionsOur findings warrant further studies on mesalazine as a potential add‐on therapy post‐MI, as perivascular fibrosis development was successfully prevented.
“…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 ).…”
Section: Discussionmentioning
confidence: 99%
“…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 ).…”
ObjectivesMyocardial infarction (MI) initiates a complex reparative response during which damaged cardiac muscle is replaced by connective tissue. While the initial repair is essential for survival, excessive fibrosis post‐MI is a primary contributor to progressive cardiac dysfunction, and ultimately heart failure. Currently, there are no approved drugs for the prevention or the reversal of cardiac fibrosis. Therefore, we tested the therapeutic potential of repurposed mesalazine as a post‐MI therapy, as distinct antifibrotic effects have recently been demonstrated.MethodsAt 8 weeks of age, MI was induced in male C57BL/6J mice by LAD ligation. Mesalazine was administered orally at a dose of 100 μg/g body weight in drinking water. Fluid intake, weight development, and cardiac function were monitored for 28 days post intervention. Fibrosis parameters were assessed histologically and via qPCR.ResultsCompared to controls, mesalazine treatment offered no survival benefit. However, no adverse effects on heart and kidney function and weight development were observed, either. While total cardiac fibrosis remained largely unaffected by mesalazine treatment, we found a distinct reduction of perivascular fibrosis alongside reduced cardiac collagen expression.ConclusionsOur findings warrant further studies on mesalazine as a potential add‐on therapy post‐MI, as perivascular fibrosis development was successfully prevented.
“…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].…”
Background and Objectives: The efficacy of hydroxy methyl glutaryl-coenzyme A reductase inhibitors (statins) in reducing the incidence of cardiovascular events pushed the target LDL-cholesterol (LDL-C) levels lower and lower in successive guidelines despite signals regarding potential cognitive side effects. We evaluated the relationship between cognitive impairment and LDL-C levels in elderly ischemic stroke patients. Materials and Methods: 29 ischemic stroke patients aged 65 and above with LDL-C levels ≤70 mg/dL, classified according to the TOAST criteria, underwent detailed neuropsychological testing comprising the MMSE test, Montreal Cognitive Assessment (MoCA) and Addenbrooke’s Cognitive Evaluation (ACE-III) test. Their performances were compared to those of 29 age-matched ischemic stroke patients with LDL-Cl levels >71 mg/dL. Results: The MMSE test failed to detect significant cognitive differences between the two groups. The MoCA and ACE-III tests detected impairments in visuo-spatial/executive function, attention, and recall/memory in patients with low LDL-C. A stepwise linear regression model of the ACE-III total scores revealed that LDL-cholesterol levels could contribute to 13.8% of the detected cognitive dysfunction, second in importance only to age, which contributed to 38.8% of the detected impairment. Conclusions: Physicians should be cautious when prescribing statins to elderly people. Hydrophilic ones may be preferred in cognitively impaired patients.
“…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.…”
Section: Statin Solubility and Cardiovascular Outcomesmentioning
Drugs can be classified as hydrophilic or lipophilic depending on their ability to dissolve in water or in lipid-containing media. The predominantly lipophilic statins (simvastatin, fluvastatin, pitavastatin, lovastatin and atorvastatin) can easily enter cells, whereas hydrophilic statins (rosuvastatin and pravastatin) present greater hepatoselectivity. Although the beneficial role of statins in primary and secondary cardiovascular prevention has been unequivocally confirmed, the possible superiority of one statin or other regarding their solubility profile is still not well-established. In this respect, although some previously published observational studies and clinical trials observed a superiority of lipophilic statins in cardiovascular outcomes, these results could also be explained by a greater low-density lipoprotein cholesterol reduction with this statin type. On the other hand, previous studies reported conflicting results as to the possible superiority of one statin type over the other regarding heart failure outcomes. Furthermore, adverse events with statin therapy may also be related to their solubility profile. Thus, the aim of the present review was to collect clinical evidence on possible differences in cardiovascular outcomes among statins when their solubility profile is considered, and how this may also be related to the occurrence of statin-related adverse effects.
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