Efficacy and safety of statin therapy in pulmonary hypertension: a systematic review and meta-analysis

Abstract

Background: Pulmonary hypertension (PH) is a multi-causal disease and no satisfactory therapeutic strategies for it. Statins have been suggested as potential drugs in PH, whose effects in different clinic types of PH have not been conclusive. In this study, we included randomized controlled clinical trials (RCTs) evaluating the efficacy and safety of statins therapy in PH.Methods: We searched databases including Medline, Embase, Cochrane, PubMed and Web of science, with time up to January 1, 2019. With 95% confidence interval (CI), weighted mean difference (WMD) or standardized mean difference (SMD) was pooled and calculated in a random or fixed effect model according to I2 statistic.Results: A total of nine RCTs with 657 patients were included. Four types of statins (atorvastatin, pravastatin, rosuvastatin and simvastatin) were used at different doses (10-80 mg daily) for up to 6 months.In the pooled-data analysis, compared with placebo, there were significant improvements in pulmonary arterial pressure (PAP), in addition to low-density lipoprotein (LDL) in patients treated with statins, but not in 6-minute walking distance (6MWD), cardiac index (CDI). No more adverse events and all-cause mortality were revealed. Subgroup analysis indicated that statins could decrease PAP in the subtype of PH due to chronic obstructive pulmonary disease (COPD), but not pulmonary arterial hypertension (PAH).Conclusions: This study indicates that statins can efficiently and safely reduce PAP in PH, especially in the subtype due to COPD. Further RCTs are needed to focus on the efficacy and safety of statin therapy in different subtypes of PH.

High-fat diet attenuates the improvement of hypoxia-induced pulmonary hypertension in mice during reoxygenation

“…Until now, the effectiveness of lipid-lowering therapy for pulmonary arterial hypertension (PAH) in previous studies has been controversial despite the association between metabolic disorder and PH [ 35 – 37 ]. In fact, it is confirmed that an intervention for dyslipidemia is less effective than the use of pulmonary vasodilators.…”

High-Fat Diet Attenuates the Improvement of Hypoxia-induced Pulmonary Artery Hypertension in Mice During Reoxygenation.

“…Until now, the effectiveness of lipid lowering therapy for PAH in previous studies have been controversial, despite the association between metabolic disorder and PAH [32][33][34]. In fact, it is con rmed that an intervention for dyslipidemia is less effective than the use of pulmonary vasodilators.…”

Interplay of Low-Density Lipoprotein Receptors, LRPs, and Lipoproteins in Pulmonary Hypertension

“…This lack of benefits might appear counterintuitive because statins have pleiotropic effects, such as lipid-lowering, antiproliferative, antioxidant, anti-inflammatory, and endothelial cell function–maintaining properties ( 49 ), which may be helpful in attenuating the progression of PAH. More recently, in 2019, another meta-analysis focused on clinical subgroup analysis: PAH and PH due to COPD ( 50 ). It suggests that statins can efficiently and safely reduce pulmonary arterial pressure in PH, especially in PH associated with COPD ( 50 ).…”

“…More recently, in 2019, another meta-analysis focused on clinical subgroup analysis: PAH and PH due to COPD ( 50 ). It suggests that statins can efficiently and safely reduce pulmonary arterial pressure in PH, especially in PH associated with COPD ( 50 ). Therefore, the effect of lipid-lowering therapies remains controversial, but it appears that their effect varies between PH subtypes and further randomized controlled trials are needed to focus on the efficacy and safety of statin therapy in different subtypes.…”

“…PH animal models do not completely recapitulate all the histological and hemodynamic features observed in human PH ( 143 ), and consequently, divergent results have been observed in PH patients while translating treatments from animal models to clinic care, as it was demonstrated for statins or beta blockers for example ( 48 , 50 , 144 , 145 ). Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications commonly used as hyperlipidemia treatment to lower cholesterol level.…”