The present study elicited three main findings. First, in the conventional treatment dose, Shanhuang Jiangzhi tablets were similar to atorvastatin in reducing TC and LDL-C. Second, compared with atorvastatin, Shanhuang Jiangzhi tablets can reduce the concentration of TG more effectively. Third, the clinical adverse reactions of Shanhuang Jiangzhi tablets are rare and have no statistical significance compared with atorvastatin.
The PSM statistical method was introduced by Rosenbaum and Rubin in the 1980s and is effective in dealing with non-randomised research data and control- or balance-confounding bias, making the research results close to those of randomised controlled research [7]. As a new method of balancing baseline data, PSM can integrate multiple confounding variables into one variable—namely tendency score—and effectively balance the distribution of confounding variables (also known as covariates) by balancing the tendency scores of two contrast groups, thus achieving the purpose of controlling confounding bias [9].
Statins reduce TC and LDL-C via the inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) [14] and are the mainstay of treatment for hyperlipidaemia [15]. Although statins are generally well tolerated, they are associated with numerous adverse effects, including hepatotoxicity [16], gastrointestinal events [17], musculoskeletal pain [18], respiratory infections [19] and headaches [20].
Many patients who take statins to treat hyperlipidaemia do not achieve optimal LDL-C goals, thus requiring additional treatment. Statin therapy can be complicated by adverse reactions (e.g. myalgias, elevated liver enzymes) and rare but life-threatening rhabdomyolysis. These issues provide an opportunity to consider the use of traditional Chinese medicine for patients who are non-adherent to statins, statin intolerant or statin resistant.
As an effective supplementary and alternative treatment, traditional Chinese medicine has attracted increasing attention. Chinese medicinal herbs are regarded as a rich source of natural drug development. Shanhuang Jiangzhi tablets are composed of 10 traditional Chinese medicines. Pueraria is one of the commonly used herbs for the treatment of hyperlipidaemia. Network pharmacology has found that the key active ingredient in the cholesterol-lowering effect of puerarin (Pueraria active extract) is β-sitosterol [21]. Liu et al. found that the increase of TC, TG and LDL-C induced by lead was effectively suppressed by puerarin. The HDL-C level in the lead treatment of rats was also increased by puerarin. Western blot analysis showed that puerarin remarkably inhibited hyperlipidaemia by regulating the expression of cholesterol 7a-hydroxylase (CYP7A1), HMGR and low-density lipoprotein receptors in the liver of lead-treated rats [22].
Gynostemma is widely used for the treatment of diseases such as hyperlipidaemia, fatty liver and obesity in China. Using H nuclear magnetic resonance spectra (1H-NMR)-based metabolomics, Wang et al. elucidated the therapeutic mechanisms of Gynostemma. It exerts its antihyperlipidaemic effect by elevating the level of phosphatidylcholine and decreasing the level of trimethylamine N-oxide [23].
Likewise, Polygonum multiflorum is widely used in the prevention and treatment of hyperlipidaemia in traditional Chinese medicine. The LDL-C, TC and TG of hyperlipidaemia rats treated with Polygonum multiflorum were significantly decreased. The key enzymes involved in lipid metabolism, HMGR, fatty acid synthase and acetyl-CoA carboxylase (ACC) in plasma were generally reduced after oral administration, which was consistent with the transcription levels of their target genes [24].
Based on lipidomic technology and network pharmacology analysis, it is thought that Salvia miltiorrhiza prevents and treats hyperlipidaemia through salvianolic acid A [25]. Alisma targeting the FKBP38/mTOR/SREBPs pathway improves hyperlipidaemia [26]. Turmeric is mainly involved in arachidonic acid metabolism, steroid hormone biosynthesis and the peroxisome proliferator-activated receptors signalling pathway to reduce the plasma TC, TG and LDL-C levels of high-fat diet-fed mice [27]. Hawthorn significantly reduces levels of TC, TG and LDL-C, with n-butanol and ethyl acetate having the highest efficacy [28, 29]. Cassia can treat hyperlipidaemic animals with elevated TC, TG, LDL-C and very low-density lipoprotein cholesterol. Hyperlipidaemia alters the protein and messenger ribonucleic acid expression levels of the key genes (sterol regulatory element-binding protein-1c, ACC1, sterol regulatory element-binding protein-2, HMGR, 3-hydroxy-3-methylglutaryl-CoA synthase, CYP7A1 and ATP-binding cassette transporter A1) in lipid metabolism and the treatment with cassia reverts these levels to those observed with atorvastatin-treated hyperlipidaemic animals [30].
In terms of safety indicators, neither the atorvastatin group nor the Shanhuang group had the risk of elevated liver enzymes. Of the 370 patients on atorvastatin, one developed muscle pain and laboratory indicators suggestive of elevated creatine kinase. However, there was no adverse reaction of muscle pain in the Shanhuang group. Only two cases had symptoms of diarrhoea, and considering the effect of rhubarb on increasing bowel movements and promoting defecation, no special treatment was given.
This study was based on a hospital database and had several limitations. First, there may have been selection bias due to the choice of drugs based on patient or cardiologist preferences. There are inherent differences in the patients who are selected for treatment with atorvastatin versus Shanhuang in routine clinical practice. Second, PSM was used to balance the potential differences between the two study groups; however, some parameters were not considered and may have confounded the study results, which is an inherent limitation of retrospective studies. Third, the sample size of 740 patients is relatively small. Moreover, the period for following up the included trial is short. Finally, the research outcomes might also be influenced by the patients’ personal diet and lifestyle, which is difficult to control.
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