It is well known that lipid-lowering therapy plays a crucial role in cardiovascular risk reduction, especially for heart failure patients. Since 2019, LDL cholesterol targets based on individual cardiovascular risk have become more stringent[1, 24]. A more intensive reduction in LDL cholesterol is associated with a greater reduction in all-cause mortality and cardiovascular mortality risk[25, 26]. The level of blood lipids in patients with CAD is closely related to morbidity and prognosis, so that it’s preferred to get the lipids (especially the level of LDL-C) in the target range in a short time. Therefore, we were interested in drugs that could help to rapidly regulate blood lipids in cardiovascular disease patients.
The significant cardiovascular protective effects of SGLT2 inhibitors, including reducing morbidity, hospitalization and poor prognosis, have been demonstrated by several large registry clinical studies[5, 27, 28]. This has led to an increasing focus on this class of drugs in the cardiovascular field. However, the effect of SGLT2 inhibitors on blood lipids remains unclear. There were a number of studies or meta-analyses that tried to explore, but the conclusions were not identical[10–17]. Some studies shown that SGLT2 inhibitors do not affect lipid metabolism, and there is no significant difference in lipid profile before and after SGLT2 inhibitors treatment[14, 16]. Others demonstrated that triglyceride levels dropped and total cholesterol, LDL-cholesterol, and HDL-cholesterol rose significantly when taking SGLT2 inhibitors[13, 15]. There were also numerous mechanistic investigations devoted to the effect of SGLT2 inhibitors on lipid metabolism[29–31]. In conclusion, SGLT2 inhibitors have varying effects on lipid metabolism, including reducing lipid oxidation, diverting the use of substrates toward ketone bodies, which are more efficient in myocardial metabolism, and reducing the production of reactive oxygen species through oxidation and the transport of intracellular lipid molecules. Additionally, they beneficially alter the proportion of LDL particles, and regulate serum lipoprotein levels[11].
In this study, our patient's lipid management was satisfactory at one month follow up after PCI receiving lipid-lowering therapy such as statins and combined with cholesterol absorption inhibitors if necessary, with or without SGLT2 inhibitors. However, after propensity score matching or weighting, it was found that SGLT2 inhibitors had no effect on short-term blood lipid profile under background lipid-lowering therapy, from the perspective of change difference, percentage and reaching target rate.
It can be explained by the conclusion of the Yusuke Nakatsu’s study, which indicated that SGLT2 inhibitors treatment significantly slowed the progression of atherosclerosis, without affecting serum lipid parameters like the levels of triglycerides, HDL-C, or LDL-C. And the anti-atherosclerotic effect of the SGLT2 inhibitors might be by preventing inflammation rather than hyperlipidemia[16]. Julieta Lazarte indicated that SGLT2 inhibitor, as a single therapy, affected the blood lipid level, but this effect could be affected by the background therapy of statins[13].
However, the short-term regulation of blood lipids by SGLT2 inhibitors in patients with CAD after PCI has not been described previously. It was the innovation and clinical value of our research result. On the one hand, SGLT2 inhibitors could not enhance lipid-lowering effect in the short term for CAD patients after PCI. On the other hand, they would not worsen blood lipid levels. This allows cardiologists to use SGLT2 inhibitors with greater confidence, without worrying about the impact on blood lipids, while achieving its long-term cardiovascular protection benefits. Furthermore, in addition to propensity score matching, IPTW and OW were applied in this study, and similar outcomes were obtained. It was also one of the strengths of this study, while making the conclusions more credible and convincing.
Naturally, this study has its limitations. Firstly, we only analyzed the lipid follow-up data 1 month after PCI, for the extended follow-up time would lead to an increase in the rate of loss to follow-up. Secondly, this study suffers from selection bias due to the retrospective nature. In the future, we can extend the follow-up time to explore the potential value of SGLT2i in the long-term blood lipid management of patients with CAD. This will contribute to the further promotion and use of SGLT2 inhibitors in the cardiovascular field.