This study used LDL-C level as an indicator to evaluate the effect of secondary prevention of coronary heart disease in China and analyzed the temporal trend of LDL-C levels. The subjects included in this study did not take lipid-lowering drugs within 1 month before PCI, which has not been analyzed in previous studies. Another study in China did not report the use of lipid-lowering drugs, and their LDL-C level baseline levels were 2.93 ±0.94 mmol/l. In Leskel's study, Fifty-eight percent of patients had previously used lipid-lowering drugs, and their LDL-C levels of baseline were 2.77 mmol/l. Their LDL-C levels of baseline were higher than our study (3.11 ±0.99 mmol/l). At the final follow-up, 51.5% of our patients reached the LDL-C target level, compared with only 31% in other studies at the same LDL-C target level (LDL-C < 1.8 mmol/l or a reduction in LDL-C level at least 50%). A study in China reported a higher rate of LDL-C control, with 56.3% of patients reaching the target level at 1-month follow-up after PCI, but the LDL-C target level was LDL-C level <1.8 mmol/l or a reduction of LDL-C level at least 50% or LDL-C level >30% if baseline LDL-C level <1.8 mmol/l. Our explanation is that this study did not report previous use of lipid-lowering drugs, and its defined LDL-C target level was somewhat different from our study, as well as the short follow-up period, so it showed a higher achievement rate than ours.
In previous studies, the temporal trend of LDL-C levels was analyzed, and the distribution of LDL-C levels remained relatively stable during the two follow-up periods, as did our results. 50% of patients experienced a change in classification during both follow-ups, and 26% fluctuated between <1.8 and≥1.8, so it is not sufficient to look only at the population mean when assessing the quality of treatment because individuals switch LDL-C levels.
Although the vast majority of patients after PCI were prescribed statins after discharge, from the current study, a large proportion of patients did not reach the LDL-C target level. The latest 2019 ESC Guidelines has proposed stricter LDL-C targets level, based on a 20% reduction in cardiovascular risk for each 1 mmol/l reduction. The greater the absolute LDL-C reduction, the greater the cardiovascular risk reduction.[13, 14] There was no increase in adverse events when LDL-C levels reached very low levels (e.g. LDL-C decreased to <0.5 mmol/L). But LDL-C control rate in our study is very low, only 8%, according to the 2019 ESC Lipids Guidelines. This suggests that statins alone may not be sufficient to achieve LDL-C targets level and requires combination therapy, such as the addition of ezetimibe or Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors (PCSK9i). At present, many studies have reported that ezetimibe or PCSK9i significantly reduce LDL-C level, combined lipid-lowering therapy can better control LDL-C level.[15, 16] So the 2019 ESC Lipids Guidelines raise the recommended level of ezetimibe and PCSK9i. But some surveys of the economic burden have found that any further lipid reduction could impose a huge economic burden on cardiovascular-related management.
The United States reported cost-effectiveness of PCSK9i added to statin therapy: an increase of $141699 per Quality-adjusted life-years. At a 60% reduction in the price of PCSK9i in the United States, the cost-effective was $56655 to $7667 per quality-adjusted life-year for very high-risk patients with atherosclerotic cardiovascular disease, meeting acceptable cost-effectiveness threshold criteria. In countries with low per capita gross domestic product, a 97% reduction would be considered cost-effective. The results of some studies are cost-effective when ezetimibe is added to ongoing statin therapy and the costs and benefits of maintaining current doses of statin therapy. However, in a 5-10 year follow-up model, ezetimibe combined with statin therapy is not a cost-effective alternative, but when the follow-up period is extended to a lifetime, combination therapy becomes a cost-effective treatment. In a Chinese study, LDL-C<1.8 mmol/l was 26.2% and 28.2% in patients using high-intensity and moderate-intensity statins, respectively. Another study showed that 63.8% of acute coronary syndrome patients had LDL-C level greater than 1.80 mmol/L, and 71.5% received high-intensity statin therapy. LDL-C control with high-intensity statins is not ideal, which requires more price reductions for ezetimibe and PCSK9i to benefit patients.
Pharmacological lipid control is one aspect of treatment, and lifestyle interventions are also important. To our knowledge, ours is the only study to report the impact of population lipid changes on major lipid indicators. Both increases and decreases in population lipid can occur with population changes in the major determinants of lipid (eg, diet, physical activity, weight loss). Randomized controlled trials have confirmed that lifestyle changes significantly affect LDL-C level.(Table 1) An Australian study urged lifestyle changes by sending health education-related text messages, leading to lower LDL-C levels in patients with CAD. Although lifestyle interventions have less impact on lipids than statins, we found a significant improvement in LDL-C control rates. Clinicians may rely excessively on lipid-lowering drugs (i.e., statins) to control blood lipids. We believe that positive lifestyle changes, such as dietary reduction of cholesterol, saturated fatty acids intake, increased dietary fiber and phytosterol intake, physical activity, weight loss, etc., should not be abandoned.