Sex-difference in cardiovascular outcomes following achieved LDL-C Levels <1.0 mmol/L in patients with coronary artery disease

Backgrounds Women with cardiovascular disease still continue to present substantially higher mortality than men, which highlights the need for appropriate anti-atherosclerotic management. Current ESC/EAS guidelines advocate achieving stricter LDL-C goals (<1.0 and 1.4 mmol/L) for the secondary prevention of ASCVD in very high-risk and extreme risk patients, respectively. However, in recent randomized controlled trials including very high-risk patients, potent agents lowered LDL-C by around 0.5–0.7 mmol/L, and reduced risks of subsequent ASCVD. These observations lead to the hypothesis that men and women with CAD may more benefit from the control of LDL-C <1.0 mmol/L rather than ESC guideline-recommended LDL-C goal (<1.4 mmol/L). Purpose To investigate cardiovascular outcomes following achieved LDL-C levels <1.0 mmol/L in men and women with CAD. Methods The current study was a multi-center, retrospective analysis of 2,560 patients with CAD receiving PCI at 3 sites (men/women=1,882/678). Achieved LDL-C level was defined as measured LDL-C levels at 2 months after PCI. Clinical demographics and cardiovascular outcomes (MACE=cardiac death + non-fatal MI + clinically-driven coronary revascularization at non-culprit segment) were compared in men and women stratified according to achieved LDL-C levels (<1.0, 1.0-1.4 and ≥1.4 mmol/L), respectively. Results The proportion of achieved LDL-C <1.0 mmol/L was significantly lower in women compared to men (6.0 vs. 10.4%, p=0.001). Men with achieved LDL-C levels <1.0 mmol/L were less likely to exhibit dyslipidemia (p<0.001) (Table). Furthermore, more intensified lipid-lowering agents (statin: p<0.001, ezetimibe: p<0.001, PCSK9-I: p<0.001) were used in those with LDL-C<1.0 mmol/L (Table). During the 2.5-year observational period, men with achieved LDL-C <1.0 mmol/l was associated with a lower likelihood of experiencing MACE (Figure, log-rank p<0.001). In women who achieved LDL-C levels <1.0 mol/L, in addition to a lower frequency of dyslipidemia (p=0.004), greater frequencies of hypertension (p=0.018) and type 2 diabetes mellitus (p=0.047) were observed (Table). As expected, they more frequently received statin (p=0.041) and PCSK9 inhibitor (p=<0.001) (Table). Similar to men, mitigating risks of MACE was observed in women who achieved LDL-C levels <1.0 mmol/L (Figure, log-rank p=0.027). There was no significant interaction about the efficacy of LDL-C levels <1.0 mmol/L on the occurrence of MACE between men and women (p-interaction=0.691). Conclusions In women with CAD, only 6.0% of them achieved LDL-C levels <1.0 mmol/L. Achieved LDL-C levels <1.0 mmol/L provided cardiovascular benefits in both men and women with CAD. These observations support LDL-C <1.0 mmol/L as a therapeutic goal in women with CAD to further mitigate risks of subsequent ASCVD. The adoption of a more stringent LDL-C goal may be clinically needed to optimize cardiovascular outcomes in not only men but women with CAD.