Sex differences in management of LDL-cholesterol in patients with chronic coronary syndrome

Abstract Background Effective management of low-density lipoprotein cholesterol (LDL-C) is crucial for preventing recurrent cardiovascular (CV) events in patients with chronic coronary syndrome (CCS). Sex may impact the LDL-C management, by gender bias and/or sex-specific responses to pharmacological interventions. Purpose We examined sex-specific LDL-C management in CCS patients, assessing target achievement rates and their implications for CV outcomes. Methods In the international CLARIFY registry, we included 22,134 CCS patients with baseline LDL-C measurements. LDL-C levels were monitored annually over the 5-year follow-up period. Target LDL-C was set at 100 mg/dL, in line with prevailing recommendations at that time. Sex-specific differences in LDL-C were adjusted for age, geographical region and indication for lipid lowering drugs (stroke, MI, PAD). The primary endpoint was the incidence of MACE, defined as CV death or MI during the 5-year follow-up, evaluated using multivariable analysis adjusted for known predictors of recurrent CV events in CCS patients. Results Of 22,134 patients, 21.6% were women. Upon inclusion (6.5 ± 6.3 years after CCS diagnosis), women were more likely than men to have LDL-C levels above the recommended threshold (45.6% vs. 37.4%; aOR 1.47, 95%CI 1.38-1.58, p<0.001) and less likely to receive statin treatment (82.7% vs. 85.4%, p<0.001). Although women and men had comparable numbers of LDL-C measurements during follow-up, the discrepancies endured over the 5-year observation period, with women consistently showing lower likelihoods of achieving LDL-C targets at 1, 2, 3, 4, and 5 years post-inclusion (p<0.001 for all time points). Overall, women were less likely than men to have all available LDL-C concentrations within the target range (37.8% vs. 44.6%; aOR 0.70, 95% CI 0.64-0.76, p<0.001) and more likely to never reach the target LDL-C goal during follow-up (22.6% vs. 17.5%; aOR 1.43, 95% CI 1.32-1.55, p<0.001). Failing to achieve at least one LDL-C concentration below 100 mg/dL was associated with an increased risk of subsequent MACE (adjusted HR 1.57, 95%CI 1.38-1.77, p<0.001), with similar associations observed in both men (aHR 1.66, 95% CI 1.44-1.91, p<0.001) and women (aHR 1.31, 95% CI 1.01-1.70, p=0.05). Conclusion In patients with CCS, women consistently showed lower likelihood of reaching LDL-C targets throughout follow-up compared to men, even after adjusting for age, geographical region and other statin indications. Notably, women were more likely to have no LDL-C concentration within recommended range during follow-up, which is particularly concerning given its association with an increased risk of CV events. A contributing factor to this sex disparity in LDL-C control is women's lower likelihood of receiving lipid-lowering drugs than men. These results highlight the need for tailored interventions to address sex-related disparities in LDL-C management and improve cardiovascular outcomes in CCS patients.