Statin alone ‘insufficient’ in meeting LDL-C targets in patients with IHD

Significant treatment gaps persist in lipid management among individuals at very high cardiovascular risk, with up to 80 percent of patients not achieving their low-density lipoprotein cholesterol (LDL-C) goals, reports a Singapore study. 

“Statin monotherapy alone appears insufficient to meet LDL-C targets in most of these patients,” the investigators said. “We found that achieving an LDL-C <1.8 mmol/L was associated with reduced mortality over 2 years in patients with ischaemic heart disease (IHD) requiring hospitalization.” 

A total of 555 patients with IHD admitted to the hospital in 2020 were included in this prospective observational cohort study. Over a 24-month period, the investigators examined the lipid-lowering therapy (LLT) prescriptions, corresponding LDL-C levels, and cardiovascular outcomes. 

Of the participants, 82.3 percent were male, and 48.5 percent identified as Chinese. High-intensity statin prescriptions rose from 45.4 percent at hospital admission to 87.1 percent at discharge. This remained stable at about 80 percent at 6, 12, and 24 months after discharge. [Singapore Med J 2025;66:154-162] 

Prescriptions of LLT combination increased from 12.3 percent at discharge to 33.8 percent at 24 months. The most prescribed second-line LLT was ezetimibe (40.8 percent), followed by inclisiran (1.09 percent) and antiproprotein convertase subtilisin/kesin type 9 monoclonal antibody therapies (0.87 percent). 

The rates of LDL-C goal achievement over 24 months were 22.1 percent for LDL-C <1.4 mmol/L and 47.2 percent for LDL-C <1.8 mmol/L. Multivariate analysis revealed that meeting the LDL-C <1.8 mmol/L target resulted in a decrease in all-cause mortality at 24 months (hazard ratio, 0.53, 95 percent confidence interval, 0.30–0.94; p=0.030). 

“However, larger studies are needed to determine the optimal duration of more intensive LDL-C lowering, such as LDL-C <1.4 mmol/L or <1 mmol/L, that would reduce mortality and be cost-effective in Asian populations,” the investigators said.  

“Given the proven reduction in cardiovascular mortality with lower LDL-C, more efforts are needed to rapidly improve LDL-C goal attainment in very-high-risk patients,” they added. 

Barriers 

Several factors may prevent LLT optimization to achieve LDL-C goals, particularly with the use of PCSK-9 inhibitors. These include medication burden, cost, administrative processes (eg, insurance claims), physician reluctance, and patients’ unwillingness to receive injections. [J Am Heart Assoc 2020;9;e014347; J Clin Med 2021;10;3828] 

“In our study, we observed fewer prescriptions for high doses of statins, such as atorvastatin 80 mg/day or rosuvastatin 40 mg/day (n=46, 11.9 percent at 24 months), likely due to concerns about the higher prevalence of statin-associated muscle symptoms in people of Asian ancestry,” the investigators said. [Eur Heart J 2015;36;1012-1022; Circ J 2018;82;1008-1016; JAMA 2023;329;1078-1087] 

Another potential reason for not escalating LLT is suspected poor medication adherence. Studies report up to 35 percent of patients being nonadherent to chronic medications, such as statin therapy, and at least 50 percent being nonadherent to statins within 1 year of initiation. [J Stroke Cerebrovasc Dis 2024;33;107561; J Manag Care Spec Pharm 2021;27;186-197] 

“Greater efforts to improve LDL-C goal attainment rates in high-risk cardiovascular patients are imperative,” the investigators said.