Association of lipid-lowering drug treatment with all-cause and cardiovascular mortality among people aged 75 years and above without cardiovascular disease: evidence from a cohort study

Abstract Background Lipid-lowering drugs are commonly prescribed for prevention of cardiovascular disease (CVD), but evidence about its efficacy in people aged ≥75 years is scarce. Purpose To examine the association of lipid-lowering drug treatment with all-cause and cardiovascular mortality among people aged ≥75 years and whether the association, if existent, varied with important characteristics such as comorbidities. Methods A nationally representative sample of 4099 adults aged ≥75 years and without CVD at baseline was drawn from the Third National Health and Nutrition Examination Survey (NHANES III) conducted between 1988 and 1994 and the 10 continuous NHANES cycles between 1999-2000 and 2017-2018 in the United States. Among these participants, 1095 were on lipid-lowering drug treatment at baseline. All-cause and cardiovascular mortality were ascertained by linkage to National Death Index records through 31 December 2019. The association of lipid-lowering drug treatment with mortality was investigated by multivariable Cox regression analysis and expressed as hazard ratio (HR) with 95% confidence interval (CI), adjusting for major risk factors of CVD and mortality. Subgroup analyses were conducted to detect potential interaction between lipid-lowering drug treatment and important patient characteristics. Sensitivity analyses were conducted by excluding the participants who died within the first year of the follow-up. Results During a median follow-up of 89 months (7.5 years), 2849 (69.5%) participants died and 1135 (27.7%) of them were attributed to CVD. Lipid-lowering drug treatment was associated with lower risks of both all-cause mortality (HR=0.77, 95% CI 0.68-0.88) and cardiovascular mortality (HR=0.65, 95% CI 0.53-0.80). Subgroup analyses to detect potential interaction suggested that the following subgroups might not benefit from lipid-lowering drug treatment in terms of all-cause mortality: those without previously diagnosed high cholesterol (HR=1.40, 95% CI 0.84-2.31), those with chronic kidney disease (adjusted HR=1.25, 95% CI 0.73-2.12), those receiving antihypertensive drug treatment (HR=0.90, 95% CI 0.76-1.06), and those receiving ≥5 medications (polypharmacy) (HR=0.83, 95% CI 0.63-1.10). Sensitivity analyses yielded consistent results with the primary analyses. Conclusion Lipid-lowering drug treatment was overall effective in reducing all-cause and cardiovascular mortality among people aged ≥75 years who had no CVD at baseline, but those without previously diagnosed high cholesterol, with chronic kidney disease, receiving antihypertensive drug treatment, or with polypharmacy appeared to gain no benefit from the treatment.