Lipid-Lowering Agents in Older Individuals: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Abstract

Background The efficacy of lipid-lowering agents on patient-important outcomes in older individuals is unclear. Methods We included randomized trials that enrolled individuals aged 65 years or older and that included at least 1 year of follow-up. Pairs of reviewers selected and appraised the trials. Results We included 23 trials that enrolled 60,194 elderly patients. For primary prevention, statins reduced the risk of coronary artery disease [CAD; relative risk (RR): 0.79, 95% CI: 0.68 to 0.91] and myocardial infarction (MI; RR: 0.45, 95% CI: 0.31 to 0.66) but not all-cause or cardiovascular mortality or stroke. These effects were imprecise in patients with diabetes, but there was no significant interaction between diabetes status and the intervention effect. For secondary prevention, statins reduced all-cause mortality (RR: 0.80, 95% CI: 0.73 to 0.89), cardiovascular mortality (RR: 0.68, 95% CI: 0.58 to 0.79), CAD (RR: 0.68, 95% CI: 0.61 to 0.77), MI (RR: 0.68, 95% CI: 0.59 to 0.79), and revascularization (RR: 0.68, 95% CI: 0.61 to 0.77). Intensive (vs less-intensive) statin therapy reduced the risk of CAD and heart failure. Niacin did not reduce the risk of revascularization, and fibrates did not reduce the risk of stroke, cardiovascular mortality, or CAD. Conclusion High-certainty evidence supports statin use for secondary prevention in older individuals. Evidence for primary prevention is less certain. Data in older individuals with diabetes are limited; however, no empirical evidence has shown a significant difference based on diabetes status.

The Prevention of Cardiovascular Disease in Older Adults

“…77 In a meta-analysis of nine primary prevention trials that enrolled patients 65 years or older, though statins reduced the incidence of CAD events for those 65 years or older, there was no significant reduction for those 75 years and older. 66 However, in a meta-analysis of the JUPITER and HOPE-3 trials, the authors concluded that the results support the use of statins to prevent CVD for older adults with low to intermediate CVD risk, up to at least 80 years of age. The recommendation is based on a reduction in the composite measure of nonfatal MI, nonfatal stroke, and CVD death.…”

“…Though there is no evidence that lipid-lowering agents help prevent incident stroke in older adults, 66 as discussed in the section below on preventing CAD, there are data that support the use of statins to prevent composite CVD outcomes in older adults who do not have a history of CVD, up to 80 years of age.…”

Statin Treatment in Specific Patient Groups: Role for Improved Cardiovascular Risk Markers

“…Ponce et al performed a comprehensive meta-analysis of 23 RCTs comprising 60,194 patients aged 65+ [ 72 ]. Cohort data was collated for each of five patient groups: ages 65–75, ages 75 and over, patients with diabetes, patients without diabetes, and patients with hypertension.…”

“…For primary prevention in those with no history of ASCVD, statin use was found to reduce the risk of coronary artery disease [CAD; RR: 0.79, 95% CI: 0.68–0.91] and myocardial infarction (RR: 0.45, 95% CI: 0.31–0.66) relative to placebo in all patient groups. However, Forest plot analysis revealed that statins did not significantly reduce the risk of heart failure (RR: 1.04, 95% CI: 0.80–1.35), all-cause mortality (RR: 0.95, 95% CI: 0.84–1.07), or cardiovascular mortality (RR: 1.01, 95% CI: 0.83–1.24) overall or in any patient group [ 72 ]. The one RCT of adults ≥75 reported an increase in all-cause mortality for 40 mg/day pravastatin vs. usual care (HR: 1.34, 95% CI: 0.98–1.84) [ 73 ].…”

“…Limited placebo-controlled RCT data is available for elderly patients with diabetes and very old adults aged 75+ [ 72 ]. Ramos et al conducted a retrospective study of 46,864 participants 75 years and older with no history of ASCVD for a median follow-up of 5.6 years [ 69 ].…”