1. In patients aged ≥75 years, LDL cholesterol-lowering therapies reduced the risk for major vascular events, including cardiovascular death, myocardial infarction, stroke, and coronary revascularization.
2. In older patients (≥75 years), the benefits in risk reduction were similar when compared to younger patients (< 75 years), and when comparing statin versus non-statin therapies.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Reductions in LDL cholesterol levels have consistently been associated with a lower risk of cardiovascular events. Yet, the clinical benefit of lipid-lowering therapy in older patients is still debated. This systematic review and meta-analysis of randomized controlled trials aimed to summarize the efficacy and safety of LDL cholesterol-lowering therapies in older patients (≥ 75 years) with respect to major cardiovascular events. Primary outcomes from each study trial included endpoints of major vascular events, cardiovascular death, acute myocardial infarction or other acute coronary syndromes, stroke, and coronary revascularization. Study findings demonstrated a significantly lower risk of major vascular events in older patients with reduced levels of LDL cholesterol. Moreover, no significant differences in risk reduction were seen when compared to younger patients or between statin and non-statin therapies. This study may benefit from the use of additional databases as there was moderate heterogeneity across the study trials. Nonetheless, this study adds value to the lack of evidence around the clinical benefit of lipid-lowering therapy for LDL cholesterol levels in patients aged 75 years and older.
In-depth [systematic review and meta-analysis]: From March 1, 2015, to August 14, 2020, MEDLINE and Embase were searched for randomized, controlled trials with cardiovascular outcomes of lipid-lowering therapies (i.e., statin, ezetimibe, evolocumab, and alirocumab). Trials were excluded if they enrolled patients with heart failure or those on dialysis. Altogether, six articles and 29 trials were included in this study. Among 244 090 patients, 21 492 (8.8%) were at least 75 years of age; of these, 11 750 (54.7%) belonged to statin trials, 6209 (28.9%) to ezetimibe trials, and 3533 (16.4%) to PCSK9 inhibitor trials. Median follow-up of patients across the 29 trials ranged from 2.2 to 6.0 years. Patients in the non-statin trials (ezetimibe 10 mg vs. placebo; ezetimibe 10 mg vs. usual care; evolocumab vs. placebo; and alirocumab vs. placebo) had a mean age of 79 years, with an equal representation of both sexes (49.2% female vs. 50.8% male).
The weighted mean reduction in LDL cholesterol concentration in the treatment groups was 0.9 mmol/L (standard deviation [SD] 0.4 mmol/L; mean range 0.4-1.3 mmol/L). Among 21 492 eligible patients, 3519 (16.4%) had a major vascular event of which the majority (77.7%) occurred in secondary prevention patients. Lipid-lowering therapies significantly reduced the risk of major vascular events by 26% per 1 mmol/L reduction in LDL cholesterol (risk ratio [RR] 0.74, 95% confidence interval [CI] 0.61-0.89, p=0.0019) in older patients. Similar findings were noted across individual endpoints, with lipid-lowering therapies reducing the risk of cardiovascular death by 15% (RR 0.85, 95% CI 0.74-0.98), myocardial infarction by 20% (RR 0.80, 95% CI 0.71-0.90), stroke by 27% (RR 0.73, 95% CI 0.61-0.87), and coronary revascularization by 20% (RR 0.80, 95% CI 0.66-0.96) for every 1 mmol/L reduction in LDL cholesterol. No statistically significant difference in risk reduction was observed when compared to younger patients (RR 0.85, 95% CI 0.78-0.92, pinteraction=0.37) or between statin (RR 0.82, 95% CI 0.73-0.91) and non-statin treatments (RR 0.67, 95% CI 0.47-0.95, pinteraction=0.64). Overall, findings from this study suggests that reducing LDL cholesterol level is as effective in reducing cardiovascular events in patients aged 75 and older as it is in younger adults.
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