A meta-analysis of individual participant data from 28 randomized controlled trials found that statin therapy is associated with substantial reductions in major vascular events, irrespective of age, yet smaller reductions in these events are found in patients >75 years old who receive a cholesterol-lowing regimen. Findings from this analysis were published in the Lancet.
A team of researchers from the Cholesterol Treatment Trialists’ Collaboration searched for randomized controlled trials that studied statin therapy lasting ≥2 years in duration. Individual participant data from a total of 22 trials with 134,537 patients and summary data from a trial with 12,705 patients were included.
Studies compared statin therapy vs control or intensive statin therapy vs less intensive statin therapy (n=39,612). In the pooled cohort, patients were categorized into 6 age groups: ≤55 years (n=39,242), 56 to 60 years (n=31,434), 61 to 65 years (n=37,764), 66 to 70 years (n=36,567), 71 to 75 years (n=27,314), and >75 years (n=14,483). The Cholesterol Treatment Trialists’ Collaboration research team evaluated the effects of statin therapy on major vascular events, cause-specific mortality, and cancer incidence (rate ratio [RR] per 1.0 mmol/L reduction in low-density lipoprotein cholesterol [LDL-C]).
During a median follow-up of 4.9 (range, 2.0-7.0) years, there was a 21% (RR, 0.79; 95% CI, 0.77-0.81) reduction in major vascular events among participants receiving statins. Significant reductions in major vascular events were found across all 6 age groups (P <.001 for all). Reductions in major vascular events decreased with age, a finding that was not statistically significant (Ptrend =.06).
Statin or more intensive therapy was associated with an overall 24% (RR, 0.76; 95% CI, 0.73-0.79) reduction in major coronary events. Increasing age was associated with a trend toward smaller reductions in major coronary event risk (Ptrend =.009).
In addition, there was a 25% (RR, 0.75; 95% CI, 0.73-0.78) reduction in the risk of undergoing coronary revascularization procedures in participants receiving statin therapy or more intensive statin therapy per 1.0 mmol/L lower LDL-C. Reductions in stroke of any type were not different across age groups (RR, 0.84; 95% CI, 0.80-0.89; Ptrend =.7).
The researchers excluded 4 trials of patients with heart failure or who were undergoing renal dialysis. Analysis of the remaining studies showed that persistently smaller proportional risk reductions with increasing age for major coronary events (Ptrend =.01) and smaller risk reductions with increasing age were nonsignificant for major vascular events (Ptrend =.3).
A 12% (RR, 0.88; 95% CI, 0.85-0.91) reduction in vascular mortality was also observed per 1.0 mmol/L reduction in LDL-C. For vascular mortality, there was a trend toward smaller reductions with increasing age (Ptrend =.004). The trend toward smaller reductions in older patients were not found after researchers excluded trials of patients with heart failure or dialysis (Ptrend =.2). There was no association between statin therapy on nonvascular mortality, cancer death, or cancer incidence in the overall cohort.
Limitations of the meta-analysis included the highly selected patient population of analyzed studies and the inclusion of older trials that may not reflect contemporary patient management.
“Statins have been associated with a slight increase in incidence of muscle pain, diabetes, and haemorrhagic stroke, but their benefits in prevention of major vascular events are shown to be much greater,” the researchers wrote. “The challenge for the health-care profession and the media is to convey risks and benefits in ways that patients can understand, enabling them to make an informed choice.”
Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet. 2019;393:407-415.