Statins for the elderly: Where do we stand now?
Statins reduce major vascular events regardless of age, including in people aged >75 years, reveals a meta-analysis of 28 randomized trials in the Cholesterol Treatment Trialists’ (CTT) Collaboration.
“Meta-analyses among older people have consistently reported evidence for beneficial effects in secondary prevention, but the evidence has been less clear for primary prevention,” according to the investigators.
Besides addressing the gap in evidence, another reason for the new CTT meta-analysis is to “reinforce the message that statins should be considered for cardiovascular [CV] prevention in people at risk, even if they are older in age,” wrote Drs Bernard Cheung and Karen Lam of Queen Mary Hospital, University of Hong Kong, in an accompanying commentary. [Lancet 2019;393:379-380]
“The present meta-analysis makes a case to reduce LDL cholesterol in people at risk of CV events regardless of age, provided that the benefits outweigh the risks and the patient accepts long-term treatment,” they added.
Does benefits change with increasing age?
Overall, taking statins or having a more intensive statin regimen led to a 21 percent proportional reduction in major vascular events for every 1.0 mmol/L reduction in LDL cholesterol, compared with placebo or a less intensive regimen (rate ratio [RR], 0.79, 95 percent confidence interval [CI], 0.77–0.81). [Lancet 2019;393:407-415]
The reductions in major vascular events were significant in all age groups; although the proportional reductions appeared to diminish slightly with increasing age, the trend was not statistically significant (p-trend=0.06).
Major vascular events were defined as the composite of major coronary events, stroke, and coronary revascularization, while the major coronary events component included coronary death and nonfatal myocardial infarction.
For major coronary events, there was a 24 percent proportional reduction with statins or more intensive therapy per 1.0 mmol/L LDL-cholesterol reduction (RR, 0.76, 95 percent CI, 0.73–0.79). The extent of proportional risk reductions became smaller as age increased (p-trend=0.009), but the reduction remained significant among patients >75 years on statins or more intensive therapy vs control or less intensive regimen (RR, 0.82, 95 percent CI, 0.70–0.96).
The risk of the other two components — coronary revascularization and stroke also reduced significantly in participants who received statins or more intensive therapy, with proportional risk reductions of 25 percent (RR, 0.75) and 16 percent (RR, 0.84), respectively for every 1.0 mmol/L reduction in LDL cholesterol. Again, no significant difference was seen across age groups (p-trend=0.6 and 0.7, respectively).
“[The age-related trend for diminishing proportional reductions in coronary events] might reflect a reduced capacity for statins to impact on advanced atherosclerotic plaques, greater diagnostic uncertainty at older ages, … and poorer long-term adherence to the assigned study treatment among older people,” explained the investigators.
The case for primary prevention
When the analysis was stratified by pre-existing vascular disease, the investigators found similar proportional reductions in major vascular events regardless of age among those with prior vascular disease (p-trend=0.2).
However, among participants with no history of vascular disease, the proportional risk reductions were smaller in magnitude as age increased, with RRs of 0.84 for those aged >70 to ≤75 years and 0.92 for those aged >75 years (p-trend=0.05).
“There is less definitive direct evidence of benefit in the primary prevention setting among patients older than 75 years, but evidence supports the use of statin therapy in older people considered to have a sufficiently high risk of occlusive vascular events,” the investigators stated.
Even though the relative risk reduction was less than expected in people >75 years, they argued that statin therapy may still be justified, saying “[given that the] untreated absolute risks of major vascular events in the general population increase exponentially with age, the absolute benefits of a given absolute reduction in LDL cholesterol with statin therapy would be expected to be substantially greater among older individuals.”
While the benefit of statins in preventing major vascular events appears to outweigh the risk in the current meta-analysis which includes people older than standard study populations, Cheung and Lam suggested that more studies in older people be done “to enrich the evidence.”
“When statins are used in people with low CV risk, the risks and benefits need to be weighed against each other,” they advised. “The challenge for the healthcare profession and the media is to convey risks and benefits in ways that patients can understand, enabling them to make an informed choice.”