Benefit of Statin use persists even beyond 75 years of age: Lancet

According to a meta-analysis, more people over the age of 75 should be taking statins. The research has found statins cut the risk of major cardiovascular disease in all ages studied, including the over-75s. The research found no adverse effects of statin therapy on non-vascular mortality or cancer. The findings of the research have been published in The Lancet.

Statins are cholesterol-lowering drugs that are widely prescribed to patients at increased risk of heart attacks or strokes. Evidence from randomised trials has shown that statin therapy reduces this risk among a wide range of individuals but there has been uncertainty about their benefits in older people.

Lead investigator, Professor Anthony Keech, Professor of Medicine, Cardiology and Epidemiology at the University of Sydney, said: 'Statin therapy has been shown to prevent cardiovascular disease in a wide range of people, but there has been uncertainty about its efficacy and safety among older people. Our study summarised all the available evidence from major trials to help clarify this issue. We found that there were significant reductions in major vascular events in each of the six age groups considered, including patients aged over 75 at the start of treatment.'

The study assessed the effects of statins in nearly 187,000 people who had taken part in 28 large clinical trials. Participants were divided into six age groups (under 55 years, 55-60, 60-65, 65-70, 70-75, and over 75 years) in order to assess the effects of statins on major vascular events (heart attacks/strokes/coronary revascularisations), cancer incidence and deaths. The study summarises evidence from 28 randomised controlled trials, including 186,854 patients, 14,483 of whom were aged over 75.

Irrespective of age, statins reduced risks of major vascular events by about a fifth per 1 mmol/L reduction in LDL cholesterol. For major coronary events, the overall reduction was about a quarter per 1 mmol/L reduction overall but ranged from about 30% in those aged <55 years to around 20% in those aged >75. The relative risk reductions for stroke and for coronary revascularization (coronary stenting or bypass surgery) were similar in all age groups.

Dr Jordan Fulcher of the Cholesterol Treatment Trialists' (CTT) Collaboration, who is based at the University of Sydney NHMRC Clinical Trials Centre, Australia, says: "Statins are a useful and affordable drug that reduce heart attacks and strokes in older patients. Until now there has been an evidence gap and we wanted to look at their efficacy and safety in older people. Our analysis indicates that major cardiovascular events were reduced by about a fifth, per mmol/L lower LDL cholesterol, by statin therapy across all age groups. Despite previous concerns we found no adverse effect on cancer or non-vascular mortality in any age group."

The analysis shows that the reduction in major vascular events - 21% per 1 mmol/L reduction in LDL cholesterol overall - is similar and significant in all age groups, including those over 75 years of age. For major coronary events the overall reduction is 24% per 1 mmol/L reduction in LDL, but decreases slightly with age. The study also shows no increased risk of non-vascular mortality or cancer in any age group.

The researchers noted that their results were influenced by four trials done exclusively among patients who had heart failure or were on renal dialysis. Statins have not been shown to be effective in these people, and are not recommended for them. When these participants were excluded, similar reductions in risk were seen across all age groups, including for major vascular events and cardiovascular mortality. A slightly smaller reduction in the risk of major coronary events with increasing age persisted.

The research also examined the effects of statins on major vascular events in people with a history of vascular disease (secondary prevention) and in people without known vascular disease (primary prevention). In the secondary prevention setting, the researchers found similar proportional risk reductions regardless of age, which would equate to a larger absolute benefit in older people. In the primary prevention setting the results were similar, but as there were fewer such older participants in the trials, the conclusions were less definite. More evidence from randomised trials in older people without previous vascular disease will be helpful and trials are ongoing.

In the primary prevention setting (ie, in individuals with no known history of vascular disease), two individuals aged 63 years and 78 years with otherwise identical risk factors might have projected major vascular event rates of 2.5% versus 4.0% per year, respectively. Reducing those risks by a fifth with a 1.0 mmol/L LDL cholesterol reduction would prevent first major vascular events from occurring each year in 50 individuals aged 63 years and 80 individuals aged 78 years per 10 000 people treated.

In the secondary prevention setting (ie, with known history of vascular disease), the absolute risks of a major vascular event are typically at least twice as large, so every year the same LDL cholesterol reduction in people with prior vascular disease would prevent first major vascular events in at least 100 individuals aged 63 years and at least 160 aged 78 years per 10,000 treated [2].

The present analyses focused on the effects of statin therapy on major vascular events, mortality and cancer, and the authors limited their meta-analysis to large trials, known to generate the most reliable evidence. Previous studies have shown that the benefits of statins outweigh the risk of other adverse events (such as myopathy), and ongoing work in this area is being conducted by the Cholesterol Treatment Trialists' Collaboration.