Statin therapy reduces risk of major cardiovascular events irrespective of age

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 revascularisation (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."

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.

In the past, trials that looked at the effect of statin therapy reported significant cardiovascular risk reductions in the 65-70 age group but there have been questions about their benefits in older patients, particularly those over 75. Statin therapy is often discontinued in older patients in part because of this question around risk and benefit.

The Cholesterol Treatment Trialists' Collaboration looked at 23 trials that compared statin treatment to a control group and a further five that investigated intensive versus standard statin therapy. They divided patients into six age groups, and investigated effects on major vascular events (comprising major coronary events, strokes and coronary revascularisations), cancer incidence and cause specific mortality.

Of the 186,854 participants in the trials that were reviewed, with a mean age of 63 years, 14,483 were older than 75 years.

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.

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.

Writing in a linked Comment, Bernard M Y Cheung of the Queen Mary Hospital at the University of Hong Kong says: "Even if risk reduction in people older than 75 years is less than expected, statin therapy may still be justified by a high baseline cardiovascular risk, which is usually present in older people. The present meta-analysis makes a case to reduce LDL cholesterol in people at risk of cardiovascular events regardless of age, provided that the benefits outweigh the risks and the patient accepts long term treatment."