Statins in older people
Another
of those questions frequently asked of
Bandolier
is what is the evidence about the use of statins in older people. A
question that is begged to some extent is what constitutes an older person. One
definition is someone a decade or so older than you, but here it is probably
someone in their eighth or ninth decades. The answer is that there is evidence
from good trials that statins work as well in older people as in younger people.
Systematic review [1]
This
examined five large randomised studies (4S, WOSCOPS, CARE, AFCAPS and LIPID)
with just under 31,000 participants, where statin had been compared with
placebo, and published before the end of 1998. Statins used were simvastatin
and lovastatin on one each, and pravastatin in three, at various doses.
The
main outcome for analysis was major coronary events, which included coronary
death, nonfatal myocardial infarction, silent infarction, or resuscitated
cardiac arrest, as well as unstable angina in one trial. Participants older
than 65 years were included in four of the trials.
Risk
was reduced by an average of 32% by statins in participants older than 65 years
(Table 1), and was similar to the risk reduction in participants younger than
65 years (31%). A similar degree of risk reduction was seen in studies with
high and low rates of previous myocardial infarction.
Table 1: Effects of statins in older people. Note that event rates for the systematic review are approximate, and that somewhat different outcomes were used in different trials
| (years) |
(years) |
|
|
|
(%, 95%CI) |
(95%CI) |
|
| 4S, CARE, AFCAPS, LIPID | |
|
|
|
|
|
|
| Heart Protection Study | |
|
|
|
|
|
|
| Heart Protection Study | |
|
|
|
|
|
|
| PROSPER | |
|
|
|
|
|
|
| Combined data | |
|
|
|
|
|
|
The
number of older people needed to be treated with statins for at least five
years to prevent one major coronary event was 23 (95% CI 17 to 33).
Heart Protection Study [2]
HPS
randomised 20,536 people aged 40-80 years with coronary disease, occlusive
arterial disease or diabetes to 40 mg simvastatin or placebo for five years.
The outcome for subgroup analysis by age with about 10,000 people over 65
years was first major coronary event (nonfatal myocardial infarction or
coronary mortality).
The
results were reported by different age ranges of 65 to 70 years, and over 70
years (Table 1). Risk was reduced with statin by 23% and 18% respectively, and
the number needed to treat for five years compared with placebo was 16 and 20
respectively (Table 1).
PROSPER [3]
This
trial randomised 5,800 men and women aged 70 to 82 years with a history of, or
risk factors for, vascular disease, to pravastatin 40 mg daily or placebo for a
mean of 3.2 years. The primary endpoint was fatal or nonfatal heart attack of
stroke.
Risk
was reduced by an average of 15% (Table 1). The number of people needed to be
treated for three years to prevent an event in one of them was 47 (25 to 358).
Comment
What
we have here is a lot of information about statins in people older than 65
years. Over 25,000 have been included in well done clinical trials, and nearly
half of them were over 70 years. There was a consistency of response over all
the studies, irrespective of the statin and dose used, the duration, or the
outcomes reported (Figure 1), and whether these older people were younger or
older than 70 years.
Figure 1: Event rates in statin trials in people over 65 years (light symbols) and over 70 years (dark symbols)
Statins
are effective in older people, and just as effective as in people aged under 65
or 70 years.
Reading
the HPS and PROSPER papers is interesting, because both examine effectiveness
by stratification, and show that low levels of HDL cholesterol increase the
risk of events. Statins were particularly effective in people with low HDL
cholesterol levels.
References:
- JC LaRosa et al. Effect of statins on risk of coronary disease: a meta-analysis of randomised controlled trials. JAMA 1999 282: 2340-2346.
- Heart protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 individuals: a randomised placebo-controlled trial. Lancet 2002 360: 7-22.
- J Shepherd et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002 360: 1623-1630.