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Statins in older people

Systematic review [1]
Heart Protection Study [2]
PROSPER [3]
Comment


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


Event rate (%)
Study/Review
Age in analysis
(years)
Duration
(years)
Number in analysis
Statin
Placebo
Risk reduction
(%, 95%CI)
NNT
(95%CI)
4S, CARE, AFCAPS, LIPID
65 or older
4.9-6.1
8998
12.0
16.4
32 (26 to 35)
23 (17 to 33)
Heart Protection Study
65 to 70
5
4891
20.9
27.2
23 (15 to 30)
16 (12 to 26)
Heart Protection Study
Over 70
5
5806
23.6
28.7
18 (11 to 25)
20 (14 to 35)
PROSPER
70 to 82
3.2
5804
14.1
16.2
15 (3 to 26)
47 (25 to 358)
Combined data
25499
16.8
21.2
21 (17 to 25)
23 (17 to 29)



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:

  1. JC LaRosa et al. Effect of statins on risk of coronary disease: a meta-analysis of randomised controlled trials. JAMA 1999 282: 2340-2346.
  2. 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.
  3. J Shepherd et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002 360: 1623-1630.

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