elderly: statins help

A large retrospective a large data-mining VA study found a significant decrease in all-cause and cardiovascular mortality in veterans > 75 years old, including the group >90 years old (see statin elderly helps jama2020 in dropbox, or doi:10.1001/jama.2020.7848)

 

Details:

-- 326,981 eligible veterans were studied, all  >75 yo, free of ASCVD at entry, no prior statin use, and had a clinical visit from 2002-2012. Data were linked to Medicare and Medicaid claims and to pharmaceutical data.

    -- There were 53,727 who were new users of statins and had additional prescriptions during follow-up; 269,813 who never had a statin prescription

-- Mean age 81, 97% men, 91% White/8% Black/4% Latinx, current smoker 7%/former smoker 72%/never smoker 21%, comorbidities: hypertension 66%/arthritis 38%/cancer 36%/anemia 17%/hyperlipidemia 16%/diabetes 13%/depression 13%

-- meds: polypharmacy (greater than 5 drugs) 39%, diuretics .7 present, ACE inhibitor 26%, alpha blocker 23%, calcium blocker 20%, beta blocker 16% current smoker 7%/never smoker 21%

-- statins prescribed: simvastatin in 85%, lovastatin 11%, pravastatin 2.5%, atorvastatin and rosuvastatin only in 0.5%

-- Main outcome: all-cause and cardiovascular mortality

-- secondary outcome: composite of ASCVD events (MI, ischemic stroke, revascularization with CABG or PCI)

-- mean follow-up of 6.8 years

 

Results:

-- a total of 206,902 deaths occurred, including 53,296 cardiovascular deaths

-- all-cause mortality:

    -- having initiated statins: 78.7 total deaths/1000 person-years

    -- statin nonusers: 98.2 total deaths/1000 person-years

-- cardiovascular deaths:

    -- statin users: 22.6/1000 person-years

    -- non-statin users: 25.7/1000 person-years

-- composite ASCVD outcomes, 123,379 events:

    -- statin users: 66.3/1000 person-years

    -- non-statin use: 70.4/1000 person-years

-- after propensity match scoring, comparing statin to non-statin use:

    -- all-cause mortality: 25% decrease, HR 0.75 (0.74-0.76), p<0.001

    -- cardiovascular mortality: 20% decrease, HR 0.80 (0.78-0.81), p<0.001

    -- totally ASCVD events: 8% decrease, HR 0.92 (0.91-0.94), p<0.001

-- by two-year increments of initiating statins:

    -- at year 2, all-cause mortality decreased 32%, HR 0.68 (0.66-0.69)

    -- at year 4, all-cause mortality decreased by 21%, HR 0.79 (0.77-0.81)

    -- at year 6, all-cause mortality decreased by 13%, HR 0.87 (0.84 0.91)

    -- there was a similar pattern for cardiovascular mortality

-- by age, all-cause mortality decreased with statins:

    -- 75-80yo: decreased 22%, HR 0.78 (0.76-0.80)

    -- 80-84yo: decreased 22%, HR 0.78 (0.77- 0.80

    -- 85-89yo: decreased 20%, HR 0.80 (0.78-0.83)

    -- >90yo: decreased 20%, HR 0.80 (0.74-.86)

-- by sex:

    -- men: 25% decrease, HR 0.75 (0.74-0.76)

    -- women: 22% decrease, HR 0.78 (0.72-0.84)

-- and no significant difference by race, diabetes, dementia (though those with dementia did somewhat better), arthritis

 

Commentary:

-- adults older than 75 are the fastest-growing segment of the population, with a projected 45 million Americans by 2050, and the greatest proportional increase in those >85yo

-- the absolute risk of ASCVD increases with age and remains the leading cause of death, reduced quality of life, and increased medical costs

-- most of the large statin trials did not enroll many people older than 75, limiting the ability to generalize statin benefit to this age group

-- there have been observational studies in older individuals in Spain, 2 in Korea, and another in France that found similar statin benefits to the above VA study

-- of note, there is an ongoing trial (STAREE) assessing the effect of atorvastatin 40 mg per day in 18,000 primary prevention patients >70 yo, which might give a more definitive answer for statin use in primary prevention.

-- as with statin use in younger people, the benefit found in the VA study accrued within the 1^st 2 years of initiation. this suggests that those with a two-year life expectancy would likely see significant benefit

-- there is concern about the adverse effects or drug-interactions of statins particularly in the elderly.  i try not to be too anecdotal, but i have had essentially all of my quite large group of older people (including many in the age range 90-105) on statins, and i do treat-to-target LDL levels (ie, many elderly are on pretty high dose statins), and i have had only one person not tolerate them (with severe rhabdo). As summarized in the blog http://gmodestmedblogs.blogspot.com/2019/02/statin-efficacy-in-older-people.html :  "studies have assessed age as a basis for several potential adverse outcomes, including risk of myopathy (no difference), diabetes (slightly higher in older people in some studies), cognitive decline (mixed results). See http://gmodestmedblogs.blogspot.com/2016/06/statins-adverse-effects-again.html so, not a huge concern"

 -- It should also be noted that a study such as the VA one has the advantage of involving community dwelling people, vs a formal trial which tends to have healthier individuals (by excluding those who are less healthy)

Limitations of study:

-- as per all retrospective observational studies, and despite propensity score matching to try to equalize comorbidities, there may well be unmeasured confounding. Hence the value of randomized controlled trials

-- frailty is not measured or included in the analysis, an important consideration in treating the elderly/adding on more meds

-- there were no data on statin discontinuation, or the effects on outcomes

-- there was no information about cardiac risk factors in general, including LDL levels. Arguably, everyone older than 75 would qualify as "high risk" by current cardiac risk calculators. However, within that there is a gradation of risk, and there may well be benefit of tracking LDL levels and trying to achieve lower target in those at higher risk

--there was no information on the mortality effects by statin type, dose, achieved LDL, HDL, etc [ie, benefit is likely to track with the achieved LDL, as noted in many studies, including as found in http://gmodestmedblogs.blogspot.com/2018/08/very-low-ldl-levels-benefit-without-harm.html )

--this was a primary prevention study, and only included patients who had not been on a statin beforehand. Both of these conditions will tend to underestimate the overall statin benefit by not including patients at the highest risk (it being likely that those not on a statin even for primary prevention have lower cardiovascular risk than a similar group on statins). The absolute statin benefit is much higher in those at higher risk.

other relevant prior blogs: 

-- A French population-based study found that stopping statins in those >75yo was associated with increased subsequent admission for cardiovascular event http://gmodestmedblogs.blogspot.com/2019/09/continuing-statins-in-elderly.html

-- a large meta-analysis found an 18% risk reduction of major vascular events in those>75yo: http://gmodestmedblogs.blogspot.com/2019/02/statin-efficacy-in-older-people.html .  

so, none of the above is particularly surprising: statins work well, work quickly (results within 6-24 months), have an absolute benefit that is greater in higher risk people (including older ones), and are overall very well tolerated (even in the elderly). And there is a pretty sizable growth of the older population. Some guidelines, eg the 2018 AHA/ACC guidelines, have been updated to suggest that statins in the elderly are a "reasonable choice", but being less prescriptive because of lack of solid data (as noted, the strongest studies did not include many elderly). This large VA study adds support to a more aggressive approach, with a large quantity of people though some limitations in quality....

geoff

 

If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@uphams.org

 

to get access to all of the blogs:

1. go to http://gmodestmedblogs.blogspot.com/ to see them in reverse chronological order

2. click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category​

3. or you can just click on the magnifying glass on top right, then  type in a name in the search box and get all the blogs with that name in them

 

please feel free to circulate this to others. also, if you send me their emails, i can add them to the list