continuing statins in elderly
Geoff A. Modest, M.D.
Mon 9/30/2019 6:51 AM
A recent nationwide French population-based cohort study found that stopping statins in those >75yo taking them for primary cardiovasc prevention was associated with an increased subsequent admission rate for a cardiovascular event (see statin elderly not stop europhrtj2019 in dropbox, or doi:10.1093/eurheartj/ehz458)
Details:
--sample: all French who turned 75 in 2012-14 (n=102,173) with no history of CVD and on a statin with a medication possession ratio (MPR) of >80% , (ie, they were taking the meds) in each of the prior 2 years
--male 41%, nursing home 0.5%, meds: BP 79%/antiplatelet 25%/anticoagulants 14%/diabetes 27%, comorbidities: chr pulmonary dz 18%/diabetes 24%/depression 4%/cancer 4%, frailty indictors 5 assessed, most common was bed confinement in 2%
--people excluded: prior diagnosis cardiovasc disease or intervention; taking antiplatelet drug (including aspirin), b-blocker, ACE/ARB
--statin discontinuation: defined as 3 consecutive months without statin exposure
--covariates assessed: sex, area deprivation index of residence (reflecting social class), residence in nursing home, cardiovascular drug use, comorbidities, frailty indicators, and hospital admission
--17,204 (14.3%) discontinued the statin
--5396 (4.5%) were admitted for a cardiovasc event, incidence rate 2.1/100 patient-yrs
--2299 with coronary event (1233 with angina, 542 with acute MI)
--2398 with cerebrovascular event (931 stroke, 525 TIA, 521 stenosis without infarction)
--769 with other vascular event (324 arterial embolism/thrombosis)
--average follow-up 2.4 year, but up to 4 years
--outcome: hospital admission for cardiovascular event
--also, looked at admissions for renal colic, as "negative control" outcome (to exclude the healthy-adherer effect)
Results:
--stopping the statin:
--33% increased risk of cardiovascular event, adjusted HR 1.33 (1.18-1.50)
--46% increased risk of coronary event, adjusted HR 1.46 (1.21-1.75)
--26% increased risk of cerebrovascular event, adjusted HR 1.26 (1.05-1.51)
--no statistically significant increased risk of “other vascular event”, adjusted HR 1.02 (0.74-1.40)
--review of their graph: increased events began at 3 months (there had to be a minimum of 3 months of discontinuation, so that was the starting point) and continued to increase linearly over the course of the study, up to 45 months
--also there were significant increases in events (though less pronounced) if used a 6 month statin gap (23%) or 12 months (17%)
--no relationship found between statin discontinuation and admissions for renal colic (ie, it did not seem that hospital utilization was associated with statin discontinuation, just the more specific target of cardiovasc events)
Commentary:
--though it is clear that statins are beneficial in those >75yo for secondary prevention, the studies on primary prevention are basically post-hoc or subgroup analyses, with inconsistent results (though the authors note that 2 interventional studies are underway, results anticipated after 2020). And no studies looked specifically at those who discontinued their statins.
--current guidelines for statin use in primary prevention for those >75yo: European guidelines had no recommendation; ACC-AHA 2018 guidelines suggested shared decision-making (though if coronary artery calcium score known to be 0, likely risks outweigh benefits; but this test is not recommended or reimbursed that I know of. And not sure what shared decision-making means in this evidence-free zone)
--no guidelines have specific recommendations that statins should be stopped
--database in this French study included all people meeting inclusion criteria (all had their health spending reimbursements linked to hospital discharge database and a comprehensive database on statin use). One advantage of all of the non-US, comprehensive health care systems is that they have good, accessible, evaluable, whole population-based data… one of many benefits to an inclusive system of care as found in essentially all other resource-rich and some less rich countries
--though overall adherence rates of statin use in primary prevention are pretty low, the 86% in this study was well above a recent meta-analysis finding 40% non-adherence in those >65yo (defined as <80% MPR), perhaps related to the fact that all of the people included in this French study had to be taking their statins consistently for the prior 2 years
--the only subgroup with an increase in cardiovascular events that did not reach statistical significance was in diabetic patients, though there were pretty few discontinuations (only 3857)
--limitations of the study include: this was not an intervention study, so unclear if there were unidentified confounding reasons why some patients stopped the statins (eg, drug interactions with meds for new serious diseases not subsequently identified, or too much polypharmacy), unclear if baseline characteristics were the same in those discontinuing vs continuing statins (eg, what were LDL levels, blood pressure, diet, exercise??…., though one might expect higher adherence rates in those at higher cardiovascular risk), or if there were unmeasured markers of frailty or comorbidities that accrued during followup (though the 5 markers of frailty did not alter the results, and the results were adjusted both for baseline and time-varying covariates)
So, though not a randomized controlled trial, this was a pretty good, large, observational trial of pretty much the complete group of French patients turning 75 in the 2 years evaluated, who had been taking their statins regularly for at least 2 years, who had a very low rate of statin discontinuation and a pretty low rate of medical comorbidities or medications (an apparently quite healthy group, less likely to achieve statin benefit), that still found a pretty large relative increase in the risk of cardiovascular events in those discontinuing statins, and in an age group with increasingly high absolute rates of these events. This result suggests a few things:
--it suggests that statins have an important role in primary prevention of cardiovasc events in the elderly, where the absolute risk of these events increases with age (though the caveat here is that this study assessed those already on statins but then discontinuing them for unknown reasons)
--this study reinforces the potential short-term harm of stopping statins in the elderly, since the increased cardiac events occurred within 3-4 months of stopping them. This suggests that statins are still therapeutic in elderly who have even a few months of further life expectancy. So, if the goal in an individual patient is to decrease medication burden, perhaps statins are ones to preferentially continue...
relevant prior blogs:
--http://gmodestmedblogs.blogspot.com/2019/02/statin-efficacy-in-older-people.html , a meta-analsyis of statin efficacy in older patients, confirming efficacy in those >75yo
--http://gmodestmedblogs.blogspot.com/2018/01/statins-for-primary-cad-prevention-in.html , a review of international guidelines for statin use in primary prevention in the elderly, with additional review of the specifics of the 2014 NICE guidelines which include recommendations for primary prevention with statins in those >85yo
geoff
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