BP medication nonadherence in the elderly

MMWR just reported on the anti-hypertensive medication adherence rate in those on Medicare (see https://www.cdc.gov/mmwr/volumes/65/wr/mm6536e1.htm?s_cid=mm6536e1_e ).

Background:

--70% of US adults >65yo have hypertension, only 50% of them controlled (BP <140/90 mmHg)

--uncontrolled BP is the main risk factor for heart disease and stroke (1^st and 3^rd leading causes of death) in those >65yo

Details of study:

--analysis was limited to Medicare D beneficiaries with 2 or more antihypertensive med scripts filled on different service dates within a measurement period of >90 days

--medication nonadherence was defined as the % of days the patient should have had access to the medications based on how often they refilled the medications, with <80% suggesting nonadherence [this is a bit more complex now that pharmacies are simply calling patients in to refill meds when their prescriptions are due to be refilled: I have seen several patients bring in their meds for me to see, with many unopened bottles in the bag...]

--18.5 million Medicare D beneficiaries were prescribed antihypertensives, but 4.9 million (26.3%) were nonadherent, with the following breakdown:

    --race/ethnicity: 38.8% in American Indian/Alaska Native, 35.7% in Black, 33.8% in Hispanic and 24.3% in White/non-Hispanic

    --income status: standard Medicare 25.4%, Medicaid 32.1%

    --health status (based on number of unique prescriptions filled): best quartile 21.8%, worst 34.4%

    --ESRD: 55.9% and 26.1% in those not with end-stage renal disease

    --number of BP med prescribers: >2 prescribers 36.8%, 1 prescriber 22.7%

    --use of combination meds (eg lisinopril-HCTZ as a single pill): 23.4% if use combo pills vs 27.0% if not

    --age: >85 29.0%, 65-74 25.4%

    ​--in continental US, nonadherence much higher in the south (eg Mississippi 32.8%, Louisiana 31.5%, DC 33.7%, Arkansas 30.4%); and much lower in the north (eg Vermont 19.1%, New York 18.9%, Wisconsin 18.8%), and the map in the article is quite striking on this difference

    --nonadherence was higher when a second antihypertensive was added [is this because of taking too many pills, or because these patients were already nonadherent, unbeknownst to their provider, leading to them being prescribed a second (or more) medication?]

 

Commentary:

--the issue of medication nonadherence is one of the most difficult in primary care, leading both to increased morbidity/mortality from untreated disease, as well as the potential to increase morbidity/mortality by overtreating (eg, adding more and more meds to achieve the target and creating more drug-drug interactions and likelihood of adverse reactions. also, I have  also seen a few patients put on their "regular meds" when in the hospital and becoming severely hypotensive)

--this med nonadherence rate is actually much better than many decades ago (historically it was in the 50% range for primary prevention studies in asymptomatic patients). and several older studies (most of which were done on BP meds) showed that we clinicians do terribly at predicting which patients do or do not take their meds regularly (as in, a 50-50 chance of being correct)

--the 80% target they chose as defining med adherence (it think) is based on older studies suggesting that that was a threshold in terms of clinical outcomes. Clearly, this is disease and medication-specific: ie, that bar is much higher for necessary compliance with HIV meds.

--the data on class-specific medication non-adherence rates are similar to other studies I have seen/sent out in the past: worst for diuretics (28.9%), best for ARBs/ACE (16.9% and 18.5%), and intermediate for calcium and beta-blockers, around 23% each. (and this is another reason not to use diuretics as first-line. See recent blog blood pressure variability increases cardiovasc disease​, appended below since was not put on BMJ website yet)

--there are lots of reasons for medication nonadherence (and this list is hardly complete, just many that I see a lot)

    --issues of health care access: patients not able to pay their copays to be seen by their provider, or for their medications. or the pharmacy is limited to  prescribe only 30 days of meds which can only be filled 2-3 days prior to running out, but the patient is out of the country, or they have 15 meds all coming due at different times of the month and they could not pick up some really important ones because their lives are more complex than just focusing on going back and forth to the pharmacy, etc etc [and, it seems pretty intuitive that it is not only more humane but actually cost-effective to prevent strokes by providing free access to primary care and meds...]

    --problems with complexity of the regimens: too many meds (and advantage of combo meds), prescribed to take meds too many times a day (and advantage of once a day dosing, which can problematic when I tell patients to take all of their meds at the same time, whenever is easiest for them to remember, but the pharmacist tells them to take their statin at night, even though with the higher potency statins there really is no difference. and even with the low-potency ones, taking it in the morning is still better than forgetting it in the evening), and many people are titrated in the hospital by using short-acting meds and are sent out on them to take many times a day, instead of changing to once-a-day equivalents....

    --educational issues: patients do not understand how to take meds (a rather common one being that the prescription ran out and they did not understand there were refills, or that the med needed to be taken long-term, or they don't understand what a "stroke" is when the clinician uses this term: always good to ask the patient)

    --cultural issues: the patient feels that taking longterm meds means that they are chronically ill; or patients do not accept their condition as being a medical problem but instead a social problem, or a spiritual problem. so taking meds does not make sense as the treatment

    --the medication recommendation does not really fit for the patient. here is where open discussion of options is important. and here is, to me, the real value of motivational interviewing: engaging the patient in a patient-centered way to find out what they know about their condition/what "their story" is of how this medical issue fits into their life;  and then, perhaps with some clinician guidance, having the patient figure out what intervention works for them and how (ie, not lecturing the patient on what to do, not giving generalizations about diet/exercise/taking meds without asking the patient what they like to do/how they take meds and trying to redirect a bit but with patient involvement)

    --other issues which should be considered: depression, difficult social situations, lack of social supports, psychosis, etc which make it hard for the patient to focus on meds

--interpretation of the subgroup analyses above (eg higher in certain ethnicities, ages, more meds): perhaps there are some common threads here -- the ethnicity and income differences might be related to social stressors; the number of BP med prescribers might be related to care fragmentation/lack of developed provider-patient relationships; use of combination pills/health status/increasing age might reflect pill burden

--a team approach to medication adherence sometimes helps, perhaps involving nurses, medical assistants who may know the patient/their culture and may have insight into how to help the patient with medication taking; pharmacists also have lots of information about medication usage by the patient; and, in one study many years ago, involving the patient's family if the patient is open to that. in that study, they invited family members and asked them to list 3 things that they could do to help the patient take their medications. this worked much more often than just educating the patient about their disease and how the medication worked.

--so, overall medication nonadherence is a huge and extremely important clinical issue in primary care (and other disciplines), but (the good news) trying to get to the bottom of the problem can often lead to improved understanding and relationships with the patient

geoff

link: https://www.dropbox.com/sh/0bmvtita8mzms11/XDTwHySFFg

go to "clinic", then to either "clinical stuff" for articles, or "powerpt presentations" for the powerpoint presentations

to access the BMJ blog, go to  http://ebm.bmj.com​ 

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

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blog from 9/7/16 (:

There has been concern about the adverse effects of blood pressure variability on cardiovascular outcomes. A prior blog (see http://gmodestmedblogs.blogspot.com/2015/07/blood-pressure-variability-and-heart.html) reviewed the ALLHAT trial, which found that visit-to-visit blood pressure variability was associated with increased CV events and commented on a 2010 issue of the Lancet that found that hour-to-hour BP variability in individuals was associated with more strokes, and, to a lesser degree, coronary events (see Rothwell PM. Lancet 2010;375:895). BMJ just had a systematic review and meta-analysis confirming the association (see bp variability and cvd bmj2016 in dropbox, or doi.org/10.1136/bmj.i4098). details:

-- 41 papers representing 19 observational cohort studies and 17 clinical trial cohorts. 24 papers studied long-term variability (monitoring blood pressure in clinics), 4 studies mid-term variability (home monitoring) and 15 short-term (ambulatory blood pressure monitoring).

--range of studies: 457 to 122,636 participants; follow-up ranged from 2514 to 490,544 person-years; mean age ranged from 48.5 to 77 yo

--Increased long term variability in systolic blood pressure was associated with:

    ​--all-cause mortality: 15% increase, HR 1.15 (1.09 to 1.22)

    --cardiovascular disease mortality: 18% increase, HR 1.18 (1.09 to 1.28)

    --cardiovascular disease events: 18% increase, HR 1.18 (1.07 to 1.30)

    --coronary heart disease: 10% increase, HR 1.10 (1.04 to 1.16)

    --stroke: 15% increase, HR 1.15 (1.04 to 1.27)

-- Increased mid-term variability (home BP) in daytime systolic blood pressure was associated with all-cause mortality [HR 1.15 (1.06 to 1.26)].

-- Increased short term variability (ambulatory BP) in daytime systolic blood pressure was also associated with all-cause mortality [HR 1.10 (1.04 to 1.16)]. The conclusions are a bit limited, since 2 studies dominated the meta-analysis.

commentary:

--as with meta-analyses, they combine different studies with differing methodologies, limiting their conclusions. For example, there is not necessarily any consistency across studies in terms of how the BP was measured, what size cuffs were used, whether using manual or automated devices, etc)

--they did not include studies on nocturnal dipping (that's the normal variation, with lower blood pressure at night on ambulatory monitoring; non-dippers seem to have higher mortality). They did exclude patients on dialysis, since blood pressure variability is basically intrinsic to hemodialysis patients. 

--as a perspective, the 15+% difference in cardiovascular events found still pales in comparison to overall effect of lowering the mean blood pressure. ie, the primary goal is to decrease the mean blood pressure. That being said, the difference from blood pressure variability in the above meta-analysis did control for the mean blood pressure, revealing an increased risk over the mean BP

--blood pressure variability during the day is normal, typically up to the 18/12 mmHg range. This variability is enhanced in those with arterial stiffness (and the above meta-analysis was skewed to older hypertensive patients), which may put these patients at higher CV risk.

--this all supports the conclusions that:

    --we should be doing more ambulatory or home BP monitoring: several analyses have found that ambulatory or home blood pressure monitoring is superior to office blood pressure at predicting cardiovascular events, perhaps since ambulatory or home measurements are more likely to pick up BP variability.

    --there are likely advantages to using BP meds that produce a more sustained, less variable blood pressure over 24 hours: amlodipine seems to be the best, ACE-I are intermediate (and there are arguments that the increased stroke rate in several studies of ACE-I may be related to the higher blood pressure in the early mornings), and HCTZ up to 25 mg is the worst (for example, see Webb AJS. Lancet 2010; 375: 906). b-blockers are also in the intermediate category.

--many prior blogs have assessed these last 2 conclusions, http://gmodestmedblogs.blogspot.com/search/label/hypertension/ . and in particular,

    -- http://gmodestmedblogs.blogspot.com/2016/04/chlorthalidone-is-better-than-hctz-for.html / showed that hydrochlorothiade is a poor choice, given both its very poor 24-hour effect (despite the fact that the blood pressure seems better controlled when we see the patients during the daytime in the office), and  there are several other analyses confirming this result (eg, the seminal studies on HCTZ in mild hypertension, done decades ago, involved using 50mg/d, which is higher than most of us use now. And the 50mg/d dose does decrease BP variability (see htn HCTZ Meta-anaylsis messerli am j cardiol 2011 in dropbox, or Messerli FH. JACC 2011; 57:590.)

    -- http://gmodestmedblogs.blogspot.com/2016/04/home-blood-pressure-monitoring.html ​  which shows that home BP monitoring is superior in terms of clinical outcomes over office-based BP, and refers to the UK's 2011 NICE guidelines which documented lots of studies showing that ambulatory BP monitoring was superior to clinic BP measurement, leading NICE to strongly support using ambulatory or home BP for diagnosis of hypertension.  Though it was done in 2011, I think the NICE document is the single best review of hypertension I have seen, with a detailed analysis of the studies up til 2011 (it even reviewed 5 or so studies showing that spironolactone was great in patients with resistant hypertension, well before it was adopted in the US), but this document unfortunately is not accessible on the internet (it is in my dropbox as Htn nice recs 2011. The NICE guidelines were updated in 2015, with the summary at https://www.nice.org.uk/Guidance/QS28 ).

    -- Using a non-clinic based BP was adopted in 2015 by the USPSTF giving an "A" rating to screen BP outside of the clinical setting. for the USPSTF recommendations and my review, see http://gmodestmedblogs.blogspot.com/2015/10/uspstf-guidelines-on-blood-pressure.html