Hypertension: add another med vs increase current one in elderly

 A large VA study confirmed that adding a new blood pressure medication was more effective than maximizing the dose of the current one, this study in older adults (see htn adding med vs intensification AIM2021 in dropbox, or doi:10.7326/M21-1456) 

 

Details: 

-- 178,562 patients in the VA system with inadequate blood pressure control were followed; 45,575 (25.5%) had a new BP med added, and 132,987 (74.5%) had their current med maximized

-- eligibility criteria: antihypertensive med intensification at the beginning of the study (versus 3 months prior); age 65 or older with hypertension and established primary care in the VA system; at least two visits between July 1, 2009 and March 30, 2012; and visits to a primary care or hypertension-treating specialist in that time period, and a mean systolic blood pressure (SBP) of at least 130 mmHg 

-- mean age 76, 98.1% men, geriatric care 2%/hypertension-treating specialty care 7%, mean SBP 142 mmHg, with 130-140 mmHg in 52%, 141-160 mmHg in 41%, and >160 mmHg in 6% 

-- chronic conditions: mean number in addition to hypertension was 4, with 71% having multi-morbidity; cardiac/cerebral/peripheral vascular disease in 32%, heart failure/valve disorder in 15%, diabetes 32%, arrhythmia 10%, current smoking 10% 

-- antihypertensive medication: mean number of medications 1, mean standardized dose 2 HDDs (hypertension daily dose: defined as one-half of the maximum beneficial dose for that medication. see below), ACE/ARB 60%, beta blocker 50%, calcium blocker 40% 

-- covariates assessed: age, baseline comorbid conditions, baseline medication count, baseline medication classes, baseline SBP, geriatric care, care provided by hypertension-managing specialist, facility location, facility characteristics (community-based outpatient center, VA Medical Center), and complexity level (low, medium, or high) 

-- slightly more people who were prescribed new medication added had a higher baseline SBP, more specialty care, and less frequent geriatric care 

    -- propensity-scoring was used to minimize the inherent bias in observational studies between the different baseline characteristics of the populations being compared (a mathematical device to make the populations analyzed more equivalent, though see http://gmodestmedblogs.blogspot.com/2020/03/tramadol-fo-oa-inc-mortalityprobs-with.html for some limitations in this technique) 

-- main outcome: comparing the outcome of these two approaches to intensify blood pressure control sustainability (i.e. continuing the treatment for the 3- and 12-month assessments) and follow-up SBP at 3 and 12 months 

-- mean time to first follow-up measurement was 97 days (1-365 days) 

 

Results: 

-- adding a new medication versus maximizing dose: 

   -- sustained intensification: less likely with adding a new medication, 49.8% (49.3% to 50.3%) at 3 months versus 65.0% (64.7% to 65.2%) with maximizing dose: difference -15.2% (-15.7% to -14.6%) at 3 months, and similarly at 12 months: -15.1% (-15.6% to -14.5%) 

-- reduction in blood pressure: mean SBP -4.6 mmHg for adding a new medication (-5.0 to -4.2 mmHg) versus -3.8 mmHg for maximizing the dose (-4.0 to -3.6 mmHg), with mean difference -0.8 mmHg (-1.2 to -0.4 mmHg), at 3 months and -1.1 mmHg (-1.6 to -0.6 mmHg) at 12 months 

-- when the baseline SBP was removed from the propensity-scoring, there was a larger difference in SBP between those with an added medication versus an increased dose: -2.2 mmHg (-2.6 to -1.8 mmHg) at 3 months and -2.7 mmHg (-3.2 to -2.2 mmHg) at 12 months, or when only patients with fewer than 3 medications at baseline were included 

 

Commentary: 

-- this is a common problem: two-thirds of patients have their blood pressure controlled with 2 medications, the one-third require some sort of intensification of their therapy 

-- the choice of adding a new drug versus augmenting the dose of an older drug is complex: adding a new drug does entail the potential of adding new adverse outcomes, as well as potentially new drug-drug or drug-disease interactions.  In addition, adding another medication may make a complex medication regimen even more complex (though there are some meds that come as combined dosages, such as ACE/ARB with a diuretic). On the other hand, argument has been raised (and supported by some studies) that increasing the dose of a current medication may well increase adverse reactions to that medication (e.g. the peripheral edema associated with amlodipine is dose-dependent) and that lower doses of multiple medications may well have fewer adverse effects and be better tolerated.

 

-- in this study, adding a new medication was associated with a less favorable 15 percentage point difference in the probability of sustained therapy, but a 1.1 mmHg greater reduction in SBP over 12 months 

-- their conclusion: “our results suggest that maximizing dose might be simpler to maintain in older adults with multiple comorbid conditions, but with a trade-off of slightly less SBP lowering effect” 

-- it is notable in this study that the initial blood pressures were overall not so high: only about 6% had blood pressures of at least 160 mmHg. The blood pressure lowering effect of a medication is significantly greater in those with higher initial blood pressures, and the low level of really high blood pressures in this study may well explaining the small absolute difference found with either therapeutic approach (typically blood pressure lowering is more in the 10+ mmHg range when adding a medication, versus their 4-5 mmHg finding (in fact, in this study, those with the highest blood pressure actually had 20mmHg reduction vs about an 8mmHg decrease in those with SBP 140-160 mmHg)

 

-- and, as a perspective to interpret blood pressure changes clinically, in a study of 48 randomized trials and almost 350,000 participants, each 5-mmHg reduction in SBP lowered the relative risk of a major cardiovascular event by 10% over an average of 4 years 

 

-- Prior studies assessing the value of adding an additional BP med have found that adding another med was much more effective than increasing the dose of a current one (one study finding that doubling the dose of a medication had 20% of the blood pressure lowering effect of adding a drug from another class): see http://gmodestmedblogs.blogspot.com/2018/03/adding-yet-another-bp-med-helps-alot.html 

-- one previously obscure issue to me was the concept of HDD (hypertension daily dose) for meds. this is basically an attempt to quantify dose intensity of different meds to compare clinical effectiveness across meds and med classes: see https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775221 , for more on the definition of HDD, including finding that lisinopril's HDD is 20mg, also noting that "hypertension trials demonstrate effectiveness as the increment in the number of BP medications", with reference to some of the big RCTs, including SPRINT. But it should be noted that this HDD determination is based on data-mining medical records from a large database (the VA system, in this case), not individual data from RCTs. and, repeatedly in my experience, there is quite a lot of variability in medication effect among different individuals: some patients given ACE inhibitors, for example, have quite exaggerated BP lowering even at low med dose, perhaps related to their salt intake or state of hydration as reflected in their renin/angiotensin levels.  which, by the way, is why i always start with low doses of meds and titrate up quickly depending on the response....)

 

Limitations:

-- as a VA study, more than 98% were men, so generalizability to women is limited

-- this was a retrospective, population-based, cohort study done 10 years ago, and not a more current randomized controlled trial which would generate more robust conclusions.

    --for example, goals of blood pressure have changed in the intervening 10 years, including in the elderly (e.g. see http://gmodestmedblogs.blogspot.com/2021/10/hypertension-lower-goal-better-in.html )

    -- the cutpoint to initiate anti-hypertension management in those over 65yo at the time of this study was felt to be much higher (eg >160mmHg, as in the best study in elderly at that time, the HYVET study. seehttps://www.nejm.org/doi/full/10.1056/nejmoa0801369 )

    -- and in this study, 50% were on beta blockers, used much less frequently as a single agent now because of questions of its clinical outcome effectiveness

-- we do not have accurate information on the medications used, the doses used, how much the dose was increased in those who had intensification of the current medication, what was the dose was of the new medication added, ...  all of which limit the interpretation of their conclusions

    -- they did not require a specific dose increase of current medications

-- there is no evident standardization of how blood pressure was measured across the VA system at that time, potentially leading to spurious and inconsistent results

-- it is not clear exactly what “sustained intensification” means for those put on a new medication: would this include patients starting at a very low dose of a new medication (the “go low, go slow” approach, as i suggest above) and then increasing that dose? would that increase mean that there was not a sustained intensification since the dose may have changed in subsequent follow-up??

-- the study relied on pharmacy records, which do not necessarily reflect medications actually taken

-- no information on adverse effects of either strategy

 

So, another article finding that adding a new medication to an inadequate antihypertensive regimen is somewhat better than just increasing the dose of the current one, this one done in an elderly VA population. a few comments:

-- their results were significantly less impressive than in more rigorous randomized controlled trials (eg see above), and a real RCT in elderly people (an increasingly important group, as their numbers continue to sky-rocket) is pretty clearly indicated

    -- perhaps this is related to differences in baseline SBP, different meds used at that time, lack of individual-based data to allow accurate quantification of the intervention done and the outcome, etc...

    -- since RCTs several years ago were pretty conclusive that adding a low dose of a new medication was superior, my personal approach as noted above has been adding a low dose of a new medication, independent of the age of the patient, when their blood pressure was significantly higher than goal (if close to goal, I would often just increase the dose). In either case I would follow the patients closely both for their blood pressure and adverse effects. And this strategy has served my patients well without significant problems.

  --I bring up this article because it does confirm that adding a low dose of a new med is beneficial in older people, though perhaps in a blunted way, and it highlights other studies which show such a dramatic difference with adding low dose of a new med....

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 (2 options):

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

 

or: go to https://www.bucommunitymedicine.org/ , a website from the Community Medicine section at Boston Medical Center.  This site does have a very searchable and accessible list of my blogs (though there have been a few that did not upload over the last year or two). but overall it is much easier to view blogs and displays more at a time.

 

 

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