intensive hypertension therapy effective in elderly

 Since I am on the track of hypertension now, I will report on a recent study finding that intensive blood pressure control was beneficial in elderly persons, independent of cardiovascular risk (see htn intensive control better indep of risk in dropbox, or DOI: 10.1161/HYPERTENSIONAHA.125.25162).

 

Details:

-- 8262 Chinese patients in the STEP trial (Strategy of Blood Pressure Intervention in Older Hypertensive Patients), a multicenter, open-label randomized controlled trial of adults aged 60-80yo who had systolic blood pressure of 140-190 mmHg or were taking antihypertensive medication. these individuals were stratified by tertiles of baseline 10-year cardiovascular risk, with the goal to assess benefit and harm, evaluating both the effect on primary cardiovascular outcomes and adverse events. Those who had had a prior stroke were excluded

-- within each tertile, patients were randomized to intensive blood pressure control (SBP 110 to <130 mmHg) versus standard blood pressure control (SBP target of 130 to <150mmHg)

-- patients were seen at one month, 2 months, and 3 months, and then every 3 months until the end of the trial

-- for blood pressure assessment, participants had a five-minute rest, then blood pressure was measured on 3 occasions at an interval of 1 to 2 minutes, and the average was recorded

-- the 10-year ASCVD risk was measured using the Framingham 10-year atherosclerotic cardiovascular disease (ASCVD) risk calculator, which had been validated in Asian ethnicity cohorts

 

-- given the expected differences in comorbidities in patients in the different tertiles, i will separate the baseline characteristics:

    -- tertile one, ASCVD 10-yr risk score <18.1%: mean age 65, 12% male, BMI 25, blood pressure 137/79 mmHg, 5% current smokers, 12% current drinkers, fasting blood glucose 160 mg/dL, total cholesterol 180/LDL 96/HDL 53/triglycerides 54, eGFR 109, average 10-year ASCVD risk 13%

        -- diabetes 5%, ASCVD 5%, on aspirin 9%, on statin 23%

    -- tertile two, ASCVD risk score 18.1%-29.8%: mean age 66, 51% male, BMI 26, blood pressure 147/83 mmHg, 17% current smokers, 89% current drinkers, fasting blood glucose 160 mg/dL, total cholesterol 190/LDL 108/HDL 47/triglycerides 60, eGFR 111, average 10-year ASCVD risk 24%

        -- diabetes 15%, ASCVD 6%, on aspirin 9%, on statin18%

    -- tertile three, ASCVD risk score >29.8%: mean age 68, 77% male, BMI 25, blood pressure 155/85mmHg, 25% current smokers, 39% current drinkers, fasting blood glucose 160 mg/dL, total cholesterol 197/LDL 110/HDL 45/triglycerides 72, eGFR 108, average 10-year ASCVD risk 42%

        -- diabetes 38%, ASCVD 7%, on aspirin 9%, on statin 16%

 

Primary outcomes:

-- a composite of stroke (ischemic or hemorrhagic), acute coronary syndrome (acute MI and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes

-- treatment related adverse events included safety outcomes (hypotension, dizziness, syncope, and fracture) and renal outcomes (composite of at least 50% decrease in eGFR in patients with chronic kidney disease (CKD) at baseline and at least 30% decrease in eGFR to <60 in those without CKD at baseline, or a creatinine increase of >1.5 mg/dL in men or >1.3 mg/dL and women

 

Median follow-up of 3.32 years

 

Results:

-- 333 total primary outcomes occurred:

    -- intensive group: 144 of 4117 (3.50%)

    -- standard therapy group: 189 of (4.56%)

        -- 24% decrease in the intensive group, HR 0.76 (0.61-0.94), p=0.011

-- overall results, stratified by treatment group:

 

-- Per this chart, though all of these groups showed a tendency to do better with intensive BP control, the results were statistically significant only for the 3rd tertile and for the combination of all tertiles

-- however, the risk of primary outcome events increased from the first to third tertile in both the standard and intensive groups, with a highly statistically significant trend, p<0.001

-- the event rates for the individual components of the primary outcome also all favored the intensive group

-- also as noted in the chart above, the absolute risk reduction increased with increasing tertiles, associated with markedly decreased numbers of patients needing to be treated as their risk profile got worse

-- redoing the analysis using the PREVENT risk calculator, the lowest tertile was <11.9% and the highest was >18.1% risk, finding very similar outcomes to the above

-- subgroup analysis by age comparing individuals less than versus more than 70 years old and by sex found lower incidence rates of the primary outcome in the intensive BP group across the subgroups and risk tertiles, again confirming the previous findings

-- of note, the average 10-year ASCVD risk score in the highest tertile group was 42.03% +/- 10.58%, a very high-risk group

-- Treatment-related adverse events:

    --  a total of 611 treatment related adverse events occurred

        -- standard treatment group: 293 events

        -- intensive treatment group: 318 events

            -- hazard ratio was 1.1 (0.94-1.28), p=0.26, not statistically significant

            -- and, there was no statistically significant trend in adverse events with increasing tertiles of risk, though those at the highest risk did have somewhat more events if on intensive therapy

    -- there was no difference also between the adverse events associated with safety concerns or with those with renal outcomes between the 2 groups

 

-- overall analysis:

 

 

-- this graph shows that for tertile one there was benefit for intensive treatment and less harm

-- in both tertiles 2 and 3, there was increasing benefit and harm, though the benefit exceeded the harm, most impressively in tertile 2

-- similar results were found using the PREVENT risk calculator

-- unfortunately, i was unable to open the supplementary materials, using access through 2 different hospital systems. So, i was unable to find out if the adverse effects were serious ones or not, nor the severity of the safety effects measured on renal outcomes

 

Commentary:

-- as noted in the recent blog on the new European as well as American hypertension guidelines, risk and treatment goals are stratified by cardiovascular risk, as are guidelines for statin initiation (http://gmodestmedblogs.blogspot.com/2025/09/new-hypertension-guidelines.html).

    -- though the guidelines do stratify patients by cardiovascular risk, the evidence for the benefits of intensive blood pressure control through this risk-stratified approach is largely unclear. the assumption here is that since adverse cardiovascular events occur more frequently in those people at higher ASCVD risk, that these individuals would derive the most benefit (as was found in this study). the downside of this assumption is that those at lower risk may not be treated so aggressively and fall off the radar screen (hence the importance of this study)

-- the SPRINT study suggested there may be more harm than benefit in patients at lower ASCVD risk (https://pubmed.ncbi.nlm.nih.gov/29525494/ )

-- age-related physiologic changes include: increased comorbidities, increased vascular stiffness, increased risk of adverse events, decreased balance and muscle strength, etc.

    -- and intensive control can be associated with hypotension, injurious falls, and acute kidney injury, especially in older individuals

 

-- The major conclusion of this trial was that intensive blood pressure control was beneficial regardless of the baseline 10-year ASCVD risk. those at the highest risk derived the most benefit with intensive BP control, but there was a highly significant trend to benefit as ASCVD risk increased.  and the overall benefit exceeded the risks for all 3 tertiles, though it was only marginally better in the highest ASCVD risk group, and this benefit was associated with the greatest absolute increase in adverse events

 

 -- interestingly, it seems that i am not the only one digging into the depths of hypertension these days: another article just came out in the Lancet that assessed the role of intensive blood pressure control in 6 studies and came to the same conclusion: benefits outweigh harms (see htn intensive bp control review Lancet2025 in dropbox, or doi.org/10.1016/ S0140-6736(25)01391-1):

    -- this article included 80,220 individuals from the ACCORD-BP, SPRINT, ESPRIT, BPROAD, CRHCP, and the current STEP studies in a post hoc, pooled participant-level analysis comparing intensive systolic blood pressure targets <120 mmHg or <130 mmHg (depending on the individual study), versus standard treatment

-- median age 64 years old, 49% male, 83% Asian/10% white

-- mean follow-up 3.2 years

-- results:

    --net difference in BP in the 2 groups: -5.7 mmHg

        -- in the group with target SBP <120mmHg, the achieved SBP was 120mmHg; if target was <130mmHg, the achieved SBP was around 128 mmHg; DBP in the group with the target SBP <120mmHg was 67mmHg vs 74mmHg in the group with target SBP <130mmHg

        -- standard (non-intensive) BP control was SBP <140mmHg

    -- composite of cardiovascular outcomes: intensive blood pressure control had 24% reduction vs standard control, HR 0.76 (0.72-0.81), p<0.0001

        -- 1.73% absolute risk reduction (1.65-1.81) in cardiovascular disease, number needed to treat (NNT)=58

            -- the driver for this benefit was in stroke reduction (to me, certainly one of the most important outcomes to improve in the array of the composite outcomes), with absolute risk reduction of 1.73% (1.65%-1.81%); the next most common benefit was in cardiovascular death (also pretty important).  the issue here in this study as in the STEP study itself, the composite cardiovascular events in the primary outcome includes really bad ones (death, stroke) with not-so-bad ones (coronary revascularization), diluting the real intensity of the clinical benefit for the individual

        -- 1.82% absolute risk increase (1.63-2.01) in adverse events of interest, number needed to harm (NNH)=55

            -- adverse effects of interest included hypotension, syncope, injurious fall, arrhythmia, angioedema, acute kidney injury, renal failure, end-stage renal disease or dialysis, a reduction of 50% or more an eGFR in those with baseline chronic kidney disease, or reduction of 30% or more in eGFR to less than 60 in those without CKD

            -- overall, net positive benefit of 1.14 (1.03-1.25) with unadjudicated weighting; net benefit still positive when adding kidney-related adverse events of 1.13 (1.01-1.24)

        -- the benefit was evident for all of the individual trials

        -- benefit was similar in those <65yo (HR 0.75, p<0.0001) and those >65yo (HR 0.77, p<0.001), as well is in those <80yo (HR 0.76 (0.72-0.81)) and those >80yo (HR 0.83 (0.66-1.05)); however, the difference between these last 2 groups was not statistically significantly different, likely related to many fewer individuals in the older age group (1326 vs 39,177); also there was no difference in outcomes by sex, educational background, if on BP meds, if baseline DBP above or below 70 mmHg, BMI >28 or less, stroke history, diabetes history, baseline CKD, or CVD risk

 

--these 2 graphs show the relative risk differences in benefits and risks (hazard ratios) in the first graph and the absolute differences in the second one including NNT and NNH, from the Lancet review article

 

 

-- this intensive blood pressure approach also brings up the tangentially-related issue of statin intensity. A 2022 Scottish study (see statin cost-effective primary prev by ARR Circulation2022 in dropbox, or DOI: 10.1161/CIRCULATIONAHA.121.057631) evaluated primary prevention of cardiovascular disease by statins, using the 10-year risk calculations through the ASSIGN risk calculator (involves input on age, sex, race, systolic and diastolic blood pressure, total HDL and LDL cholesterol levels, history of diabetes, smoking, if on treatment for hypertension or on aspirin or a statin). they compared the value of age-stratified risk thresholds of ASSIGN score >10% vs score >20%, finding that with the cost of generic (and cheaper) statins, absolute risk reduction (ARR)-guided therapy increased treatment rates in individuals with elevated cholesterol levels, and this was both cost-effective and would improve population health (ie, it was beneficial and cost-effective to use a lower cutpoint of cardiovascular risk to prescribe statins)

 

Limitations:

-- the average age in this study was around 65 years old, limiting the generalizability to those significantly older (they did assess younger vs older than 70, but unclear how many were much older than 70)

-- this study was done in Chinese communities, affecting the generalizability of these results to other areas, especially since the comorbidities and socioeconomic issues are likely different from other areas

-- adverse events are reported by patients, and there may well be differences in reporting in different countries. It was notable in the SPRINT trial that there was more acute kidney injury, but that trial also had people on more diuretics as well as ARBs

-- this was a post-hoc study, so the results should be treated as exploratory and not definitive

-- the Framingham study has been validated in different populations, but it was originally developed in European descent populations, so perhaps less accurate (though validated in Asian countries)

-- this study did not include metrics of quality of life, functional status, or frailty indices which are really important in elderly individuals

-- a general concern with composite outcomes as in this study is that the individual components do not necessarily reflect equivalent values to patients (i.e. stroke or all-cause mortality or myocardial infarction may be feared significantly more than coronary revascularization)

-- this study also had only baseline data and over its 3.3 years; but this baseline data may have changed over that time period (people may have stopped smoking a day after enrollment...), making it difficult to interpret the results fully. This short time-span also makes it difficult to assess longer-term outcomes such as cognitive decline or changes in life expectancy

-- and, as mentioned above, i was unable to open the supplementary materials, using access through 2 different hospital systems. So, i was unable to find out if the adverse effects were serious ones or not, nor the severity of the safety effects measured on renal outcomes. And any useful risk/benefit analysis needs an understanding of the seriousness of the adverse outcomes

 

So,

-- this study found that intensive blood pressure control helps independently of the anticipated cardiovascular risk of the groups, suggesting that we really should focus intensive lowering of the blood pressure management on all patients, limited by their being intolerant of too low a blood pressure

-- however, the rate of adverse events also increases with increased cardiovascular risk, suggesting that patients need to be involved in shared decision-making regarding the intensity of blood pressure management, reflecting the importance of individualized treatment decisions

-- i personally start patients with low doses of meds, and almost always start with single meds, but with frequent followup (if blood pressure high, sometimes every week). This is because i have seen a few patients over the years who were treated more aggressively (eg starting moderate to high dose ACEi) who had dramatic falls in their blood pressures and had syncope.  And, lowering the blood pressure too aggressively can lead to ischemic strokes because of cerebral vasospasm decreasing blood flow. in addition, patients with quite high blood pressure have often been living at that level for a long time, and waiting a few weeks with gradual lowering of the blood pressure in asymptomatic people in a more controlled way is unlikely to do much harm

geoff

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