Less brain damage with intensive BP-lowering in older hypertensives, but no functional improvement

ACC 2019 The randomized INFINITY trial showed a significant reduction in accrual of subcortical white matter disease in older people receiving more intensive antihypertensive therapy, but mobility and cognitive function were not improved.

Primary Results of the Intensive versus Standard Ambulatory Blood Pressure Lowering to Lessen Functional Decline in the Elderly Trial (INFINITY)

Presented at ACC.19 by William B White (Farmington, CT, USA)

Subcortical small vessel disease of the brain, characterized by white matter hyperintensity (WMH) on magnetic resonance images (MRI), is linked to functional decline in older subjects with hypertension. The use of ambulatory blood pressure (BP) measures to guide longitudinal treatment is new in clinical research and practice, despite its superiority to predict target organ involvement in subjects with hypertension. Previous data have shown that 24-hour systolic BP (SBP) was a better predictor of progression of microvascular disease of the brain, compared to BP measured in the clinic setting. This study therefore evaluated 2 target levels of 24-hour average SBP on WMH progression and cognitive and mobility function.

INFINTY was a prospective, randomized, blinded endpoints vascular and functional outcomes trial comparing a target of 24-hour SBP of 130 mmHg (intensive BP-group) vs. 145 mmHg (standard BP-group) in 199 patients aged ≥75 years with systolic hypertension, MRI-evidence of WMH and normal baseline cognitive and mobility function. Eligible participants were followed for 3 years post-randomization with sequential MRIs and functional evaluations. Exclusion criteria were unstable CV conditions or chronic neurologic conditions, such as stroke, Parkinson’s disease or dementia, or clinically impaired gait. Systolic hypertension, confirmed by 24-hour ambulatory SBP, was defined as 150-170 mmHg if taking ≥1 antihypertensive drugs or >170 mmHg on 0-1 antihypertensive drug.

Primary and secondary outcomes were changes from baseline in mobility and cognitive function and accrual of WMH volume as evidence for damage to brain white matter, respectively, following 3 years in the intensive vs. standard ambulatory BP conditions.

Main results

• 3 Years post-randomization, 24-hour BPs were 131/65 mmHg and 146/74 mmHg in the intensive-BP and standard-BP groups, respectively.
• In the intensive-BP group, WMH was reduced by 40% (0.29% vs. 0.48%, P=0.03), compared to the standard-BP group.
• Reduced cerebrovascular damage was not significantly linked to differences in mobility decline.
• In the intensive-BP group, only 1 out of 6 cognitive parameters (sequential reaction time) was significantly improved (-23±16 ms vs. 33±15 ms) compared to the standard-BP group.
• Significantly fewer major CV events (MI, stroke, HHF, and arrythmias [4 vs. 17; RR: 0.24, 95%CI: 0.08-0.68, P<0.01]) were seen in the intensive-BP group, compared to the standard-BP group.
• Falls and syncope were not significantly different between the two treatment groups.

Conclusion

INFINITY, the first hypertension study using ambulatory BP to guide treatment in patients with vascular disease of the brain, showed a significant reduction in accrual of subcortical white matter disease in older people receiving more intensive antihypertensive therapy. White dampened the enthusiasm based on the effect on brain damage, because the primary endpoint for function was not met: there was no difference in mobility and only 1 out of 6 tested cognitive parameters was significantly improved. Thus, he concluded that lowering BP to dampen the growth of brain damage worked, but this did not positively affect function. It is likely that three years was too short to observe functional improvement between treatment groups. He added that the data are in line with what was seen in SPRINT: we should not keep elderly at high BP.

Discussion

The discussant Eileen Handberg was enthusiastic; she said that maybe sometimes we are too focused on the primary outcome. The study shows that it is doable to get the BP down in these patients, and it demonstrated a mechanism. These are important signals.

During the discussion, it was asked whether a similar effect may be anticipated in younger patients. The current data can probably not be extrapolated to younger patients, because for example in 50-year old hypertensive, small vessel disease is undetectable. Indeed, in the recently published SPRINT-MIND, with a population of about 15 years younger than in INFINITY, no large effect on cognition was seen; no effect on dementia, but only on mild cognitive decline.

- Our coverage of ACC.19 is based on the information provided during the congress -