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Lower BP target reduces CV risk, all-cause mortality in older adults
Adults aged at least 75 years experienced lower CV risk and all-cause mortality when their systolic BP was treated to a target of less than 120 mm Hg, according to new data from the SPRINT trial.
“The many complications of hypertension — HF, MI, stroke — are the very things associated with disability and loss of independence in older people. That is what makes this study so important,” Jeff D. Williamson, MD, MHS, of the Wake Forest School of Medicine, said in an interview with Cardiology Today.
Jeff D. Williamson
Geriatric subgroup
Williamson and colleagues randomly assigned patients with hypertension to a systolic BP target of less than 120 mm Hg or less than 140 mm Hg and conducted an analysis of participants aged 75 years or older (n = 2,636; mean age, 80 years; 37.9% women). The main results were presented in November.
The primary endpoint was a composite of MI, ACS not resulting in MI, stroke, acute decompensated HF and CV mortality. Secondary endpoints included all-cause mortality, renal disease and a composite of the primary outcome and all-cause mortality. For patients with chronic kidney disease at baseline, a renal disease endpoint was assessed. Median follow-up was 3.14 years.
The results were presented at the American Geriatrics Society 2016 Annual Scientific Meeting and published in JAMA.
The rate of frailty at randomization was 33.4% in the intensive-treatment group and 28.4% in the standard-treatment group; the overall prevalence of slow gait speed (<0.8 m/s) was 28.1%. During follow-up, BP differences by treatment group were smaller in frail participants (P = .01), but gait speed had no effect on treatment group differences in BP.
One hundred two patients in the intensive-treatment group experienced the primary endpoint compared with 148 patients in the standard-treatment group (HR = 0.66; 95% CI, 0.51-0.85), Williamson and colleagues found. There were 73 deaths in the intensive-treatment group compared with 107 in the standard-treatment group (HR = 0.67; 95% CI, 0.49-0.91).
The rate of serious adverse events was similar in both groups (intensive-treatment group, 48.4%; standard-treatment group, 48.3%; HR = 0.99; 95% CI, 0.89-1.11). For certain adverse events, however, the rate was numerically higher in the treatment group: hypotension (2.4% vs. 1.4%; HR = 1.71; 95% CI, 0.97-3.09), syncope (3% vs. 2.4%; HR = 1.23; 95% CI, 0.76-2), electrolyte abnormalities (4% vs. 2.7%; HR = 1.51; 95% CI, 0.99-2.33) and acute kidney injury or renal failure (5.5% vs. 4%; HR = 1.41; 95% CI, 0.98-2.04).
Williamson, however, said that while there is a risk for kidney injury, it is (small?) relative to the benefits. “These adverse events pale in comparison to the complications of hypertension,” he said.
Clinical effect
Williamson told Cardiology Today that the biggest takeaway from the findings was that treating systolic BP below 130 mm Hg in older people is safe even for those who are frail, but the results do not apply to seniors with HF or those living in nursing homes, and it is still important to individualize treatment because some people tolerate the intensive therapy well, while others do not.
“The present results have substantial implications for the future of intensive BP therapy in older adults because of this condition’s high prevalence, the high absolute risk for [CVD] complications from elevated BP, and the devastating consequences of such events on the independent function of older people,” the researchers wrote.
Aram V. Chobanian, MD, of the Boston University School of Medicine, wrote in an editorial that, “Achieving the systolic BP goal of less than 130 mm Hg may be challenging for clinicians because doing so could require use of additional medications, more careful monitoring, and more frequent clinic visits.”
However, Chobanian wrote, these findings “cannot be discounted, and unless unexpected adverse effects are observed on further examination of the trial data, then major changes in treatment goals for patients 75 years or older with hypertension will be warranted.” – by Tracey Romero
References:
Williamson J, et al. Falls prevention in older adults. Presented at: American Geriatrics Society 2016 Annual Scientific Meeting; May 19-21, 2016; Nashville, Tenn.
Chobanian AV. JAMA. 2016;doi:10.1001/jama.2016.7070.
Williamson JD, et al. JAMA. 2016;doi:10.1001/jama.2016.7050.
Disclosure: Williamson reports receiving nonfinancial support from Takeda Pharmaceuticals and Arbor Pharmaceuticals during the study. Please see full study for a list of the other researchers’ relevant financial disclosures. Chobanian reports no relevant financial disclosures.
Perspective
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The results of the recent preplanned, appropriately powered subgroup analysis of the SPRINT trial in persons aged 75 years or older is helpful in expanding our understanding of BP control in older people.
The results in this subgroup of participants aged 75 years or older showed impressive reductions in CVD events and total mortality with intensive as compared with standard therapy and serve to provide evidence to quell the fear of many practitioners that lower is not better in the elderly, as the panel convened for the Eighth Joint National Committee implied.
In the United States, you have a 90% chance of being hypertensive if you live to age 80 and were normotensive at age 55. More than 75% of individuals aged 75 years or older have hypertension, and the lifetime risk for developing hypertension exceeds 90%. In addition, hypertension remains a major cause of CHD, congestive HF, stroke and renal failure in older patients.
The SPRINT is different from other studies in older people. The Systolic Hypertension in the Elderly Program (SHEP) demonstrated that lowering systolic BP to less than 150 mm Hg in patients 60 years or older with isolated systolic hypertension was beneficial in reducing stroke. The Hypertension in the Very Elderly (HYVET) Trial, involving patients 80 years or older with hypertension, was closer to SPRINT than SHEP in that the diastolic BP was much higher in these very old people, averaging 82 mmHg at baseline. The achieved systolic BP in this trial was around 145 mm Hg, yet there was, like SPRINT, a tremendous reduction in risk for HF and mortality. In fact, in recent reviews all trials in people over age 65 demonstrate a benefit with reductions of systolic BP down to the low 140s. SPRINT is the only trial that demonstrates additional risk reduction, especially for HF and CV death, when BP is reduced to levels in the low 120s.
Before clinicians totally embrace the results for use in practice, a few issues need to addressed. First the method of measuring BP in the trial, while pristine and correct, is not what occurs in clinical practice and hence, the values in clinical practice are 5 mm Hg to 7 mm Hg higher than achieved in the trial. Thus, while the mean BP achieved in this subgroup in the trial was 123 mm Hg, in office practice, that would roughly be 128 mm Hg to 130 mm Hg. Additionally, the cohort recruited was closer to the HYVET than the SHEP trial, in that the lowest mean diastolic BP achieved in the intensive group was 62 mm Hg; hence, no one had a baseline diastolic pressure below 60 or even in the mid-60s. Thus, while there was no evidence of a J curve in this cohort, the data from this trial cannot be extrapolated to anyone who didn’t meet the entry criteria.
There were no people with diabetes in this trial so the results are not directly applicable to those with diabetes. However, three recent meta-analyses and a follow-up study of the ACCORD trial demonstrate that the intensive-BP group that achieved a BP around 120 mm Hg did have fewer CVD events and strokes in the usual glycemic-control group, as there was an interaction between glycemic control groups. Therefore, there is equipoise for BP control across groups regardless of diabetes presence. Nevertheless, the exclusion criteria of SPRINT preclude the results being extrapolated to individuals with diabetes, HF, prior stroke, or postural decreases in BP. Furthermore, only ambulatory, community-based persons were recruited into the study, so the results may not be relevant to frail individuals and others restricted to their homes or to institutions.
The safety price paid for this more aggressive reduction in BP was an increased incidence of hypotension, syncope, or acute changes in renal function, but these appeared to be more than offset by the large benefits of treatment. However, patients recruited in clinical trials are often not representative of the broader population that would have a wider range of concomitant diseases and medications than study participants.
Based on these findings, clinicians should not be afraid to further lower BP among those over 75 years of age with criteria that fit the SPRINT cohort. Those with very wide pulse pressures or diastolic values at or near 60 mm Hg prior to treatment should not be aggressively lowered. Also, other common-sense approaches to issues of orthostatic hypotension of associated disease etiologies yielding such responses should preclude more aggressive management of BP in such individuals.
The key message is to know that thiazide-type diuretics and calcium antagonists are the most efficacious for lowering BP in older adults, and that monotherapy in almost all cases is insufficient to control BP to levels in the range of 125 mm Hg to 130 mm Hg. So this range should be the goal for older individuals who meet the SPRINT criteria.