Lower Blood Pressure Also Better in Elderly Patients With Hypertension, SPRINT Analysis Affirms
Aiming for a systolic blood pressure (BP) goal of 120 mm Hg instead of 140 mm Hg improves clinical outcomes among hypertensive patients 75 years and older, a prespecified secondary analysis of the SPRINT trial shows. Moreover, the findings suggest that the effects are consistent across categories of frailty and gait speed.
“On average, the benefits that resulted from intensive therapy required treatment with one additional antihypertensive drug and additional early visits for dose titration and monitoring,” note researchers led by Jeff Williamson, MD (Wake Forest School of Medicine, Winston-Salem, NC). “Future analyses of SPRINT data may be helpful to better define the burden, costs, and benefits of intensive BP control.”
“However,” they add, “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 cardiovascular disease complications from elevated BP, and the devastating consequences of such events on the independent function of older people.”
The findings were reported online May 19, 2016, ahead of print in the Journal of the American Medical Association to coincide with a presentation at the American Geriatrics Society meeting in Long Beach, CA.
Support for Lower Target
The SPRINT trial included 9,361 patients ages 50 years and older with a systolic BP of 130 to 180 mm Hg and increased cardiovascular risk. Reported in November 2015, the main results showed that treating to a systolic BP goal of less than 120 mm Hg rather than the standard goal of less than 140 mm Hg reduced the risk of the primary composite outcome of MI, ACS other than MI, stroke, acute decompensated heart failure, or cardiovascular death.
The trial was designed to address the impact of more intensive treatment in the subgroup of patients ages 75 years and older. The current analysis included 2,636 patients in this age group (mean age 79.9 years). Overall, 30.9% were considered frail, 55.2% were deemed “less fit,” and 28.1% had a slow gait speed.
During follow-up, mean systolic BP was 123.4 mm Hg with intensive treatment and 134.8 mm Hg with standard treatment. The between-group difference of 11.4 mm Hg was smaller than the difference of 14.8 mm Hg seen in the overall trial population.
Nevertheless, the benefits of treatment to the lower goal were still observed. Through a median follow-up of 3.14 years, more intensive treatment lower the risk of the primary composite outcome (2.59% vs 3.85% per year; HR 0.66; 95% CI 0.51-0.85) and of all-cause mortality (1.78% vs 2.63% per year; HR 0.67; 95% CI 0.49-0.91). The numbers needed to treat were 27 and 41, respectively.
Those findings appeared to be consistent across frailty and gait-speed groups. “However, these analyses should be interpreted cautiously,” the authors note. “The analyses were not prespecified in the trial protocol and were possibly underpowered because SPRINT was designed to consider only the ability to detect a treatment effect in participants aged 75 years or older as a whole.”
Overall, serious adverse events occurred at similar rates in both groups. However, several side effects occurred at numerically—but nonsignificantly—higher rates in the intensive-treatment group, including hypotension, syncope, electrolyte abnormalities, and acute kidney injury. The rate of injurious falls was nonsignificantly lower with treatment to the lower target.
Renal disease outcomes did not differ based on treatment intensity among patients with chronic kidney disease at baseline, but among those without chronic kidney disease, intensive BP lowering increased the risk of patients having a 30% decrease in estimated glomerular filtration rate (eGFR) from baseline to an eGFR less than 60 mL/min/1.73 m2 (1.70% vs 0.58%; HR 3.14; 95% CI 1.66-6.37).
This “may be related to a reversible intrarenal hemodynamic effect of the reduction in BP and more frequent use of diuretics, [ACE] inhibitors, and angiotensin II receptor blockers in the intensive-treatment group,” the authors say. “Although there is no evidence of permanent kidney injury associated with the lower BP goal, the possibility of long-term adverse renal outcomes cannot be excluded and requires longer-term follow-up.”
Reconsideration of BP Goals for Older Patients
Despite evidence from multiple trials of the benefits of lowering BP in elderly patients, “many clinicians still have concerns about reducing [systolic BP] to less than 160 mm Hg in older patients, with their reluctance based on such factors as the very high prevalence of systolic hypertension in their practices, potential adverse effects of medications in older persons, the need to use two or more antihypertensive medications to achieve recommended BP goals, and hesitation of both clinicians and patients to add more drugs to regimens that already may include several other medications for treating concomitant illnesses,” Aram Chobanian, MD (Boston University Medical Center, Boston, MA), writes in an accompanying editorial.
Uncertainty about what to do has also been fueled by conflicting recommendations in various guidelines, he says.
In such an environment, SPRINT “should have a substantial influence on future clinical practice,” he says, adding that the findings of the current analysis “warrant the reconsideration of optimal BP goals for patients in this age group.”
Chobanian calls the safety data “somewhat reassuring” and says the potential increases in some adverse effects with intensive treatment seemed to be outweighed by the benefits. “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,” he points out. “Moreover, the full effect of the trial results may not become apparent until further data become available on the already known adverse events as well as on other important areas such as the influence of treatment on cognitive function.”
Even with that uncertainty, however, Chobanian recommends a stepwise approach to lowering BP starting with a systolic goal of less than 140 mm Hg. If that is well tolerated, he says, then consideration should be given to treating to a target below 130 mm Hg, with a focus on avoiding orthostatic hypotension.
“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,” Chobanian says. “Nevertheless, the important results reported by Williamson et al . . . 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.”
- Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥ 75 years: a randomized clinical trial. JAMA. 2016;Epub ahead of print.
- Chobanian A. SPRINT results in older patients: how low to go? JAMA 2016;Epub ahead of print.
- SPRINT was funded by the National Institutes of Health and supported in part with resources and use of facilities through the US Department of Veterans Affairs. Azilsartan and chlorthalidone (combined with azilsartan) were provided by Takeda.
- Williamson reports receiving nonfinancial support from Takeda Pharmaceuticals and Arbor Pharmaceuticals during the conduct of the study.
- Chobanian reports no relevant conflicts of interest.