SPRINT Makes Case for Even Lower BP Target in Many Hypertensive Patients


ORLANDO, FL—Treating systolic blood pressure to a target below 120 mm Hg vs the standard target of less than 140 mm Hg reduces the rate of adverse clinical outcomes in nondiabetic patients who are at high risk for cardiovascular events, the SPRINT trial shows. That comes at the cost, however, of an increase in some adverse events, including hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure.

Take Home:  SPRINT Makes Case for Even Lower BP Target in Many Hypertensive Patients

The findings, presented by Paul Whelton of Tulane University (New Orleans, LA) at the American Heart Association 2015 Scientific Sessions and published simultaneously online in the New England Journal of Medicine, add to the ongoing debate over the most appropriate blood pressure targets for hypertensive patients and seem to support goals lower than what is currently recommended.

“Overall, we interpret these results to show that the benefits of the more intensive blood pressure lowering exceeded the potential for harm,” Whelton said.

Daniel Jones, MD, of the University of Mississippi Medical Center (Jackson, MS), who delivered a commentary after Whelton’s presentation, told TCTMD that the absolute risk difference between the treatment arms in the annual rate of composite cardiovascular events—about 0.5%—is clinically meaningful, making it worthwhile to attempt to get blood pressure down to the lower target.

“It would be a lot of lives saved,” he said. “There is nothing else on the horizon that we can do that will get us this much bang for the buck for preventing cardiovascular disease.”

But the push for lower targets presents practical challenges, co-author Jackson Wright Jr., MD, PhD, of University Hospitals Case Medical Center (Cleveland, OH), and colleagues say in the paper, noting that control to a higher goal of less than 140/90 mm Hg is achieved in only about half of the general hypertensive population in the United States.

SPRINT did not include patients with severe hypertension and those in the more-intensive treatment group required 1 additional antihypertensive agent, on average, they add. Even then, more than half of patients in that group still had a systolic pressure above 120 mm Hg.

“These observations suggest that achieving a systolic blood pressure goal of less than 120 mm Hg in the overall population of patients with hypertension would be more demanding and time-consuming for both providers and patients than achieving a goal of 140 mm Hg, and would necessitate increased medication costs and clinic visits,” Wright and colleagues say.

Nevertheless, in an editorial accompanying the study, Vlado Perkovic, MBBS, PhD, and Anthony Rodgers, MBChB, PhD, of the University of Sydney in Australia say, “SPRINT redefines blood pressure target goals and challenges us to improve blood pressure management.”

More Intensive Control Improves Outcomes, But With Some Risk

SPRINT, conducted at 102 sites in the United States, included 9,361 patients ages 50 years and older (mean age 68 years) with a systolic blood pressure of 130 to 180 mm Hg (mean 139.7 mm Hg) and an increased cardiovascular risk. Patients with diabetes or a history of stroke were excluded. The average number of antihypertensives used at baseline was 1.8 in both the intensive and standard treatment groups.

Treatment algorithms were similar to those used in the ACCORD trial, with no mandated approach in terms of specific medications to achieve the assigned blood pressure targets. Patients attended monthly visits for the first 3 months and then every 3 months for the remainder of the study. Lifestyle modification was encouraged.

At 1 year, mean systolic pressure was 121.4 mm Hg in the intensive group and 136.2 mm Hg in the standard group, with similar values seen throughout the entire follow-up period. The average numbers of antihypertensives used were 2.8 and 1.8, respectively.

The trial was stopped early on August 20, 2015, after a median follow-up of 3.26 years had accrued, when interim analyses showed a reduced risk of the primary composite outcome (MI, ACS other than MI, stroke, acute decompensated heart failure, or cardiovascular death) with intensive treatment. In results reported at AHA, there was a 25% relative risk reduction and a 0.5% absolute risk reduction in the composite outcome with the lower blood pressure target, with similar significant or nonsignificant trends for each of the individual components, with the exception of ACS (table).

 Table. Annual Rates of Adverse Clinical Outcomes


The number needed to treat (NNT) to prevent 1 event was 61 for composite outcomes and 172 for cardiovascular death.

All-cause mortality also was lower in patients treated to the lower target (1.03% vs 1.40% per year; HR 0.73; 95% CI 0.60-0.90), with an NNT of 90. The separation was apparent by about 2 years.

The primary outcome and all-cause mortality findings were consistent across patient subgroups, including in patients ages 75 and older.

The researchers also evaluated renal outcomes in patients with or without chronic kidney disease at baseline. In the former group, the intensity of blood pressure-lowering did not affect the occurrence of a composite outcome defined by a decrease in estimated glomerular filtration rate (eGFR) of at least 50% or the development of end-stage renal disease. In patients with chronic kidney disease, however, intensive treatment was associated with a greater risk of having an eGFR decline of at least 30% to a level below 60 mL/min/1.73 m2 (1.21% vs 0.35% per year; HR 3.49; 95% CI 2.44-5.10).

Although the overall rate of serious adverse events did not differ between the intensive and standard groups (38.3% vs 37.1%; P = .25), patients treated to the lower target were more likely to develop hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure and to have a serious event classified as possibly or definitely related to the intervention (4.7% vs 2.5%; P < .001). Rates of injurious falls and bradycardia were similar in both trial arms.

The researchers say that the increase in adverse renal outcomes “may be related to a reversible intrarenal hemodyamic effect of the greater reduction in blood pressure and greater use of diuretics, [ACE] inhibitors, and angiotensin-receptor blockers in the intensive-treatment group.”

They add that “there is no evidence of substantial permanent kidney injury associated with the lower systolic blood-pressure goal; however, the possibility of a long-term adverse renal outcome cannot be excluded. These observations and hypotheses need to be explored further in analyses that incorporate more clinical outcomes and longer follow-up.”

In their editorial, Perkovic and Rodgers, say “these higher rates appear unlikely to outweigh the benefits overall.”

Support for Lower Targets, But What About ACCORD?

The optimal target for blood pressure control has been the subject of much debate, particularly in recent years. Observational studies have shown that cardiovascular risk rises along with systolic blood pressure at readings above 115 mm Hg, but randomized trials have only shown a benefit of reducing systolic pressure to less than 150 mm Hg in the general hypertensive population.

“SPRINT now provides evidence of benefits for an even lower systolic blood pressure target than that currently recommended in most patients with hypertension,” Wright and colleagues argue.

They address the inevitable comparison between SPRINT and ACCORD, which tested the same treatment targets. ACCORD failed to show a benefit of lowering systolic blood pressure to less than 120 mm Hg, but there are several differences between the 2 trials, the authors point out: ACCORD only included diabetics, had half the sample size, enrolled a younger cohort on average, and also involved randomized comparisons of standard vs intensive glycemic and lipid treatment targets.

“Thus, the difference in results between the trials could be due to differences in study design, treatment interactions, or the play of chance,” they say. “An inherent difference in the cardiovascular benefits of systolic blood pressure lowering between the population with diabetes and the population without diabetes seems unlikely but cannot be ruled out.”

Clinical Challenges

Editorialists Perkovic and Rodgers state that “SPRINT strongly supports pharmacotherapy decisions based on absolute risk levels, in a similar way to current recommendations for lipid lowering. For people at high cardiovascular risk, a systolic goal of less than 120 mm Hg is appropriate.”

But they acknowledge that “substantial effort and resources are required: initial combination therapy was the norm in SPRINT, with monthly visits until blood pressure was at the target level. Even with intensive lifestyle modification and medical therapy, blood pressure will remain above target in many patients, which suggests the need for population-level initiatives (eg, reduced sodium content in food), new therapies, and multifactorial intervention.”

In an accompanying perspective, Aram V. Chobanian, MD, of Boston University Medical Center (Boston, MA), also supports lower targets, but notes that more aggressive goals will increase the already substantial percentage of hypertensive patients who have uncontrolled blood pressure in the United States.

More intensive treatment presents challenges, he says, noting the average use of nearly 3 antihypertensive medications in patients treated to a goal of less than 120 mm Hg. “Currently, many clinicians and their patients with hypertension are reluctant to go beyond 2 different antihypertensive drugs, and adherence to therapy suffers with increasing complexity of clinical regimens.

“Achieving stricter goals,” he continues, “will probably require more careful titration of medications, greater use of combination drug preparations, more monitoring for adverse effects, and more frequent patient visits than currently occur, even though hypertension is already the most common diagnosis present in persons attending outpatient visits in the United States.”


Sources: 
1. Wright JR Jr, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;Epub ahead of print.
2. Perkovic V, Rodgers A. Redefining blood-pressure targets—SPRINT starts the marathon [editorial]. N Engl J Med. 2015;Epub ahead of print.
3. Chobanian AV. Time to reassess blood-pressure goals [perspective]. N Engl J Med. 2015;Epub ahead of print.

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Disclosures
  • SPRINT was sponsored by the National Heart, Lung, and Blood Institute, with cosponsorship by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Neurological Disorders and Stroke, and the National Institute on Aging.
  • Wright reports receiving grant support from the NIH and some of the medication for the trial from Arbor Pharmaceuticals and Takeda Pharmaceuticals International.
  • Perkovic reports receiving grant support from Baxter, grant support and personal fees from AbbVie, Janssen, and Servier, and personal fees from Astellas, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, and Pfizer.
  • Rodgers reports receiving salary support in part from George Health Enterprises, which has received investment for the development of fixed-dose combination therapy containing statin, aspirin, and blood pressure-lowering medications.
  • Chobanian, Jones, and Whelton report no relevant conflicts of interest.

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