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SPRINT: Aggressive BP target confers lower risk for death, CV events

ORLANDO, Fla. — A systolic BP target of less than 120 mm Hg was associated with lower rates of death and CV events compared with a target of less than 140 mm Hg, according to results from the SPRINT trial.

Top-line results of the large NIH-funded trial were made public in September. Researchers presented full results at the American Heart Association Scientific Sessions and the data were published in The New England Journal of Medicine.

Appropriate BP targets for reduction of CVD and mortality have been a controversial topic in recent years, with multiple guidelines coming to different conclusions.

Paul K. Whelton, MB, MD, MSc

Paul K. Whelton

Paul K. Whelton, MB, MD, MSc, from the department of epidemiology at Tulane University School of Public Health and Tropical Medicine, said investigators for the SPRINT trial randomly assigned 9,361 people with systolic BP ≥ 130 mm Hg and high CV risk but no diabetes to an intensive treatment regimen with target systolic BP < 120 mm Hg or a standard treatment regimen with target systolic BP < 140 mm Hg.

The primary outcome was a composite of MI, other ACS, stroke, HF and death from CV causes. Another outcome of interest was all-cause mortality.

“SPRINT was designed to examine the effect of more intensive [BP] reduction than we currently are recommended to use in patients on antihypertensive therapy,” Whelton said during a press conference. “Overall, we deem that the benefits are outweighing the potential for risk.”

Effect on BP

At 1 year, mean systolic BP was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group, Whelton said. During the study period, the intensive-treatment group was prescribed an average of 2.8 hypertensive medications compared with 1.8 for the standard-treatment group. All prescribed medications were guideline-directed therapies commonly used for BP reduction, he said.

According to Whelton, SPRINT was stopped after a median follow-up of 3.26 years because the researchers observed a much lower rate of the primary outcome in the intensive-treatment group: 1.65% per year vs. 2.19% per year; HR = 0.75; 95% CI, 0.64-0.89. The curves began to separate at 1 year and widened over time, Whelton said.

In addition, he said, all-cause mortality was lower in the intensive-treatment group than in the standard-treatment group (HR = 0.73; 95% CI, 0.6-0.9). According to the researchers, the curves for mortality separated at 2 years, and death from CV causes was 43% lower in the intensive-treatment group (HR = 0.57; 95% CI, 0.38-0.85).

The number needed to treat to prevent one primary outcome event was 61. The number needed to treat to prevent one death was 90 and to prevent one CV death was 172, according to results presented.

The results were consistent across all subgroups. Treating death as a competing risk in a Fine-Gray model did not change the results for the primary outcome (HR = 0.76; 95% CI, 0.64-0.9).

HF impacted greatly

Among components of the primary outcome, the one that favored the intensive-treatment group the most was HF (HR = 0.62; 95% CI, 0.45-0.84), according to the researchers. MI and stroke favored the intensive-treatment group to a lesser extent (HR for MI = 0.83; 95% CI, 0.64-1.09; HR for stroke = 0.89; 95% CI, 0.63-1.25), and there was no difference in ACS (HR = 1; 95% CI, 0.64-1.55). Patients with prior stroke were excluded from SPRINT, so that might explain why the stroke results were not as dramatically different as those for HF, Whelton said.

“There was a very powerful effect on those with HF,” Whelton said. “HF itself was very carefully specified. It’s not just edema; almost all were hospitalized and seriously sick with HF.”

The overall rate of serious adverse events was similar in both groups (intensive-treatment group, 38.3%; standard-treatment group, 37.1%; HR = 1.04; P = .25).

However, Whelton said, serious adverse events related to hypotension, syncope, electrolyte abnormalities and acute kidney injury or failure were higher in the intensive-treatment group compared with the standard-treatment group.

There was no difference between the groups in rate of injurious falls, a common adverse event in people with hypotension. Nor was there a difference in bradycardia.

The intensive-treatment group was more likely to have a serious adverse event definitively related to the intervention (4.7% vs. 2.5%; HR = 1.88; P < .001).

Adverse event pattern and magnitude was similar for those aged 75 years or older and the overall cohort, Whelton and colleagues found.

In patients with chronic kidney disease at baseline, there was no difference between the groups in a decrease ≥ 50% in estimated glomerular filtration rate or onset of end-stage renal disease, according to the researchers. Among those without CKD at baseline, the intensive-treatment group was more likely to have a decrease in eGFR by at least 30% to < 60 ml/min/1.73m2 (1.21% per year vs. 0.35% per year; HR = 3.49; 95% CI, 2.44-5.1).

“In the group without kidney disease, we set a lower threshold and did see a signal,” Whelton said. “It was a little more common to see slight reductions [in eGFR]. We don’t exactly know what that means. It’s something we need to follow up on.”˗ by Erik Swain

References:

Whelton PK, et al. Late-Breaking Clinical Trials 5. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.

The SPRINT Research Group. N Engl J Med. 2015;doi:10.1056/NEJMoa1511939.

Disclosure: The study was funded by the NIH. Whelton reports receiving nonfinancial support from Arbor Pharmaceuticals and Takeda Pharmaceuticals. See the full study for a list of the other researchers’ relevant financial disclosures.

ORLANDO, Fla. — A systolic BP target of less than 120 mm Hg was associated with lower rates of death and CV events compared with a target of less than 140 mm Hg, according to results from the SPRINT trial.

Top-line results of the large NIH-funded trial were made public in September. Researchers presented full results at the American Heart Association Scientific Sessions and the data were published in The New England Journal of Medicine.

Appropriate BP targets for reduction of CVD and mortality have been a controversial topic in recent years, with multiple guidelines coming to different conclusions.

Paul K. Whelton, MB, MD, MSc

Paul K. Whelton

Paul K. Whelton, MB, MD, MSc, from the department of epidemiology at Tulane University School of Public Health and Tropical Medicine, said investigators for the SPRINT trial randomly assigned 9,361 people with systolic BP ≥ 130 mm Hg and high CV risk but no diabetes to an intensive treatment regimen with target systolic BP < 120 mm Hg or a standard treatment regimen with target systolic BP < 140 mm Hg.

The primary outcome was a composite of MI, other ACS, stroke, HF and death from CV causes. Another outcome of interest was all-cause mortality.

“SPRINT was designed to examine the effect of more intensive [BP] reduction than we currently are recommended to use in patients on antihypertensive therapy,” Whelton said during a press conference. “Overall, we deem that the benefits are outweighing the potential for risk.”

Effect on BP

At 1 year, mean systolic BP was 121.4 mm Hg in the intensive-treatment group and 136.2 mm Hg in the standard-treatment group, Whelton said. During the study period, the intensive-treatment group was prescribed an average of 2.8 hypertensive medications compared with 1.8 for the standard-treatment group. All prescribed medications were guideline-directed therapies commonly used for BP reduction, he said.

According to Whelton, SPRINT was stopped after a median follow-up of 3.26 years because the researchers observed a much lower rate of the primary outcome in the intensive-treatment group: 1.65% per year vs. 2.19% per year; HR = 0.75; 95% CI, 0.64-0.89. The curves began to separate at 1 year and widened over time, Whelton said.

In addition, he said, all-cause mortality was lower in the intensive-treatment group than in the standard-treatment group (HR = 0.73; 95% CI, 0.6-0.9). According to the researchers, the curves for mortality separated at 2 years, and death from CV causes was 43% lower in the intensive-treatment group (HR = 0.57; 95% CI, 0.38-0.85).

The number needed to treat to prevent one primary outcome event was 61. The number needed to treat to prevent one death was 90 and to prevent one CV death was 172, according to results presented.

The results were consistent across all subgroups. Treating death as a competing risk in a Fine-Gray model did not change the results for the primary outcome (HR = 0.76; 95% CI, 0.64-0.9).

HF impacted greatly

Among components of the primary outcome, the one that favored the intensive-treatment group the most was HF (HR = 0.62; 95% CI, 0.45-0.84), according to the researchers. MI and stroke favored the intensive-treatment group to a lesser extent (HR for MI = 0.83; 95% CI, 0.64-1.09; HR for stroke = 0.89; 95% CI, 0.63-1.25), and there was no difference in ACS (HR = 1; 95% CI, 0.64-1.55). Patients with prior stroke were excluded from SPRINT, so that might explain why the stroke results were not as dramatically different as those for HF, Whelton said.

“There was a very powerful effect on those with HF,” Whelton said. “HF itself was very carefully specified. It’s not just edema; almost all were hospitalized and seriously sick with HF.”

The overall rate of serious adverse events was similar in both groups (intensive-treatment group, 38.3%; standard-treatment group, 37.1%; HR = 1.04; P = .25).

However, Whelton said, serious adverse events related to hypotension, syncope, electrolyte abnormalities and acute kidney injury or failure were higher in the intensive-treatment group compared with the standard-treatment group.

There was no difference between the groups in rate of injurious falls, a common adverse event in people with hypotension. Nor was there a difference in bradycardia.

The intensive-treatment group was more likely to have a serious adverse event definitively related to the intervention (4.7% vs. 2.5%; HR = 1.88; P < .001).

Adverse event pattern and magnitude was similar for those aged 75 years or older and the overall cohort, Whelton and colleagues found.

In patients with chronic kidney disease at baseline, there was no difference between the groups in a decrease ≥ 50% in estimated glomerular filtration rate or onset of end-stage renal disease, according to the researchers. Among those without CKD at baseline, the intensive-treatment group was more likely to have a decrease in eGFR by at least 30% to < 60 ml/min/1.73m2 (1.21% per year vs. 0.35% per year; HR = 3.49; 95% CI, 2.44-5.1).

“In the group without kidney disease, we set a lower threshold and did see a signal,” Whelton said. “It was a little more common to see slight reductions [in eGFR]. We don’t exactly know what that means. It’s something we need to follow up on.”˗ by Erik Swain

References:

Whelton PK, et al. Late-Breaking Clinical Trials 5. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.

The SPRINT Research Group. N Engl J Med. 2015;doi:10.1056/NEJMoa1511939.

Disclosure: The study was funded by the NIH. Whelton reports receiving nonfinancial support from Arbor Pharmaceuticals and Takeda Pharmaceuticals. See the full study for a list of the other researchers’ relevant financial disclosures.

    Perspective
    Lawrence Fine, MD

    Lawrence Fine

    When you start a clinical trial, you always have equipoise. We didn’t really know whether we would find a difference, whether there would be benefit in the more intensive arm or whether the standard arm would do better.

    Guideline committees like those of the AHA and the American College of Cardiology are probably going to look very carefully at the SPRINT study and other information and decide how that impacts their recommendations. We will have to wait until that happens to see what changes might be made. There undoubtedly will be some changes that impact practice, but we don’t know how precisely. The guideline process is underway and is making progress on a large number of questions.

    • Lawrence Fine, MD
    • Branch Chief, Clinical Applications and Prevention Branch
      Division of Cardiovascular Sciences, NHLBI

    Disclosures: Fine reports being employed by the NHLBI.

    Perspective
    Gregg C. Fonarow, MD

    Gregg C. Fonarow

    HF in every antihypertensive trial has had oversized benefit, where we see 40% to 70% reductions in new-onset HF with antihypertensive therapies. This study shows it continues down to systolic BP levels around 120 mm Hg. Eighty percent of patients who present with HF have hypertension. It is critically important for nationwide efforts to prevent HF that we apply these SPRINT results. If they are put into clinical practice, there is going to be a marked reduction in HF, the leading cause of hospitalization in older adults. These are critically important data. Approximately 870,000 patients per year develop new-onset HF. Half of them will not be alive within 5 years of diagnosis. HF prevention is absolutely key, and here is an essential strategy that has now been identified to lower that risk.

    Hypertension is a leading determinant of developing HF because of the longstanding impact on the myocardium, both for how well it squeezes and relaxes. Hypertension is the leading population-attributable risk to HF. Directly lowering BP translates to less of that adverse effect on the myocardium and makes the patient at substantially lower risk for developing HF.

    The key challenge will be how quickly we can get the guidelines updated, how quickly we can get new performance measures and how quickly we can develop new initiatives that will drive this into practice. This is why the AHA and the American Medical Association have partnered around a new Target: BP initiative to help accelerate all of the existing knowledge and guidelines, to do a better job, to commit to getting more patients to goal. As the guidelines get updated, these findings will be integrated into the program and drive this data into actual clinical practice so the whole population of individuals at risk can benefit. We can make tremendous progress at reducing death and disability due to CVD by applying these results.

    This is a phenomenal breakthrough. These are data we have been waiting for 20-plus years to have the answer. And now we have the answer that a lower BP target is absolutely essential and safe and has benefits that outweigh risk. Now the implementation science becomes so critical. Can we be practice-changing? Nobody wants to be here 10 years from now seeing the needle having moved so little, and still having huge gaps where patients are not aware, are not being treated and are not at goal.

    • Gregg C. Fonarow, MD, FACC, FAHA
    • Professor of Medicine
      Director, Ahmanson-UCLA Cardiomyopathy Center
      Co-Director, UCLA Preventative Cardiology Program
      Co-Chief, UCLA Division of Cardiology
      Eliot Corday Chair in Cardiovascular Medicine and Science
      UCLA Medical Center and David Geffen School of Medicine at UCLA
      Spokesperson, American Heart Association

    Disclosures: Fonarow reports no relevant financial disclosures.

    Perspective

    This is the most important BP study in the last 40 years. I thought if the study was done, it would have results like this. I didn’t think the study would ever be done. In time, especially after we see a change in guidelines giving new direction on systolic BP goals, this is going to change practice. I think we’ll see it adopted by both practitioners and patients.

    • Daniel W. Jones, MD
    • Director, Clinical and Population Science
      Sanderson Chair in Obesity, Metabolic Diseases and Nutrition
      Mississippi Center for Obesity Research
      University of Mississippi Medical Center
      Jackson, Mississippi

    Disclosures: Jones reports no relevant financial disclosures.

    Perspective
    Kim Allan Williams, MD

    Kim Allan Williams

    We’ve had, especially in individuals such as African Americans with multiple risk factors, observational data suggesting that there’s an increase in events that begins when you get above systolic BP 115 mm Hg. And yet, treatment to reduce BP has obvious financial costs and costs in terms of side effects, particularly with concerns about inducing renal failure and or losing balance and falling with lower pressures. In trying to harmonize all those issues, the committee that was compiled for the Eighth Joint National Committee (JNC 8) came to the conclusion that for older people, one should have a higher target. This was not endorsed by any societies or the NHLBI. 

    Hence, the SPRINT study really does give us a more information about which patients may benefit from a lower target, without increasing mortality. But we have to apply it selectively to the type of patients included in the study. We look forward to further information on the impact of lower pressures on cognitive function.  

    Based on the Seventh Joint National Committee (JNC 7) recommendations, we always aim for the lowest possible pressure we could get without pharmacological therapy, when appropriate, and then adding drugs when individuals were above 130 mm Hg systolic BP, particularly when they had high-risk conditions such as impaired renal function or African American ethnicity. These were similar to recommendations from the International Society of Hypertension in Blacks in 2010 and the European Society of Cardiology guidelines of 2012, which talked about matching the BP target to the risk of the patient. But there are still some gaps, such as prior stroke, for example. The SPRINT trial give us more guidance than we’ve had, but we will still need to address some at-risk populations with future studies.

    • Kim Allan Williams, MD
    • Cardiology Today Editorial Board Member
      James B. Herrick Professor
      Chief, Division of Cardiology
      Rush University Medical Center, Chicago
      President, American College of Cardiology

    Disclosures: Williams reports no relevant financial disclosures.

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