Intensive SPRINT Blood Pressure Reduction Would Prevent 100,000 Deaths per Year
If every individual in the United States who met the criteria for the Systolic Blood Pressure Intervention Trial (SPRINT) were treated to the more intensive blood-pressure target of 120 mmHg, more than 100,000 lives could be saved each year. Those are the conclusions of a new analysis from the National Health and Nutrition Examination Survey (NHANES), a representative survey of the US population, presented today at the American Heart Association’s Council on Hypertension 2016 Scientific Sessions in Orlando, FL.
Speaking with TCTMD, lead investigator Holly Kramer, MD (Loyola Medical Center, Maywood, IL), said that concerns have been raised about lowering blood pressure to the targets outlined in SPRINT. “There is definitely a lot of inertia for physicians to apply the intensive systolic blood-pressure lowering in their patients who would meet the SPRINT criteria,” said Kramer. “We wanted to see if we were to apply the intensive blood-pressure lowering intervention in the US population—those who meet the SPRINT criteria—how many lives would be saved.
As reported previously, the SPRINT trial included 9,361 patients aged 50 years and older with a systolic blood pressure of 130 to 180 mm Hg and increased cardiovascular risk. Half of these patients were randomized to a systolic blood-pressure target of 120 mm Hg, while the other half were randomized to the standard target of 140 mm Hg. Patients with diabetes and stroke were excluded from the trial.
SPRINT was stopped early for clinical benefit and showed that treating patients to the lower systolic blood-pressure target of 120 mm Hg resulted in a significant 25% reduction in the primary composite endpoint of MI, ACS, stroke, heart failure, or cardiovascular death. In addition, there was a statistically significant 27% reduction in all-cause mortality with intensive blood-pressure lowering compared with standard treatment (1.03% vs 1.40% per year; HR 0.73; 95% CI 0.60-0.90).
In this latest analysis, the researchers focused solely on all-cause mortality as NHANES is linked with the national death index, allowing them to assess the benefit of intensive treatment if applied to eligible US patients.
Overall, Kramer et al identified 18.1 million adults who met the SPRINT criteria, and these patients had an annual mortality rate of 2.2%. Based on their calculations, the reduction in all-cause mortality achieved with intensive blood-pressure lowering would translate into 107,453 deaths prevented each year. For adults with systolic blood pressure of 145 mm Hg or greater, the annual mortality rate was 2.5%. Again, based on the mortality reduction observed in SPRINT, intensive blood-pressure lowering to 120 mm Hg would prevent 60,908 deaths in this group each year.
“Now you are going to have an increase in adverse events,” said Kramer. “SPRINT showed a statistically significant increase, albeit small, in electrolyte abnormalities, hypotension, and acute kidney injury. There will be more of these adverse events—about 30,000 events per year—but those events can generally be managed by reducing blood-pressure medications or providing fluid. You can get past it. The fact that you have such a large reduction in mortality, to many patients, it would be worth the headache of taking another medication. It would be worth it to have blood drawn to monitor for electrolyte abnormalities.”
Kramer said intensive blood-pressure lowering does require greater physician effort, noting that some patients will require closer monitoring, but stressed it is worthwhile. “The fact that we can extend lives and patients can live a better life longer, it means to me we should be trying to implement the SPRINT intervention clinically,” she said.
While physicians have raised concerns about an increased risk of falls in elderly patients treated to low systolic blood pressure, Kramer noted, SPRINT did not show the concern was warranted. Additional analyses from the trial have shown a clinical benefit in frail and elderly patients. As one of the site investigators in SPRINT, she said, they treated very elderly patients—some in their late 80s, early 90s—and though she was nervous about lowering blood-pressure to 120 mm Hg in these individuals, such patients fared well.
SPRINT Study Protocol Needs Further Clarity
Speaking with TCTMD, Sripal Bangalore, MD (NYU Langone Medical Center, New York, NY), who was not involved in SPRINT or the latest analysis, said that before the full impact of SPRINT on outcomes such as all-cause mortality and other adverse events is known, there is a need for more clarity about the trial.
“There’s been some controversy, particularly in that we’re not entirely clear how blood pressure was measured in SPRINT,” he said. “There have been differing opinions about whether the medical personnel were in the room when the blood pressure was measured.”
In fact, in a letter to the editor after the trial was published in the New England Journal of Medicine in 2015, Brendan McCormick, MD, Swapnil Hiremath, MD, and Marcel Ruzicka, MD (University of Ottawa, Canada), first questioned the blood-pressure measurement technique. In their letter, the group noted SPRINT used a programmed automated oscillometric blood-pressure meter that required approximately 8 minutes of quiet rest, with measurements designed to be taken when medical personnel were outside the room.
“An unattended blood-pressure measurement would have a large impact on how we would interpret the results [of SPRINT],” Bangalore told TCTMD, noting other clinical trials measured blood pressure with the physician or nurse in the room. “If it was unattended, the 121 mm Hg achieved in the intensive arm, many would argue that translates into 130 or 135 mm Hg in office blood pressures, which is what many of us have been doing when reducing blood pressure to less than 140 mm Hg. In other words, SPRINT wouldn’t provide any new information.”
Franz Messerli, MD (Icahn School of Medicine at Mount Sinai, New York, NY), agreed with that assessment, telling TCTMD by email that the “clinical implications of the SPRINT study and its usefulness for the practicing physician, and hypertension guidelines, stand and fall with the methodology of blood pressure measurements.” Like Bangalore, he said unwitnessed measurements can be at least 10 mm Hg lower than routine clinic measurements.
For this reason, Bangalore thinks the reduction in mortality—more than 100,000 lives saved—if SPRINT was applied to all US patients is a “bit of stretch.” This looks great, he said, but “we need to pause as there are many questions that still need to be answered.” Messerli made a similar point, calling the 100,000 figure is “inappropriate hype.” He believes that the AHA message of lowering systolic blood pressure to 120 mm Hg in all hypertensive patients would expose many of them to considerably more harm than good.
In a separate analysis published online September 14, 2016, in JAMA Cardiology, Ilana Richman, MD (Palo Alto Veterans Affairs Health Care System, CA), and colleagues analyzed the economic aspects of SPRINT, concluding that standard treatment yielded 9.6 quality-adjusted life-years (QALYs) and accrued $155,261 in lifetime costs. Comparatively, intensive blood-pressure lowering yielded 10.5 QALYs and accrued $176,584 in costs. This translated into $23,777 per QALY gained with intensive management, meaning the treatment is cost-effective by typical thresholds.
Kramer H, Bress A, Beddhu S, et al. Intensive systolic blood pressure lowering will prevent over 100,000 deaths annually. Presented at American Heart Association Council on Hypertension Scientific Sessions 2016. September 14, 2016. Orlando, FL.
Richman IB, Fairley M, Jørgensen ME, et al. Cost-effectiveness of intensive blood pressure management. JAMA Cardiology. 2016;Epub ahead of print.
- Kramer, Richman, and Bangalore report no conflicts of interest.