SPRINT Substudy Detects Mortality Signal

–Aggressive blood pressure lowering may sometimes be deadly.

BARCELONA — A new examination of data from the SPRINT trial raises the fear that adopting the aggressive blood pressure target of 120 mm Hg in some hypertensive patients with baseline BP of 160 mm Hg or more may increase the risk of death.

Tzung-Dau Wang, MD, National Taiwan University), the lead researcher, said the result should be interpreted with caution. Nevertheless, “despite of the hypothesis-­generating nature, it seems prudent to recommend targeting a systolic blood pressure of less than 140 mm Hg rather than 120 mm Hg” in similar patients. This latest analysis was reported at a clinical trial update session at the European Society of Cardiology meeting here.

The post-hoc analysis from researchers in Taiwan used patient-level data from SPRINT. A main reason why SPRINT sparked considerable enthusiasm was the finding that patients randomized to the lower 120 mm Hg target had a significant 27% reduction in all cause mortality. But the Taiwanese investigators wondered whether the ideal target would be different for people with different baseline blood pressures and cardiovascular risk scores.

They identified a small subgroup with systolic BP of 160 mm Hg or greater and a 10-year Framingham risk score of 31.3% or lower who had a threefold increase in the risk of death with the lower blood pressure target.

The researchers noted that there were only 480 patients in SPRINT in this subset, representing only 5% of the study population. However, they pointed out that in the general population about one-seventh of hypertensive adults 50 years of age or greater fall into this category.

A very important limitation of the new analysis is that there were only 14 deaths in this subgroup (BP >160, FRS < 31.3%), 10 in the intensive treatment group and four in the standard treatment group.

Wang recommended an individualized approach to blood press control. “Not everybody should have the same target,” he said in a press conference. “There was an intricate interaction between each individual’s baseline blood pressure, their inherent cardiovascular risk, and their degree of blood pressure reduction,” he concluded in his talk. “We have to consider all three of these elements in managing hypertensive patients.”

Sripal Bangalore, MD, of NYU Langone Medical Center said that “although the hypothesis is good (i.e., large reductions in BP can potentiate a J-curve phenomenon), this analysis is highly problematic. It is a tiny subgroup (5%) of the original cohort and the death signal would be nonsignificant if there was just one more death in the standard group.”

Hypertension researcher Michael Weber, MD, of Downstate Medical Center) observed that the findings were based on baseline BP groupings but there were “no details given about actual BPs at baseline and during treatment and likewise no details given about medications being taken at baseline and at the end of drug titration.” He also noted that “in people with very high baseline BPs there is concern about whether they are actually taking their medications at all — this is now recognized as a common problem in clinical trials that can affect the validity of conclusions.”

Finally, Sanjay Kaul, MD, of Cedars Sinai had a similar criticism, pointing to the small number of events and the limitations of subgroup analyses. But, Kaul said, he was “sympathetic with the authors’ premise” but “I cannot justify using a less aggressive BP target on the basis of these results.” On the other hand, it may not matter, since “none of my thoughtful colleagues use a SBP target of <120 routinely for their patients!”


  1. “none of my thoughtful colleagues …”: OK, but what do they use as evidence on which to deploy their thinking?

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