What is the clinical evidence from this study?

Study design: RCT. Population: Hypertension with increased cardiovascular disease risk (n=8526). Intervention: Intensive systolic BP control vs. Standard systolic BP control (target <140 mm Hg). Primary outcome: Cardiovascular composite (nonfatal myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or cardiovascular death) (HR 0.67, 95% CI 0.56-0.78).

July 19, 2019Journal of the American Society of NephrologyOpen Access

Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT

Q: What are the key findings of this study?

Intensive systolic BP lowering reduced cardiovascular events (total effect HR 0.67), and causal mediation analysis showed no evidence that early eGFR decline attenuated this benefit (indirect effect HR 0.99).

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Key result

Intensive systolic BP lowering reduced cardiovascular events (total effect HR 0.67), and causal mediation analysis showed no evidence that early eGFR decline attenuated this benefit (indirect effect HR 0.99).

Why the study?

Intensive systolic BP control in SPRINT reduced mortality and cardiovascular events but caused an early eGFR decline, leaving the clinical implications of this decline unclear.

Does intensive systolic BP control reduce cardiovascular events and all-cause mortality without attenuation by early eGFR decline in persons with elevated cardiovascular disease risk?

Population

4270 participants in the intensive group and 4256 participants in the standard arm of SPRINT

Comparison

Intensive systolic BP targeting (<120 mm Hg) vs standard targeting (<140 mm Hg)

Design

Post hoc causal mediation analysis of a randomized trial

Follow-up

27,849 person-years after the 6-month visit

Authors

SBSrinivasan BeddhuSprint (United States)JSJincheng ShenUniversity of Utah ACAlfred K. CheungSprint (United States)

Discussion

Member takes

Implication

Early eGFR decline does not attenuate CV benefits of intensive BP lowering; hypothesis-generating, requires randomized confirmation.

Study Design

Type

RCT (n=8,526)

Blinding

Open-label

Randomization

Randomized

Multicenter

Yes

Structured PICO

Does intensive systolic BP control reduce cardiovascular events and all-cause mortality without attenuation by early eGFR decline in persons with elevated cardiovascular disease risk?

Population

8,526 persons with elevated cardiovascular disease risk (4,270 in intensive group, 4,256 in standard arm)

Intervention

Intensive systolic BP control (targeting <120 mm Hg)

Comparator

Standard systolic BP control (targeting <140 mm Hg)

Outcome

SPRINT primary cardiovascular composite and all-cause mortalitycomposite

Main Result

Effect estimate: HR 0.67 (95% CI 0.56-0.78)

Early eGFR decline associated with intensive systolic BP lowering does not mediate or modify the cardiovascular and mortality benefits of the intervention.

Limitations

Relatively short duration of follow-up in the SPRINT trial.
Post hoc nature of the analyses.
Estimates of direct and indirect effects may be biased due to unmeasured confounding.
Very few hard kidney end point events prevented extending mediation analyses to a kidney event outcome.
Very few participants with stage 4 CKD, limiting extrapolation to those with more advanced kidney disease.
Longer-term follow-up studies with causal modeling are needed to better understand the downstream effects of the early reduction in eGFR

Cite This Study

Beddhu et al. (2019) conducted an RCT in Hypertension with increased cardiovascular disease risk (n=8,526). Intensive systolic BP control vs. Standard systolic BP control (target <140 mm Hg) was evaluated on Cardiovascular composite (nonfatal myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or cardiovascular death) (HR 0.67, 95% CI 0.56-0.78). Intensive systolic BP lowering reduced cardiovascular events (total effect HR 0.67), and causal mediation analysis showed no evidence that early eGFR decline attenuated this benefit (indirect effect HR 0.99).

synapsesocial.com/papers/6a1d507a55e77e71452f172c https://doi.org/10.1681/asn.2018121261

Topics

Hypertension management Women and heart disease Cardiovascular prevention

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July 19, 2019Journal of the American Society of NephrologyOpen Access

Implications of Early Decline in eGFR due to Intensive BP Control for Cardiovascular Outcomes in SPRINT

View Full Paper

Ask AI

Bookmark

Key result

Why the study?

Intensive systolic BP control in SPRINT reduced mortality and cardiovascular events but caused an early eGFR decline, leaving the clinical implications of this decline unclear.

Does intensive systolic BP control reduce cardiovascular events and all-cause mortality without attenuation by early eGFR decline in persons with elevated cardiovascular disease risk?

Population

4270 participants in the intensive group and 4256 participants in the standard arm of SPRINT

Comparison

Intensive systolic BP targeting (<120 mm Hg) vs standard targeting (<140 mm Hg)

Design

Post hoc causal mediation analysis of a randomized trial

Follow-up

27,849 person-years after the 6-month visit

Authors

SBSrinivasan BeddhuSprint (United States)JSJincheng ShenUniversity of Utah ACAlfred K. CheungSprint (United States)

Discussion

Member takes

Implication

Early eGFR decline does not attenuate CV benefits of intensive BP lowering; hypothesis-generating, requires randomized confirmation.

Study Design

Type

RCT (n=8,526)

Blinding

Open-label

Randomization

Randomized

Multicenter

Yes

Structured PICO

Does intensive systolic BP control reduce cardiovascular events and all-cause mortality without attenuation by early eGFR decline in persons with elevated cardiovascular disease risk?

Population

8,526 persons with elevated cardiovascular disease risk (4,270 in intensive group, 4,256 in standard arm)

Intervention

Intensive systolic BP control (targeting <120 mm Hg)

Comparator

Standard systolic BP control (targeting <140 mm Hg)

Outcome

SPRINT primary cardiovascular composite and all-cause mortalitycomposite

Main Result

Effect estimate: HR 0.67 (95% CI 0.56-0.78)

Early eGFR decline associated with intensive systolic BP lowering does not mediate or modify the cardiovascular and mortality benefits of the intervention.

Limitations

Relatively short duration of follow-up in the SPRINT trial.
Post hoc nature of the analyses.
Estimates of direct and indirect effects may be biased due to unmeasured confounding.
Very few hard kidney end point events prevented extending mediation analyses to a kidney event outcome.
Very few participants with stage 4 CKD, limiting extrapolation to those with more advanced kidney disease.
Longer-term follow-up studies with causal modeling are needed to better understand the downstream effects of the early reduction in eGFR

Cite This Study

synapsesocial.com/papers/6a1d507a55e77e71452f172c https://doi.org/10.1681/asn.2018121261

Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

Topics

Hypertension management Women and heart disease Cardiovascular prevention

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