From Wiki Journal Club
Jump to: navigation, search
Zhang W, et al. "Trial of intensive blood-pressure control in older patients with hypertension". The New England Journal of Medicine. 2021. 385(14):1268-1279.

Clinical Question

In elderly patients with hypertension, dose intensive systolic blood pressure control (110-<130 mmHg) reduce the instance of cardiovascular event?

Bottom Line

Among a group of 60-80 year old Han Chinese adults without prior hemorrhagic or large ischemic stroke, intensive BP control (SBP 110 to <130 mm Hg) was associated with fewer CVD events when compared to conventional BP control (SBP 130 to <150 mm Hg).

Major Points

Higher blood pressure is a continuous risk factor for CV events, including CHD, stroke, and heart failure. While the ACCORD BP (2010) and SPS3-BP (2013) did not show a benefit for intensive lowering of SBP below a 140 mm Hg target in diabetes and those with prior stroke, SPRINT 2015 found intensive BP lowering to reduce CV events and all-cause mortality among adults CVD risk factors. Largely because of SPRINT's findings, the ACC/AHA-led 2017 hypertension guidelines lowered hypertension's threshold from 140/90 mm Hg to 130/80 mm Hg, recommending initiation of antihypertensives in the 130/80 to 139/89 mm Hg range among those with CVD risk factors, and at 140/90 mm Hg for all others. (See Guidelines section below for additional details.) SPRINT was a diverse, high-quality RCT and provided strong evidence for more intensive hypertension treatment thresholds. The ACC/AHA 2017 guidelines were somewhat controversial, with the ACP/AAFP releasing guidelines in 2017 recommending initiation of antihypertensive medications primarily among those with SBP above a 150 mm Hg SBP range, with only a weak recommendation for 140 or 130 mm Hg thresholds.[1] The ACP/AAFP recommendations highlight the lack of multiple trials demonstrating a benefit from intensive BP control. There was a need for replication of SPRINT.

Published in 2021, the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial randomized 8,511 Han Chinese adults (i.e., excluding Chinese minority groups) with hypertension to intensive BP control (SBP 110 to <130 mm Hg) or standard BP control (SBP 130 to <150 mm Hg) at 42 centers in China. Those with prior large ASCVD stroke or hemorrhagic stroke were excluded. Unlike SPRINT, there was no requirement for additional CVD risk factors to be enrolled. With a median follow-up of 3.34 years, there was a statistically significant reduction in stroke, ACS (MI or UA hospitalization), ADHF, coronary revascularization, HF, or CV mortality with intensive BP control (3.5% vs. 4.6%; HR 0.74; 95% CI 0.60-0.92; P=0.007). Adverse events were similar between arms. Though there was a lower event rate in STEP than SPRINT, the point estimate for reduction in endpoints was nearly identical to that of SPRINT. Unlike SPRINT's mortality benefit, there was no difference in mortality between arms in STEP. The mortality rate was lower in STEP. Taken together, STEP and SPRINT help to shore up the evidence base for lower targets of BP control among adults.


2017 ACC AHA AAPA ABC ACPM AGS APhA ASH ASPC NMA PCNA Hypertension (2017, adapted)[2] Note: This guideline was published 4 years prior to STEP

  • New definitions for BP ranges: Normal BP is <120/<80, elevated BP is 120-129/<80, stage 1 HTN is 130-139/80-89, and stage 2 HTN is ≥140/≥90 mm Hg
  • Use antihypertensive medications if prior clinical CVD or 10-year ASCVD risk score is ≥10% and BP is ≥130/≥80 mm Hg (COR I, LOE A for SBP and C-EO for DBP)
  • Use antihypertensive medications if no prior clinical CVD and 10-year ASCVD risk score is <10% and BP is ≥140/≥90 mm Hg (COR I, LOE C-LD)
  • First line agents include thiazide diuretics (chlorthalidone preferred), CCBs, and ACE-inhibitors or ARBs (COR I, LOE A)
    • Initial use of two first-line agents from different classes is recommended if stage 2 HTN and average BP is >20/10 mm Hg above target (COR I, LOE C-EO)
    • Initial use of one first-line agent is reasonable if stage 1 HTN and BP goal <130/80 mm Hg (COR IIa, LOE C-EO)
  • Specific population recommendations:
    • Among black adults without CKD or HF, initial treatment should be with a thiazide or CCB (COR I, LOE B-R)
      • Black adults are likely to need ≥2 agents to achieve BP <130/90 mm Hg (COR I, LOE C-LD)
    • Age ≥65
      • Community-dwelling - Treat SBP to <130 mm Hg (COR I, LOE A)
      • High burden of comorbidities and limited life expectancy - Consider patient preference and use a team-based approach to decide intensity of BP lowering and choice of antihypertensives (COR IIa, LOE C-EO)
    • Stable CAD - Treat to BP goal <130/80 mm Hg (COR I, LOE B-R for SBP and C-EO for DBP)
      • Preferred medications are proven beta-blockers, ACE-inhibitors, or ARBs for compelling reasons (prior MI, stable angina), with addition of other medications including dihydropyridine-CCBs (especially for angina; COR I, LOE B-NR), thiazide diuretics, and/or mineralocorticoid receptor antagonists as needed (COR I, LE B-R for SBP and C-ED for DBP)
    • Prior stroke or TIA- Restart or initiate antihypertensives within a few days of the index event (COR I, LOE A for restarting; COR I, LOE B-R for initiation if BP >140/90); a BP goal <130/80 may be reasonable (COR IIb, LOE B-R)
      • If no history of HTN and BP <140/90, the usefulness of antihypertensives is not well-established (COR IIb, LOE C-LD)
      • If lacunar infarct, a target SBP <130 mm Hg may be reasonable (COR IIb, LOE B-R)
      • Preferred agents are thiazide diuretic, ACE-inhibitor or ARB, or combination of thiazide+ACE-inhibitor (COR I, LOE A)
    • CKD - Treat to BP goal <130/80 mm Hg (COR I, LOE B-R for SBP and C-EO for DBP)
      • If CKD stage ≥III or stage I or II with albuminuria ≥300 mg/day or ≥300 mg/g alb:creat, treating with ACE-inhibitor (COR IIa, LOE B-R) or ARB (COR IIb, LOE C-EO) is reasonable to slow kidney disease progression
      • If kidney transplantation, it's reasonable to target BP <130/80 mm Hg (COR IIa, LOE B-NR for SBP and C-EO for DBP), with calcium antagonist as choice to improve GFR and kidney survival (COR IIa, LOE B-R)
    • DM - Treat to BP goal <130/80 mm Hg (COR I, LOE B-R for SBP and C-EO for DBP)
      • Any first-line medication is effective (COR I, LOE A), but consider ACE-inhibitors and ARBs if albuminuria (COR IIb, LOE B-NR)
    • PAD - Treat similarly to patients with HTN and no PAD (COR I, LOE B-NR)
    • Increased risk for development of HF - Treat to <130/80 (COR I, LOE B-R for SBP and C-EO for DBP)
    • HFrEF - Treat with goal-directed medical therapy (e.g., proven beta-blockers, ACE-inhibitors or ARBs, etc.) targeting BP <130/80 mm Hg (COR I, LOE C-EO)
      • Do not use non-dihydropyridine CCBs (COR III, LOE B)
    • HFpEF and volume overload - Use diuretics to control HTN (COR I, LOE C-EO)
      • If persistent HTN and managed volume overload, use ACE-inhibitors or ARBs and beta-blockers to attain an SBP <130 mm Hg (COR I, LOE C-LD)


  • Multicenter, prospective, randomized, controlled trial
  • N=8511
    • Intensive (n=4243)
    • Standard (n=4268)
  • Setting: 42 clinical centers in China
  • Enrollment: January 2017 - December 2017
  • Median follow-up: 3.34 years
  • Analysis: Intention-to-treat
  • Primary outcome: Stroke, ACS (MI or UA hospitalization), ADHF, coronary revascularization, HF, or CV mortality


Inclusion Criteria

  • Systolic BP 140-190 mm Hg in 3 screening visits or current use of BP medication.
  • Age 60-80 years
  • Han Chinese persons

Exclusion Criteria

  • Systolic BP ≥190 mm Hg or diastolic BP ≤60 mm Hg
  • Secondary hypertension
  • History of large ASCVD-related ischemic stroke or hemorrhagic stroke (lacunar infarct and TIA were not exclusion criteria)
  • Hospitalization for MI in prior 6 months
  • PCI or CABG in the last 12 months or planned for in the next 12 months
  • Heart failure class III-IV or recent heart failure hospitalization
  • Sustained AF or ventricular arrhythmias that affect measurement of BP (WJC ed note: automated oscillometric devices are generally not designed for use with such arrhythmias)
  • Severe valve disease
  • Hypertrophic cardiomyopathy, dilated cardiomyopathy, rheumatic heart disease, congenital heart disease
  • Uncontrolled diabetes (fasting >200, HbA1c >8%)
  • One of these severe diseases: Liver, kidney, "somatic" (eg, cancer), cognitive impairment, "mental disorder"

Baseline Characteristics

From the intensive group.

  • Demographics: Age 66 years, male sex 76%
  • Anthropometrics: BMI 25.5 kg/m2, BP 146/83 mm Hg
    • SBP range (mm Hg): ≤138 33%, 139-151 33%, ≥152 34%
  • Labs: Fasting glucose 6.2 mmol/L; tchol 4.9 mmol/L, HDL 1.3 mmol/L, LDL 2.7 mmol/L
  • eGFR <60 ml/min/1.27 m2: 2.4%
  • PMH: DM 19%, HLD 38%, CVD 6%
  • Framingham risk score ≥15%: 65%


  • Randomized to intensive (110 to <130 mm Hg) or standard (130 to 150 mm Hg) target SBP
  • Medications included olmesartan, amlodipine, and HCTZ
  • Blood pressure was monitored at home weekly, with in-clinic monitoring every 1-3 months


Comparisons are intensive treatment vs. standard treatment.

Primary Outcomes

Stroke, ACS (MI or UA hospitalization), ADHF, coronary revascularization, HF, or CV mortality
3.5% vs. 4.6% (HR 0.74; 95% CI 0.60-0.92; P=0.007)
Components of the primary outcome are secondary outcomes, but are presented here for simplicity.
Stroke: 1.1% vs. 1.7% (HR 0.67; 95% CI 0.47-0.97)
ACS (MI or UA hospitalization): 1.3% vs. 1.9% (HR 0.67; 95% CI 0.47-0.97)
ADHF: 0.1% vs. 1.3% (HR 0.27; 95% CI 0.08-0.98)
Coronary revascularization: 0.5% vs. 0.7% (HR 0.69; 95% CI 0.4-1.18)
AF: 0.6% vs. 0.6% (HR 0.96; 95% CI 0.55-1.68)
CVD mortality: 0.4% vs. 0.6% (HR 0.72; 95% CI 0.39-1.32)

Secondary Outcomes

All-cause mortality
1.6% vs. 1.5% (HR 1.11; 95% CI 0.78-1.56)
Major adverse cardiac events
Components of the primary outcome except stroke.
2.4% vs. 3.2% (HR 0.72; 95% CI 0.56-0.93)

Additional Outcomes

Renal outcomes
≥50% reduction in eGFR among patients with prevalent CKD: 1.0% vs. 1.0% (RR 1.01; 95% CI 0.06-16.09; P=0.99)
≥30% reduction to <60 ml/min/1.73 m2 in patients without : 1.3% vs. 1.5% (RR 0.90; 95% CI 0.63-1.30; P=0.58)
Creatinine >1.5 mg/dl elevation in men: 3.6% vs. 3.6% (RR 0.99; 95% CI 0.71-1.30; P=0.95)
Creatinine >1.3 mg/dl elevation in women: 1.9% vs. 2.1% (RR 0.91; 95% CI 0.60-1.38; P=0.67)
eGFR <30 ml/min/1.73 m2: 0.3% vs. 0.3% (RR 0.93; 95% CI 0.42-2.04; P=0.85)

Subgroup Analysis

From Figure S7 of the supplementary appendix, page 29.[3] There were no obvious differences between prespecified subgroups.

Adverse Events

SBP <110 mm Hg or DBP <50 mm Hg
3.4% vs. 2.6% (HR 1.31; 95% CI 1.02-1.68; P=0.03)
1.1% vs. 1.1% (HR 0.92; 95% CI 0.61-1.39; P=0.70)
Syncope (a serious adverse event)
0.1% vs. <0.1% (HR 3.02; 95% CI 0.61-14.97; P=0.18)
Fracture (a serious adverse event)
0.4% vs. 0.4% (HR 0.79; 95% CI 0.4-1.56; P=0.50)


  • Homogenous population of Han Chinese, somewhat limiting generalizability. However, these findings are consistent with those of SPRINT, which was a diverse US-based RCT.
  • Framingham Risk Score may overestimate CVD risk in Chinese adults.


Chinese Academy of Medical Science and other grants

Further Reading

  1. Qaseem A et al. Pharmacologic Treatment of Hypertension in Adults Aged 60 Years or Older to Higher Versus Lower Blood Pressure Targets: A Clinical Practice Guideline From the American College of Physicians and the American Academy of Family Physicians. Ann Intern Med 2017. 166:430-437.
  2. Whelton PK et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017. :.
  3. Supplementary appendix