Antihypertensive treatment does not result in reduced mortality or CV events in low-risk patients with mild hypertension

Benefits and Harms of Antihypertensive Treatment in Low-Risk Patients With Mild Hypertension

Literature - Sheppard JP, Stevens S, Stevens R et al. - JAMA Intern Med 2018: published online ahead of print

Introduction and methods

High-risk patients with a blood pressure (BP) of ≥130/80 mmHg and all individuals with a BP of ≥140/90 mmHg regardless of risk should be treated with pharmacologic therapy, according to current guidelines from the American College of Cardiology/American Heart Association (ACC/AHA) [1]; however, clinical evidence to support initiation of pharmacologic treatment in people with low cardiovascular (CV) risk and mild hypertension is lacking [2-7]. Therefore this study examined the association between antihypertensive treatment prescriptions and all-cause mortality, CVD, and adverse events in low-risk patients with mild hypertension by using routine electronic health records.

This retrospective, longitudinal cohort study included 19,143 individuals (aged >25 years) with mild hypertension and low CV risk (excluding those with a history of CVD, left ventricular hypertrophy, atrial fibrillation, diabetes, chronic kidney disease, or family history of premature heart disease) who were matched to 19,143 similar untreated patients, and used linked data from the Clinical Practice Research Datalink (CPRD), Basic Inpatient Hospital Episode Statistics and Office for National Statistics mortality register from January 1, 1998 through September 30, 2015. Median follow up period was 5.8 years (IQR: 2.6-9.0).

Mild hypertension was defined as three consecutive BP readings of 140/90-159/99 mmHg within 12 months and CV risk as QRISK2 score. All antihypertensive treatments prescribed in the 12 months between hypertension diagnosis and the index date were accounted.

The primary outcome was all-cause mortality and secondary outcomes included death or hospitalization from major CV events (myocardial infarction [MI], non-MI acute coronary syndrome [ACS], stroke, heart failure, or death from CVD), death or hospitalization from stroke, MI, non-MI ACS, heart failure, or cancer, and hospitalization with suspected adverse effects to medication (hypotension, syncope, bradycardia, electrolyte abnormalities, falls, or acute kidney injury).

Main results

  • Overall mortality was 4.08% (95%CI: 3.80-4.37) in the control group and 4.49% (95%CI: 4.20-4.80) in the treatment group, with a risk difference of 0.41% (95%CI: 0.02-0.85). No significant difference was observed between groups in time to death (HR: 1.02, 95%CI: 0.88-1.17, P=0.81).
  • No significant associations were found between antihypertensive treatment and CVD (HR: 1.09, 95%CI: 0.95-1.25, P=0.23), stroke (HR: 0.97, 95%CI: 0.78-1.21, P=0.76), MI (HR: 1.00, 95%CI: 0.80-1.25, P=0.98), heart failure (HR: 1.34, 95%CI: 0.96-1.21, P=1.86), or non-MI acute ACS (HR: 1.19, 95%CI: 0.74-1.91, P=0.47).
  • A significant association was seen between baseline antihypertensive treatment exposure and time to adverse events, including hypotension (HR: 1.69, 95%CI: 1.30-2.20, P<.001), syncope (HR: 1.28, 95%CI: 1.10-1.50, P=0.002), electrolyte abnormalities (HR: 1.72, 95%CI: 1.12-2.65, P=.01), and acute kidney injury (HR: 1.37, 95%CI: 1.00-1.88, P=0.048), but not with falls (HR: 1.15, 95%CI: 0.63-2.09, P=0.65) or bradycardia (HR: 1.11, 95%CI: 0.75-1.65, P=0.59).
  • At 5 and 10 years, numbers needed to harm for treatment prescription were 580 (95%CI: 253-3610) and 111 (95%CI: 49-687), respectively, for electrolyte abnormalities, 135 (95%CI: 77-385) and 35 (95%CI: 20-100) for syncope, 291 (95%CI: 127-501) and 41 (95%CI: 24-93) for hypotension, and 467 (95%CI: 198-75225) and 91 (95%CI: 39-14552) for acute kidney disease.
  • Baseline treatment exposure was not associated with the negative control (time to cancer: HR: 1.01, 95%CI: 0.92-1.11, P=0.79).


This observational study provided no evidence regarding the association between antihypertensive treatment and reduced mortality or rates of CVD among low-risk patients with mild hypertension, suggesting that caution should be exercised when considering antihypertensive treatment in this population.


1. Whelton PK, Carey RM, Aronow WS, et al. 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: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol.2017; 2017.published Online First:2017/11/18. doi:10.1016/j.jacc.2017.11.006

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Find this article online at JAMA

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