Benefits and harms of antihypertensive treatment for low-risk patients with mild hypertension

James P. Sheppard, Sarah Stevens, Richard Stevens, Una Martin, Jonathan Mant, Richard Hobbs, Richard J. McManus

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)


Importance: Evidence to support initiation of pharmacological treatment in patients with low-risk mild hypertension is inconclusive, with previous trials underpowered to demonstrate benefit. Clinical guidelines across the world are contradictory.

Objective: Use electronic health records to examine whether treatment is safe and effective at reducing the risk of mortality and cardiovascular disease in low-risk mild hypertensives.

Design: Longitudinal cohort study.

Setting: Linked electronic health records from primary and secondary care in England.

Participants: Data were extracted from patients in the Clinical Practice Research Datalink, between 1998-2015, aged 18-74 years, with mild hypertension (untreated blood pressure between 140/90-159/99mmHg) and no previous treatment. Anyone with a history of cardiovascular disease (CVD) or CVD risk factors was excluded. Patients exited the cohort if follow-up records became unavailable or they experienced an outcome of interest.

Exposures: Prescription of antihypertensive medication. Propensity scores predicting likelihood of treatment were constructed using a logistic regression model. Individuals treated within 12 months of diagnosis were matched to untreated patients by propensity score using the nearest neighbour method.

Main Outcome(s) and Measure(s): The rate of mortality, cardiovascular disease and adverse events in patients prescribed antihypertensive treatment at baseline, compared to those not, using Cox regression.

Results: A total of 19,143 treated patients (mean age 54.7±11.8 years, 55.9% female) were matched to 19,143 similar untreated patients. During a median follow-up period of 5.8 years, no evidence of an association was found between antihypertensive treatment and mortality (HR 1.02, 95%CI 0.88-1.17), CVD (HR 1.09, 95%CI 0.95-1.25) or any individual cardiovascular disease endpoints. Treatment was associated with an increased risk of adverse events including hypotension (HR 1.69, 95%CI 1.30-2.20; number needed to harm at 10 years [NNH10], 41), syncope (HR 1.28, 95%CI 1.10-1.50, NNH10=35), electrolyte abnormalities (HR 1.72, 95%CI 1.12-2.65, NNH10=111) and acute kidney injury (HR 1.37, 95%CI 1.00-1.88, NNH10=91)

Conclusions and Relevance: This pre-specified analysis found no evidence to support guideline recommendations which encourage initiation of treatment in patients with low-risk mild hypertension (140/90-159/99mmHg). There was evidence of an increased risk of adverse events and physicians should exercise caution when following guidelines which generalise findings from trials conducted in high-risk subjects to younger populations and those at lower risk.
Original languageEnglish
Pages (from-to)1626-1634
Number of pages9
JournalJAMA internal medicine
Issue number12
Early online date29 Oct 2018
Publication statusPublished - Dec 2018


  • primary prevention
  • cardiovascular diseases
  • adverse effects
  • electronic helath records
  • propensity score analysis
  • primary care


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