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Original Investigation
December 2018

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

Author Affiliations
  • 1Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom
  • 2School of Pharmacy, University of Birmingham, Birmingham, United Kingdom
  • 3Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
JAMA Intern Med. 2018;178(12):1626-1634. doi:10.1001/jamainternmed.2018.4684
Key Points

Question  Is antihypertensive treatment associated with lower risk for mortality and cardiovascular disease in patients with mild hypertension?

Findings  In this study of electronic health records of 38 286 low-risk patients with mild hypertension, no evidence of an association was found between exposure to antihypertensive treatment and mortality or cardiovascular disease. There was evidence that treatment may be associated with an increased risk of adverse events, such as hypotension, syncope, and acute kidney injury.

Meaning  The findings suggest that physicians should be cautious when initiating treatment in low-risk patients with mild hypertension, particularly because such an approach may affect millions of individuals with little evidence of benefit.


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

Objective  To examine whether antihypertensive treatment is associated with a low risk of mortality and cardiovascular disease (CVD) in low-risk patients with mild hypertension.

Design, Setting, and Participants  In this longitudinal cohort study, data were extracted from the Clinical Practice Research Datalink, from January 1, 1998, through September 30, 2015, for patients aged 18 to 74 years who had mild hypertension (untreated blood pressure of 140/90-159/99 mm Hg) and no previous treatment. Anyone with a history of 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 for 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-neighbor method.

Main Outcomes and Measures  The rates of mortality, CVD, and adverse events among patients prescribed antihypertensive treatment at baseline, compared with those who were not prescribed such treatment, using Cox proportional hazards regression.

Results  A total of 19 143 treated patients (mean [SD] age, 54.7 [11.8] years; 10 705 [55.9%] women; 10 629 [55.5%] white) were matched to 19 143 similar untreated patients (mean [SD] age, 54.9 [12.2] years; 10 631 [55.5%] female; 10 654 [55.7%] white). During a median follow-up period of 5.8 years (interquartile range, 2.6-9.0 years), no evidence of an association was found between antihypertensive treatment and mortality (hazard ratio [HR], 1.02; 95% CI, 0.88-1.17) or between antihypertensive treatment and CVD (HR, 1.09; 95% CI, 0.95-1.25). 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 prespecified analysis found no evidence to support guideline recommendations that encourage initiation of treatment in patients with low-risk mild hypertension. There was evidence of an increased risk of adverse events, which suggests that physicians should exercise caution when following guidelines that generalize findings from trials conducted in high-risk individuals to those at lower risk.

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    3 Comments for this article
    Reminds me of Sir George Pickering and his common sense
    Trevor Hart, LAW post grad, Zoology | RETIRED ex Management Consultancy, Pharmaceuticals
    I remember that over 40 years ago Sir George Pickering had stated that 150/100 was a starting point for pharmaceutical intervention. Oxford have been at the forefront ever since including the ISIS studies. Home of the famous Cochrane Library. It is good to see that Oxford maintains its unbiased views. Even with my pharmaceutical industry background I believe that this is a very important study into "the routine use of drugs following set guidelines v common sense" Every patient is an individual.
    Many in treatment group may not have been treated
    Larry Whitted, Pest Management | Self-employed
    Unfortunately, we do not know how many of the people in the "treatment" group filled their prescription and took the medication. In many cases we may be comparing people who did not take medication with other people who received a prescription but also did not take medication or took it for only a short time.
    Older patients might be at even higher risk
    Fatih Tufan, Assoc. Prof. | Private Practice
    Although the authors did not find a difference in adverse effects of antihypertensive treatment between people older or younger than 65 years old, this does not mean older and younger people have similar risks associated with treatment. One of the reasons is that people over the age of 74 were not included in this study. Secondly, people over 64 years old commonly have comorbidities and they are usually excluded from such trials. Lastly, even if older and younger people experience similar rates of adverse events related to treatment, older people are generally more seriously injured from these events. For instance, falls result in fractures and intracranial bleeding more commonly in older people. Thus, more caution should be taken before initiating antihypertensive treatment to an older person with mild hypertension.