For mild hypertension in low-risk adults, harms of drug therapy outweigh benefits

Prior to publication of the controversial 2017 ACC/AHA clinical practice guideline, stage 1 or "mild" hypertension was defined as a systolic blood pressure of 140-159 mm Hg and/or diastolic blood pressure of 90-99 mm Hg. Although guidelines have recommended that persons with mild hypertension receive anti-hypertensive drug therapy if lifestyle modification does not lower blood pressure below 140/90, a Cochrane review found that such therapy did not reduce cardiovascular disease (CVD) events, stroke, or mortality compared to placebo. A 2015 meta-analysis that included high-risk persons (patients with diabetes and/or who had received prior antihypertensive treatment) suggested that drug therapy for mild hypertension may prevent CVD events, but others have argued that this analysis mixed apples with oranges and did not establish benefits for adults at low CVD risk.

A retrospective cohort study recently published in JAMA Internal Medicine sought to clarify the benefits and harms of drug therapy in low-risk adults with mild hypertension using data from 40,000 patients in an electronic health records database in the United Kingdom. The authors compared the outcomes of persons aged 18 to 74 with mild hypertension who were prescribed anti-hypertensive medications within 12 months of diagnosis to those in similar untreated persons. Persons with a history of CVD, left ventricular hypertrophy, atrial fibrillation, diabetes, chronic kidney disease, or a family history of premature heart disease were excluded from the study.

After a median follow-up duration of 5.8 years, there were no differences between the groups in all-cause mortality, stroke, myocardial infarction, acute coronary syndrome, or heart failure. However, the treated group had an increased risk of hypotension (number needed to harm = 41 at 10 years), syncope (NNH = 35), electrolyte abnormalities (NNH = 111), and acute kidney injury (NNH = 91).

Although ideally the findings from this observational study should be confirmed in a randomized, controlled trial, it is unlikely that a trial will ever be performed due to the large number of participants that would be needed in order to provide enough statistical power to detect a difference in mortality or rare CVD events in this population. In the meantime, the best available evidence suggests that the harms of drug therapy outweigh benefits for low-risk adults with a systolic blood pressure of 140-159 mm Hg and/or diastolic blood pressure of 90-99 mm Hg (recently redefined by the ACC/AHA as stage 2 hypertension). In these patients, family physicians and other primary care clinicians should emphasize nonpharmacologic management strategies such as a diet with a high intake of vegetables, fruits, and whole grains; moderating excessive sodium intake and alcohol consumption; and at least 150 minutes per week of moderate-intensity aerobic physical activity, as recommended in the latest Physical Activity Guidelines for Americans.

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A slightly different version of this post first appeared on the AFP Community Blog.