Antihypertensive treatment for low-risk patients with mild hypertension does not appear to be beneficial
EBM Focus - Volume 13, Issue 39
Reference: JAMA Intern Med 2018 Oct 29 (level 2 [mid-level] evidence)
How can clinicians keep up with hypertension management when guidelines across the world vary and thresholds and stages of hypertension are constantly changing? The recent American Heart Association/ American College of Cardiology (AHA/ACC) hypertension guideline lowered the threshold for labeling patients as hypertensive and initiating therapy, raising concerns. The American College of Physicians and the American Academy of Family Physicians declined to endorse these recommendations. Of particular concern is the recommendation by the AHA/ACC to treat to a blood pressure of < 130/80 in all comers once the decision to initiate pharmacotherapy is made, considering they only evaluated outcomes in patients at moderate to high risk of cardiovascular disease (CVD). Low outcome event rates in a low-risk population would necessitate such a large number of participants in order to adequately power a prospective trial that, to date, no trial data evaluating the benefit of antihypertensive treatment in a low-risk population exist. To explore this question, a group of investigators designed a cohort study to examine the benefits and harms of treating patients with mild hypertension and low risk of CVD.
This retrospective longitudinal cohort study extracted individual data from an electronic health record database in England from 1998-2015. 19,143 patients aged 18-74 years with mild hypertension (defined as 3 consecutive blood pressure readings of 140/90-159/99 mm Hg) treated with antihypertensives were compared to 19,143 untreated propensity-matched controls. Patients with CVD (defined as the composite of fatal and nonfatal stroke, myocardial infarction [MI], acute coronary syndrome [ACS], and heart failure [HF]), risk factors for CVD, or previous treatment with antihypertensives were excluded. Mean follow-up was 5.8 years. In order to reduce some of the bias inherent in a nonrandomized study, a negative control (cancer) was used to validate propensity matching for this study.
No difference was found between the groups for overall mortality, with rates of 4.49% (95% CI 4.20%-4.80%) in treated patients and 4.08% (95% CI 3.80%-4.37%) in untreated controls. There were also no significant associations between treatment and time to death, CVD (hazard ratio 1.09; 95% CI 0.96-1.25), stroke, MI, heart failure, or non-MI ACS. These results are consistent with a Cochrane review from 2012 looking at subgroups of patients from 4 randomized trials, which also found no mortality or cardiovascular benefit in treating mild hypertension (Cochrane Database Syst Rev 2012 Aug 15;(8):CD006742), although that systematic review did not include the subsequent SPRINT trial (N Engl J Med. 2015 Nov 26). However, treatment was associated with a number of harms (at 10 years) including hypotension (number needed to harm [NNH]=41), electrolyte abnormalities (NNH=111), acute kidney injury (NNH=91), and syncope (NNH=35). While this is not a randomized trial, it does reflect real world outcomes where the strict rules of a formal trial are not in place, and the duration of follow up is longer than the SPRINT trial.
Focus Point: Stop doing the blood pressure limbo. We should not be continually lowering the bar for blood pressure targets for low risk patients in the absence of stronger evidence of benefit, especially in light of this new data demonstrating potential harms associated with the blood pressure treatment targets in low-risk populations recommended by the AHA/ACC.