Refractory Hypertension

The term resistant hypertension has been used since the early 1960s to identify patients with difficult-to-treat hypertension, meaning mostly, resistance to pharmacological therapy. In the 5 decades since the term was seemingly first applied, resistant hypertension has been consistently defined as failure to control high blood pressure despite of use of ≥3 antihypertensive agents of different classes, including a diuretic. The 2008 American Heart Association Scientific Statement on resistant hypertension included in its definition patients whose blood pressure had been uncontrolled with 3 medications, but controlled with ≥4 medications. Although the number of medications required to satisfy the definition is arbitrary, the purpose of creating a category of resistant hypertension is to identify patients who, because of the difficulty in controlling their blood pressure, may benefit from special diagnostic and therapeutic considerations, including referral to a hypertension specialist. Having an agreed on definition that can be reliably applied to different cohorts has also facilitated research for this subgroup of patients, including identification of risk factors and underlying mechanisms, assessing outcomes and developing targeted treatments. The term refractory hypertension has often been used interchangeably with resistant hypertension to also refer to patients with difficult-to-treat hypertension. However, based on the number of respective PubMed citations resistant hypertension has been used much more often than refractory hypertension to indicate patients with hypertension resistant to pharmacological treatment. Recently, the term refractory hypertension has been applied to a small group of patients who are truly refractory to treatment, that is, patients who fail to achieve target blood pressure on maximal antihypertensive therapy. Determining whether such patients simply represent extreme cases of resistant hypertension or a novel phenotype in terms of risk and cause has been the focus of initial attempts to define and characterize the phenotype and potentially identify mechanisms of antihypertensive treatment failure. In this brief review, we discuss the emerging data pertaining to this novel phenotype of antihypertensive treatment failure and how it compares and contrasts with resistant hypertension in terms of definition, prevalence, patient characteristics, risk factors, and possible underlying causes. We hope that an early discussion of the 2 phenotypes will serve to distinguish refractory from resistant hypertension and engender further research testing the clinical significance of that distinction. Definition