Because of the frequency with which medication non-adherence occurs in this population, the term apparent treatment resistant hypertension has appeared in the literature with increasing frequency. If addition of spironolactone is being considered, it should be remembered that spironolactone will interfere with the tests that are ordered as part of the evaluation for hyperaldosteronism, a secondary form of HTN. If a secondary HTN workup is planned, initiation of therapy with spironolactone should be delayed until that workup is complete. Drugs other than spironolactone may be more appropriate for the RHT patient who has a history of hyperkalemia, has significantly impaired kidney function, sexual dysfunction, or has developed either mastodynia or gynecomastia upon exposure to this drug in the past. A number of different drugs are available for the RHT patient whose blood pressure remains uncontrolled. As this is a Reviewed, New-replaced recommendation, the Work Group systematically reviewed the evidence related to this recommendation. The following three SRs or meta-analyses [150-152] and two RCTs [154,155] identified in the evidence review conducted as part of this guideline update were evaluated in detail. The strengths and weakness of the data in this literature are summarized above. The benefits of taking once-daily spironolactone outweighs the potential for AEs when the RHT patient is chosen carefully and monitored closely as therapy is initiated. Epidemiologically, patients who meet the criteria for RHT are at increased risk for fatal and non-fatal cardiovascular events. Yet there are no outcome data to guide the clinical practitioner on which fourth-line drug will have the greatest effect on cardiovascular events. Furthermore, little is known about the impact of age, gender, and comorbidities like diabetes, CKD, CAD, or prior stroke on the response to specific medications in patients with RHT. VIII. 