[145-147] Although these trials primarily studied high-risk patients (those with at least one of the following conditions: vascular disease, diabetes, CKD, or diabetic nephropathy), the majority of patients either had a diagnosis of HTN or were being treated with antihypertensive medications.[145-147] As this is a Not Reviewed, Not Changed recommendation, the Work Group did not systematically review evidence related to this recommendation. Based on the evidence reviewed during the 2014 VA/DoD HTN CPG update, the Work Group s confidence in the quality of the evidence was moderate.[147] Two additional studies that were not part of the 2014 VA/DoD HTN CPG evidence review, but were included in the previous discussion, provide support for the lack of benefit and potential harm with combination therapy.[145,146] Other considerations regarding this recommendation include the potential harm of adverse events, which was significant, and lack of outcome benefit, outweighing the minimal potential benefit of additional blood pressure reduction. Patient values and preferences were considered to be similar. The Work Group decided to carry forward the Strong against recommendation against use of combination therapy with an ACEI, ARB, or DRI, so as to inform providers of the rationale against this practice. Recommendation 27. For the treatment of hypertension, there is insufficient evidence to recommend for or against initiating combination therapy over initiating monotherapy with the sequential addition of another medication. (Neither for nor against | Reviewed, New-replaced) Discussion Combination therapy for treating HTN is common. The ACCOMPLISH study confirmed that combination therapy is safe and effective.[144] Patients in ALLHAT often utilized combination therapy,[137] with only 26% of participants reaching goal blood pressure (<140/90 mm Hg) with monotherapy.[148] Generally speaking, larger reductions of blood pressure (e.g.