[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., 20/10 mm Hg or more) often require at least two medications to achieve blood pressure control, and initiating therapy with two drugs is effective and well tolerated, apart from a slight increase in dizziness incidence for some combination dosing, in most However, evidence is lacking on the effect of various treatment approaches on important primary outcomes (e.g., mortality, cardiovascular events, stroke). Specifically, additional studies are needed on initiating therapy with one drug and sequentially titrating agents compared to starting two drugs simultaneously and titrating as necessary. The systematic evidence review conducted for this CPG update did not identify any studies that met inclusion criteria. From a practical perspective, providers and patients depending on their preferences as well as a patient s comorbid conditions and the anticipated magnitude of blood pressure lowering may wish to consider combination therapy when selecting initial therapy. Initial combination therapy may reduce the number of titrations and visits to achieve blood pressure goal. Patients with a compelling indication for more than one class of antihypertensive agent may benefit from initial combination therapy, as well. Additionally, combination pills, when available, may reduce medication co-payments for some patients. Whether using sequential or initial combination therapy, providers should attempt to achieve dosing ranges that have been found to impact important clinical outcomes. As this is a Reviewed, New-replaced recommendation, the Work Group systematically searched for evidence related to this recommendation in the evidence review conducted as part of this guideline update; however, no evidence met inclusion criteria. Therefore, this recommendation is based on evidence cited in the 2014 VA/DoD HTN CPG.