Combination therapy with the ACE inhibitor lisinopril and the calcium channel blocker (CCB) amlodipine is appropriate for this patient with stage 2 hypertension, which is defined as a systolic blood pressure ≥160 mm Hg and/or a diastolic blood pressure ≥100 mm Hg. There is general agreement among hypertension societies that a single agent is unlikely to control blood pressure in patients who are >20/10 mm Hg above target blood pressure. In this circumstance, initial therapy may include a combination of two agents either separately or in a fixed-dose pill. A combination of two agents at moderate doses is often more successful at achieving blood pressure goals than one blood pressure agent at maximal dose and minimizes the side effects that are more commonly noted at higher doses. Several combination regimens are appropriate, including the combination of a thiazide diuretic with an ACE inhibitor or angiotensin receptor blocker (ARB), or an ARB with a CCB; these combinations have been supported by both the eighth report from the Joint National Committee (JNC 8) and the European Society of Hypertension as reasonable approaches to management. However, there is evidence from the Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial that a reduced rate of cardiovascular events may occur with the combination of an ACE inhibitor and CCB compared to an ACE inhibitor and thiazide. The combination of a thiazide and CCB is also an effective strategy for blood pressure lowering, although there is less evidence of the effectiveness of this regimen compared with other combination therapies.

There is general consensus that the dual use of renin-angiotensin-aldosterone agents (ACE inhibitor, ARB, or the direct renin inhibitor aliskiren) should not be used because of evidence showing that combining these medications is not associated with improved cardiovascular or renal end points and results in increased adverse events, including hypotension and hyperkalemia.

Given this patient's degree of hypertension (measurement of 160/92 mm Hg at her current visit), it is unlikely that a single agent will achieve her treatment goal of <140/90 mm Hg. Therefore, combination therapy is indicated as initial treatment.