Although many other drugs and drug classes are available, either confirmation that these agents decrease clinical outcomes to an extent similar to that of the primary agents is lack- ing, or safety and tolerability may relegate their role to use as sec- ondary agents. In particular, there is inadequate evidence to support the initial use of beta blockers for hypertension in the absence of specific cardiovascular comorbidities (see Section 9). When the initial drug treatment of high BP is being consid- ered, several different strategies may be contemplated. Many patients can be started on a single agent, but consideration should be given to starting with 2 drugs of different classes for those with stage 2 hypertension (see Section 8.1.6.1). In addition, other patient-specific factors, such as age, concur- rent medications, drug adherence, drug interactions, the over- all treatment regimen, out-of-pocket costs, and comorbidities, should be considered. From a societal perspective, total costs must be taken into account. Shared decision making, with the patient influenced by clinician judgment, should drive the ulti- mate choice of antihypertensive agent(s). Many patients started on a single agent will subsequently require 2 drugs from different pharmacological classes to reach their BP goals.S8.1.4-12,S8.1.4-13,S8.1.4-14 Knowledge of the pharmacological mechanisms of action of each agent is important. Drug regimens with complementary activity, where a second antihypertensive agent is used to block com- pensatory responses to the initial agent or affect a different pressor mechanism, can result in additive lowering of BP. For example, thiazide diuretics may stimulate the renin-angio- tensin-aldosterone system. By adding an ACE inhibitor or ARB to the thiazide, an additive BP-lowering effect may be Use of combination therapy may also improve adherence. 