For pharmacologic management of mild hypertension, blood pressure can be normalized in many patients with a single drug. Most patients with moderate to severe hypertension require two or more antihypertensive medications (see Box: Resistant Hypertension & Polypharmacy). Thiazide diuretics, ACE inhibitors, angiotensin receptor blockers, and calcium channel blockers have all been shown to reduce complications of hypertension and may be used for initial drug therapy. There has been concern that diuretics, by adversely affecting the serum lipid profile or impairing glucose tolerance, may add to the risk of coronary disease, thereby offsetting the benefit of blood pressure reduction. However, a large clinical trial comparing different classes of antihypertensive mediations for initial therapy found that chlorthalidone (a thiazide diuretic) was as effective as other agents in reducing coronary heart disease death and nonfatal myocardial infarction, and was superior to amlodipine in preventing heart failure and superior to lisinopril in preventing stroke. Beta blockers are less effective in reducing cardiovascular events and are currently not recommended as first-line treatment for uncomplicated hypertension.
The presence of concomitant disease should influence selection of antihypertensive drugs because two diseases may benefit from a single drug. For example, drugs that inhibit the renin-angiotensin system are particularly useful in patients with diabetes or evidence of chronic kidney disease with proteinuria. Beta blockers or calcium channel blockers are useful in patients who also have angina; diuretics, ACE inhibitors, angiotensin receptor blockers, β blockers, or hydralazine combined with nitrates in patients who also have heart failure; and α1 blockers in men who have benign prostatic hyperplasia. Race may also affect drug selection: African Americans respond better on average to diuretics and calcium channel blockers than to β blockers and ACE inhibitors. Chinese patients are more sensitive to the effects of β blockers and may require lower doses.
If a single drug does not adequately control blood pressure, drugs with different sites of action can be combined to effectively lower blood pressure while minimizing toxicity (“stepped care”). If three drugs are required, combining a diuretic, an ACE inhibitor or angiotensin receptor blocker, and a calcium channel blocker is often effective. If a fourth drug is needed, a sympathoplegic agent such as a β blocker or clonidine should be considered. In the USA, fixed-dose drug combinations containing a β blocker, plus an ACE inhibitor or angiotensin receptor blocker, plus a thiazide; and a calcium channel blocker plus an ACE inhibitor are available. Fixed-dose combinations have the drawback of not allowing for titration of individual drug doses but have the advantage of allowing fewer pills to be taken, potentially enhancing compliance.
Assessment of blood pressure during office visits should include measurement of recumbent, sitting, and standing pressures. An attempt should be made to normalize blood pressure in the posture or activity level that is customary for the patient. Although there is still some debate about how much blood pressure should be lowered, the recent Systolic Blood Pressure Intervention Trial (SPRINT) and several meta-analyses suggest a target systolic blood pressure of 120 mm Hg for patients at high cardiovascular risk. Systolic hypertension (> 150 mm Hg in the presence of normal diastolic blood pressure) is a strong cardiovascular risk factor in people older than 60 years of age and should be treated. Recent advances in outpatient treatment include home blood pressure telemonitoring with pharmacist case management, which has been shown to improve blood pressure control.