Q: At what blood pressure is it prudent to treat newly diagnosed hypertension with 2 antihypertensive agents, and what criteria should guide selection of the 2 drugs?

A: As recommended in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 report), dual-drug therapy should be initiated in patients with newly diagnosed stage 2 hypertension—that is, blood pressure greater than 160/100 mm Hg.¹ The goal is less than 140/90 mm Hg in patients with uncomplicated hypertension and ideally less than 130/80 mm Hg in patients with chronic progressive renal disease, diabetes, and possibly also the metabolic syndrome.

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Selection of agents for combination therapy. All classes of antihypertensives are effective at lowering blood pressure and have acceptable adverse-effect profiles. Consider a fixed combination, which can provide effectiveness with once-daily administration. Another issue to consider is whether the patient has any cardiovascular risk factors. The Table lists agents that have demonstrated benefits for specific indications based on clinical outcomes studies or current clinical guidelines; it may be of help in selecting the components of a fixed combination tablet.

Thiazide diuretics have a long history of safety and effectiveness when administered in dosages of 12.5 to 25 mg/d, and they are now available in combination with agents from all of the other major classes of antihypertensive drugs. A number of clinical trials have been cited to support claims of benefit for specific drugs (usually studied along with other comparator drugs). It is extremely difficult to directly compare clinical trials, given the differences between patient populations, treatment regimens, and other drugs used as add-on therapy to achieve treatment goals. Even though the discrepancies between these clinical trials remain unresolved, the results still do indicate that for most patients, a low-dose diuretic should be one of the components in a combination regimen. Thus, for patients with newly diagnosed stage 2 hypertension who have no other compelling comorbidities (such as congestive heart failure, history of myocardial infarction, high risk of coronary disease, diabetes, chronic kidney disease, or risk of recurrent stroke) a combination of a thiazide diuretic and a second agent is usually appropriate.

The renin angiotensin system inhibitors (angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]) have attracted attention in recent years. ARBs have an established record of efficacy and the lowest incidence of adverse effects of all currently available agents. When ACE inhibitors or ARBs are administered with a diuretic, blood pressure lowering is significantly enhanced. In addition, a number of clinical trials now suggest that these agents may offer benefits beyond their blood pressure-lowering effects, particularly in patients with cardiovascular comorbidities. Ongoing clinical trials should provide better perspective on some of these potential effects.