Guidance emerges on specific types of combo therapy for hypertension

With single-pill, fixed-dose combinations of antihypertensive agents, as well as triple-therapy, single-pill agents emerging, updated guidance on specific types of combination therapy for hypertension has emerged.

Guidance on specific types of combination therapy for hypertension were published in last month’s Prescriber’s Letter:

• You’ll use more drug combos for uncomplicated hypertension.

• At least 75% of patients need 2 or more drugs to reach blood pressure goals.

• Combining 2 synergistic drugs lowers blood pressure about 5 times more than doubling the dose of one drug.

• But certain combos work better than others.

An angiotensin-converting enzyme inhibitor (ACEI) plus a thiazide has a good BP-lowering effect. The ACEI helps the thiazide work better and reduces hypokalemia.

Consider using chlorthalidone...especially for harder to control hypertension. It’s longer-acting and more potent than hydrochlorothiazide.

An ACEI plus a dihydropyridine calcium channel blocker (CCB) also works well...and may improve outcomes better than an ACEI plus hydrochlorothiazide. An ACEI also reduces edema due to the dihydropyridine (amlodipine, etc).

Save angiotensin II receptor blockers (ARBs) for patients who can’t take an ACEI...and aliskiren (Tekturna) for those who can’t take an ACEI or ARB. There’s less evidence that ARBs improve outcomes...and none yet for aliskiren.

Don’t use an ACEI plus ARB just for hypertension because this combo causes more side effects...and doesn’t improve outcomes.

In general, save beta-blockers for patients who need them for angina, heart failure, after a heart attack, etc. For hypertension, beta-blockers don’t improve outcomes as well as other blood pressure medications.

Pick combos for uncomplicated hypertension using this summary:

Preferred Combos:

ACEI + thiazide

ACEI + dihydropyridine CCB

ARB + thiazide

ARB + dihydropyridine CCB

Acceptable Combos:

CCB + thiazide

Thiazide + potassium-sparing diuretic

Aliskiren + thiazide or CCB

B-blocker + diuretic or dihydro CCB

Not Preferred Combos:

ACEI + ARB

B-blocker + ACEI or ARB

B-blocker + Nondihydropyridine CCB

B-blocker + Central acting (clonidine, etc)

• Start with 2 drugs for patients who are 20 mmHg or more above their systolic goal...or 10 mmHg or more above their diastolic goal.

• When appropriate, use a combo product, such as a generic ACEI plus hydrochlorothiazide...or generic amlodipine plus benazepril. These may improve adherence and sometimes reduce costs.

This guidance mirrors a recent American Society of Hypertension (ASH) position paper on combination therapy in hypertension, George Bakris, MD, director, Hypertensive Diseases Unit, University of Chicago Hospitals, told Drug Topics.

“The implication of the ASH position paper is that formularies should have fixed dose combinations available for treatment of hypertension since more than 75% of people with hypertension will require 2 or medications to achieve blood pressure goal and the more pills needed to achieve goal, the less likely goal will be achieved. Simplicity to therapy is the key and this position paper provides a rational approach,” said Dr Bakris, one of the position paper’s authors.