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Harvard Commentaries
Harvard Commentaries
Reviewed by the Faculty of Harvard Medical School

Man to Man Man to Man

Treating High Blood Pressure -- Are Two Drugs Better Than One?

March 21, 2014

By Harvey B. Simon M.D.

Harvard Medical School

There are dozens of high blood pressure drugs — antihypertensives — that doctors can prescribe. That's no surprise. Some 76 million Americans, about 1 of every 3 adults, have high blood pressure (also called hypertension). A similar number of people have prehypertension. But since high blood pressure causes 395,000 deaths a year in the United States, about 1 of every 6 deaths, these medicines are falling short on the job. Why?

  • High blood pressure is called the "silent killer." There are no symptoms until it has caused permanent damage to the heart, brain, kidneys, or eyes. The only way to find out if you have hypertension, is to have your pressure checked (see the table below). Unfortunately, nearly a quarter of people with high blood pressure don't even know they have the condition.
  • Half of the patients who are being treated for the disease don't have good blood pressure control. You can prevent nearly all the complications of this common disease with good control.
Category Systolic Blood
Pressure (mm Hg)
  Diastolic Blood
Pressure (mm Hg)
Normal Less than 120 and Less than 80
Prehypertension 120-139 or 80-89
Stage 1 140-159 or 90-99
Stage 2 160 or higher or 100 or higher

Patients have to do their part by following important lifestyle guidelines and taking their medicines correctly. And doctors have to do a better job of prescribing antihypertensive medicines. A new approach to drug therapy can help.

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The Single-Drug Plan

Lifestyle changes are the first step in treating high blood pressure. The next step is medication.

Low-Pressure Living

Lifestyle changes are an essential part of treating high blood pressure. And because lower blood pressures are better for health, the following five steps are an excellent plan for anyone with a pressure above 115/70.
  • Diet. Reduce your sodium (salt) intake to less than 1,500 milligrams a day. Eat lots of potassium-rich fruits and vegetables, as well as whole grains and non- or low-fat dairy products. Eat less animal fat and fewer processed foods.
  • Exercise. Moderate exercise, such as walking 30 minutes a day, is excellent. It may even be better than intense exercise, according to some studies.
  • Weight control. Diet and exercise will help you lose weight. Every pound will help, even if you never become thin.
  • Alcohol. Light to moderate drinking (1 to 2 drinks a day) won't raise your blood pressure, but heavy drinking will.
  • Stress control. It's easier said than done in today's hectic world, but winding down can help you keep your pressure down.

The traditional approach is the single-drug plan. The doctor picks a drug that fits the patient's specific needs and then gradually increases the dose until the patient reaches his target blood pressure. This is called stepped care. The doctor adds a second drug only after the first medicine doesn't lower the patient's blood pressure enough, even at the highest safe dose.

The idea behind taking one drug is that the patient is exposed to fewer side effects than taking two medications at the same time. One drug should be easier to remember to take, which improves compliance. And in many cases, a full dose of one drug is less expensive than a small dose of two medications.

But often, single-drug therapy falls short. One reason is that the stepped care method was developed when the goal of treatment was a "normal" reading of 150/90. Now, however, the targets are lower. People who are in good general health apart from hypertension should bring their pressures below 140/90. Patients with diabetes, chronic kidney disease or any form of heart and artery disease should be below 130/80. It's a strict goal, and if present trends continue, target blood pressures may get even lower.

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A New Approach

If one drug isn't enough, combination therapy is a necessity. But what about a new tactic — giving two drugs from the start?

  • A 2003 study helped set the stage for a new approach called low-dose combination therapy. First, researchers evaluated the five most important types of antihypertensive medications: thiazide diuretics, beta-blockers (BB), angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs). In standard doses, all five groups lowered systolic pressure by about 9.1 mm Hg and diastolic pressure by 5.5 mm Hg. But cutting the standard dose in half did not reduce benefit by half; instead, it cut effectiveness by only 20%, to a systolic reduction of 7.1 mm Hg and a diastolic reduction of 4.4 mm Hg. And except for the cough produced by ACEIs, the side effects of all medications were substantially less common at lower doses than at full doses.
  • A 2009 study looked at combined therapy. British scientists reviewed 42 trials that included 10,968 patients with hypertension. Each individual trial compared one drug therapy with two drug combinations. They used thiazides, beta-blockers, ACEIs or CCBs. Even though many different drug combinations were studied, the basic results were strikingly similar: Low-dose combination therapy works. In fact, it works very well. Adding a second drug is about five times more effective than doubling the dose of one drug. That means combination therapy will prevent four heart attacks or strokes for every one that would be prevented by doubling the dose of a single drug. In addition, the risk of side effects from two drugs at half the usual doses is lower than the risk from one drug at the full dose.

Because they are newer, ARBs were not included in the British meta-analysis. Still, four additional studies show they work well in combination with a thiazide or CCB. Similarly, although their study did not evaluate combining three drugs, the British researchers speculate that low-dose triple therapy would be more effective and safer than full-dose double therapy.

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More Ways to Tailor Treatment

There are many ways to treat hypertension. Lifestyle therapy is always important. It may do the job for patients with mild hypertension or for others with hypertension who make major improvements in their weight, exercise or diet.

But when more help is needed, doctors can choose between traditional stepped care with one drug and low-dose combination treatment. Either way, the choice of drugs will depend on the patient's exact needs. In many cases, drug therapy will be based on taking a thiazide diuretic. But other classes of drugs may be a better choice — either alone or in low-dose combinations — depending on other health conditions a person has.

  • Diabetes – Angiotension converting enzyme inhibitor (ACEI); angiotensin receptor blocker (ARB)
  • Previous heart attack – Beta-blocker (BB); ACEI; ARB
  • Previous stroke – Thiazide; ACEI; ARB
  • Kidney disease – ACEI; ARB
  • High risk of coronary artery disease – Thiazide, BB, calcium-channel blocker (CCB), ACEI, ARB

Whether your doctor prescribes one drug or two, your job will be to:

  • Take your medicines.
  • Follow good lifestyle habits.
  • See your doctor to be sure your blood pressure is where it should be and that you are free of side effects.

The new British meta-analysis suggests that two meds are better than one. Old-fashioned common sense says that two heads — you and your doctor — are better than one.

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Harvey B. Simon, M.D. is an Associate Professor of Medicine at Harvard Medical School and a member of the Health Sciences Technology Faculty at Massachusetts Institute of Technology. He is the founding editor of the Harvard Men's Health Watch newsletter and author of six consumer health books, including The Harvard Medical School Guide to Men's Health (Simon and Schuster, 2002) and The No Sweat Exercise Plan, Lose Weight, Get Healthy and Live Longer (McGraw-Hill, 2006). Dr. Simon practices at the Massachusetts General Hospital; he received the London Prize for Excellence in Teaching from Harvard and MIT.

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