Beta blockers for blood pressure: A second opinion

Content provided by the Faculty of the Harvard Medical School

Beta blockers for blood pressure: A second opinion

Medicine is a dynamic science; if there is anything constant about the profession, it's that things change.

One of the most important areas of change has come in our understanding of blood pressure and our management of hypertension (high blood pressure). Dr. Scipione Riva-Rocci developed the sphygmomanometer (blood pressure cuff) in 1896, and Dr. Nikolai Korotkoff learned how to team it with a stethoscope to get reliable measurements in 1905. In the early days, the readings were just numbers, but doctors gradually learned that high numbers predict an increased risk of stroke, heart attack, kidney failure, cognitive impairment, and premature death. At first, they believed that only the diastolic blood pressure (the lower reading, measured while the heart is relaxing and refilling with blood between beats) was important. But scientists have learned that both numbers count, and that the systolic blood pressure (the higher number, measured while the heart is pumping blood) is actually more important.

The definition of a hypertensive pressure has also changed. First, it fell from 160/90 mm Hg to 140/90. Then, in 2003, the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure issued its Seventh Report (JNC7), which turned the world of hypertension upside down. Based on a wealth of new data, JNC7 explained that 120/80 is the highest reading that qualifies as normal. The report also established a new diagnostic category of prehypertension for readings between 120/80 and 140/90, and it confirmed 140/90 as the standard for full-blown hypertension.

New goals

Using the new standards, the American Heart Association tells us that some 65 million Americans have hypertension and another 59 million have prehypertension. That means nearly half of all American adults need to reduce their blood pressure. Lifestyle modification is important for everyone (see below), but many people need medication to achieve the JNC7 goal of reducing pressure to below 140/90, or 130/80 for people with diabetes, kidney disease, or heart disease. In fact, many people need two or more medications — but which drugs are best?

Choosing medications

With more than 75 antihypertensive medications belonging to nine different drug groups, doctors have a huge number of options. But not all medications are created equal. Lowering pressure is the major benefit of these medications, but even when they produce similar blood pressure reductions, some medications do a better job of lowering the risk of complications from hypertension. To ensure the best results, JNC7 established guidelines for choosing an antihypertensive drug.

For most patients, a thiazide diuretic should be the first choice. By far the oldest and least expensive major antihypertensive, the thiazides act by flushing sodium (salt) into the urine; they are effective even in people on low-sodium diets. Thiazides are generally safe and well tolerated, but some people develop low potassium levels, frequent urination, or dehydration. Less common side effects include erectile dysfunction, sun sensitivity, elevated blood sugar levels, and gout.

JNC7 put thiazides first because of their unrivaled ability to reduce the risk of stroke, heart attack, congestive heart failure, and premature death in patients with hypertension. But some people can't take a thiazide, and many need more than one medication. As a result, JNC7 endorsed four other classes as excellent, first-line medications. The table below lists representative drugs in each class.

Beta blockers are one of the five recommended drug classes. But new data suggest they may drop down a notch by the time the Joint Committee issues its eighth report.

The beta blocker background

The beta blockers act by blocking some actions of the stress hormone adrenaline. They lower blood pressure by widening arteries, relaxing the heart muscle, and slowing the heart rate. Potential side effects include excessive slowing of the heart rate, fatigue, cold extremities, and sleep disturbances. Wheezing may occur, particularly in patients with emphysema or asthma, but it is less common with cardioselective beta blockers such as atenolol and metoprolol.

When used appropriately, beta blockers are good for the heart. Because they reduce the risk of recurrent heart attacks, they are part of the standard therapy for patients who have had heart attacks. They also reduce the frequency of chest pain in patients with angina. And although they were once shunned for patients with congestive heart failure, they have proven their value as part of multidrug regimens for these patients.

Since the heart is a major casualty of hypertension, it's not surprising that beta blockers rapidly gained acceptance as first-line therapy for high blood pressure.

The new studies

A major European trial of beta blockers for hypertension was published in late 2005. The ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm) study randomly assigned 19,257 hypertensive patients to one of two regimens: (1) a beta blocker (atenolol) plus, when needed to reach the blood pressure goal, a thiazide diuretic (bendroflumethiazide), or (2) a long-acting calcium-channel blocker (amlodipine), plus, when needed, an angiotensin converting–enzyme inhibitor (ACE inhibitor; perindopril). The study was halted early by the Safety Monitoring Board when it became clear that the patients on the beta blocker–based regimen were being increasingly disadvantaged as time went on. Even after relative blood pressure reductions were taken into account, the calcium-channel/ACE inhibitor patients enjoyed a 30% lower risk of developing diabetes, 13% fewer coronary events, 23% fewer strokes, a 24% lower cardiovascular mortality rate, and an 11% lower overall mortality rate.

ASCOT-BPLA was an exceptionally large and careful trial, but it's only one study. More recently, however, Swedish researchers reported a meta-analysis of 13 randomized controlled trials that compared a beta blocker with another drug and 7 randomized trials that compared a beta blocker with a placebo. More than 27,000 hypertensive patients were included in the placebo-controlled trials. Compared with a placebo or no treatment, beta blockers reduced the risk of stroke by 19% but did not reduce the risk of heart attack or the overall mortality rate. More than 105,000 hypertensive patients were included in the beta blocker vs. another blood pressure drug trials. Compared to the other medications, beta blockers were associated with a 15% higher risk for stroke; there was no difference in the risk of heart attacks.

Time for a change?

Many European experts say it is. They suggest carefully switching patients from beta blockers to other medications and dropping these drugs from first-line status when new treatment guidelines are written. The British Hypertension Society did just that in 2006.

They make a good case, but treatment decisions are made by physicians for individual patients, while guidelines are designed to help doctors treat typical patients. Some experts point out that most of the disappointing trials have used atenolol and that other beta blockers might be better. Others suggest that beta blockers may retain their usefulness for young hypertensive patients.

At present, doctors would probably be wise to start treating new hypertension without using a beta blocker. But all the experts agree that attaining treatment goals is the most important result. If a patient is not well controlled on a beta blocker, a switch seems wise. Still, it may be hard to persuade doctors to switch patients who have achieved excellent blood pressure control without side effects on beta blockers.

The results are important and are likely to change future guidelines. Time will tell if they are compelling enough to convince doctors to act against the well-established dictum, "If it ain't broke, don't fix it."

Even if beta blockers are demoted to second-line status for hypertension, they will remain useful add-on drugs for patients who need multiple medications to lower stubbornly elevated blood pressures. And they will surely remain important for many other purposes, including reducing the risk of recurrent heart attacks, relieving the pain of angina, controlling certain abnormal heart rhythms, treating congestive heart failure, preventing migraines, preventing gastrointestinal bleeding in some patients with cirrhosis, and managing stage fright. So whatever their eventual role in hypertension, beta blockers are here to stay.

Last updated:	September 05, 2008