Tenoretic

Drugs that lower high blood pressure are the cornerstone of preventive medicine. Clearly they have prevented many a heart attack or stroke, but it's getting harder and harder for doctors to know who should get what drug ... and who should not be treated at all. Every few years a committee of hypertension experts (often with strong ties to the pharmaceutical industry) lowers the threshold for the definition of normal hypertension, steadily expanding the pool of people who should be on drugs.

And every few years a study produces the bad news that a certain anti-hypertensive drug or drug combination kills more people than other drugs or drug combinations. Last December, for example, HealthFacts reported a study that found an older, supposedly tried and true beta-blocker drug called atenolol (some brand names: Tenoretic, Apo-Atenolol) was causing more strokes and cardiac deaths than other commonly prescribed anti-hypertensives.

Many people have high blood pressure but no heart disease, and as a group they are less likely to have a large benefit from drug therapy than the people with heart disease. There are exceptions, of course, such as diabetics. And some people with high blood pressure gain nothing at all from drug therapy. A 2003 Cochrane review of all anti-hypertensive drug trials that included women found that white women under the age of 55 years showed no benefit, nor were they harmed by the drugs.

To complicate things further, there is a wide range of anti-hypertensive drugs on the market. To keep them all straight, researchers refer to them by their drug classes, for example, ACE inhibitors, calcium channel blockers, etc. Altogether there are six drug classes and within each, multiple brand names [see page 3].

Last month, the British journal The Lancet published a commentary by three scientists who questioned the excessive focus on high blood pressure when there are many other risk factors--smoking, family history, diabetes, etc.--that determine who will die of heart disease. Instead, they argue for changing the focus to the prevention of blood-pressure-related diseases. "...clear evidence now shows that several blood-pressure-lowering drugs reduce the risks of major vascular events [e.g. stroke] in a broad range of non-hypertensive individuals with highrisk disorders, such as cerebrovascular disease, diabetes, or coronary heart disease."

The Lancet commentary makes sense given the fact that studies show some anti-hypertensives (ACE inhibitors) can produce cardiovascular benefits while making only modest reductions in blood pressure. Conversely, other drugs (calcium channel blockers) are good at lowering blood pressure without doing much for the odds of having a heart attack or stroke.

How would you know whether you are taking the right drug or drug combination for your particular circumstances? Is your doctor able to keep up with all the new information--and, again, how would you know?

In 2002, a major anti-hypertensive drug trial rocked the international medical establishment with findings that challenged widely held beliefs. It found that diuretics, the oldest and cheapest anti-hypertensive drug class, are just as effective and, in some circumstances, better than the newer, expensive drugs. But just when it appeared that, at last, there is definitive anti-hypertensive drug news, the same study made it clear that many people with hypertension need another drug in addition to a diuretic.

This 2002 landmark trial, known as the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), included over 33,000 men and women over age 55 years with mild to moderate hypertension who were at high risk for developing heart disease (e.g. 36% had diabetes). The ALLHAT had randomly assigned participants to take daily doses of a calcium channel blocker, an alpha blocker, an ACE inhibitor, or a diuretic.

Whenever a drug failed to control blood pressure, the study participants were put on a second or third additional drug selected from the other three. In other words, everyone in this study was on anti-hypertensive drugs, often two or three on a daily basis. The ALLHAT participants were broadly representative of the U.S. population in terms of race, gender, socioeconomic status, and geographical region.

Here are some of the ALLHAT findings:

* A diuretic should be the first-choice treatment for high blood pressure;

* the total or overall mortality--that is, the deaths from all causes--was the same for all treatments;

* calcium-channel-blocker drugs increased the incidence of heart failure;

* participants taking the alpha-blocker (doxazosin) were stopped prior to the intended conclusion of ALLHAT because they showed a significantly increased rate of angina, stroke, and congestive heart failure;

* whether they were treated with a diuretic, ACE inhibitor, or an alpha blocker, the occurrences of heart-related death, and non-fatal heart attack were virtually identical.

Because most anti-hypertensive drug trials have combined the results for men and women, some researchers have pointed out that this might inflate drug therapy's benefit to women who typically do not have heart attacks or heart-related fatalities until they are much older than men. Also, there might be gender-differences in harms associated with drugs that would show up as non-cardiac deaths.

A 2003 Cochrane review of all trials that included women concluded that in white women over 55 years, drugs reduced the rate of fatal and non-fatal cerebrovascular "events" (e.g., stroke, trans ischemic attacks), and fatal and non-fatal cardiovascular events, but they do not reduce the cardiovascular or overall mortality. Black women of any age, however, benefited on all counts (except overall mortality) from drug therapy because their cardiovascular risk is higher to begin with. Black women tend to develop hypertension earlier in life than white women. In the trials included in this Cochrane review, they also were more likely to be smokers and diabetics than white women.

Another attempt to clarify things was an all-woman study published at the end of last year (JAMA, 12/15/04). A research team led by S. Wassertheil-Smoller evaluated different drug combinations in over 30,000 older women--50 to 79 years--with hypertension but no heart disease or diabetes. They had been followed for almost six years. This is what researchers call an observational study because it looked at the different ways women with hypertension are treated in "the real world" as opposed to a clinical trial based at an academic medical center where researchers determine the treatments and assign them randomly to participants.

Here are some of the findings:

*Of the women taking only a diuretic, this drug was equal to or superior to other drugs taken singly in preventing cardiovascular disease complications;

* of the women taking only one drug: those on a calcium channel blocker had a higher rate of death from heart disease than those taking only a diuretic;

* the women who took only a calcium channel blocker had a higher rate of death from heart disease compared with those who took a diuretic plus a beta-blocker;

* and women taking a diuretic plus a calcium channel blocker had a greater rate of cardiovascular death than those on a diuretic plus a beta blocker or a diuretic plus an ACE inhibitor.

Bottom Line:

Diuretics are the first-choice drug for men and women. While it would seem reasonable to conclude that the calcium channel blocker should be avoided completely, hypertension researchers see it as a "drug of last resort". The ALLHAT did not include low-risk people with hypertension--that is, healthy adults whose only risk for heart disease is high blood pressure. When trials show a reduction in cardiovascular deaths but not in overall deaths, this suggests that the heart-related survival benefit may be canceled by treatment-related deaths. Anti-hypertensive drug trials follow people five or six years, at most, whereas people are expected to take these drugs for life.

Many heart disease researchers believe that physicians should not focus solely on high blood pressure when deciding drug therapy. Instead, a person's entire risk profile should be taken into consideration. And finally, this from the authors of the all-woman study: "An important question is whether it is the blood pressure lowering effect of anti-hypertensive drug therapy that is the critical element in preventing cardiovascular disease sequelae or whether particular drug classes offer benefits beyond their effects in lowering blood pressure."

COPYRIGHT 2005 Center for Medical Consumers, Inc.
COPYRIGHT 2005 Gale Group