According to the National Institutes of Health, almost 24 million Americans are taking drugs to lower high blood pressure, spending an estimated $15.5 billion each year. High blood pressure, or hypertension , is defined as systolic pressure greater than 140 mmHg and/or diastolic pressure greater than 90 mmHg, although individuals whose blood pressure exceeds 130/85 mmHg are at a high risk of becoming hypertensive in the near future. High blood pressure—seen in one in every four adults—increases the risk of coronary heart disease, stroke, and congestive heart failure, and can eventually lead to kidney failure and blindness if left uncontrolled. Because blood pressure lowering drugs (antihypertensives) can significantly reduce the risk of hypertension-related disability and death, a great number of drugs have been developed to treat this condition.

In the beginning, antihypertensive therapy primarily involved prescribing thiazide diuretics or beta-blocker medications. In the last 10 –15 years, new classes of antihypertensives have joined the ranks, including angiotensin-converting enzyme [ACE] inhibitors, calcium channel blockers, alpha-adrenergic blockers, and angiotensin-receptor blockers. Many of these newer drugs can be more than five to ten times as expensive as the older diuretics. Past research has focussed mostly on how well antihypertensives reduce blood pressure compared to a placebo (inactive) pill. There has been less research on which of these medications is best at reducing the risk of hypertensive complications. Results from an eight-year clinical trial, published in the December 18, 2002 issue of the Journal of the American Medical Association , suggest that less expensive thiazide-type diuretics are just as effective as—in some cases even better than—more expensive ACE-inhibitors and calcium channel-blocker drugs in preventing major coronary events and increasing survival.

About the Study

Researchers for the Antihypertensive and Lipid-Lowering Treatment to Prevent Health Attack Trial (ALLHAT) studied 33,357 men and women (aged 55 years or older) who had hypertension plus at least one additional risk factor for heart disease (previous heart attack or stroke, type 2 diabetes, etc.). Study participants were selected from 623 centers from across the United States, Canada, Puerto Rico, and the U.S. Virgin Islands and were randomly assigned to receive a diuretic (chlorthalidone: 12.5 to 25 mg/d); a calcium channel blocker (amlodipine: 2.5 to 10 mg/d); or an ACE inhibitor (lisinopril: 10 to 40 mg/d). Additional antihypertensives were also prescribed if a participant’s doctor thought it was necessary to control his or her blood pressure.

Once enrolled, information was collected on age, ethnicity, gender, education, blood pressure, body mass index, and current medication use (including aspirin use and estrogen supplementation) for each participant, and medical check-ups were conducted every three months for the first year and then every four months after that.

Over the average five years of follow-up, the researchers recorded whether the study participants had fatal coronary heart disease, nonfatal heart attack, coronary artery bypass surgery, or fatal or nonfatal stroke. They then compared the systolic blood pressure and risk of developing the various cardiovascular outcomes in those taking the diuretic with those taking the ACE inhibitor or the calcium channel blocker.

The Findings

After 5 years of follow-up there was no statistically significant difference in the majority of cardiovascular outcomes observed between those who took the diuretic and those who took the ACE inhibitor or the calcium channel blockers. However, the researchers did note the following:

Compared to participants who were taking the diuretic (chlorthalidone), those on the calcium channel blocker (amlodipine) had

  • On average, about a 1 mm HG higher systolic blood pressure
  • 38% higher risk of developing heart failure with a subsequent 35% higher risk of being hospitalized or dying

Compared to participants who were taking the diuretic, those on the ACE inhibitor (lisinopril) had

  • On average, about a 2 mm HG higher systolic blood pressure
  • 19% higher risk of developing heart failure
  • 15% higher risk of stroke (40% higher in African Americans)
  • 11% greater risk of being hospitalized or treated for angina (chest pain)
  • 10% greater risk of having to undergo a coronary revascularization (such as a coronary artery bypass surgery )

While the average systolic blood pressure for African-Americans and those over 65 were higher; age, race, sex, diabetes status, or baseline coronary heart disease did not affect the risk of hypertensive complications in the study.

The diuretics were better tolerated than the ACE inhibitors, and there appeared to be no special advantage for diabetics taking the newer drugs, as some have previously suggested. In fact, the older diuretic was superior to the ACE inhibitor (lisinopril) for several cardiovascular outcomes and superior to the calcium channel blocker (amlodipine) for heart failure in both diabetic and nondiabetic participants.

Although these results are significant, there are limitations to this study. First, since no adjustments were made for the additional antihypertensive prescribed by some doctors, it is possible that the combinations of these drugs could have influenced the results. Second, because of the timing of the study there was no opportunity to evaluate other new drugs (angiotensin-receptor blockers, selective aldosterone antagonists) so we still don’t know how they might compare to the older diuretics. Finally, no adjustments were made for diet, physical activity, supplement use, and medication use that could have possibly had an influence on individual blood pressure declines over the course of the study.

How Does This Affect You?

According to the study, thiazide-type diuretics are unsurpassed in their tolerability and cost-effectiveness. Now more than ever, doctors have reason to seriously consider using diuretics as first-line treatment for most of their hypertensive patients, while saving the newer, more expensive drugs for those who need additional drug therapy.

Though in most cases the cause of hypertension is unknown, there are many steps you can take to reduce your blood pressure, which may help you avoid the need to take a diuretic or any other medication: