7 Jun

The ALLHAT study validated current national hypertension treatment guidelines by demonstrating that using chlorthali-done as the initial treatment was as effective as using a drug from one of the alternative classes of antihypertensive agents known as ACE-inhibitors (lisinopril) and a calcium-channel blocker (amlopidine) in decreasing blood pressure and reducing the incidence of fatal coronary heart disease or nonfatal myocardial infarction (MI) and all-cause mortality. The study did not conclude that other classes of antihypertensive drugs are ineffective or unnecessary for treatment.

Some differences were observed; for instance, patients assigned to the diuretic group experienced a lower incidence of heart failure and stroke than patients assigned to the other groups. However, a cause-and-effect relationship cannot be firmly established without further study to account for the effects of variables such as the other drugs used in combination with the diuretic.

Physician guidelines for treating hypertension and reducing its complications have existed since the early 1900s; until recently, however, these recommendations were based solely on observations and expert opinions. The first validation by a controlled clinical trial did not occur until the late 1960s. Since then, the health care industry has increased its emphasis on research evidence as the basis for treatment decision guidelines. The National Institutes of Health (NIH) Guidelines (JNC 7) recommend diuretics, alone or in combination with other antihypertensive agents, for the initial pharmaceutical treatment of hypertension in the absence of “compelling reasons to the contrary.”

Many observational studies and clinical trials have shown that patients tolerate diuretics and beta blockers. These are the least costly antihypertensive medications and are as effective as the newer drugs in reducing morbidity and mortality. The current guidelines also emphasize the value of combination therapy. The rationale is that most patients will require more than one agent to bring blood pressure to recommended goals (JNC 7).

The NIH recommendations for treating hypertension define circumstances and indications for which the evidence favors certain classes of antihypertensive agents:

  • beta blockers after a heart attack
  • ACE-inhibitors for patients with heart failure and/or patients who have poor kidney function caused by diabetes
  • calcium-channel blockers for patients prone to angina pain, bronchial spasms, or some types of irregular heartbeat
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As a class, calcium-channel blockers have had better patient acceptance because of their once-daily dosing, the absence of drowsiness or impotence (common with other antihyper-tensive medications, including diuretics), and a decrease in the frequency of office visits for monitoring. In addition to their effectiveness in lowering blood pressure, these drugs do not interact with other commonly prescribed medications for hypertension and do not cause metabolic changes requiring blood tests.

The ALLHAT patients who received alpha blockers showed a highly significant (25%) excess risk of major cardiovascular events, causing researchers to terminate that part of the study early. In light of this outcome, revised guidelines will probably recommend alpha blockers only if other agents (i.e., low-dose diuretics, beta blockers, and ACE-inhibitors) are ineffective in lowering blood pressure.

The ALLHAT data confirmed a tenet fostered by the current national hypertension guidelines: most patients require a combination of drugs for adequate control of hypertension. In fact, the researchers built step-up drug therapy into the study’s protocol by permitting the addition of non-study classes of anti-hypertensive agents if the study drug alone was ineffective. ALLHAT statistics reported for the diuretic group, the ACE-inhibitor group, and the calcium-channel blocker group indicate that, of the patients remaining in the study by the end of the fifth year, 8.6% had been switched to a study drug other than the one initially assigned, and more than 70% of those still taking the initially assigned study drug were taking more than one drug to control their hypertension (Table 1).

Table 1   Changes in ALLHAT Group Participation and Medication Use over Five Years



No. patients originally assigned to group




No. patients still in group at end of year ffivef




• No. patients still receiving study drug




• No. patients receiving study drug plus additional antihypertensive drugs




• No. patients switched to a different drug




Mean No. of antihypertensive drugs patients were receiving




At the end of five years, the mean number of drugs per patient across the three groups was 1.9 per patient. Given the variability resulting from the combined effects of added drugs, and given the high attrition rate among participants (only 59% of the original total remained in the study at the end of the fifth year), experts will probably remain cautious in making generalizations or in changing recommendations based solely on these findings.


Hypertension is a complex disease with several root causes, an array of major risk factors, and a variety of complications, the most serious of which are organ (e.g., kidney, heart) damage, central nervous system injury, and heart disease. It is important to understand that studies look at population averages and not at individual patients. When prescribing drugs for hypertension, physicians must consider each patient’s unique medical history—metabolic state (evidence of diabetes or gout), kidney function, any heart muscle damage, and heart efficiency (cardiac output)—because each factor affects the choice of the initial and any subsequent therapy. silagra 100

Perhaps the most unfortunate consequence of the publicity surrounding the announcement of the ALLHAT study is that it created undue public concern about antihypertensive drugs, when the real danger is that hypertension remains untreated or uncontrolled in near-epidemic numbers of Americans. The potential benefit to be gained from a subtle shift in treatment recommendations is relatively small, when compared with costs associated with the underuse of all antihypertensive drugs nationwide.

In 2002, the National Committee on Quality Assurance reported that of the more than 18 million workers with known and unknown hypertension in the U.S., “78 percent are not reaching established goals of adequate blood pressure control and therefore are at risk of a serious cardiovascular event.”