Blood Pressure Drugs and Heart Failure

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The summary below is from the full report titled "Relationship of Antihypertensive Treatment Regimens and Change in Blood Pressure to Risk for Heart Failure in Hypertensive Patients Randomly Assigned to Doxazosin or Chlorthalidone: Further Analyses from the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial." It is in the 3 September 2002 issue of Annals of Internal Medicine (volume 137, pages 313-320). The authors are BR Davis, JA Cutler, CD Furberg, JT Wright Jr., MA Farber, JV Felicetta, and JD Stokes, for the ALLHAT Collaborative Research Group.

What is the problem and what is known about it so far?

High blood pressure (hypertension) is a chronic condition that damages blood vessels and body organs. It increases the risk for heart attacks, heart failure, strokes, and kidney failure. Although the many types of drugs used to treat hypertension may reduce blood pressure by a similar amount, their ability to prevent complications of hypertension may vary. Also, different drugs cause different side effects.

Researchers showed that heart failure occurred more often in hypertensive patients taking an -blocker (doxazosin) than a diuretic (chlorthalidone). However, the -blocker reduced blood pressure slightly less than the diuretic. Patients taking the -blocker also used more drugs (different types) to help reduce their blood pressure. Thus, it was difficult to sort out whether the heart failure was due to the -blocker itself, the additional drugs, or the higher blood pressure in patients taking the -blocker.

Why did the researchers do this particular study?

To compare heart failure outcomes among adults with high blood pressure who were taking a diuretic (chlorthalidone) or an -blocker (doxazosin).

Who was studied?

24,005 adults older than age 55 years who had high blood pressure and at least one other risk factor for heart disease (prior heart attack, stroke, diabetes, smoking, cholesterol problems, or an enlarged heart).

How was the study done?

Patients were randomly assigned to take doxazosin or chlorthalidone. Both drugs were given once a day in the morning. Neither the patients nor their doctors knew which drug the patients received. Blood pressure was taken every 1 to 3 months. If blood pressures were higher than 140/90 mm Hg, higher drug doses and/or additional drugs (different types) were given. For the 3 years that patients were followed, researchers checked for heart failure diagnoses. They then compared the frequency of heart failure in patients assigned to doxazosin or chlorthalidone. They examined whether differences between groups could be due to differences in blood pressure or additional drugs.

What did the researchers find?

Patients assigned to chlorthalidone had slightly better blood pressure control than those assigned to doxazosin. Fewer of them needed additional drugs for blood pressure control (59% vs. 68%). Heart failure occurred significantly more often in patients receiving doxazosin than in those receiving chlorthalidone, even after differences in blood pressure control and use of other drugs were considered. Risks for heart failure with doxazosin versus chlorthalidone were highest in patients receiving only those drugs and lowest in patients receiving additional drugs.

What were the limitations of the study?

The study cannot tell us whether doxazosin caused heart failure, whether chlorthalidone prevented heart failure, or some combination of both effects.

What are the implications of the study?

Worse blood pressure control with doxazosin versus chlorthalidone does not explain higher heart failure risks of doxazosin. Increased risks for heart failure with doxazosin versus chlorthalidone decrease but do not disappear when other antihypertensive drugs are used.