Doxazosin and ALLHAT trial: a response

We are following with great interest the discussion in the American Journal of Hypertension about the use of doxazosin in hypertension, as reflected by the correspondence between Drs. Poulter and Williams and Drs. Krakoff and Alderman regarding the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).1 In 1997 to 1998 we conducted a relatively large local study (not to compare to the size of ALLHAT of course) in which diabetic hypertensive patients treated with angiotensin converting enzyme (ACE) inhibitor were changed to doxazosin. The purpose of our study was to compare the effect of doxazosin, in different doses, to ACE inhibitor, regarding glucose levels, glucose tolerance, and lipid profile on a 1-year of close follow-up. One hundred eight patients were included in the study and visited the hypertension clinic at least once a month for regular blood pressure (BP) measurement, treatment adjustment, and compliance evaluation. Questionnaire on complaints, side effects, and hospitalization were filled out. Blood glucose, lipid and kidney functions were monitored every 3 months. Our main findings were an equally well-controlled BP both on ACE inhibitor and doxazosin (144/83 mm Hg v 139/80 mm Hg), a very small drop out rate for minor side effects (12 patients, one with dyspnea), and not even one case of hospitalization for congestive heart failure. There was a favorable change in blood lipid levels with borderline significance (HDL mg/dL, 46 v 49 mg/dL; LDL, 136 mg % v 129 mg %; triglycerides, 170 mg/dL v 159 mg/dL).2 These results are surprising with regard to the ALLHAT study, as most of the adverse events as congestive heart failure or combined cerebrovascular disease in that study appeared during the first year of follow-up. In 4 years there was 25.45% of event, with in the first year alone, close to 10%. That means that the expected occurrence of cerebrovascular events in our study, according to ALLHAT study findings, should have been 10%, about 10 to 11 patients, mainly congestive heart failure. This kind of statement can never be accurate, but at least the range of 5% to 15% can be claimed. Surprisingly, we did not have even one hospitalization for congestive heart failure during the period of our study. It is unlikely that our patients were totally different from the ALLHAT population.3 In our study we included diagnosed diabetic patients; although past or present known cerebrovascular complications were excluded, still diabetes mellitus is considered a major risk factor for cerebrovascular diseases. Were there major differences in age or other risk factors such as blood lipids and demographic characteristics? Comparing the data from the publication in 1996 to 2000,2,3 no obvious difference can be detected. Was the follow-up less close or less accurate? The opposite is true. Our patients were seen at least once a month or even more often by a hypertension specialist. Our patients were all white, younger than 65 years (mean age, 64 years); but these variables did not affect the ALLHAT findings; therefore, they should not affect our results. Our study was not designed with the same end point as ALLHAT. However, the close follow-up of a relatively large group of high-risk diabetic patients for 1 year would enable us to detect all cerebrovascular events. We would like to add to the conclusion of the editors so well stated that there are still unanswered questions about the use of doxazosin in low cardiac risk patients, patients with glucose intolerance, elevated lipid levels, or the use in combination with diuretics.