Inpharma 1233 - 15 Apr 20001. ALLHAT Officers and Coordinators for the ALLHAT Collaborative ResearchChlorthalidone superior to Group. Major cardiovascular events in hypertensive patients randomized to

doxazosin vs chlorthalidone: the Antihypertensive and Lipid-Loweringdoxazosin in hypertensionTreatment to prevent Heart Attack Trial (ALLHAT). JAMA: the Journal of theAmerican Medical Association 283: 1967-1975, 19 Apr 2000.

The diuretic chlorthalidone is superior to the α- 2. Lasagna L. Diuretics vs alpha-blockers for treatment of hypertension: lessonsfrom ALLHAT. JAMA: the Journal of the American Medical Association 283:blocker doxazosin in the treatment of older patients with2013-2014, 19 Apr 2000.hypertension who have other risk factors for 800763498

cardiovascular disease, reports the ALLHAT*» Editorial comment: The above-mentioned study andCollaborative Research Group from the US and Canada.1editorial have been released by JAMA via the Internet prior toThey report the results of an interim analysis oftheir publication date. They will be published in the 19 Apriloutcomes among 24 335 patients with hypertension2000 issue of JAMA.aged ≥ 55 years who had ≥ 1 additional risk factor for

coronary heart disease (CHD) and who wererandomised to the chlorthalidone and doxazosin arms ofthe study.** Patients received chlorthalidone 12.5–25mg/day (n = 15 268) or doxazosin 2–8 mg/day; themedian duration of follow-up was 3.3 years.

Higher relative risksThere were no significant between-group differences

in the primary composite endpoint of fatal CHD andnonfatal myocardial infarction (MI) or in all-causemortality. However, doxazosin, compared withchlorthalidone, recipients had an increased risk ofcombined CHD [relative risk (RR) = 1.1; 95% CI1–1.12], stroke (RR = 1.19; 95% CI 1.01–1.4) andcombined cardiovascular disease (RR = 1.25; 95% CI1.17–1.33).†

Compared with chlorthalidone recipients, doxazosinrecipients also had higher risks of some components ofthe combined endpoints, including overall congestiveheart failure (CHF; RR = 2.04; 95% CI 1.79–2.32), fataland nonfatal CHF requiring hospitalisation (RR = 1.83;95% CI 1.58–2.13), coronary revascularisation (RR =1.15; 95% CI 1–1.32) and angina pectoris (RR = 1.16;95% CI 1.05–1.27).

‘Major implications’Dr Louis Lasagna from Tufts University School of

Medicine, Boston, Massachusetts, US, says thatalthough the above-mentioned results are only the firstof many to be provided by ALLHAT, ‘the trial already hasprovided important results with substantial potentialinfluence on the treatment of hypertension’.2

Dr Lasagna says that these initial findings ‘have majorimplications for the recommendations for treatment ofhypertension, which currently include doxazosin as afirst-line agent’. He notes that the between-groupdifference seen in the data ‘was robust acrosssubgroups’, making the findings ‘unlikely to be spuriousor isolated’. Furthermore, Dr Lasagna says that ‘theassumption that the most important parameter intreating hypertension is lowering blood pressure, ratherthan the drug with which blood pressure is lowered, ischallenged substantially by these results’; he suggeststhat ‘these results will likely have profound implicationsfor future antihypertensive drug development’.* Antihypertensive and Lipid-Lowering Treatment to Prevent HeartAttack Trial** The doxazosin arm of the study was discontinued following reviewsof the interim data [see Inpharma 1229: 5, 18 Mar 2000; see Inpharma1229 p5; 800801966].† The combined CHD endpoint comprised CHD death, nonfatal MI,revascularisation procedures and hospitalised angina. The combinedcardiovascular disease endpoint comprised CHD death, nonfatal MI,stroke, revascularisation procedures, angina pectoris, congestive heartfailure and peripheral arterial disease.

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Inpharma 15 Apr 2000 No. 12331173-8324/10/1233-0001/$14.95 Adis © 2010 Springer International Publishing AG. All rights reserved