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Journal Club: ALLHAT

Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

Known as the "ALLHAT" Trial, discussed September 20, 2019

Key clinical take-aways from this article: 

• Why we should know it: In patients with hypertension, chlorthalidone, amlodipine, and lisinopril performed similarly in regards to fatal CAD and nonfatal MI.

• Prior to this, antihypertensives used to lower blood pressure were diuretics and beta blockers. This study set out to see how ACEs, calcium-channel blockers, alpha-adrenic blockers were as good or better than diuretics in preventing coronary heart disease or other cardiovascular disease

  • They started with 4 groups (were originally comparing Chlorthalidone, Amlodipine, Lisinopril, and Doxazosin), but the Doxazosin study drug was discontinued early

    • Chlorthalidone was found to be superior to Doxazosin & was previously reported after early termination of the Doxazosin arm of the trial. (lost 9061 participants of total from this arm)

• Older population studied - had to be older than 55, average was ~67 yo; 47% white, nonhispanic, 47% women

• Group thinks: African American patients should reach first for Calcium Channel blockers or thiazides, ACE inhibitors last

• Drawbacks:

  • They did not include beta blockers in their trial, which were already seen as something worth looking at during this time

  • They put weight on HF but this wasn't something they originally set out to look at/screen for - not something they had rigorous guidelines on

  • A large proportion of the participants may have had salt-sensitive hypertension, which may have swayed benefit towards the diuretic arm

  • The step-up therapy regimen may have introduced poorly tolerated antihypertensives to certain arms, which may have biased the results

Further food for thought:

• Dhruva SS, Huang C, Spatz ES, Coppi AC, Warner F, Li SX, Lin H, Xu X, Furberg CD, Davis BR, Pressel SL, Coifman RR, Krumholz HM. Heterogeneity in Early Responses in ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial). Hypertension. 2017 Jul;70(1):94-102. doi: 10.1161/HYPERTENSIONAHA.117.09221. Epub 2017 May 30. PubMed PMID: 28559399.
  • "Although diuretics are the most commonly prescribed antihypertensive therapy, hydrochlorothiazide is overwhelmingly used, with 50 million prescriptions in 2013 (excluding fixed-dose combinations). Chlorthalidone only accounted for 3% of prescriptions in patients with resistant hypertension, who may need a more potent diuretic. It is an open question, however, if hydrochlorothiazide has the same cardiovascular benefit as chlorthalidone."

Citation Information

Wright JT, et al. "Major Outcomes in High-Risk Hypertensive Patients Randomized to Angiotensin-Converting Enzyme Inhibitor or Calcium Channel Blocker vs. Diuretic". Journal of the American Medical Association. 2002. 288(23):2981-2997.

https://www.ncbi.nlm.nih.gov/pubmed/12479763

Additional Resources

1. ALLHAT Findings Revisted in the Context of Subsequent Analyses, Other Trials and Meta-Analyses

2.