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Specific guide to this web site for:

 1.  Medical School
      in Statistics

 2.  Medical Students

 3.  Science media writers

 4.  High School & College
     Statistic Teachers


1. Harvard led MI study

2. JACC study 

   (J. of Amer. Coll.

3. NEJM cath study

4. Amer. J. of Cardio.
    review of literature


Oat bran study

Pregnancy & Alcohol

Are Geminis really
9. Columbia 'Miracle' Study  

Additional Topics:


Limitations of Meta-Analyses

Large Randomized Clinical Trials

Tale of Two Large

Advocate meta-analyses

Network meta-analyses





The ALLHAT hypertension trial1 is a large study concerning the treatment of blood pressure which compares three drug treatment protocols. 

 Blood pressure treatment trials are usually not the simple comparison of one single drug to another.

Since multiple drugs are often needed for blood pressure control, trials are actually comparing specific multiple drug treatment protocols against one another, rather individual antihypertensive  drugs. 

A set of drugs can have a good initial drug, but if the subsequent sequence of follow up drugs are not an optimal fit for the initial drug, it places the initial drug at a disadvantage.

One treatment strategy in the ALLHAT trial started with a diuretic. A second treatment strategy was initiated with lisinopril, an ACE inhibitor. A third treatment strategy started with amlodipine, a calcium channel blocker.

However, the ALLHAT trial protocol specified subsequent drugs to be given in combination with lisinopril and amlodipine that do not reflect optimal care or current medical practice. 

An ACE inhibitor such as lisinopril is most commonly followed by a diuretic when a second drug for blood pressure is required. This combination was prohibited by the ALLHAT trial protocol until multiple other suboptimal choices for combination with lisinopril had been employed (atenolol, reserpine and clonidine). The potentially efficacious combination of a calcium channel blocker and ACE inhibitor was also not allowed by ALLHAT trial protocol. Neither an ACE inhibitor nor a calcium channel blocker could be used with a diuretic as a second medication.

The ALLHAT trial results reflect the outcome for the particular combination of drugs defined by trial protocol, not the outcome for the initial drugs in isolation.

Unfortunately, the ALLHAT authors came to conclusions unwarranted by the results and limitations of the trial. This same trial subsequently affected the current hypertension treatment guidelines (JNC7) in the United States.

The ALLHAT trial results are only broadly applicable to the treatment of hypertension if the following fallacies are true: 

  1. The initial treatment with an ACE inhibitor or a calcium channel blocker precluded the use of a diuretic.
  2. Starting an ACE inhibitor or calcium channel blocker required stopping diuretic therapy, including in patients with prior myocardial infarction or patients with LVH.
  3. An ACE inhibitor and calcium channel blocker could not be used in combination.

  4. Equivalent blood pressure endpoints could not be achieved if an ACE inhibitor was used as the initial drug.

1. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. 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). JAMA 2002; 288: 2981-2997