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Grant E. Deger MD FACP

It is both a responsibility and a joy for health care professionals to keep current in their respective medical literature. For in giving our patients the best advice, we are also giving them the best outcomes. We must do what we can to protect our patients from bias, testimonials, and unproven treatments. But for us to find truth and a semblance of certainty in a sea of print is often a relentless and difficult search.

Let me introduce you to a major NIH (National Institute of Health) research project, which, because of its sheer size and diversity, will shed as much clarity on issues of hypertension and lipid treatment as possible. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) is the largest long-term blood pressure and cholesterol lowering drug intervention trial ever attempted.

Remember that atherosclerosis is the leading cause of death and disability. Its dominant position on death certificates will actually increase over the next 30 years. Developing countries face an epidemic of cardio-vascular disease. A good working knowledge of ALLHAT will ultimately shape the best cardiovascular interventions for your patients in the realm of hypertension and lipid control. ALLHAT has recruited 42,453 high-risk patients age 55 and older, the average age being 67. Participants will be followed for an average of 6 years. In ALLHAT the demographics are as follows: women 47%, history of heart disease 45%, African-Americans 36%, diabetics 36%, current smokers 22%, and Hispanics 16%.

There are two components to this huge trial. The first component is a double blind comparative study of four antihypertensive regimens. Patients are randomized to one of these four drugs representing major classes of antihypertensives: 1.chlorthalidone (diuretic), 2. lisinopril, (angiotensin converting enzyme inhibitor), 3.amlodipine (calcium channel blocker), and 4. doxazosin (alpha-one blocker). The end point for the first component is non-fatal heart attack and all CHD death.

The second component is a randomized open-label subset wherein lipid-lowering therapy with pravastatin, an HMG-CoA inhibitor is compared to usual care. This wing has 10,359 participants randomized from the larger group above. The average age of these clients is 66 with 1/3 of the total being 70 years of age or older. Other demographics of this subset are as follows: women 49%, coronary and/or vascular disease 48%, diabetics 35%, blacks 34%, current smokers 23%, ECG LVH 19%, and low HDL 11%. The end point of the cholesterol-lowering wing is total mortality.

Why perform this vast study in the first place? With all the hypertensive and lipid studies to date, why do we need yet another? The answer is clear. The issues ALLHAT has chosen to solve remain left to be unraveled. The major classes of antihypertensive drugs all lower blood pressure (the surrogate marker) well. But are the newer and more expensive classes able to reduce end points better than a simple diuretic? Does any class of blood pressure medication stand out as preferable for smokers, elderly, diabetics, minorities, or women? What is the effect of lipid lowering on the diverse subsets of ALLHAT populations, many of who are elderly?

Issues about diabetes are in the fore today, and ALLHAT has the statistical power to provide answers. Let’s review some of the recently completed trials and decide if all the answers are in. The diabetic population in the Syst-Eur Trial experienced superior outcomes compared to their non-diabetic fellows, and nitrendipine, a calcium channel was the major drug. The UKPDS trial showed no difference between captopril and atenolol as far as macrovascular or microvascular diabetic complications. The CAPPP study evidenced no difference in primary endpoints such as fatal & nonfatal MI, strokes, and other CV deaths between captopril vs. atenolol/HCTZ. The FACET research effort found no difference in lipids, renal function, or diabetic control when fosinopril was compared to amlodipine. But CV events were two times more common in the amlodipine group.



The HOT & UKPDS studies enhanced the credibility of the JNC VI recommendation to treat diabetics to a lower BP (130/85) than had been commonly accepted before. JNC VI also left open the question of primary therapy for hypertensive diabetics, finding cause to use any of the major classes of antihypertensives. Atenolol was found safe and appropriate in Type II diabetics with hypertension (UKPDS). There was no advantage in renal outcomes for ACE (UKPDS, ABCD, and FACET). The ACE groups had fewer CVD events than the dihydropiridine calcium channel blocker groups in FACET & ABCD. But there was no advantage for renal outcomes with ACE in these studies.

Are you somewhat confused by the data on diabetics just presented? Remember that ALLHAT has 15,000 hypertensive diabetics and substantial statistical power to help us make the best choices for this subset of our hypertensive practices. ALLHAT will also answer whether cholesterol lowering with a stain will lower all cause mortality in a group of 10,359 participants in a primary prevention lipid-lowering trial with a substantial representation of elderly, minorities, women, and persons with diabetes.

Antihypertensive drugs have multiple actions, most of which are good, but not all are desirable. Which of the drugs have the best long-term risk-benefit ratio? Which is most cost effective? Which drugs if any will become the choice for specific subgroups of hypertensives (elderly, diabetics, blacks, Hispanics, women, smokers, and patients with CHD, LVH, low HDL or hypercholesterolemia)?

Be aware of ALLHAT. Anticipate its far ranging results as it concludes in March 2002.


Grant E. Deger MD FACP

ALLHAT Investigator, Site 223A

*References to the initialed studies and reports cited above:

ABCD = Appropriate Blood pressure Control in Diabetes –470 diabetic patients

CAPPP = Captopril Primary Prevention Program –10,985 patients with a diabetic subgroup of 572

FACET = Fosinopril Amlodipine Cardiovascular Events Trial – 380 hypertensive diabetic patients

HOT = Hypertension Optimal Treatment –18,790 hypertensive patients with a diabetic subgroup of 1501

JNC VI = sixth report of the Joint National Commission on hypertension

Syst-Eur = Systolic Hypertension in Europe - 4695 hypertensive patients with a diabetic subgroup of 492

UKPDS = United Kingdom Prospective Diabetes Study - 1148 newly diagnosed diabetics

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