When hypertension mega-trials disagree-what do you do?

The topic of conflicting results from BP treatment trials was considered in a roundtable discussion in the July 2005 issue of The Journal of Clinical Hypertension by Drs.Thomas Giles,Marvin Moser and Suzanne Oparil.The JCH is on line but not all articles are available including this one. Here are some of the highlights and my thoughts.The starting point is the assertion that there are major differences between the outcome of ALLHAT, the second Australian National BP Study (ANBP2),and ASCOT. Giles said they all actually show the same thing,namely lowering BP is a good thing and the benefits derive from the BP lowering per se. This is not to say phenotypic differences may not be important.There were apparent phenotypic differences evident in ALLHAT. 36% of the 42,000 participants(when we say mega trial for ALLHAT we really mean MEGA)were African Americans and in that group the diuretic was better in regard to stroke and heart falure than was an ACE inhibitor. Dr. Oparil said that in ALLHAT African Americans from the southeastern United states were "over-sampled" and many of that group had higher BMIs (the average was almost 30).In ANBP2,an ACE inhibitor seemed better and the participants were mostly white.So the population from which these two trial recruited participants was clearly different and that could explain some of the apparent differences in outcomes.These trials are context dependent,ie. which drugs,which dose of the drugs, which combination(often the combination and the sequencing of additions of drugs seems contrived and not realistic) to which group of patients for how long.It should also be remembered that with large numbers, small difference in outcomes become statitstically - but not necessarily clinically -significant and when multiple subgroups are analyzed statistically significant differences always are found. Another issue is are the drugs always compared fairly.
For example, in ASCOT the beta-blocker (atenolol) was begun at a 50 mg per day dose, which -according to Dr. Giles- is not an adequate dose. Dr. Oparil pointed out that another issue is the duration of the trials ( often 3- 4.5 years) may not allow adequate time to discern the longer term metabolic effects e.g. diuretics and glucose intolerance risks.
The bottom lines may be: 1)the lowering of BP may be more important that the particular drugs used (with the proviso that in certain groups of patients a particular class of drugs may be important to use as in ACE inhibitors in diabetics)
2.Mega-trials are complex both in design, interpretation and in selection of participants.The devils really are in the details and overblown pretentious "final" conclusions re choice of BP medications made today and codified in guidelines may well seem naive and silly to future students of Blood Pressure.
Some- but not all- patients with HBP are salt sensitive which might serve to remind us that maybe we should take over-emphasized conclusions taken to be universally true with a grain of salt.