The largest analysis to date of
the role of blood pressure drugs in provoking diabetes
finds that the newer drug classes are the safest when
it comes to avoiding this most dangerous of side effects.
Writing in the January 20 issue
of the Lancet, researchers at Rush University,
Chicago, pooled results from 22 randomized long-term
trials of ACE inhibitors, angiotensin receptor blockers
(ARBs), calcium channel blockers, beta blockers and
diuretics. The trials, which dated from 1966 to 2006,
involved 143,153 patients. Some were head-to-head, others
placebo-controlled.
NOVEL
TECHNIQUE
This potpourri of research data has been pooled using
what the authors call a novel statistical technique,
allowing results from different trials to be compared,
even when the drugs never went head-to-head in actual
trials.
"Most other studies of the association
between drugs used mostly for high blood pressure could
have been confused by differences in the patients studied,"
said author Dr William Elliott. "By only including studies
that used randomization to minimize and balance differences
between those assigned to different antihypertensive
drugs, and by using a novel technique that can attribute
risk both between agents that have been directly compared,
and those that compare the results indirectly, we can
see differences that other techniques cannot."
The 22 trials comprised a total
of 48 treatment groups. Placebo, beta blockers and calcium
channel blockers were tested in nine different groups;
diuretics and ACE inhibitors in eight groups apiece,
and ARBs in five groups. Seventeen of the trials involved
patients with diagnosed hypertension, the rest involved
either high-risk patients or those with heart failure.
The researchers discovered that
ARBs and ACE inhibitors reduce the risk of new-onset
diabetes in hypertensive patients, beta blockers and
diuretics increase the risk, and calcium channel blockers
appear not to affect risk. Patients taking diuretics
can expect to develop diabetes at a rate nearly 50%
higher than those taking placebo.
NATIONAL
VARIANCES
The authors are quick to note that they aren't making
treatment recommendations, given all the other considerations
that the prescribing physician must take into account.
A patient who's just had a heart attack will clearly
need a beta blocker, while a patient with kidney disease
is still in need of a diuretic, they suggest. In these
cases, the risk of diabetes simply has to be borne.
Those comments naturally fit the
American treatment paradigm rather better than the Canadian
one, in which recent heart attack patients are likely
to get both a beta blocker and an ACE inhibitor, while
kidney patients are likely to get both an ACE inhibitor
and a thiazide diuretic. In cases of intolerance to
ACE inhibitors, Canadian doctors generally switch to
an ARB in both patient categories.
That means these Canadian patients
are getting one drug which allegedly increases diabetes
risk, and another which apparently lowers it. Where
that leaves these patients is unclear, as such combinations
weren't studied in the Lancet meta-analysis.
The findings will have different
significance to different countries. In the US, where
the diuretic is king, it may prompt some second thoughts.
In Britain, where the combination of diuretics and beta-blockers
is now officially discouraged because of diabetes risk,
it will be taken as a vindication.
While Americans still rely heavily
on older drugs, they tend to use them much more aggressively
than most countries. Americans have always believed
they keep a firmer lid on hypertension than other countries,
and this opinion seems borne out by a new study in the
Archives of Internal Medicine, which found the
US markedly outperformed five European countries in
getting high blood pressure under control.
The study compared 21,053 patients
in six countries — the US, Britain, France, Germany,
Italy and Spain. The American patients were being spotted
earlier, with pre-treatment readings averaging 161/94
mmHg, compared to 170/97 in Europe. And their latest
reading averaged 134/79, compared to 142/82 in Europe.
Patients whose blood pressure did not fall after beginning
treatment were much more likely to get a dose increase
in the US.
Interestingly, this study found
diuretic use equally common in both continents, and
combination therapy more common in the US, suggesting
that many American doctors are going above and beyond
the minimum requirements of their national guidelines.
NEW
BP GUIDANCE
While there are no figures allowing a direct comparison
of Canadian treatment, Canada makes a noble effort to
match the Americans' zeal in attacking hypertension.
New guidelines issued last month by the Canadian Hypertension
Society announced an ambitious new target: from now
on, patients in the "high-normal" category, meaning
those who don't quite meet the criteria for hypertension
but who average over 130/85, should have annual blood
pressure measurements.
These high-normal patients, it's
now estimated, run a more than 40% risk of developing
full-blown hypertension in the next four years, or 60%
if they are overweight. Two-and-a-half million Canadians
are believed to fall into this category.
Having said that, even normotensive
55-year-olds are now estimated to have a 90% chance
of developing hypertension over the next 20 years. In
fact, the Canadian Hypertension Society and the Heart
and Stroke Foundation now estimate that 90% of all Canadian
adults will develop hypertension at some point in their
lives.
The guidelines don't recommend
actually treating patients in the high-normal category.
But given the terrifying number of heart attacks that
occur in patients hovering just below 140/90, it may
only be a matter of time before our whole treatment
paradigm is shifted 10 mmHg downwards. That could put
about a third of Canadian adults on antihypertensive
treatment in years to come.
The new guidelines still cling
to the fantastically complicated multiple visit method
of eliminating "white coat hypertension," the tendency
for false positive tests of nervous patients in doctors'
offices. Depending on the readings, this system can
involve up to five visits before a diagnosis is made.
But the Heart and Stroke Foundation is painfully aware
that patients aren't being overdiagnosed, they're actually
being underdiagnosed. Evidence is piling up that delaying
treatment of hypertension by just a couple of months
can dramatically increase the risk of cardiovascular
events a few years down the road.
So there are now shortcuts to diagnosis,
of which the most effective is the ambulatory home blood
pressure monitor. The new guidelines encourage the use
of these devices and even recommend specific models.
It's vital to remember with this method that hypertension
is diagnosed at lower readings: 135/85 for a daytime
ambulatory average, and just 130/80 for a 24-hour average.
The guidelines can be downloaded
at: www.hypertension.ca/chep/en/Recommendations.asp
or email info@hypertension.ca
for a pamphlet.
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