The arrival in Canada last month
of the first in a promising new class of antihypertensive
drugs has been met with enthusiasm by physicians.
Aliskiren has been eagerly anticipated.
"In 15 years we have not had a new class of antihypertensive
agents," says Dr Ernesto Schiffrin, the Canada Research
Chair in Vascular and Hypertension Research and chief
physician at the Jewish General Hospital in Montreal.
Aliskiren, he says, is "new, effective and devoid of
major side effects."
Nevertheless, the drug's release
has stirred up some controversy after an American researcher
challenged the generally accepted claims about aliskiren's
safety.
CHAIN
REACTION
Aliskiren is the first antihypertensive medication to
inhibit renin, an enzyme secreted by the kidneys to
raise the body's blood pressure after a drop in blood
volume is detected.
Once in the bloodstream, renin
initiates a chain reaction. It splits the molecule angiotensinogen
to produce Angiotensin I, or Ang I. Ang I is then transformed
by angiotensinconverting enzymes (ACEs) into Angiotensin
II, or Ang II. And finally, Ang II binds with angiotensin
receptors that, in turn, trigger vasoconstriction.
Existing antihypertensives, like
ACE inhibitors and Ang II receptor blockers (ARBs),
target the links in that chain reaction that occur only
after renin is released.
A July 2007 study in The Lancet
found that eight weeks of combined therapy with aliskiren
and the ARB valsartan had a massive effect on hypertension
— around a 40% greater drop in blood pressure in
patients who received the combo than those who received
just one of the drugs. Research has shown aliskiren
works as well as other antihypertensive medications
and it has no major side effects at recommended doses
(except in pregnant patients). "When I get the right
patient," Dr Schiffrin says, "I plan on prescribing
it."
REACTIVE
REACTIONS
The controversy surrounding aliskiren stems from a May
2007 review in the American Journal of Hypertension
that raises serious questions about the drugs safety.
The paper, authored by the journal's editor, Dr John
Laragh, and his wife, Dr Jean Sealy, suggests that in
some patients aliskiren may actually cause a blood pressure
increase.
"Aliskiren causes a greater reactive
rise in renin production than any other antihypertensive,
which could be dangerous for patients with the most
highly reactive renin systems," Dr Laragh told Medscape
last year. But the vast majority of hypertension specialists
disagree with that interpretation, some quite vehemently.
"This is all hogwash," Dr Matthew
Weir, a University of Maryland professor and an author
of several papers on aliskiren, fumed to Medscape. "The
blood pressure lowering data with aliskiren are similar
to all other marketed drugs. The FDA agrees. It does
lots of good things."
ENDPOINT
DATA NEEDED
The Laragh-Sealy paper has been roundly dismissed. For
the most part, Canadian hypertension specialists agree
with Dr Weir's assessment of the controversy as "theoretical
mumbo jumbo." "The paper did not make sense," Dr Schiffrin
says.
Dr Schiffrin cautions that the
true test of any new antihypertensive medication is
whether it improves heart function in the long run.
"We always need heart outcome data," he stresses. And
although comprehensive, longterm heart outcome results
for aliskiren are not yet available, he says, the appropriate
studies are underway.
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