Follow-up on Dr. Joe’s e-news, aspirin/ACE inhib
The issue of my recent recommendation on avoiding aspirin
when using an ACE inhibitor has raised some serious questions
and a lot of them. Unfortunately I am unable to respond to all the
individual inquiries. Hopefully this will answer your questions.
Currently, it is perceived that a significant part of the beneficial
effect of ACE inhibitors is related to augmentation of bradykinin
levels, which among other effects stimulate the release of
prostacyclin. Aspirin, on the other hand, inhibits the production
of prostacyclin by blocking cyclooxygenase. Prostaglandins play
an important endogenous vasodilatory role and counteract the
enhanced peripheral vasoconstriction state in congestive heart
failure. Thus, the counteracting effect of ASA on the
augmentation of prostacyclin synthesis by ACE inhibitors could
result in a potential reduction of the beneficial effects of the ACE
inhibitor’s and could be of great importance.
Arch Intern Med 2000 May 22;160(10):1409-13
The Basic Vascular Protection, which we have put together, is just
basic, but we do constantly review it for drug-drug interaction of
any significance. This is the first time in 3-4 years we have made
any changes, but all this is under constant evaluation. It is not until
thought leaders reach a consensus or our data reaches significance
do me make changes. For patients, see below.
"Antihypertensive efficacy of angiotensin converting enzyme
inhibition and aspirin counteraction.
AUTHORS: Guazzi MD; Campodonico J; Celeste F; Guazzi M;
Santambrogio G; Rossi M; Trabattoni D; Alimento M
AUTHOR AFFILIATION: Istituto di Cardiologia dell’Universita
degli Studi, Centro di Studio per le Ricerche Cardiovascolari
CNR, Fondazione Monzino, IRCCS, Milano, Italy.
SOURCE: Clin Pharmacol Ther 1998 Jan;63(1):79-86
RESULTS: The 100 mg dose was ineffective. However, 300 mg
aspirin had an antagonistic effect in 57% of patients in group 1 and
50% of patients in group 2: mean arterial pressure was lowered by
63% and 91% less, respectively. Results were independent of the
drug administration order. In "responders," aspirin significantly
attenuated the renin rise associated with ACE inhibition.
CONCLUSIONS: These findings suggest that a number of
ACE-inhibited patients are susceptible to 300 mg/day aspirin,
regardless of hypertension severity. Antagonism may be mediated
through prostaglandin inhibition according to predominance, in an
individual patient, of prostaglandin activation (also as a renin
secretory stimulus) or angiotensin blockade by enalapril."
So faced with the fact that this may be a dose related phenomenon,
why not use low dose aspirin? The answer lies in the complexity
of aspirin use in diabetes. Will the aspirin/ACE connection
· Block ACE kidney effects?
· Block eye effects?
· Block nerve effects?
· Be worth these risks to avoid heart disease?
As was mentioned in another eNews, there is now L-arginine,
an alternative that can play a role in preventing heart disease.
Our preliminary data indicates that this substance does
not harm in areas outside of heart disease.
If you want to do the Medline search
that I have done, the search
(Boolean) strategy I used was angiotensin converting enzyme
inhibitor/aspirin/drug interaction and you will find 32 reports
on this subject since 1966. You will note that indomethacin, a
precursor to all the Advil-like medications, set all this off. It was
felt to be a problem in the long run, not in the brief time that
most of the medication was used. If the plan is to use it long
term, this and all medications like it should be watched.
You are now being exposed to the next level of medical
judgment. This is what your doctor does daily. It is not just a
single piece of news but a compendium of information. When
you leave the doctor s office you have to know what to do. How
to live your life when you also know that the there is no medicine
that is completely safe. What you do know is that not to participate
with your doctor in these decisions exposes you to the highest, most
cruel risk of all the natural history of diabetes.
There is no quick consensus. When you look at the 32 articles that
are on Medline, about a third of them say conflicting data or we
don’t have enough data to be sure . A consensus in medicine means
that 80 % of doctors agree. My epiphany came while listening to
one of the major experts in hypertension say don’t use them
together . If we were faced with an inferior or more expensive
alternative, I might stay with the aspirin.
As we watch people over the years, we are seeing a subtle new
thing.
· In the early 90 s we virtually stopped all renal disease
· In the late 90 s heart disease also responded well.
Now we are seeing in some people, a slow progression of renal
problems that make it a concern that we are not doing enough or
is it that low dose aspirin counteracting the ACE? You and I
have to make a decision as to what to do. We don’t have the
luxury of awaiting for all the scientific data to come in. It’s your
time.
Dr. Joe, the Diabetes Doctor