Nonsteroidal anti-inflammatory drugs (NSAIDs) are common
medications, available over the counter as well as by prescription, used to
relieve pain, reduce fever and decrease inflammation caused by arthritis, low
back problems and soft tissue injury. There are many NSAIDs on the market
including ibuprofen (Motrin, Advil), naproxen (Naprosyn, Aleve), indomethacin
(Indocin), diclofenac (Voltaren) and celecoxib (Celebrex). NSAIDs have been around since the 1960’s and
may be the most widely prescribed class of medications in the world. Along with
their beneficial effects, NSAIDs have significant side effects including
gastrointestinal bleeding, kidney problems and several adverse cardiac effects.
What are the cardiac side effects and how important are they?
Can NSAIDs increase the risk for a heart attack? Heart
attacks occur when a plaque in a heart artery ruptures, a blood clot is formed
over the rupture and blood flow to the heart muscle is stopped. Plaque in a
heart artery is comprised of cholesterol and inflammation is felt to play an
important role in plaque build up. In fact, in addition to their usual
properties, aspirin and statins are felt to lower the risk for a heart attack
due to their anti-inflammatory effects. Do
the anti-inflammatory effects of NSAIDs provide the same protection against
heart attacks? Unfortunately the answer is no.
Prior to 2004, NSAIDs were felt to be safe for heart patients. In 2004,
the NSAID rofecoxib (Vioxx) was removed from the market due to its increased
risk for heart attack and stroke, especially with prolonged use and at high
doses. After the withdrawal of Vioxx, a
large study testing the heart risks of many NSAIDs was performed and recently concluded.
The study found that all NSAIDs (including Naprosyn, which was thought to have
acceptable cardiac safety) increased the risk for heart attack. The risk starts
in the first week, is greatest in the first month of usage and is increased at
high doses.
Can NSAIDs increase blood pressure and cause swelling? If a
patient goes to the doctor with new onset of swelling in the legs or with an
increase in blood pressure, one of the first questions asked is whether the
patient is taking an NSAID. NSAIDs mechanism of action is to reduce certain
factors that result in inflammation. Unfortunately, those same factors have a
good effect on kidney function. Reducing these factors leads to a reduction in
the blood flow to the kidneys. If the
blood flow to the kidneys decreases, the kidneys feel the body is dehydrated
and respond by retaining more sodium (salt) and water. This leads to increased swelling and an
increase in blood pressure. In addition, NSAIDs can block the effect of certain
high blood pressure medications (ACE or ARBs), leading to hormonal activation
and further retention of salt and water. Due to these effects, all NSAIDs have
warnings on their labels stating that they may increase blood pressure or cause
swelling.
Can NSAIDs cause congestive heart failure (CHF)? The link
between NSAIDs and CHF has been known for more than 20 years. NSAIDs can cause CHF
in several ways. NSAIDs can increase the blood pressure, increasing the workload
of the heart. If there is a weakened heart for any reason, that extra workload can
tip the heart into CHF. In addition, if
more salt and water is retained in a patient with a weak heart, the excess
fluid accumulates in the lungs and CHF occurs.
In fact, the use of any NSAID was associated with a 19% increase in admission
to the hospital for CHF.
All of this data does not imply that NSAIDs are bad drugs or
drugs that should be avoided. On the other hand, NSAIDS are not harmless over
the counter medications that can be taken without risk. Patients who are at a high
risk for a heart attack, patients with CHF or high blood pressure perhaps
should avoid NSAIDs or use them at the lowest possible dose and for a short
period of time. Low risk patients should be able to take NSAIDs with
appropriate caution.