Risks of NSAIDs use and

cardiovascular adverse effects

Dr.Nancy Safwat Younis

Student name: Hadeel Alqahtani
Academic number: 220010256
 Introduction

NSAIDs are an extensively used class of medications, maybe the most widely utilized in the
world, because they have been linked to the treatment of pain in a variety of conditions (1).
NSAIDs have important analgesic and anti-inflammatory benefits in people with systemic
inflammatory diseases(2) (3) Despite this, NSAIDs are no longer the first-line treatment for
patients with systemic inflammatory illnesses due to their inability to control disease progression
and a variety of side effects, particularly at the gastrointestinal(4) and cardiac (5) levels.

Mechanism of action

By inhibiting the two forms of cyclooxygenase known as COX-1 and COX-2, NSAIDs reduce
the synthesis of prostaglandins and prostacyclins (6) Aspirin and other NSAIDs reduce the
production of thromboxane, which helps to their antiplatelet effect. Other NSAIDs, such as
ibuprofen, naproxen, diclofenac, and COX-2 inhibitors, work by inhibiting COX-2 more
effectively. COX-2 selective inhibitors (coxibs) have more anti-inflammatory, antipyretic, and
analgesic effects (7). Nonselective NSAIDs have a high risk of bleeding, especially
gastrointestinal bleeding, which is considered to be caused by gastric irritation, antiplatelet
effects, and a loss of prostaglandin-mediated mucosal healing (8)

COX-1 is expressed in most tissues on a constant basis, whereas COX-2 is largely triggered by
inflammation and endothelial tissue shear stress (9) As a result, COX-1 inhibition is responsible
for the majority of NSAID gastrointestinal side effects, whereas NSAIDs that specifically inhibit
COX-2 may minimize the risk of gastrointestinal toxicity. Early trials evaluating coxibs vs.
standard NSAIDs appeared to demonstrate similar analgesic efficacy and fewer gastrointestinal
effects (10) Unfortunately, later placebo-controlled trials have conclusively shown that coxibs are
linked to an increased risk of atherothrombotic vascular events.

NSAIDs are contentious when it comes to cardiovascular safety. Randomized placebo-controlled

clinical trials have shown an elevated risk of significant cardiovascular disease for various
coxibs(12) (15) However, the cardiovascular safety of older conventional NSAIDs is unknown
(16). According to meta-analyses of observational studies(17)(18), cardiovascular risk varies by
pharmacological class, with diclofenac having a higher risk than naproxen. Otherwise, according
to a meta-analysis of clinical trials(16), diclofenac and ibuprofen are more dangerous than
naproxen (Table 1). Researchers observed a link between ischemic cardiovascular events and the
use of nonselective and widely available NSAIDs such as ibuprofen and diclofenac, especially
when taken together at higher doses and by patients with known cardiovascular disease(16) based
on observational studies (19).
(Table 1)

NSAIDS and cardiovascular side effects

 People who take NSAIDs for a long time—weeks, months, or even years—face higher risks and
problems. People who take an over-the-counter NSAID for more than 10 days should consult a
doctor, and NSAIDs should be taken in the smallest effective dose for the shortest time possible,
according to the US Food and Drug Administration.(20)
- Cardiovascular Risks
The US Food and Drug Administration has said that some people taking NSAIDs are at an
increased risk of heart attack or stroke, based on research.(20)(21)It can happen as early as the
first few weeks of taking an NSAID. Is the most dangerous for persons who have had a heart
attack or who have other cardiac problems or have risk factors for heart events The risk of
NSAIDs appears to be greatest at larger doses of medication, according to research. There were
several important findings from the analysis:
When high doses of the NSAID diclofenac were taken, the risk of heart attack or stroke increased
by one-third.(22) Celecoxib (Celebrex) and ibuprofen posed similar risks (Advil, Motrin).(22)
There was no evidence that using naproxen (Aleve, Naprosyn) increased the risk of heart attack
or stroke.3 All four NSAIDs studied—diclofenac, ibuprofen, celecoxib, and naproxen—increased
the risk of heart failure by double.
Ibuprofen and naproxen both have the potential to cause cardiovascular complications. They thin
the blood, which might cause to bleeding if done too often. Individuals using blood thinners or
anticoagulants should avoid ibuprofen because of this thinning effect and naproxen. Ibuprofen
and naproxen also can reduce the effectiveness of some blood pressure medications and diuretics
(water pills). According to several studies, celecoxib can increase the risk of cardiovascular
issues (Celebrex).(22) The FDA does not consider any NSAID to be riskier than another,
however the American Heart Association recommends that those who are already at risk for
cardiovascular events use celecoxib only if no other options are available.(23) Individuals who
use celecoxib should also have their blood pressure and kidney function checked as a precaution,
according to the American Heart Association. Stopping NSAIDs Suddenly Poses Heart-Related
Risks
Despite the risks associated with taking NSAIDs daily, people who have been taking NSAIDs
daily for long periods of time should not stop taking them abruptly.(24)
The body's reaction to such a cutoff may increase the chance of blood clots, increasing the risk of
heart attack or stroke. Instead, someone who takes NSAIDs on a regular basis should consult a
physician about the best approach to taper off. Risk of Stomach Problems
Because of the danger of bleeding in the gastrointestinal tract, especially the stomach, NSAIDs
should be avoided by people who have ulcers or sensitive stomachs.(23)
People over the age of 65, as well as those using blood thinners or corticosteroids, are
more susceptible to gastrointestinal issues. These problems include:
 Upset stomach\sUlcers
 Stomach bleeding
 Drinking alcohol can increase the risk of stomach problems.
Anyone taking NSAIDs orally should eat something before taking them. When using
NSAIDs, a doctor or pharmacist may recommend that you take another medication to
protect your stomach.
- Kidney Damage Risks
This increased risk exists because NSAIDs can reduce the amount of blood reaching the kidneys,
slowing kidney function. Water and salt retention, high blood pressure, and electrolyte
imbalances have been linked to NSAIDs’ effect on the kidneys. In rare cases, kidney failure can
result.(25)
NSAIDs should not be taken without consulting a doctor if you have compromised kidney
function.(25)
- NSAID Allergic Reaction
There is a chance of an allergic reaction, just like with other drugs. Allergic response symptoms
include:
 Inflammation of the face
 Wheezing
 Hives or a rash on the skin
 Blisters
 Face flushed
Anyone having problems breathing should seek medical help right away. Any responses or
adverse effects should be reported to the doctor, even if they do not appear to be serious.(26)

Conclusion

In conclusion, NSAIDs use exhibits a great risk of major cardiovascular events occurrence and
the safest drug in terms of cardiovascular side-effects is naproxen. Despite this, clinical
recommendations advise caution while using NSAIDs in patients with a history of cardiovascular
disease due to their adverse effects profile and concerns about the link between NSAIDs and
greater incidence of ischemic cardiovascular events.(27)(28)

However, because these medications are readily available, generally well tolerated, and often an
alternative treatment in patients with severe or functionally impairing arthritis, physicians are
often pushed to use them, despite their cardiovascular risk profile.(8)
Thus, an accurate selection of patients and an adequate drugs’ choice should be always advised
and performed to minimize the risk of serious adverse(28)

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