HEART DISEASE RISK IN PATIENTS WHO CONSUME ANTI

INFLAMMIC DRUGS NON STEROID

Novia Susanti, Achmad Wahdi, Ahmad Fudhali

ABSTRACT
Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs that are often
prescribed by doctors and sold freely in the community. This drug has analgesic,
anti-inflammatory and anti-pyretic effects so its use is very common in the
community. A non-steroidal anti-inflammatory drug that is selective for the
enzyme cyclooxygenase-2 is safer for patients with gastric dysfunction because it
is protective against gastrointestinal, but this non-steroidal anti-inflammatory drug
can be dangerous for patients who have cardiovascular disease (heart failure,
hypertension, kidney disease and myocardial infarction). So that the use of
non-steroidal anti-inflammatory drugs is of particular concern to patients who
have a history of heart so as not to take drugs without a doctor's prescription and
consume excessively. So the aim of the journal review is to determine the risk of
heart disease in patients taking non-steroidal anti-inflammatory drugs.
INTRODUCTION
Non steroidal anti-inflammatory drugs (NSAIDs) are one of the most widely
used drugs in the world and these drugs are often prescribed by doctors and sold
freely in the community. But its use is limited due to gastrointestinal side effects,
and cardiovascular. NSAIDs are often used because of their good effectiveness as
analgesics, anti-inflammatory, and antipyretics. The effectiveness of NSAIDs is
derived from its ability to inhibit prostaglandin synthesis through inhibition of
cyclooxygenase enzymes. Cyclooxygenase enzyme is known to work on the
pathway of arachidonic acid conversion to prostaglandin and thromboxane, so that
when this enzyme is inhibited, arachidonic acid cannot be converted to
prostaglandin and thromboxane.
NSAIDs are developed based on their ability to inhibit the action of both
cyclooxygenase enzyme isoforms, both cyclooxygenase-1 and cyclooxygenase-2
enzymes. Selective NSAIDs against the enzyme cyclooxygenase-2 are considered
safer because they have protective properties against the gastrointestinal mucosa,
but it turns out that these drugs can aggravate heart disease in patients who
already have cardiac dysfunction.
The purpose of this study was to determine the risk of heart disease in
patients taking non-steroidal anti-inflammatory drugs.
Contents
Non-steroidal anti-inflammatory drugs are anti-inflammatory drugs that are
often used in the management of pain and inflammation. but has a risk of
gastrointestinal disorders (peptic ulcer), bleeding, and hypertension. Besides
having anti-inflammatory effects, NSAIDs also have the effect of being analgesic
and antipyretic.
NSAIDs are anti-inflammatory drugs that have a molecular structure that is
different from steroids. Chemically, NSAIDs are derivatives of acetic acid,
propionic acid, pyrazole, and other chemicals. NSAIDs work by inhibiting the
action of the cyclooxygenase enzyme. This enzyme plays an important role in the
pathway of arachidonic acid metabolism, which works to catalyze the change of
arachidonic acid to prostaglandin and thromboxane. There are two
cyclooxygenase enzyme isoforms namely cyclooxygenase-1 and
cyclooxygenase-2. Both of these enzymes have a similar structure, but in the
substrate binding channel the enzyme cyclooogsinegase-2 has a different side to
the cyclooxygenase-1 enzyme. This is what underlies the selectivity of this
enzyme inhibition by NSAIDs.
Cyclooxygenase-1 enzyme is found in platelets, vascular endothelium,
gastrointestinal epithelium, brain, spine, and kidneys. This enzyme functions to
regulate platelet function, protect the gastrointestinal mucosa, and protect against
kidney function if perfusion is impaired. The cyclooxygenase-2 enzyme is
activated by several cytokines and induces an inflammatory cascade. This enzyme
is found in atherosclerotic plaques, macula densa, and interstitial kidney medulla.
This enzyme plays a role in pain perception and metabolism of water and salt. The
NSAID work spectrum is divided into two: conventional NSAIDs that inhibit the
action of both cyclooxygenase enzyme isoforms and selective NSAIDs that only
work on cyclooxygenase-2.
 The end result of metabolic arachidonic acid catalyzed by cyclooxygenase
enzyme is prostaglandin I2 and thromboxane. Prostacyclin (prostaglandin I2) has
an anti-thrombotic effect and is produced from endothelial cells with the help of
the cyclooxygenase-2 enzyme, while thromboxane is produced by platelets with
the help of the cyclooxygenase-1 enzyme and has a pro-thrombotic effect.
The most commonly known side effect of NSAIDs is peptic ulcer, so
NSAIDs have been developed that selectively inhibit the enzyme
cyclooxygenase-2 and are believed to be safer for the stomach. But various studies
have shown an increased risk of cardiovascular disease in NSAID use, so the use
of NSAIDs is now a concern especially for patients who have had cardiovascular
disease from the start.
From the results of NSAID-inhibited arachidonic acid metabolism,
prostacyclin plays an important role in the pathophysiology of cardiovascular
disorders due to NSAIDs. Reduction in vasodilator levels of prostacyclin and
prostaglandin E2 and increased vasoconstrictor thromboxane levels in
non-selective NSAID use will lead to thrombosis, atheroma plaque
destabilization, and atherogenesis. Cyclooxygenase-2 enzyme is known as the
main source that helps the production of prostacyclin, which has a
cardioprotective effect on reperfusion injury in ischemic conditions. Prostaglandin
I2 (prostacyclin) has an important physiological role in the kidneys, so inhibition
of its synthesis can cause fluid retention. Fluid retention caused by inhibition of
prostaglandin synthesis can interfere with cardiovascular system homeostasis so
that patients who have cardiovascular disease will be susceptible to side effects
from the use of these NSAIDs. Inhibition of the cyclooxygenase-2 enzyme also
causes exacerbations of heart failure and hypertension, as well as cardiac
ventricular remodeling.
Semiselective NSAIDs (eg diclofenac and meloxicam) and non-selective
(for example ibuprofen and naproxen) increase the risk of cardiovascular disease.
A meta-analysis of clinical trials showed an increased risk of vascular disease by 3
times in patients taking selective NSAIDs compared to the placebo group.
Diclofenac increases the risk of coronary disease by 1.41 times greater than
placebo, while ibuprofen is 2.22 times greater. The meta-analysis showed that
high doses of naproxen were not associated with an increased risk of vascular
disease (RR 0.93; 95% CI 0.69-1.27) and coronary disease (RR 0.84; 95% CI
0.52-1 , 35).
Epidemiological studies have shown that NSAID consumption is not
associated with an increased risk of heart failure in people who did not have heart
disease before, but reported that edema occurs in 5% -10% of NSAID-consuming
patients, both non-selective and selective NSAIDs. The cause of this edema is
probably due to hypertension, increased capillary permeability, and sodium
retention. This is considered a side effect on the kidneys from NSAID use. The
results also did not show any cardiac dysfunction in patients with edema due to
NSAID consumption, so it can be concluded that NSAIDs do not directly cause
heart failure in patients without prior cardiovascular disorders. For patients with
congestive heart failure, NSAID use can aggravate and exacerbate heart failure.
This is evidenced from the Rotterdam study which showed a 10-fold increase in
the risk of eczema in heart failure patients who received one NSAID prescription
(RR 9.9; 95% CI 1.7-57). The pathophysiology underlying exacerbation of heart
failure is the inhibition of prostaglandin production causing sodium and water
retention, increasing systemic vascular resistance, and reducing the body's
response to diuretics.
From the results of Chatterjee's research, et al showed the prevalence of GI
complications (30.08%), heart disease (42.77%) and kidney (27.88%) with
NSAID use in India. So the most complications in heart disease due to excessive
use and drug use without the doctor's approval.
Summary
Non-steroidal anti-inflammatory drugs (NSAIDs) work as analgesic,
anti-inflammatory and anti-pyretic by inhibiting the cyclooxygenase enzyme.
NSAIDs are divided into two based on their selectivity: conventional NSAIDs that
inhibit the cyclooxygenase-1 and cyclooxygenase-2 enzymes, and selective
NSAIDs that only inhibit the cyclooxygenase-2 enzyme. The effectiveness and
side effects arising from NSAID consumption are related to prostaglandin
synthesis and thromboxane which are affected. Selective NSAIDs of the
cyclooxygenase-2 enzyme are safer for patients with gastric dysfunction because
they are protective against gastrointestinal, but this type of NSAID can be
dangerous for patients who have cardiovascular disease (heart failure,
hypertension, kidney disease, and myocardial infarction). In addition to worsening
cardiac function, NSAIDs can also interact with cardiovascular drugs, thereby
reducing the effectiveness of these drugs. So the use of NSAIDs is of particular
concern to patients who have a history of heart so as not to take drugs without a
prescription and consume excessively.