Download Caution urged in use of NSAIDs in heart patients

There is an urgent need for national guidelines on the safe use of
NSAIDs in patients with a history of IHD, write Caroline O’Connor
and Judith Kavanagh
40 FORUM September 2013
Figure 1: Indication for NSAID prescribing
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Recent evidence in a large Danish cohort suggests that
even short-term (less than one week) use of nonsteroidal
anti-inflammatory drugs (NSAIDs) in those with a previous
history of myocardial infarction (MI), significantly increases
recurrent MI and risk of death from MI.1 This research, as
well as a review carried out in October 2012 by the European Medicines Agency, indicates an increase in the risk
of cardiovascular adverse effects with diclofenac compared
with other non-selective NSAIDs, similar to the risk with
COX-2 inhibitors.2
The Danish study showed that diclofenac was associated
with a higher risk of death at the beginning of a course
of treatment than rofecoxib, which was withdrawn from
the market in 2004 due to the increased risk of stroke/
MI. The National Medicines Information Centre (NMIC) and
the Irish Medicines Board have highlighted this research in
their recent bulletins.3,4
NSAIDs are commonly prescribed in primary care.5 The
latest data expands on previous studies of NSAID safety, and
raises several important questions for GPs. What are the indications for NSAID prescribing in the primary care setting?
For what duration should we prescribe them? Could safer
alternatives be considered? And how common is the problem
of NSAID prescribing in those with documented ischaemic
heart disease (IHD), or with significant risk factors for IHD?
Aims
We carried out an analysis of the prescribing of NSAIDs in
a large Dublin general practice, by examining:
• Individual agents favoured
• Indication
• Duration
• The concomitant prescribing of paracetamol.
We set out to identify the number of patients who had
a history of IHD or a significant risk factor for this, and
who were prescribed NSAIDs. We aimed to address whether
there is a need for prescribing guidelines on the use of
NSAIDs in those with IHD.
Methods
The clinic’s active patient list (n=10,000) was studied by examining the practice management software to
identify patients over 50 years of age who had been prescribed NSAIDs for any duration, over a two-month period
in late 2012. Those with documented IHD as well as
those with diabetes and/or hypertension were identified.
A documented history of IHD was taken to mean previous diagnosis of angina, myocardial infarction, coronary
artery stenting or coronary artery bypass grafting (CABG).
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Caution urged in use of
NSAIDs in heart patients
All of the prescribed NSAIDs at the clinic were included
(diclofenac, ibuprofen, mefenamic acid, naproxen, etoricoxib and celecoxib). A record was kept of the indication
for treatment and the duration of prescription, as well as
whether the patient was also prescribed paracetamol.
Results
Demographics, agents prescribed, duration of prescription
Of the 108 patients prescribed NSAIDs during the period
of the study, 45 were male (42%). Ages ranged from 50-87
years. Diclofenac was the NSAID prescribed in 60/108
(56%) of cases (includes four patients prescribed Arthrotec,
a combination of diclofenac and misoprostol), naproxen in
13/108 (12%) of cases (includes 12 patients prescribed
Vimovo, a combination of naproxen and esomeprazole), ibuprofen in 11/108 (10%), mefenamic acid 11/108 (10%)
and etoricoxib or celecoxib 14/108 (13%).
IHD/risk factors for IHD
Some 39/108 (36%) patients had established ischaemic
heart disease or risk factors for cardiovascular disease at
the time they were prescribed NSAIDs. Hypertension was
the risk factor in 19/108 cases (18%), diabetes in 6/108
(5.5%), hypertension and diabetes in 6/108 (5.5%), IHD
in 4/108(4%), previous MI in 2/108 (2%) and previous
coronary artery bypass grafting in 1/108 (<1%).
The mean duration of treatment in the 39 patients with
IHD was 265 days and 22/39 (56%) were prescribed
NSAIDs for longer than one month; 6/39 (15%) were prescribed NSAIDs for a year or longer.
Indications for NSAID prescribing, and prevalence of
concomitant paracetamol prescription
Figure 1 displays the indications for the NSAIDs prescribed in the 108 patients. Some 29 of the 108 patients
(27%) were concomitantly prescribed paracetamol. For
those prescribed NSAIDs for longer than one month, 17/59
(29%) were also prescribed paracetamol.
Discussion
The safety of prescribing NSAIDs even for short duration
(<1 week) has been challenged.1
It is likely that our study underestimates those with, or
at risk of, IHD. The analysis is reliant on correct coding
of risk factors. In addition, we have not identified those
with hyperlipidaemia or those who smoke. Indeed, advancing age and sex in themselves can each independently be
considered inherent risk factors. Bearing these factors in
mind, it is likely that the number of patients at higher risk
of cardiovascular events is underestimated in our study.
It is disconcerting that diclofenac is the most commonly
prescribed NSAID in this study. When diclofenac was specifically investigated in the Danish study, it was noted that
the increased risk of death and MI became apparent immediately after patients start to take it, and the risk persisted
throughout the course of treatment. It was shown that
naproxen and ibuprofen were not as high risk as diclofenac.
Diclofenac was prescribed as the preferred agent in
53.9% of (NSAID) prescriptions filled in Ireland in 2010,
making it by far the most commonly prescribed NSAID.6
This is clearly represented in the data gathered in this
study, where it can be seen that 56% of NSAID prescriptions were for diclofenac.
Many indications for NSAIDs in this study do not have
an underlying inflammatory component. Nearly all patients
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would likely benefit from either replacing the NSAID with
paracetamol, or the addition of paracetamol to their NSAID
prescription with a view to limiting the cumulative dose of
the latter. Although NSAIDs have been shown to be superior
to paracetamol in their analgesic effect, this difference is
small.7 As an example, recent recommendations in treating
osteoarthritis do not advocate NSAIDs over paracetamol.8
Conclusion
In light of the growing evidence implicating NSAIDs in
cardiovascular risk, and the prevalence of NSAID prescribing in the ‘at-risk’ group, there is a need for alternatives
to NSAIDs. Many current recommendations, including very
reputable sources, appear out of date; for example, the
NHS Evidence Clinical Knowledge Summary9 dates from
2008, although an update is imminent.
We contend that many patients could safely be prescribed paracetamol, as a trial, instead of or in addition to
their NSAID. If NSAIDs cannot be avoided, alternatives to
diclofenac, such as ibuprofen or naproxen should be considered. On the basis of this study, a strong case can be made
that urgent national guidelines should be introduced to assist
physicians in the safer prescribing of these medications.
Caroline O’Connor is a GP registrar and Judith Kavanagh is
in general practice at Mercer’s Medical Centre, Dublin. The
authors would like to thank all the staff at Mercer’s Medical
Centre, RCSI and the Mercer’s Foundation
References on request