Table
2 Adherence to OMT by self-report and HPLC MS/MS
Adherence to prescribed, protocol-directed cardiovascular medications as
measured by self-report and HPLC MS/MS (detected). Self-reported
adherence data are shown for each drug in response to the question “How
many days in the preceding week did you take this medication?” A drug
was ‘expected’ if prescribed for that patient and a urinalysis sample
was tested. A drug was marked ‘detected’ if present in the urine on HPLC
MS/MS. P-values are shown for the between groups difference in
proportion of drug detected. ACEi – angiotensin converting enzyme
inhibitor, AP -anti-platelet drug, ARB – angiotensin II receptor
blocker, BB – beta blocker, CCB – calcium channel blocker, PCI –
percutaneous coronary intervention.
Discussion
Overall adherence levels in our trial population were >90%
for almost all drugs at both pre-randomisation and follow-up, as
measured by patient self-reporting of adherence and by urine HPLC MS/MS.
There were no significant between-group differences at pre-randomisation
or at follow-up and medication taking patterns did not change following
treatment with PCI. There were no differences between self-reported and
direct adherence measurement in our population, owing to near-perfect
adherence levels by both measures.
Our results have shown that adherence levels in ORBITA were high in both
groups at both stages, greater than is typically seen in clinical
practice10 and also greater than expected for a
clinical trial population11. Adherence was higher than
the widely-used 80% threshold12 for good adherence
throughout, high at pre-randomisation and maintained through 6 weeks of
follow-up, suggesting that it was not influenced by treatment assignment
to PCI or to placebo. Furthermore, adherence was maintained for all
protocol-directed drugs and classes of drug and patients were therefore
not selectively adherent to one class of drug or another, nor was this
influenced by treatment assignment. The OMT protocol and assessments of
adherence within ORBITA were designed firstly to maximise the potential
therapeutic impact of guideline directed anti-anginal drugs and secondly
to identify any bias or chance variation in drug usage between the PCI
and placebo procedure groups. These results emphatically corroborate the
findings in the main ORBITA results paper, indicating that there was no
difference in drug adherence between the 2 groups that might otherwise
complicate interpretation of the ORBITA trial.
Within ORBITA, two research fellows had distinct roles, and both
maintained close contact with patients throughout their involvement in
respective phases of the study. Patients were committed to the study,
received detailed study literature and had many opportunities to ask
questions and learn more about their condition and available treatment
options. This created an environment that fostered good doctor-patient
communication and may have promoted good medication taking behaviour,
which could in part explain these very high adherence rates. Initially
this took time and effort, but once patient contact had been made,
implementation of the protocol was managed remotely via regular
telephone clinics. This is a model that has the potential to be
replicated in any clinical setting13,14. In the UK,
where cardiac rehabilitation for patients with stable angina is not
universally available the delivery of such a service rests with general
practitioners and cardiology clinics. We are pleased to note that stable
angina as an indication for cardiac rehabilitation in the UK is the
subject of a themed research call by the NIHR for further clinical
research15. In the interim, medication optimisation
must remain a key focus for clinicians treating patients with stable
angina, not least in the aftermath of the ISCHEMIA trial which reported
that, with good medical therapy, there is no additional benefit of an
upfront invasive strategy in stable CAD16.
In the midst of the COVID-19 pandemic outpatient consultations have
moved online at a rapid pace across a multitude of medical specialties
including clinical cardiology17,18. Faced with
necessary social distancing measures clinicians have rapidly adapted to
carrying out clinical reviews using telehealth and for many patients
this has become an expected way of accessing clinical
care19. The telehealth approach implemented in ORBITA
provides supportive evidence of how good medication optimisation can be
achieved by telephone.
There are limitations to interpretation of the adherence assessments
that must be acknowledged. The HPLC MS/MS measure directly captures
adherence to each drug at the time of testing but nonetheless remains
vulnerable to the ‘white coat adherence’ phenomenon whereby patients
ingest a single dose of drug just before testing to avoid detection of
non-adherence20. Equally self-reported adherence is
open to reporting bias21.
Overall however, ORBITA has shown that implementation of a simple
protocol of OMT is feasible and practical with limited resources. The
high adherence rates seen are evidence that the OMT protocol was
successfully implemented and the study methodology therefore offers a
model of how optimisation can be achieved in clinical practice using
telehealth.
*ORBITA Study
Investigators
Rasha Al-Lamee, David Thompson, Sayan Sen, Ricardo Petraco, Christopher
Cook, Yousif Ahmad, James Howard, Matthew Shun-Shin, Jamil Mayet, Jaspal
Kooner, Simon Thom, Justin Davies, Darrel Francis, and Ramzi Khamis
(Imperial College London, London, UK and Imperial College Healthcare NHS
Trust, London, UK); Kare Tang, John Davies, and Thomas Keeble (Essex
Cardiothoracic Centre, Basildon, UK); Raffi Kaprielian, Iqbal Malik,
Sukhjinder Nijjer, Amarjit Sethi, Christopher Baker, Punit Ramrakha,
Ravi Assomull, Rodney Foale, Nearchos Hadjiloizou, Masood Khan, Michael
Bellamy, Ghada Mikhail, and Piers Clifford (Imperial College Healthcare
NHS Trust, London, UK); Andrew Sharp (Royal Devon and Exeter NHS Trust,
Exeter, UK); Robert Gerber (East Sussex Healthcare NHS Trust, Hastings,
UK); Suneel Talwar, Peter O’Kane, Terry Levy, and Rosie Swallow (Royal
Bournemouth and Christchurch NHS Trust, Bournemouth, UK); and Roland
Wensel (Imperial College London, London, UK).
Declaration of Interests
Nothing to declare.
Data
Data available on request from the authors22.
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