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.

Citations

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