Achieving Optimal Medical Therapy: Insights From the ORBITA Trial

Abstract

Background In stable coronary artery disease, medications are used for 2 purposes: cardiovascular risk reduction and symptom improvement. In clinical trials and clinical practice, medication use is often not optimal. The ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was the first placebo-controlled trial of percutaneous coronary intervention. A key component of the ORBITA trial design was the inclusion of a medical optimization phase, aimed at ensuring that all patients were treated with guideline-directed truly optimal medical therapy. In this study, we report the medical therapy that was achieved. Methods and Results After enrollment into the ORBITA trial, all 200 patients entered a 6-week period of intensive medical therapy optimization, with initiation and uptitration of risk reduction and antianginal therapy. At the prerandomization stage, the median number of antianginals established was 3 (interquartile range, 2-4). A total of 195 patients (97.5%) reached the prespecified target of ≥2 antianginals; 136 (68.0%) did not stop any antianginals because of adverse effects, and the median number of antianginals stopped for adverse effects per patient was 0 (interquartile range, 0-1). Amlodipine and bisoprolol were well tolerated (stopped for adverse effects in 4/175 [2.3%] and 9/167 [5.4%], respectively). Ranolazine and ivabradine were also well tolerated (stopped for adverse effects in 1/20 [5.0%] and 1/18 [5.6%], respectively). Isosorbide mononitrate and nicorandil were stopped for adverse effects in 36 of 172 (20.9%) and 32 of 141 (22.7%) of patients, respectively. Statins were well tolerated and taken by 191 of 200 (95.5%) patients. Conclusions In the 12-week ORBITA trial period, medical therapy was successfully optimized and well tolerated, with few drug adverse effects leading to therapy cessation. Truly optimal medical therapy can be achieved in clinical trials, and translating this into longer-term clinical practice should be a focus of future study. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02062593.

Keywords: adverse effects; angina; compliance/adherence; medical therapy; randomized controlled trial.

Conflict of interest statement

Dr Sharp is a consultant for Philips Volcano. Drs Sen, Petraco, and Nijjer have received speaker’s honoraria from Philips Volcano. Dr Al‐Lamee has received speaker’s honoraria from Philips Volcano and Menarini Pharmaceuticals. Dr Keeble has received research grants from Philips Volcano. The remaining authors have no disclosures to report.

Figures

Figure 1. The antianginal decision‐making process that was used in the ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial, based on the National Institute of Health and Care Excellence and European Society of Cardiology guidelines. 11

Ca indicates calcium; GTN, glyceryl trinitrate; and MI, myocardial infarction.

Figure 2. Antianginal drugs per patient from enrollment to follow‐up.

Points shown are mean and 95% CI.

Figure 3. Antianginal medication: number of patients established on each medication class, achieving target dose and stopping for adverse effects.

ISMN indicates isosorbide mononitrate.

Figure 4. Logistic regression showing the association between the number of prescribed antianginal therapies and log odds of freedom from angina.

There is no discernible relationship. PCI indicates percutaneous coronary intervention.