Discussion
ischemia, Angioplasty, angina, angioplasty
STABLE ANGINA, ISCHEMIA, DISEASE, STENOSES, EVENTS
In this placebo-controlled trial in patients with stable angina on little or no antianginal medication, with coronary-artery stenoses causing ischemia, PCI improved the angina symptom score. Reduction in the angina symptom score appeared to result from reduction in daily angina episodes. Assignment to the PCI group was associated with a more than three-fold greater odds of becoming free from angina at the 12-week follow-up. The reduction in angina following PCI was observed immediately and persisted throughout the blinded follow-up period.The results from ORBITA-2 differed from ORBITA because the studies were designed to answer different questions. In ORBITA, patients adhered to guideline-directed antianginal medications, with PCI as add-on therapy.ORBITA-2 introduces a new end point, informed by patient and public engagement and involvement, that is centered on contemporaneous documentation of daily angina on a smartphone application. This has several advantages: high temporal fidelity of data, minimizing recall bias and maximizing data completeness. This tool is being employed in several clinical trials (NCT05459051, NCT04280575, NCT04892537). The ordinal angina symptom score builds on these daily symptom data, incorporating antianginal medication use and relevant clinical events.The ORBITA trial demonstrated the ethical basis, feasibility and necessity of placebo-controlled trials for studies examining PCI.However, despite decades of technical advances in PCI, including the introduction of stents, the effect of PCI on exercise time in the blinded ORBITA-2 trial is still 37 seconds lower than the 96 second effect attributed to balloon angioplasty in the unblinded Angioplasty Compared to Medicine (ACME) trial performed three decades ago.With background antianginal medications and PCI, 61% of patients in ORBITA had residual symptoms. In ORBITA-2, with PCI and antianginal medications only if required, 59% still had residual symptoms. Notably, there was no difference in antianginal medication use between the PCI and placebo groups. In both trials, the PCI group had near normalized ischemia detected by stress echocardiography. These trials did not ascertain the cause of the residual symptoms. Perhaps for angina relief, the first therapy administered, either antianginal medication or an antianginal procedure, such as PCI, has the greatest chance of efficacy.Our study had limitations. The study follow-up period ran for only a 12-week follow-up period. However, the daily data showed that the effect of PCI was immediate and sustained. The study also ceased antianginal medications against guideline recommendations. However, only this design allowed PCI to be tested as antianginal monotherapy. Withdrawal of antianginal medication may have led to unmeasured behavioral changes. The use of nitroglycerin spray was recorded as part of the SAQ but not included in the angina symptom score. While patients with single and multivessel disease were enrolled, 80% had ischemia in a single territory when tested systematically, similar to routine clinical practice.In summary, among patients with stable angina on little or no antianginal medication and objective evidence of ischemia, PCI improved the angina symptom score compared to placebo.