ORBITA-2 Shows PCI Relieves Chest Pain and Improves Exercise Capacity

November 11, 2023—The American Heart Association (AHA) announced that findings from the ORBITA-2 trial provide the first robust data confirming that percutaneous coronary intervention (PCI) relieves stable chest pain and improves exercise capacity among patients taking little or no chest pain medication.

The ORBITA-2 study was presented by Christopher Rajkumar, MBBS, during a late-breaking science session at the AHA scientific sessions held November 11-13 in Philadelphia, Pennsylvania. The ORBITA-2 results were simultaneously published online by Dr. Rajkumar et al in The New England Journal of Medicine.

Dr. Rajkumar is a clinical research fellow at Imperial College London in London, United Kingdom.

As noted in the AHA press release, the first ORBITA trial was the only previous blinded trial examining whether stenting relieves chest pain. The results from the ORBITA trial were reported at TCT 2017 and published simultaneously in The Lancet (2018;391:31-40).

ORBITA showed that stenting did not improve exercise tolerance or chest pain any more than a placebo procedure.

“However, it is possible that the effect of stenting in ORBITA was diminished by high levels of guideline-directed background, antianginal medication, which are difficult to achieve in clinical practice,” stated ORBITA-2 Principal Investigator Rasha Al-Lamee, MBBS, in the AHA press release. Dr. Al-Lamee is Reader (equivalent of Associate Professor) in Cardiology, British Heart Foundation intermediate research fellow, and interventional cardiology consultant at Imperial College London and Imperial College Healthcare NHS Trust.

The ORBITA study did demonstrate the feasibility of conducting placebo-controlled trials of established interventional procedures and made it possible to design subsequent research applied to a wider population of patients and clinical practice.

According to AHA, ORBITA-2 enrolled a broader range of patients with both single and multivessel disease who were randomly assigned to either coronary stenting or a placebo procedure. Neither patients nor the medical or research teams were aware of which procedure they had received.

The ORBITA-2 trial enrolled 301 patients at 14 centers in the United Kingdom; 79% of patients were men, and average age was 64 years. Study patients had other health conditions, including hypertension (63%), type 2 diabetes (28%), and high cholesterol (72%).

Patients were taken off their background chest pain medication before they were randomly assigned to one of the two treatment groups. Chest pain medication was restarted if the patient contacted the blinded research team to report symptoms. Medication restarts and dose increases were managed by blinded trial researchers who did not know whether the patient had received a stent or placebo procedure and who followed a specific trial protocol.

Throughout the trial, patients reported whether they were experiencing chest pain every day using a dedicated smartphone application. These daily symptom reports and the need for chest pain medication were used to calculate the angina symptom score, which is a first-of-its-kind primary study endpoint.

Dr. Al-Lamee explained, “We calculated an ‘angina symptom score’ daily for each participant based mainly on how much chest pain they experienced and their need for antianginal medication. We found that stents improved symptoms compared to the placebo procedure.”

As outlined in the AHA press release, the study found:

• Patients who had stents were three times more likely to be free from angina at the end of the trial compared to patients who had the placebo procedure.
• Stenting improved the angina symptom score, with follow-up scores of 2.9 in the PCI group and 5.6 in the placebo group.
• Exercise time increased by 60 seconds more among patients who received stenting compared to patients who received the placebo procedure.
• The effect of stenting was immediate and sustained during the 12-week follow-up period.
• Heart attacks occurred in four patients in the stenting group and six patients in the placebo group. There were no deaths.

“We expected that PCI would be more effective than a placebo procedure in patients taking little or no chest pain medication, and indeed, the results proved our hypothesis was correct,” stated Dr. Al-Lamee in the press release.

She continued, “Going forward, patients and medical teams have a choice of two pathways for chest pain relief: chest pain medication or PCI. The key finding of this trial is that it is the first therapy initiated that seems to have the maximum effect. Although PCI is neither risk-free nor cost-free, its use as an upfront procedure can now be considered evidence based.”

Dr. Al-Lamee concluded, “The ORBITA and ORBITA-2 trials together suggest the American and European guidelines for stable coronary artery disease may require updating. Perhaps restricting stenting to patients with inadequate response to chest pain medications may inadvertently be selecting the group of patients with the least to gain.”

However, she noted there are several reasons the findings should be interpreted cautiously:

• PCI only provided a 60-second improvement in exercise time. This is a smaller effect than many cardiologists would have believed from unblinded data and similar to the effect of one full-dose antianginal medication.
• PCI is not universally effective. In this study, 59% of patients who received stents continued to experience chest pain even after a successful procedure and near-normalization of the blood supply to the heart.

Finally, Dr. Al-Lamee commented, “I hope that the two trials will be used together to give patients and medical teams the choice of two treatment strategies with similar levels of benefit. They each have their own benefits, risks, and limitations that should form part of the decision-making process. Importantly, the first therapy administered, antianginal medication or PCI as an antianginal procedure, appears to deliver most of the available symptomatic response.”

In a separate press release, the Society for Cardiovascular Angiography & Interventions (SCAI) congratulated the ORBITA-2 trial investigators.

“The ORBITA-2 trial is a well-designed and executed study despite great challenges,” commented SCAI President George D. Dangas, MD, in the society’s press release. “While study enrollment was small, the results show unequivocal anginal benefit from PCI, without the use of medication in ischemic patients.”

Dr. Dangas continued, “SCAI recommends the use of PCI for symptom relief in appropriate patients. ORBITA-2 confirms the benefit of PCI in helping stable ischemic heart disease patients, consistent with other prior trials.”

SCAI encourages the development of individualized treatment plans to ensure the best patient-centered care possible and stated that the ORBITA-2 trial findings underscore the importance of shared medical decision-making between physicians and patients.