Riociguat shows striking benefit in intractable coronary spasm, a case report.

Symptom control in patients with coronary spasm often remains a challenge, and available treatment options are limited. As first-ever evidence from the case report published in JACC by Pereyra et al, the sGC-stimulator riociguat has shown striking relief in angina due to coronary artery spasm when all other conventional drugs failed to ameliorate pain.

A 77-year-old woman presented with recurrent angina symptoms and dyspnea occurring at rest and during exertion. She had experienced these symptoms for the last 30 years, and they had led to severe impairment of her quality of life. Her first evaluation dates back to 1995 when TMT suggested ischemic changes but coronary angiography (CAG) did not show obstructive coronary artery disease (CAD). Over the years she received antianginals among other medications and back in 2005, a acetylcholine (Ach) challenge had confirmed the cause of angina to be diffuse coronary spasm in left system. Subsequently, anti-vasospastic treatment was initiated.

But the anginal symptoms continued and repeat coronary angiograms were done. The fifth (since 1995) CAG revealed a focal obstructive lesion in LCx which was stented. However, the patient continued to have recurrent angina symptoms refractory to various pharmacological treatment options.

In 2018, ischemic ECG changes could be observed on a resting ECG, and the patient reported increasing chest pain both during exercise and at rest. To evaluate a possible progression of coronary artery disease or an in-stent restenosis, as well as to assess coronary vasomotion again, coronary angiography was carried out, including ACh provocation testing after a standardized protocol. Coronary spasm could be elicited in left system except for the stented segment of LCx.

During a period of several years, various antianginal drugs were prescribed including combinations of a beta-blocker, calcium-channel blockers, an angiotensin-converting enzyme inhibitor, and nitrates. Moreover, second-line drugs such as ranolazine and nicorandil did not significantly improve the patient's symptoms.

The authors then decided on an off-label use of riociguat, a drug licensed for the treatment of pulmonary hypertension. Treatment with riociguat, a stimulator of the soluble guanylate cyclase (sGC), which is an enzyme with a pivotal role in the regulation of vascular tone, was initiated under close clinical supervision. The patient was primarily discharged with 0.5 mg riociguat 3 times daily. During weekly follow-ups, they increased the dosage of riociguat stepwise up to 6 mg/day until the patient reported a significant improvement of her health status.

They quantitatively assessed the patient's angina symptoms and health-related quality of life using the Seattle Angina Questionnaire during follow-up visits, as well as after a period of 10 months of riociguat treatment (6 mg/day). Furthermore, the patient underwent repeated ACh provocation testing to validate the anti-vasospastic effect of riociguat on the coronary arteries. Strikingly, under full riociguat medication, epicardial coronary artery spasm could not be elicited with 100 μg ACh, unlike in the previous examination in 2018 (Figure).

Approximately 50% of patients with angina pectoris have unobstructed coronary arteries on diagnostic coronary angiography. In approximately 60% of these patients, the genesis of symptoms can be traced back to coronary vasomotor disorders (e.g. coronary artery spasm), which can be diagnosed with ACh provocation testing. After these efforts to ameliorate the patient's symptoms, the patient reported that she was finally almost symptom-free, leading to a significant improvement in quality of life.

"These findings suggest that the sGC-pathway may be a novel therapeutic target in patients with coronary artery spasm. However, randomized controlled clinical trials are needed to reinforce this assumption", noted the authors.

Source: JACC case reports: J Am Coll Cardiol Case Rep. Feb 24, 2021. Epublished DOI: 10.1016/j.jaccas.2020.11.043