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Three-A-Day Dosing of Selexipag in the Treatment of Pulmonary Arterial Hypertension: A Case Series
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A3719 - Three-A-Day Dosing of Selexipag in the Treatment of Pulmonary Arterial Hypertension: A Case Series
Author Block: N. Habib1, J. P. Feldman2; 1Internal Medicine, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States, 2Arizona Pulmonary Specialists, Phoenix, AZ, United States.
RationaleIn 2015, selexipag was approved as the first oral prostacyclin receptor agonist for the treatment of pulmonary hypertension (PH), with twice daily (BID) dosing. To reduce prostanoid-type side effects and increase efficacy, we postulated that 8-hour/TID dosing may yield better results. We report on 3 cases in which we utilized three daily (TID) dosing.Case SeriesCase 1 - A 26-year-old male presented with a history of familial PH, diagnosed in 2007 with initial mean PA pressure (mPAP) 77 mmHg, cardiac output (CO) 3.5, cardiac index (CI) 1.37, with initial 6-minute walk distance (6MWD) 1430 ft. Treatment was started with sildanefil and then SC, IV, and PO treprostinil; however, it was complicated by multiple side effects, despite achieving his best 6MWD (1900) and best mPAP (35) on SC treprostinil. Ambrisentan was added. He continued to decline and was switched to selexipag, initially at 1600 mcg BID dosing, but with persistent Class III symptoms 3 months later. We then increased his selexipag to TID. Three months later his symptoms improved to Class II.Case 2 - A 71-year-old female presented with a history of BOOP and MCTD, diagnosed with PH approximately 2007 with initial mPAP 58, CO 5.3, CI 2.94, 6MWD 400. She was treated with sildanefil and SC treprostinil, with good response (peak 6MWD 1400, mPAP 38); and transitioned to oral treprostinil and tadalafil. Six months later her mPAP was 35. After 2 years, she experienced gradual decline and was switched to selexipag 1600 mcg TID. Side effects improved greatly, and last 6MWD was 1050 ft on this combination. Case 3 - A 60-year-old female with a history of scleroderma, CREST, and DVT who was diagnosed with PAH in 2010, with mPAP 68, CO 4.6. She was treated initially with tadalafil and SC treprostinil, on which she achieved her best mPAP (31). Ambrisentan was added and she was transitioned to oral treprostinil. Her hemodynamics deteriorated over 2 years and in January 2017 she was transitioned to selexipag 1600 mcg BID. Repeat RHC 9 months later showed inadequate response, so we increased her dose to 1600 mcg TID. She achieved her best 6MWD (1630) on this dosing.ConclusionsSelexipag was demonstrated to lead to a decrease in hospitalizations and PAH progression in the Phase 3 GRIPHON trial, with maximal dosing at 1600mcg BID. Here, we demonstrate proof of concept that selexipag can be safely and beneficially used with TID dosing. Further study is warranted.
Author Block: N. Habib1, J. P. Feldman2; 1Internal Medicine, St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States, 2Arizona Pulmonary Specialists, Phoenix, AZ, United States.
RationaleIn 2015, selexipag was approved as the first oral prostacyclin receptor agonist for the treatment of pulmonary hypertension (PH), with twice daily (BID) dosing. To reduce prostanoid-type side effects and increase efficacy, we postulated that 8-hour/TID dosing may yield better results. We report on 3 cases in which we utilized three daily (TID) dosing.Case SeriesCase 1 - A 26-year-old male presented with a history of familial PH, diagnosed in 2007 with initial mean PA pressure (mPAP) 77 mmHg, cardiac output (CO) 3.5, cardiac index (CI) 1.37, with initial 6-minute walk distance (6MWD) 1430 ft. Treatment was started with sildanefil and then SC, IV, and PO treprostinil; however, it was complicated by multiple side effects, despite achieving his best 6MWD (1900) and best mPAP (35) on SC treprostinil. Ambrisentan was added. He continued to decline and was switched to selexipag, initially at 1600 mcg BID dosing, but with persistent Class III symptoms 3 months later. We then increased his selexipag to TID. Three months later his symptoms improved to Class II.Case 2 - A 71-year-old female presented with a history of BOOP and MCTD, diagnosed with PH approximately 2007 with initial mPAP 58, CO 5.3, CI 2.94, 6MWD 400. She was treated with sildanefil and SC treprostinil, with good response (peak 6MWD 1400, mPAP 38); and transitioned to oral treprostinil and tadalafil. Six months later her mPAP was 35. After 2 years, she experienced gradual decline and was switched to selexipag 1600 mcg TID. Side effects improved greatly, and last 6MWD was 1050 ft on this combination. Case 3 - A 60-year-old female with a history of scleroderma, CREST, and DVT who was diagnosed with PAH in 2010, with mPAP 68, CO 4.6. She was treated initially with tadalafil and SC treprostinil, on which she achieved her best mPAP (31). Ambrisentan was added and she was transitioned to oral treprostinil. Her hemodynamics deteriorated over 2 years and in January 2017 she was transitioned to selexipag 1600 mcg BID. Repeat RHC 9 months later showed inadequate response, so we increased her dose to 1600 mcg TID. She achieved her best 6MWD (1630) on this dosing.ConclusionsSelexipag was demonstrated to lead to a decrease in hospitalizations and PAH progression in the Phase 3 GRIPHON trial, with maximal dosing at 1600mcg BID. Here, we demonstrate proof of concept that selexipag can be safely and beneficially used with TID dosing. Further study is warranted.
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