Long‐Term Safety of a Coordinated Delivery Tablet of Enteric‐Coated Aspirin 325 mg and Immediate‐Release Omeprazole 40 mg for Secondary Cardiovascular Disease Prevention in Patients at GI Risk

Abstract

SummaryIntroductionIn two, 6‐month, randomized, double‐blind Phase 3 trials, PA32540 (enteric‐coated aspirin 325 mg and immediate‐release omeprazole 40 mg) compared to aspirin alone was associated with fewer endoscopic gastric and duodenal ulcers in patients requiring aspirin therapy for secondary cardiovascular disease (CVD) prevention who were at risk for upper gastrointestinal (UGI) events.AimsIn this 12‐month, open‐label, multicenter Phase 3 study, we evaluated the long‐term cardiovascular and gastrointestinal safety of PA32540 in subjects who were taking aspirin 325 mg daily for ≥3 months for secondary CVD prevention and were at risk for aspirin‐associated UGI events. Enrolled subjects received PA32540 once daily for up to 12 months and were assessed at baseline, month 1, month 6, and month 12.ResultsThe overall safety population consisted of 379 subjects, and 290 subjects (76%) were on PA32540 for ≥348 days (12‐month completers). Adverse events (AEs) caused study withdrawal in 13.5% of subjects, most commonly gastroesophageal reflux disease (1.1%). Treatment‐emergent AEs occurred in 76% of the safety population (11% treatment‐related) and 73% of 12‐month completers (8% treatment‐related). The most common treatment‐related AE was dyspepsia (2%). One subject had a gastric ulcer observed on for‐cause endoscopy. There were five cases of adjudicated nonfatal myocardial infarction, one nonfatal stroke, and one cardiovascular death, but none considered treatment‐related.ConclusionsLong‐term treatment with PA32540 once daily for up to 12 months in subjects at risk for aspirin‐associated UGI events is not associated with any new or unexpected safety events.

Yosprala: Coordinated Delivery of a Proton Pump Inhibitor and Aspirin

“…Of the 380 patients in the study, 292 completed the study. 8 Patients completed the study if they received PA32540 for at least 348 days. The 88 patients who did not finish the study reported the top reason for discontinuation to be adverse events (13.4%).…”

“…6 Although there is astounding evidence on the use of ASA for the secondary prevention of cardiovascular events, adherence rates to this medication are varied and have been reported to be as low as 47% and as high as 72%. [7][8][9] The low adherence is often attributed to the gastrointestinal (GI) adverse effects associated with ASA. These effects include upper GI bleed, GI ulcers, gastroesophageal reflux disease (GERD), and dyspepsia.…”

“…These effects include upper GI bleed, GI ulcers, gastroesophageal reflux disease (GERD), and dyspepsia. 6,[8][9][10] In fact, patients are at a 2-fold increased risk for GI-related adverse effects when taking ASA versus placebo. 6,8 Discontinuing ASA increases the risk of life-threatening cardiovascular events that may occur without this medication.…”

“…6,[8][9][10] In fact, patients are at a 2-fold increased risk for GI-related adverse effects when taking ASA versus placebo. 6,8 Discontinuing ASA increases the risk of life-threatening cardiovascular events that may occur without this medication. 5,6 Patients at risk for GI-related adverse events (ie, patients over 55 years old, patients 18 to 55 years old with a history of GI ulcers, patients on dual antiplatelet therapy, or patients with concurrent use of a nonsteroidal antiinflammatory drug [NSAID], and ASA) are often placed on a proton pump inhibitor (PPI).…”

“…Co-prescribing of medications generally results in lower adherence rates. 8 Low adherence to the PPI, when paired with ASA, will result in more GI-related events. This return of GI events could lead to the discontinuation of ASA and, again, increase the risk for life-threatening cardiovascular events.…”