Role of Yosprala™ in At-Risk Patients Requiring Low-Dose Aspirin

Devada Singh-Franco, PharmD

Disclosures

March 27, 2018

Efficacy/Tolerability

A pooled analysis of two 6-month, double-blind, active-control studies (NCT00960869 and NCT00961350) described the effect of daily Yosprala325 mg delayed-release aspirin/40 mg immediate-release omeprazole (N = 524) versus EC-ASA 325 mg (N = 525) in subjects with established CV or cerebrovascular disease receiving aspirin 325 mg daily for ≥ 3 months.[12,13] Although concomitant use of omeprazole with clopidogrel is not recommended,[14] those on clopidogrel were allowed in the study,[15] while those positive for Helicobacter pylori or ulcers as per baseline endoscopy were excluded. Of note, 98 subjects who were screened at baseline and excluded due to presence of ulcers per endoscopy were all asymptomatic.[12,13]

At 6 months, participants receiving Yosprala had fewer endoscopically verified gastric ulcers overall compared with those receiving EC-ASA (Table 1). Significantly fewer participants with and without baseline gastric erosions and receiving Yosprala had gastric erosions during the study or developed gastric ulcers.[12,13] Any GI-related adverse events occurred most frequently in those receiving EC-ASA, with dyspepsia occurring significantly more often. Discontinuations due to upper GI adverse events also occurred most often in those receiving EC-ASA.[12,13] While a prespecified list of GI adverse event preferred terms were provided (eg, abdominal discomfort, hematemesis, esophagitis), the specific GI adverse events leading to discontinuation were not reported.

Table 1. Select Study Results of Yosprala vs EC-ASA[12,13]

  Yosprala
325 mg/40 mg
EC-ASA
325 mg
Gastric ulcers
Overall 3.2% (17/524) 8.6% (45/525)*
NSAID users 4.5% (2/44) 10.2% (5/49)
Non-NSAID users 3.1% (15/480) 8.4% (40/476)
Gastric erosions in those with and without erosions at baseline
Present at baseline 41.5% (216/521) 38.3% (200/522)
Present at any postbaseline visit 39.4% (85/216) 76.5% (153/200)
Absent at baseline 58.5% (305/521) 61.7% (322/522)
Present at any postbaseline visit 20.7% (63/305) 41.3% (133/322)
Gastric ulceration in those with and without erosions at baseline
Erosions present at baseline 4.2% (9/216) 13% (26/200)§
No erosions at baseline 2.6% (8/305) 5.9% (19/322)**
GI-related adverse events
Any 54.3% (283/521) 76% (398/524)
Dyspepsia 11.3% (59/521) 30.2% (158/524)††
Erosive gastritis 11.5% (60/521) 26.3% (138/524)
Discontinuations
Upper GI adverse events 1.5% (8/521) 8.2% (43/524)‡‡
Clopidogrel users only 17.1% (19/111) 28.2% (31/110)
Adjudicated cardiovascular events in clopidogrel users 6.3% (7/111) 3.6% (4/110)
* P < .001 for proportion of patients who developed a gastric ulcer
P < .001 for proportion of patients with erosions at baseline and at any point postbaseline
P < .001 for proportion of patients with no erosions at baseline but had erosions at any point postbaseline
§ P = .001 for proportion of patients with erosions at baseline and progressed to gastric ulceration
** P < .05 for proportion of patients with no gastric erosions at baseline and progressed to gastric ulceration
†† P < .001 for proportion of patients with dyspepsia
‡‡ P < .001 for proportion of patients discontinuing treatment due to upper GI adverse events
EC-ASA = enteric-coated aspirin; GI = gastrointestinal; NSAID = nonsteroidal anti-inflammatory drug

Among clopidogrel users, study discontinuation also occurred most commonly in those receiving EC-ASA. The proportion of participants experiencing an adjudicated CV event was similar for both groups. While 21% of participants received clopidogrel at baseline, no data were provided on the proportion of clopidogrel users who experienced gastric ulcers and GI-related adverse events.[12,13]

In addition to these clinical trials, a 12-month, open-label study (NCT00995410) was conducted to determine the CV and GI safety of daily Yosprala325 mg delayed-release aspirin/40 mg immediate-release omeprazole in subjects receiving aspirin 325 mg daily for secondary cardiovascular disease (CVD) prevention who were at risk for upper GI events (N = 379).[16]

The proportion of participants completing the study at 6 and 12 months was 85% and 76.3%, respectively. Seventy-six percent of all participants had treatment-emergent adverse events, and 13.5% discontinued treatment due to adverse events, including GERD (n = 4), upper abdominal pain (n = 3), diarrhea (n = 2), and dyspepsia (n = 2).[16]

Eight potential events were sent to a GI Clinical Event Committee for adjudication as potential bleeding events, but only one participant with documented melena (no bleeding site identified) met the predefined endpoint. Serious cardiac adverse events were reported for 20 participants, and 14 experienced a major CV event, including myocardial infarction (n = 5), acute coronary syndrome (n = 3), and unplanned revascularization (n = 3). As per the authors, no new or unexpected safety concerns were identified during this 12-month open-label study.[16]

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