The effect of alternating use of enteric-coated aspirin and clopidogrel on gastrointestinal symptoms and patient compliance in elderly patients with coronary heart disease

Q: What are the key findings of this study?

Monthly alternating aspirin and clopidogrel stabilized 6-month GSRS symptom scores vs continuous DAPT (15.84 vs 19.59, P<0.05) and improved medication adherence (72.50% vs 51.25%, P=0.006).

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Stable coronary artery disease (n=160). Intervention: Monthly alternating enteric-coated aspirin (100 mg/day) and clopidogrel (75 mg/day) vs. Continuous dual antiplatelet therapy (enteric-coated aspirin 100 mg/day plus clopidogrel 75 mg/day). Primary outcome: Gastrointestinal Symptom Rating Scale (GSRS) total score at 6 months (MD -3.75, p=<0.05).

Q: What does this research mean for the field?

Monthly alternating use of aspirin and clopidogrel stabilizes gastrointestinal symptoms and improves medication adherence compared to continuous dual antiplatelet therapy in elderly patients with stable coronary artery disease. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the effects of monthly alternating aspirin and clopidogrel compared with continuous dual antiplatelet therapy on gastrointestinal symptoms, medication adherence, and major adverse cardiovascular events in elderly patients with stable coronary artery disease.

Xiaoqing Dai

doi:10.36721/pjps/2026.40.17106.1

October 17, 2026Pakistan Journal of Pharmaceutical SciencesOpen Access

The effect of alternating use of enteric-coated aspirin and clopidogrel on gastrointestinal symptoms and patient compliance in elderly patients with coronary heart disease

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Key result

Alternating aspirin and clopidogrel monthly is linked to ~4-point lower gastrointestinal symptom scores than continuous DAPT.

MD -3.75
P<0.05
n=160

Why the study?

Dual antiplatelet therapy is essential for secondary prevention of CAD, but gastrointestinal intolerance often causes elderly patients to self-reduce the dose or discontinue medication. This study compared monthly alternating aspirin and clopidogrel against continuous DAPT on GI symptoms, medication adherence, and 6-month MACE in elderly community patients with stable CAD.

Does monthly alternating use of enteric-coated aspirin and clopidogrel improve gastrointestinal symptoms and medication adherence compared to continuous dual antiplatelet therapy in elderly patients with stable coronary artery disease?

Key Points

To evaluate the effects of monthly alternating aspirin and clopidogrel compared with continuous dual antiplatelet therapy on gastrointestinal symptoms, medication adherence, and major adverse cardiovascular events in elderly patients with stable coronary artery disease.
Retrospective cohort study of 160 elderly patients (age ≥60 years) with stable coronary artery disease treated at a single community health center from June 2022 to June 2025.
Patients received either alternating monthly therapy (aspirin 100 mg/day during odd months and clopidogrel 75 mg/day during even months; n=80) or continuous dual antiplatelet therapy (n=80) over a 6-month observation period.
Gastrointestinal symptoms were measured using the Gastrointestinal Symptom Rating Scale (GSRS), adherence was evaluated with the Morisky Medication Adherence Scale (MMAS-8), and clinical adverse events were documented at baseline and 6 months.
At 6 months, GSRS total scores remained stable in the alternating group (15.14±4.52 to 15.84±4.89, change +0.70, P>0.05) but significantly worsened in the continuous group (15.18±4.48 to 19.59±5.67, change +4.41, P<0.05; between-group P<0.05).
The alternating group achieved higher MMAS-8 scores (7.58±0.76 vs. 6.94±1.15, P<0.001), higher adherence rates (72.50% vs. 51.25%, P=0.006), and lower total gastrointestinal adverse events (6.25% vs. 18.75%, P=0.017).
Major adverse cardiovascular events occurred in 3 patients (3.75%) in each group (P=1.000; statistical power was severely insufficient to establish non-inferiority), and gastrointestinal bleeding did not differ significantly between groups (1.25% vs. 5.00%, P=0.174).

Study Design

Type

Cohort (n=160)

Multicenter

No

Structured PICO

Does monthly alternating use of enteric-coated aspirin and clopidogrel improve gastrointestinal symptoms and medication adherence compared to continuous dual antiplatelet therapy in elderly patients with stable coronary artery disease?

P

Population

160 elderly patients (mean age 70.1 years, 43.8% female) with stable coronary artery disease (≥50% stenosis), free of prior peptic ulcer or GI bleeding and recent PCI/CABG, followed for 6 months.

E

Exposure

Alternating monthly oral regimens of enteric-coated aspirin 100 mg once daily (in odd-numbered months) and clopidogrel bisulfate 75 mg once daily (in even-numbered months) for 6 months, added to standard background therapy for coronary artery disease (statins, beta-blockers, ACEIs/ARBs) with as-needed short-term PPIs.

C

Comparator

Continuous dual antiplatelet therapy consisting of oral enteric-coated aspirin 100 mg once daily combined with clopidogrel bisulfate 75 mg once daily for 6 months, added to standard background therapy for coronary artery disease (statins, beta-blockers, ACEIs/ARBs) with as-needed short-term PPIs.

O

Outcome

Gastrointestinal symptoms assessed by the Gastrointestinal Symptom Rating Scale (GSRS) total score and dimension scores, and medication adherence assessed by the Morisky Medication Adherence Scale (MMAS-8) score and adherence rates at 6 months.patient reported

Main Result

Mean Difference: -3.75

Absolute Event Rate: 15.84% vs 19.59%

p-value: p=<0.05

In elderly community patients with stable CAD, alternating aspirin and clopidogrel monthly over 6 months prevented the progressive worsening of gastrointestinal symptoms and improved medication adherence compared to continuous DAPT, though larger prospective trials are needed to establish cardiovascular safety.

Limitations

Single-center retrospective cohort design with non-randomized treatment allocation and potential indication bias
Small sample size (n=160) and low event rate (3 MACE per group) with severely insufficient statistical power to establish cardiovascular non-inferiority
Unmeasured confounding from unrecorded on-demand proton pump inhibitor (PPI) usage
Short 6-month follow-up duration
Reliance on subjective symptom scales without objective endoscopic assessment
Exclusion of patients with prior peptic ulcer disease limits generalizability to higher-risk populations
Single-center, retrospective cohort design with non-randomized treatment allocation introducing potential indication bias
Severely insufficient statistical power to infer cardiovascular non-inferiority or safety equivalence for MACE (only 3 events per group) without a prior power calculation
Specific types, dosages, durations, and actual usage rates of as-needed PPIs could not be obtained, acting as an unmeasured confounding factor
Assessment of mucosal lesions relied on symptom scales without objective endoscopic evaluation such as gastroscopy, which may underestimate asymptomatic ulcers or erosions
Exclusion of patients with prior peptic ulcer disease limits generalizability

Implication

Alternating therapy was associated with stable GI symptoms and higher adherence; leaves open cardiovascular safety, requiring randomized trials in elderly stable CAD.

Abstract

Background: Dual antiplatelet therapy (DAPT) is essential for secondary prevention of coronary artery disease (CAD), but gastrointestinal (GI) intolerance often leads elderly patients to self-reduce the dose or discontinue medication. Objectives: To compare the effects of monthly alternating aspirin and clopidogrel versus continuous DAPT on GI symptoms, medication adherence and 6‑month major adverse cardiovascular events (MACE) in elderly community patients with stable CAD. Methods: This retrospective cohort study included 160 elderly patients with stable CAD, who were non-randomly assigned to alternating DAPT (n=80) or continuous DAPT (n=80) according to their documented antiplatelet regimens in clinical practice. GSRS, MMAS-8 and adverse events were evaluated at baseline and 6 months. Results: At 6 months, the observation group’s GSRS total score remained stable (15.14±4.52 to 15.84±4.89, +0.70, P>0.05), while the control group significantly worsened (15.18±4.48 to 19.59±5.67, +4.41, P<0.05); the between-group difference was significant (P<0.05). The MMAS-8 score was higher in the observation group (7.58±0.76 vs. 6.94±1.15, P<0.001), with higher adherence rates (72.50% vs. 51.25%, P=0.006). Total GI adverse events were lower in the observation group (6.25% vs. 18.75%, P=0.017), but GI bleeding did not differ significantly. MACE occurred in 3 cases (3.75%) in each group (P=1.000); however, statistical power was severely insufficient to infer cardiovascular non‑inferiority. Conclusion: Alternating monthly use of aspirin and clopidogrel during the 6-month observation period of this study did not show a significant increase in the risk of MACE. Under these conditions, this regimen attenuated the progressive worsening of gastrointestinal symptoms in elderly patients (scores remained stable rather than significantly worsening) and significantly improved medication adherence. Within this study's specific population (stable elderly CAD patients) and 6-month observation window, this strategy offers a promising alternative worthy of further investigation. Its long-term benefits and cardiovascular safety require confirmation by prospective large-scale trials.

Discussion

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Cite This Study

Xiaoqing Dai (2026) conducted a cohort in Stable coronary artery disease (n=160). Monthly alternating enteric-coated aspirin (100 mg/day) and clopidogrel (75 mg/day) vs. Continuous dual antiplatelet therapy (enteric-coated aspirin 100 mg/day plus clopidogrel 75 mg/day) was evaluated on Gastrointestinal Symptom Rating Scale (GSRS) total score at 6 months (MD -3.75, p=<0.05). Monthly alternating aspirin and clopidogrel stabilized 6-month GSRS symptom scores vs continuous DAPT (15.84 vs 19.59, P<0.05) and improved medication adherence (72.50% vs 51.25%, P=0.006).

synapsesocial.com/papers/6ae28e75cbadf70daf6c4297 https://doi.org/10.36721/pjps/2026.40.17106.1

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The effect of alternating use of enteric-coated aspirin and clopidogrel on gastrointestinal symptoms and patient compliance in elderly patients with coronary heart disease

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

The effect of alternating use of enteric-coated aspirin and clopidogrel on gastrointestinal symptoms and patient compliance in elderly patients with coronary heart disease

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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