P2Y12 inhibitor adherence trajectories in ACS

Prognostic implications of P2Y12 inhibitor adherence trajectories in patients with acute coronary syndrome undergoing percutaneous coronary intervention

Turgeon RD, et al. Eur Heart J. 2022.

Key Takeaway

This population-based cohort study evaluating the P2Y12 inhibitor adherence trajectories among patients with ACS after PCI using the APPROACH^* registry demonstrated:

• Patients follow one of five distinct P2Y12 inhibitor adherence trajectories that are associated with several socioeconomic and clinical risk factors
• Rapid decline and delayed initiation of P2Y12 inhibitors were associated with a higher risk of MACE
• Early consistent nonadherence trajectory was significantly associated with "MACE", only in patients with a drug-eluting stent
• Future studies evaluating decision support tools are needed, which can identify patients at risk of a non-adherent trajectory, plus individualized intervention to modify these trajectories.

Why This Matters

• P2Y12 inhibitor nonadherence is common among patients with ACS, which can lead to an increased risk of recurrent MACE.
• Nonadherence can follow several different patterns or trajectories, which may have distinct causes that may allow for tailored interventions.

Study Design

Adult patients ≥18 years of age who underwent PCI for ACS between 1 April 2012 and 31 March 2016 in the province of Alberta, Canada were included.

Exclusion criteria 

• Prevalent P2Y12 inhibitor users
• First fill for prasugrel
• Patients who died during or post index ACS hospitalization

Outcomes evaluated

Patients were followed for 12 months after discharge to assess:

• P2Y12 inhibitor adherence trajectories (primary outcome)
• MACE occurrence (secondary outcome)

Key Results

Overall, 12,844 patients were included in this analysis (mean age = 62.4 years; female = 24.6%)

Five distinct P2Y12 inhibitor adherence trajectories were seen

Group	Adherence trajectory	Observation	Prevalence (%) within the cohort
1	Early consistent non-adherence	No initiation or prompt discontinuation of P2Y12 inhibitor use within the first month	11.0%
2	Rapid decline	Discontinuation of P2Y12 inhibitor use after persisting for 3 months	7.7%
3	Delayed initiation	Poor initial P2Y12 inhibitor adherence with improvement over study period	6.0%
4	Gradual decline	Initial high P2Y12 inhibitor adherence with steady decline	20.5%
5	Persistent adherence	High P2Y12 inhibitor adherence throughout study period	54.8%

Risk factors for P2Y12 inhibitor use trajectories

Group	Risk factors significantly associated with P2Y12 inhibitor use as compared to group 5 (Persistent adherence)
1	Older age and lower likelihoods of PVD, ticagrelor or PPI use
1 and 2	Prior PCI, current smoking, heart failure, malignancy, bare-metal stent, PCI without stent, lower eGFR, and lower concomitant use of other preventive medications
2	High Pampalon material deprivation
3	Younger age, lower socioeconomic status, higher likelihood of smoking, bare-metal stent or no stent, EF <20%, and lower ACEI/ARB, beta-blocker, statin, or PPI use
4	Younger age, lower socioeconomic status, higher likelihood of prior PCI or CABG, smoking, bare-metal stent placement, EF 20–34%, ticagrelor use, and lower ACEI/ARB, or PPI use ≤120 days after index date

Association of P2Y12 inhibitor use with mace*

Risk factors significantly associated with P2Y12 inhibitor use as compared to group 5 (Persistent adherence)
Group	HR†	95% CI	Status
1	1.10	0.86–1.40	Not significant risk
2	1.23	1.01–1.49	Significantly higher risk
3	1.41	1.12–1.78	Significantly higher risk
4	1.11	0.96–1.29	Not significant risk

Association of P2Y12 inhibitor use with mace in group 1^*

Risk of mace in group 1
Group	HR†	95% CI	Status
≥1 drug-eluting stent	2.44	1.60–3.71	Significantly higher risk
Bare-metal stents	0.85	0.62–1.17	Not significant risk

^* Statistically significant associations are displayed in bold
^† Adjusted for significant variables

Association of P2Y12 inhibitor use with major bleeding*

Risk of major bleeding compared to group 5‡
Group	HR†	95% CI	Status
1	1.50	1.12–2.02	Higher risk§
2	1.40	1.09–1.79	Higher risk§

^* Statistically significant associations are displayed in bold
^†Adjusted for significant variables
^‡No association was seen for Groups 3 and 4
^§A higher risk was seen early after the index event

Limitations

• Data from a central prescription drug dispensation registry was used to measure P2Y12 inhibitor exposure and adherence, which assumed that patients took them as filled and may overestimate true adherence.
• Despite adjustment and measurement for known angiographic, clinical, and laboratory variables, residual unmeasured confounding may persist while evaluating associations between adherence trajectories and MACE.

^*APPROACH: Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease

MAT-BH-2300018/V1/JAN2023