Dual antiplatelet therapy for secondary prevention in ischemic stroke –Trends in prescription patterns after pivotal trials and guideline updates

Xian Y, et al. JAMA Intern Med. 2022.

Key Takeaway

The publication of 2 pivotal trials (CHANCE and POINT) and serial AHA/ASA guideline updates showed:

  • Increased adoption of DAPT for secondary prevention in:

    • Minor ischemic strokes (for which guidelines recommended DAPT use)

    • Nonminor ischemic strokes (for which the riskbenefit ratio of DAPT has not been fully established)

  • Underuse of DAPT in patients with minor ischemic stroke (53.0% patients did not receive) despite class I, level A evidence recommendation

The findings suggest an important opportunity to improve adherence to evidence based antiplatelet therapy for secondary prevention in AIS.

Why This Matters

  • Recommendations for DAPT (aspirin and clopidogrel) for secondary prevention in AIS have evolved over time*, but the degree to which physicians follow them in routine clinical practice is unknown.
  • This study evaluated the antiplatelet prescription patterns at discharge in patients with AIS after the release of pivotal trials and serial AHA/ASA guideline updates in the US.

Study Design

ASSESSMENT OF ANTIPLATELET PRESCRIPTION

 

  1. Before CHANCE trial
  2. Before 2014 AHA/ASA guideline updates
  3. Before POINT trial and 2018 AHA/ASA guideline updates
  4. Before 2019 AHA/ASA guideline updates
  5. After 2019 AHA/ASA guideline updates

ANTIPLATELET AGENT CATEGORIZATION

  1. Aspirin monotherapy
  2. Clopidogrel bisulfate monotherapy
  3. DAPT of aspirin and clopidogrel
  4. Aspirin and dipyridamole
  5. Other antiplatelet agents‡

ANALYSES

  • Proportions of antiplatelet medication over time were evaluated by the Cochran-Armitage test for trend.
  • Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline was followed.
  • Two-sided P <0.05 was considered as statistically significant.

Key Results

PATIENT CHARACTERISTICS
NUMBER OF PATIENTS 1,281,034
MEAN AGE (IQR) 68 (59-78) years
MEN/WOMEN 51.2% / 48.8%
ASIAN 3.1%
HISPANIC 7.9%
NON-HISPANIC BLACK 20.8%
NON-HISPANIC WHITE 64.1%
OTHER RACE 4.1%
PATIENTS RECEIVING ANTIPLATELET THERAPY AT DISCHARGE
  • Aspirin monotherapy = 54.5%
  • Clopidogrel monotherapy = 12.4%
  • DAPT = 30.8%
  • Aspirin and dipyridamole = 1.8%
  • Other antiplatelet agents or combination = 0.6%
PRESCRIPTION PATTERNS OF DAPT
  BEFORE CHANCE TRIAL (N = 106,725) BEFORE 2014 AHA/ASA GUIDELINE UPDATES (N = 76,357) BEFORE POINT TRIAL AND 2018 AHA/ASA GUIDELINE UPDATES (N = 653,883) BEFORE 2019 AHA/ASA GUIDELINE UPDATES (N = 302,818) AFTER 2019 AHA/ASA GUIDELINE UPDATES (N = 141,251)
USE OF DAPT 19.4% 23.1% 27.6% 37.2% 44.9%
USE OF DAPT IN MINOR STROKES (NIHSS SCORE ≤ 3) 19.5% 23.6% 28.1% 38.3% 47.0%
USE OF DAPT IN NONMINOR STROKES (NIHSS SCORE > 3) 19.4% 22.8% 28.0% 36.5% 42.6%

USE OF DAPT AFTER 2019 AHA/ASA GUIDELINE UPDATES

• Potential underuse in patients with minor strokes:
53.0% (95% CI: 52.7%–53.4%) did not receive DAPT

• Potential overuse in patients with nonminor ischemic stroke:
42.6% (95% CI: 42.1%–43.0%) received DAPT

Limitations

  • Lack of documented reasons for:

    • Prescribing or not prescribing DAPT

    • Timing of the initiation

    • Duration of antiplatelet treatment

    • Generalizability to patients treated at non-registry hospitals or in other countries

  • Lack of information on prescribing trends post June 2020

* CHANCE and POINT trials showed short-term use of DAPT (21–90 days) to be effective in reducing the risk of recurrent ischemic stroke in patients with minor ischemic stroke; AHA/ASA updated recommendations for DAPT in routinesecondary prevention after ischemic stroke from “risk ≥ benefit” (class III) in 2011, to “benefit >>> risk” (class I, level ofevidence A) in 2019

† Between October 1, 2012, and June 30, 2020
‡ Ticlopidine hydrochloride, prasugrel, ticagrelor monotherapy, or their combination with aspirin

ABBREVIATIONS:

AHA/ASA, American Heart Association and American Stroke Association; AIS, acute ischemic stroke; CI, confidence interval; DAPT, dual antiplatelet therapy; IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale.

    Xian Y, Xu H, Smith EE, Fonarow GC, Bhatt DL, Schwamm LH, et al. Evaluation of evidence-based dual antiplatelet therapy for secondary prevention in US patients with acute ischemic stroke. JAMA Intern Med. 2022. doi: 10.1001/jamainternmed.2022.0323. Epub ahead of print. PMID: 35344009.

MAT-BH-2300013/V1/JAN2023