Clinician underprescription of and patient nonadherence to clinical practice guideline-recommended medications for peripheral artery disease: a systematic review and meta-analysis
Bibliographic record
Abstract
Background: Guidelines recommend that adults with peripheral artery disease (PAD) take antiplatelets, statins, and antihypertensives. However, it is unclear how frequently clinicians do not prescribe these medications (ie, underprescription), how often patients fail to fill/refill their prescriptions (ie, nonadherence), which factors increase underprescription/nonadherence risk, and whether underprescription/nonadherence are associated with outcomes. Methods: We searched MEDLINE, EMBASE, CENTRAL, and Evidence-Based Medicine Reviews (January 1, 2006-to-February 18th, 2025) for studies reporting cumulative incidences/point prevalences of clinician underprescription and/or patient nonadherence to antiplatelets, statins, and/or antihypertensives; adjusted-risk factors for underprescription/nonadherence; and adjusted-outcomes associated with underprescription/nonadherence among adults with PAD. Two investigators independently screened citations, extracted data, and assessed risk of bias. Data were pooled using random-effects models. Estimate certainty was communicated using GRADE. The study was registered on PROSPERO (CRD42022362801). Findings: Among 4206 citations identified, 125 studies (n = 14,681,801 participants; 37% female) were included. The pooled cumulative incidence of antiplatelet, statin, and antihypertensive (among those with PAD and hypertension) underprescription was 28% (95% confidence interval [CI] = 21-36%; moderate-certainty), 34% (95% CI = 31-38%; high-certainty), and 43% (95% CI = 33-53%; moderate-certainty), respectively. The cumulative incidence of antiplatelet, statin, and antihypertensive nonadherence was 27% (95% CI = 20-35%; moderate-certainty), 28% (95% CI = 24-33%; high-certainty), and 23% (95% CI = 22-24%; low-certainty), respectively. Underprescription was more common in population-based studies and those enrolling more females and past/current smokers while nonadherence was more common in studies enrolling more patients with diabetes. Underprescription risk factors included female sex, advanced age, malignancy history, and chronic limb-threatening ischemia (all moderate-certainty). Nonadherence risk factors included advanced age, comorbidity burden, and receiving specialist mental health care (all moderate-certainty). Underprescription was associated with increased major adverse cardiac events, all-cause mortality, and decreased amputation-free time (all moderate-certainty). Interpretation: One-quarter-to-one-half of adults with PAD are not prescribed antiplatelets, statins, and antihypertensives. Further, approximately one-quarter of these patients do not adhere to these medications after prescription. Funding: This research was supported by a 2024 Vanier Canada Graduate Scholarship (awarded to AMK and supervised by DJR), a Graham Farquharson Physician Services Incorporated Knowledge Translation Fellowship (awarded to DJR), and a Research Program Award, University of OttawaDepartment of Surgery Annual Competition (awarded to DJR).
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.024 | 0.061 |
| Meta-epidemiology (narrow) | 0.003 | 0.002 |
| Meta-epidemiology (broad) | 0.021 | 0.040 |
| Bibliometrics | 0.008 | 0.009 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.003 | 0.002 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".