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Intervention May Improve Medication Appropriateness in Those With Multimorbidity, Polypharmacy


Investigators in Spain tested whether the tool would work in elderly patients in the primary care setting.

Results of a cluster-randomized clinical trial conducted in Spain, Improving Prescription in Primary Care Patients With Multimorbidity and Polypharmacy (Multi-PAP), revealed the intervention sustainably improved medication appropriateness over the follow-up time.

However, authors cautioned the small magnitude of the effect necessitates limited interpretation of the results.

Just under 40% of the Spanish population has multimorbidity while around 11% suffer from at least 5 chronic conditions, researchers explained. For adults between the ages 67 and 74, the average number of chronic conditions is 2.8. In addition, polypharmacy—defined as taking between 4.5 and 8 drugs a day—is present in around 20% of elderly adults treated in primary care.

“Spain has a well-established framework to address polymedication in patients aged 75 and over, but the population under this age is not subject to specific control or prevention strategies regarding polymedication,” authors said.

The Medication Appropriateness Index (MAI) is the most accepted method to quantify and reduce potentially inappropriate prescribing and works by rating each medication based on indication, effectiveness, correct dosage and other metrics.

Similarly, the Ariadne principles “propose the agreement of realistic therapeutic goals between the physician and the multimorbidity and polypharmacy patient, taking their preferences and desires into account and ensuring their individualized care management and monitoring,” researchers noted.

In an effort to determine the effectiveness of a complex intervention under the primary care Multi-PAP model based on the implementation of the Adrianne principles, investigators conducted a pragmatic, cluster randomized, controlled trial in primary care centers throughout 2 regions of Spain.

All participants were between the ages of 65 and 74, had at least 3 different chronic conditions, and polypharmacy. Patients were recruited between 2016 and 2017. Family physicians (FP) in the control group continued to provide normal care to patients, while participants in the intervention group received the Multi-PAP intervention based on the Ariadne principles.

FPs in the intervention group underwent a 4 week Multi-PAP training course with content created by Multi-PAP researchers. Training content included information on multimorbidity, polypharmacy, appropriateness of prescribing, treatment adherence, the Ariadne principles, therapeutic cascade, deprescription and physician–patient shared decision-making basic concepts. FPs also conducted patient interviews in the intervention cohort.

Appropriateness of prescribing, measured via between-group differences in mean MAI score change from baseline to 6-month follow-up served as the primary trial outcome.

A total of 117 FPs and 593 patients were included in the final study. The intervention group consisted of 59 FPs and 298 patients. After 6 months, follow-up data were available for 96% of participants compared with 92% at 12 months.

Analyses revealed:

  • Average age was 69.7 (2.7), and 55.8% were women
  • Median number of diseases was 5.0 (IQR 4.0–7.0)
  • Median number of drugs was 7.0 (6.0–9.0)
  • Mean (SD) and median baseline summated MAI score was 17.5 (16.8) and 14.0 (5.0–25.0), respectively
  • In the intention-to-treat analysis, the between-group difference for the mean MAI score change after a 6-month follow-up was −2.42 (95% CI, −4.27 to −0.59; P = .009)
  • Between baseline and a 12-month follow-up, between-group difference was −3.40 (95% CI, −5.45 to −1.34; P = .001)
  • Both groups showed significant improvements in measures of patient-centered care

“The power for subgroup analysis is limited, no evidence was found of a differential effect in any of our predefined subgroup analyses at 6 months, except for physicians being postgraduate tutors, who showed a greater difference in the MAI score change,” authors wrote.

Blinding was not possible in the current study marking a limitation, although primary outcomes were evaluated by 3 blinded family physician investigators with access to full patient medical records.

“Although we observed a significant difference across groups of the a priori (per protocol) defined magnitude, we acknowledge that a larger difference would provide more convincing evidence of the positive impact of the intervention,” researchers concluded.


del Cura-González I, López-Rodríguez JA, Leiva-Fernández F, et al. How to improve healthcare for patients with multimorbidity and polypharmacy in primary care: a pragmatic cluster-randomized clinical trial of the MULTIPAP intervention. J Pers Med. Published online May 6, 2022. doi:10.3390/jpm12050752

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