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Original research
Sex differences in the adherence of antihypertensive drugs: a systematic review with meta-analyses
  1. Annalisa Biffi1,2,
  2. Federico Rea1,2,
  3. Teresa Iannaccone2,3,
  4. Amelia Filippelli2,3,
  5. Giuseppe Mancia4,5,
  6. Giovanni Corrao1,2
  1. 1Unit of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milan–Bicocca, Milano, Italy
  2. 2National Centre for Healthcare Research and Pharmacoepidemiology, University of Milan-Bicocca, Milan, Italy
  3. 3Department of Medicine, Surgery and Dentistry, University of Salerno, Fisciano, Italy
  4. 4University of Milan–Bicocca, Milano, Italy
  5. 5Policlinico di Monza, Monza, Italy
  1. Correspondence to Dr Annalisa Biffi; annalisa.biffi{at}


Objectives Poor worldwide rate of blood pressure control is largely due to poor adherence to antihypertensive (AHT) drug treatment. The question of whether sex affects adherence has long been debated but conflicting findings have been reported on this issue. Our objective was to evaluate sex differences in the adherence to AHT therapy.

Research design and methods Studies were identified through a systematic search of PubMed, CINAHL, PsycINFO, Web of Science and Google Scholar (through January 2020) and manual handsearching of relevant articles. Observational studies reporting adherence to AHT drugs measured by self-report or pharmacy refill prescription-based methods among men and women were included. Summarised estimates of ORs with 95% CIs were calculated using random-effects model and meta-regression models.

Results From 12 849 potentially relevant publications, 82 studies (15 517 457 men and 18 537 599 women) were included. No significant between-sex differences in adherence to AHT were observed, whether all study-specific estimates were summarised (ORs 1.04, 95% CI 1.00 to 1.09, p=0.07), nor estimates were pooled according to the method for measuring adherence. Among patients aged 65 years or older, lower self-reported adherence was observed in women (ORs 0.84, 95% CI 0.72 to 0.97, p=0.02), while the main result remained unchanged according to other subgroup analyses.

Conclusions Definitive evidence of sex differences in adherence to AHT therapy cannot be drawn. Our little knowledge about factors affecting adherence, in particular of sex effect among elderly, urgently requires high-quality studies investigating these issues.

  • hypertension
  • clinical pharmacology
  • epidemiology

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  • Contributors GC generated the study idea and wrote the final manuscript. AB and FR contributed to study search and selection; AB carried out the statistical analyses. TI, AF and GM assisted in interpreting the results under clinical prospective. All authors edited the manuscript and approved the final version.

  • Funding This study was supported by grants from the Italian Ministry of the Education, University and Research (‘Fondo d’Ateneo per la Ricerca’ portion, year 2017).

  • Competing interests GC received research support from the European Community (EC), the Italian Agency of Drug (AIFA) and the Italian Ministry for University and Research (MIUR). He took part to a variety of projects that were funded by pharmaceutical companies (ie, Novartis, GSK, Roche, AMGEN and BMS). He also received honoraria as member of Advisory Board from Roche. GM has received honoraria for participation as speaker/chairman in national/international meetings from Bayer, Boehringer Ingelheim, CVRx, Daiichi Sankyo, Ferrer, Medtronic, Menarini Int., Merck, Novartis, Recordati and Servier.

  • Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information.

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