Association between medication adherence and cardiovascular outcomes in patients with both diabetes and hypertension in primary care settings in Canada: A retrospective cohort study

PLoS One. 2025 Apr 16;20(4):e0319991. doi: 10.1371/journal.pone.0319991. eCollection 2025.

Abstract

Objectives: The impact of concurrent adherence to antihypertensives, antidiabetics, and statins on cardiovascular disease (CVD) outcomes and intermediate clinical outcomes in people with hypertension and diabetes remains unclear. This study aimed to evaluate the association between medication adherence and CVD outcomes in such patients.

Methods: This retrospective cohort study analyzed the electronic medical records of 36,211 adults aged 18 or older diagnosed with hypertension and diabetes between January 2008 and June 2016 in Canada. Patients were prescribed antihypertensives, antidiabetics, and statins, with a minimum 1-year follow-up post-diagnosis. Medication adherence was determined by the proportion of days covered (PDC). For monotherapy, a PDC≥80% and <80% was reflected high and low adherence respectively. In multiple medication scenarios, adherence was considered high when each medication was at PDC≥80%; low when any medication fell below 80%. The primary outcome encompassed cardiac events, including coronary heart disease, stroke, and heart failure. Intermediate clinical outcomes included changes in diastolic blood pressure (DBP), Systolic Blood Pressure (SBP), glycated hemoglobin (HbA1c), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC). Cox regression models assessed the association between medication adherence and CVD morbidity, all-cause mortality, and intermediate clinical outcomes.

Results: High adherence to antidiabetic and statin monotherapy was associated with a lower all-cause mortality risk (aHR=0.67, P=0.001; aHR=0.68, P<0.001, respectively). For patients simultaneously prescribed three medications, higher adherence was linked to significant reductions in DBP (6 months: coefficient -0.52, P=0.01; 12 months: coefficient -0.44, P=0.02; 18 months: coefficient -0.55, P=0.004) and LDL-C (6 months: coefficient -0.04, P=0.02; 12 months: coefficient -0.05, P=0.01; 18 months: coefficient -0.04, P=0.02).

Conclusions: High adherence to antidiabetic and statin monotherapy correlated with lower all-cause mortality risk and improved intermediate clinical outcomes. However, simultaneous adherence to three medications did not significantly affect CVD outcomes, but influenced intermediate outcomes. Therefore, improving adherence to antihypertensives, antidiabetics, and statins among patients with hypertension and diabetes is important in primary care settings.

MeSH terms

  • Adult
  • Aged
  • Antihypertensive Agents* / therapeutic use
  • Blood Pressure / drug effects
  • Canada / epidemiology
  • Cardiovascular Diseases* / drug therapy
  • Cardiovascular Diseases* / epidemiology
  • Diabetes Mellitus* / drug therapy
  • Diabetes Mellitus* / epidemiology
  • Female
  • Glycated Hemoglobin
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypertension* / complications
  • Hypertension* / drug therapy
  • Hypertension* / epidemiology
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Medication Adherence*
  • Middle Aged
  • Primary Health Care
  • Retrospective Studies

Substances

  • Antihypertensive Agents
  • Hypoglycemic Agents
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Glycated Hemoglobin