Adverse Drug Reactions to Antihypertensive Therapy: A Prospective Evaluation of Causality and Severity Using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) and Hartwig-Siegel Scales

Background: Hypertension is one of the most prevalent chronic non-communicable diseases worldwide and remains a leading cause of cardiovascular morbidity and mortality, particularly in low- and middle-income countries such as India. Although antihypertensive pharmacotherapy is effective in reducing cardiovascular risk, adverse drug reactions (ADRs) may compromise treatment adherence and long-term blood pressure control. Systematic identification and evaluation of ADRs using validated causality and severity assessment tools are essential to strengthen pharmacovigilance and optimize therapeutic outcomes. This study is a continuation of our previously published work evaluating prescribing trends of antihypertensive medications in the same tertiary care setting and study population. The present study focuses on the incidence, pattern, causality, and severity of ADRs associated with antihypertensive therapy. Methods: A prospective observational study was conducted over one year from February 15, 2025, to February 15, 2026, in the Medicine Outpatient Department of a tertiary care teaching hospital in India. Adult patients newly diagnosed with hypertension, defined as systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg, documented on at least two separate visits and initiated on antihypertensive therapy, were enrolled. Blood pressure measurements were obtained using a validated sphygmomanometer following standard protocol. Patients were followed longitudinally after treatment initiation, and suspected ADRs were documented using structured case record forms. Causality was assessed using the World Health Organization-Uppsala Monitoring Centre (WHO-UMC) scale, and severity was graded using the Hartwig-Siegel severity assessment scale. Descriptive statistical analysis was performed using the IBM SPSS Statistics for Windows, version 24 (released 2016; IBM Corp., Armonk, New York, United States). Results: A total of 250 newly diagnosed hypertensive patients were included in the study. The majority of patients were aged > 50 years (150, 60%), overweight or obese (175, 70%), literate (245, 98%), and belonging to socioeconomic Class III (242, 96.8%). Diabetes mellitus (119, 47.6%) and cardiovascular disease (57, 22.8%) were the most common comorbidities. During follow-up, 31 ADRs occurred, corresponding to an incidence of 31 (12.4%). Gastrointestinal and central nervous system reactions were most frequent (six, 19.4% each), followed by cardiovascular (five, 16.1%) and musculoskeletal reactions (four, 12.9%). Angiotensin receptor blockers, particularly telmisartan, were most commonly implicated. According to the WHO-UMC, 14 (45.2%) ADRs were probable and 17 (54.8%) possible. Hartwig-Siegel assessment revealed that most ADRs were mild (27, 87.1%), three (9.7%) moderate, and one (3.2%) moderate-to-severe; no ADR fulfilled WHO seriousness criteria. Most of them improved after dose adjustment or drug discontinuation. Conclusion: ADRs associated with antihypertensive medications were relatively infrequent and predominantly mild in severity; however, their occurrence highlights the importance of active pharmacovigilance and early detection strategies. Integration of ADR monitoring into routine clinical practice may enhance medication safety, improve adherence, and contribute to better long-term hypertension management outcomes.