Trends in antihypertensive drug utilization in British Columbia, 2004–2019: a descriptive study

Background: Clinical guidelines for hypertension were updated with lower blood pressure targets following new studies in 2015; the real-world impact of these changes on antihypertensive drug use is unknown. We aimed to describe trends in antihypertensive drug utilization from 2004 to 2019 in British Columbia. Methods: We conducted a longitudinal study to describe the annual prevalence and incidence rate of use of 5 antihypertensive drug classes (thiazides, angiotensin-converting enzyme [ACE] inhibitors, angiotensin II receptor blockers [ARBs], calcium channel blockers and β-blockers) among BC residents aged 30–75 years. We also conducted a cohort study to compare the risk of discontinuation and switch or add-on therapy between incident users of the above drug classes. We used linkable administrative health databases from BC. We performed a Fine–Gray competing risk analysis to estimate subhazard ratios. Results: Among BC residents aged 30–75 years (population: 2 376 282 [2004] to 3 014 273 [2019]), the incidence rate of antihypertensive drug use decreased from 23.7 per 1000 person-years in 2004 to 18.3 per 1000 person-years in 2014, and subsequently increased to 22.6 per 1000 person-years in 2019. The incidence rate of thiazide use decreased from 8.9 per 1000 person-years in 2004 to 3.2 per 1000 person-years in 2019, and incidence rates for the other drug classes increased. Incident users receiving thiazide monotherapy had an increased risk of discontinuing any antihypertensive treatment compared with ACE inhibitor monotherapy (subhazard ratio 0.96, 95% confidence interval [CI] 0.95–0.97), ARB monotherapy (subhazard ratio 0.84, 95% CI 0.81–0.87) and thiazide combination with ACE inhibitor or ARB (subhazard ratio 0.86, 95% CI 0.84–0.88), and had the highest risk of switching or adding on. Interpretation: First-line use of thiazides continued to decrease despite a marked increase in incident antihypertensive therapy following updated guidelines; incident users receiving ARB monotherapy were least likely to discontinue, and incident users receiving thiazide monotherapy were more likely to switch or add on than users of other initial monotherapy or combination. Further research is needed on the factors influencing treatment decisions to understand the differences in trends and patterns of antihypertensive drug use.

[1]  K. Kario,et al.  Seasonal variation in blood pressure: current evidence and recommendations for hypertension management , 2021, Hypertension Research.

[2]  A. Pottegård,et al.  Use of hydrochlorothiazide in Denmark following publication of skin cancer risk findings , 2021, Pharmacoepidemiology and drug safety.

[3]  A. S. Kim,et al.  Etiology and management of hypertension in patients with cancer , 2021, Cardio-Oncology.

[4]  B. Manns,et al.  Antihypertensive Prescribing for Uncomplicated, Incident Hypertension: Opportunities for Cost Savings , 2021, CJC open.

[5]  M. Johansen,et al.  The Ecology of Antihypertensives in the United States, 1997–2017 , 2020, Journal of General Internal Medicine.

[6]  Lawrence A Leiter,et al.  Hypertension Canada's 2020 Comprehensive Guidelines for the Prevention, Diagnosis, Risk Assessment, and Treatment of Hypertension in Adults and Children. , 2020, The Canadian journal of cardiology.

[7]  M. Johansen,et al.  The Ecology of Antihypertensives in the United States, 1997-2017 , 2020, medRxiv.

[8]  Jiang He,et al.  The global epidemiology of hypertension , 2020, Nature Reviews Nephrology.

[9]  George Hripcsak,et al.  Comprehensive comparative effectiveness and safety of first-line antihypertensive drug classes: a systematic, multinational, large-scale analysis , 2019, The Lancet.

[10]  L. Lix,et al.  Trends in chronic disease incidence rates from the Canadian Chronic Disease Surveillance System. , 2019, Health promotion and chronic disease prevention in Canada : research, policy and practice.

[11]  F. McAlister,et al.  The History of Hypertension Guidelines in Canada. , 2019, The Canadian journal of cardiology.

[12]  G. Mancia,et al.  Two-Drug Combinations as First-Step Antihypertensive Treatment. , 2019, Circulation research.

[13]  H. Quan,et al.  Prevalence of Hypertension, Treatment, and Blood Pressure Targets in Canada Associated With the 2017 American College of Cardiology and American Heart Association Blood Pressure Guidelines , 2019, JAMA network open.

[14]  G. Lip,et al.  2018 ESC/ESH Guidelines for the management of arterial hypertension. , 2018, European heart journal.

[15]  Jackson T. Wright,et al.  2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. , 2018, Journal of the American Society of Hypertension : JASH.

[16]  A. Pottegård,et al.  Association of Hydrochlorothiazide Use and Risk of Malignant Melanoma , 2018, JAMA internal medicine.

[17]  L. Tomlinson,et al.  Seventeen-Year Nationwide Trends in Antihypertensive Drug Use in Denmark. , 2017, The American journal of cardiology.

[18]  A. Pottegård,et al.  Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case‐control study from Denmark , 2017, Journal of the American Academy of Dermatology.

[19]  G. Nijpels,et al.  Factors associated with antihypertensive medication non-adherence: a systematic review , 2017, Journal of Human Hypertension.

[20]  B. Dobbs,et al.  Secondary Hypertension: Discovering the Underlying Cause. , 2017, American family physician.

[21]  J. Hallas,et al.  Hydrochlorothiazide use is strongly associated with risk of lip cancer , 2017, Journal of internal medicine.

[22]  Jason P Fine,et al.  Practical recommendations for reporting Fine‐Gray model analyses for competing risk data , 2017, Statistics in medicine.

[23]  M. Abrahamowicz,et al.  Comparative effectiveness of antihypertensive drugs in nondiabetic patients with hypertension: A population‐based study , 2017, Journal of clinical hypertension.

[24]  Lawrence A Leiter,et al.  Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. , 2017, The Canadian journal of cardiology.

[25]  P. McFarlane,et al.  Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. , 2016, The Canadian journal of cardiology.

[26]  F. McAlister,et al.  Epidemiology of Hypertension in Canada: An Update. , 2016, The Canadian journal of cardiology.

[27]  S. Anderson,et al.  Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis , 2016, The Lancet.

[28]  F. Messerli,et al.  Efficacy of Low-Dose Chlorthalidone and Hydrochlorothiazide as Assessed by 24-h Ambulatory Blood Pressure Monitoring. , 2016, Journal of the American College of Cardiology.

[29]  M. Woodward,et al.  Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis , 2016, The Lancet.

[30]  L. Smeeth,et al.  The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) Statement , 2015, PLoS medicine.

[31]  M. Tonelli,et al.  Healthcare Costs Attributable to Hypertension: Canadian Population-Based Cohort Study. , 2015, Hypertension.

[32]  J. Kostis,et al.  Head-to-Head Comparisons of Hydrochlorothiazide With Indapamide and Chlorthalidone: Antihypertensive and Metabolic Effects , 2015, Hypertension.

[33]  L. Brewster,et al.  Effects of Thiazide-Type and Thiazide-Like Diuretics on Cardiovascular Events and Mortality: Systematic Review and Meta-Analysis , 2015, Hypertension.

[34]  J. Václavík,et al.  Reasons for Switching Antihypertensive Medication in General Practice , 2014, Medicine.

[35]  G. Mancia,et al.  Individualization of Antihypertensive Drug Treatment , 2013, Diabetes Care.

[36]  H. Parise,et al.  Initial Combination Therapy Reduces the Risk of Cardiovascular Events in Hypertensive Patients: A Matched Cohort Study , 2013, Hypertension.

[37]  F. McAlister,et al.  Canadian provincial trends in antihypertensive drug prescriptions between 1996 and 2006. , 2011, The Canadian journal of cardiology.

[38]  F. McAlister,et al.  Antihypertensive drug persistence and compliance among newly treated elderly hypertensives in ontario. , 2010, The American journal of medicine.

[39]  D. Ellison,et al.  Thiazide Effects and Adverse Effects: Insights From Molecular Genetics , 2009, Hypertension.

[40]  G. Bakris,et al.  Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. , 2008, The New England journal of medicine.

[41]  A. Rodgers,et al.  Global burden of blood-pressure-related disease, 2001 , 2008, The Lancet.

[42]  Yu-Kang Tu,et al.  Simpson's Paradox, Lord's Paradox, and Suppression Effects are the same phenomenon – the reversal paradox , 2008, Emerging themes in epidemiology.

[43]  G. Skrepnek,et al.  Persistence, Adherence, and Risk of Discontinuation Associated with Commonly Prescribed Antihypertensive Drug Monotherapies , 2007, The Journal of the American Board of Family Medicine.

[44]  R. Stafford,et al.  Changes in Antihypertensive Prescribing During US Outpatient Visits for Uncomplicated Hypertension Between 1993 and 2004 , 2006, Hypertension.

[45]  S. Morgan,et al.  Toward a standard definition and measurement of persistence with drug therapy: Examples from research on statin and antihypertensive utilization. , 2006, Clinical therapeutics.

[46]  Thomas A Burke,et al.  Discontinuation of antihypertensive drugs among newly diagnosed hypertensive patients in UK general practice , 2006, Journal of hypertension.

[47]  M. Brisson,et al.  Persistence and discontinuation patterns of antihypertensive therapy among newly treated patients: a population-based study , 2005, Journal of Human Hypertension.

[48]  A. Ciampi,et al.  Determinants of discontinuation of new courses of antihypertensive medications. , 2002, Journal of clinical epidemiology.

[49]  Thomas Kahan,et al.  [2018 ESC/ESH Guidelines for the management of arterial hypertension]. , 2019, Kardiologia polska.

[50]  Daniel W. Jones,et al.  Potential U.S. Population Impact of the 2017 ACC/AHA High Blood Pressure Guideline. , 2018, Journal of the American College of Cardiology.

[51]  V. Musini,et al.  First-line drugs for hypertension. , 2018, The Cochrane database of systematic reviews.

[52]  C. Escobar Cervantes,et al.  [A randomized trial of intensive versus standard blood pressure control]. , 2016, Semergen.

[53]  H. M. A. Abraham,et al.  The Comparative Efficacy and Safety of the Angiotensin Receptor Blockers in the Management of Hypertension and Other Cardiovascular Diseases , 2014, Drug Safety.

[54]  D. Wald,et al.  Combination Therapy Versus Monotherapy in Reducing Blood Pressure: Meta-analysis on 11,000 Participants from 42 Trials , 2010 .