First-line drugs for hypertension
=================================

* J. David Spence

In his recent series of *CMAJ* articles on choosing a first-line drug in the management of elevated blood pressure, James Wright repeatedly uses the phrase “low cost.”1,2,3 Unfortunately, what he is referring to is purchase price, not all-in system costs. Because purchase decisions are being restricted by third-party payers (such as the British Columbia Ministry of Health, to which Wright's Therapeutics Initiative is advisory), it is important to understand the difference.

Hypertension is well controlled for only 16% of Canadians with high blood pressure.4 This lack of good blood pressure control has an enormous avoidable cost associated with stroke, renal failure, heart failure and coronary artery disease. 

Hughes and McGuire reported that in the British National Health Service the total cost of treating hypertension was £76.5 million per annum, of which £26.9 million was attributed to the costs of discontinuation or switching of therapy.5

It is thus very important to recognize that there is much less persistence in actual practice than in clinical trials. Cheaper drugs that are not taken because of adverse effects may cost the system a great deal. Caro and colleagues recently reported that the choice of initial therapy influenced persistence with therapy. Among Canadian patients started on angiotensin-converting-enzyme inhibitors, persistence after 6 months was 89%, compared with 86% for patients taking calcium-channel antagonists, 85% for those taking β-blockers and 80% for those taking diuretics.6 After 1 year, persistence was down to 78%.7

In a US study of drug utilization from the records of over 1.3 million enrollees in health maintenance organizations, Bloom8 found that after 1 year persistence with the initial class of medication was substantially higher for drug classes with fewer adverse effects: 64% for angiotensin antagonists, 58% for angiotensin-converting-enzyme inhibitors, 50% for calcium-channel antagonists, 43% for β-blockers and 38% for diuretics. Persistence with any class of drug prescribed subsequently was about 10% higher for each group. This suggests that once patients experience an adverse effect from one drug, they are more likely to stop taking any other class of drug they are prescribed. I call this the “poison pill” effect.

In considering the cost of therapy, it is therefore necessary to consider not only the purchase price of drugs but also the system costs including dispensing fees, frequency of visits and cost of investigations for adverse effects, cost of switching medications and cost of downstream adverse outcomes that result from poor control of blood pressure. A silo budget mentality that is focused on restricting choice to drugs with cheap purchase prices is probably self-defeating.

Competing interests*:* Dr. Spence has received speaker fees, consultant fees and travel assistance from various pharmaceutical companies as well as from provincial and federal formulary committees.

## References

1.  1. Wright JM. Choosing a first-line drug in the management of elevated blood pressure: What is the evidence? 1: Thiazide diuretics. CMAJ 2000; 163(1):57-60.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo4OiIxNjMvMS81NyI7czo0OiJhdG9tIjtzOjIwOiIvY21hai8xNjQvMi8xNzYuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

2.  2. Wright JM. Choosing a first-line drug in the management of elevated blood pressure: What is the evidence? 2: β-Blockers. CMAJ 2000;163(2): 188-92.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo5OiIxNjMvMi8xODgiO3M6NDoiYXRvbSI7czoyMDoiL2NtYWovMTY0LzIvMTc2LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

3.  3. Wright JM. Choosing a first-line drug in the management of elevated blood pressure: What is the evidence? 3: Angiotensin-converting- enzyme inhibitors. CMAJ 2000;163(3):293-6.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo5OiIxNjMvMy8yOTMiO3M6NDoiYXRvbSI7czoyMDoiL2NtYWovMTY0LzIvMTc2LmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==) 

4.  4. Joffres MR, Ghadirian P, Fodor JG, Petrasovits A, Chockalingam A, Hamet P. Awareness, treatment and control of hypertension in Canada. Am J Hypertens 1997;10:1097-1102.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1016/S0895-7061(97)00224-0&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9370379&link_type=MED&atom=%2Fcmaj%2F164%2F2%2F176.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=A1997YC21400003&link_type=ISI) 

5.  5. Hughes D, McGuire A. The direct costs to the NHS of discontinuing and switching prescriptions for hypertension. J Hum Hypertens 1998; 12:533-7.
    
    [CrossRef](http://www.cmaj.ca/lookup/external-ref?access_num=10.1038/sj.jhh.1000649&link_type=DOI) 
    
    [PubMed](http://www.cmaj.ca/lookup/external-ref?access_num=9759987&link_type=MED&atom=%2Fcmaj%2F164%2F2%2F176.atom) 
    
    [Web of Science](http://www.cmaj.ca/lookup/external-ref?access_num=000075743600007&link_type=ISI) 

6.  6. Caro JJ, Speckman JL, Salas M, Raggio G, Jackson JD. Effect of initial drug choice on persistence with antihypertensive therapy: the importance of actual practice data. CMAJ 1999; 160(1):41-6.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo4OiIxNjAvMS80MSI7czo0OiJhdG9tIjtzOjIwOiIvY21hai8xNjQvMi8xNzYuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

7.  7. Caro JJ, Salas M, Speckman JL, Raggio G, Jackson JD. Persistence with treatment for hypertension in actual practice. CMAJ 1999;160(1):31-7.
    
    [Abstract/FREE Full Text](http://www.cmaj.ca/lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoiY21haiI7czo1OiJyZXNpZCI7czo4OiIxNjAvMS8zMSI7czo0OiJhdG9tIjtzOjIwOiIvY21hai8xNjQvMi8xNzYuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9) 

8.  8. Bloom BS. Continuation of initial antihypertensive medication after 1 year of therapy. Clin Ther 1998; 20:1-11.
    
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