Polytherapy with two or more antihypertensive drugs to lower blood pressure in elderly Ontarians. Room for improvement

doi:10.1016/S0828-282X(07)70827-9

Canadian Journal of Cardiology

Volume 23, Issue 10, August 2007, Pages 783-787

https://doi.org/10.1016/S0828-282X(07)70827-9 Get rights and content

Background

Although guidelines now recommend polytherapy to achieve blood pressure targets, little is know about which antihypertensive drugs are combined in clinical practice.

Objective

To examine current practices for the coprescribing of antihypertensive agents.

Methods

A population-based cohort study was performed using linked administrative databases on all Ontario residents 66 years of age or older who were newly treated for hypertension between July 1, 1994, and March 31, 2002, and did not have diabetes or other relevant comorbidities. All patients were followed for two years to determine which antihypertensives were prescribed concurrently.

Results

Of the 166,018 patients in the described cohort, 1819 (1%) were prescribed a combination therapy tablet as their first-line therapy. The number of patients prescribed antihypertensive polytherapy within the first two years of diagnosis increased from 2071 (21%) of the 9825 hypertensive patients starting treatment in the second half of 1994 to 2578 (37%) of the 6988 hypertensive patients beginning treatment in the first quarter of 2002 (P<0.0001). Overall, 11,003 (27%) of polytherapy prescriptions were for drugs without additive hypotensive effects when combined and this proportion did not change over time.

Conclusions

Although there has been an increase in the use of polytherapy in elderly hypertensive patients without comorbidities in Ontario over the past decade, more than one-quarter of the two drugs prescribed together have not been proven to have additive hypotensive effects. Because this likely contributes to suboptimal blood pressure control rates, future guidelines and educational programs should devote increased attention to the choice of optimal polytherapy combinations.

Contexte

Bien que la polychimiothérapie soit recommandée dans les lignes directrices pour faciliter l’atteinte des valeurs cibles de la pression artérielle, on connaît peu de choses sur l’association des antihypertenseurs en clinique.

But

L’étude avait pour but d’examiner la pratique actuelle en matière d’emploi concomitant des antihypertenseurs.

Méthode

Une étude de cohorte, fondée sur une population, a été menée à partir du recoupement de plusieurs bases de données administratives concernant toutes les personnes âgées d’au moins 66 ans, demeurant en Ontario, nouvellement traitées pour de l’hypertension artérielle entre le 1^er juillet 1994 et le 31 mars 2002 et non atteintes de diabète ou d’autres maladies concomitantes, liées à la première affection. Les patients ont été suivis pendant deux ans pour permettre de déterminer quels antihypertenseurs étaient prescrits en association.

Résultats

Au total, 166 018 patients ont été inclus dans la cohorte en question; sur le nombre, 1819 (1%) patients ont été soumis à la polychimiothérapie orale comme traitement de première intention. Le nombre de patients qui ont reçu une ordonnance de polychimiothérapie antihypertensive au cours des deux années suivant la pose du diagnostic est passé de 2071 (21%) sur les 9825 hypertendus ayant commencé le traitement au cours de la seconde moitié de 1994 à 2578 (37%) sur les 6988 hypertendus ayant commencé le traitement au cours du premier trimestre de 2002 (p < 0,0001). Sur l’ensemble des ordonnances de polychimiothérapie, 11 003 (27%) l’étaient pour des médicaments dépourvus d’effet hypotenseur additif lorsqu’ils étaient employés en association, et la proportion n’a pas changé au fil du temps.

Conclusions

Bien que le recours à la polychimiothérapie ait augmenté chez les personnes âgées hypertendues, non atteintes de maladies concomitantes, en Ontario, au cours de la dernière décennie, plus du quart des traitements prescrits, composés de deux médicaments ne produisaient pas d’effet hypotenseur additif avéré. Comme cela conduit vraisemblablement à une maîtrise sous-optimale de la pression artérielle, il faudrait que les futures lignes directrices et les nouveaux programmes de formation comportent un volet sur le choix des médicaments susceptibles d’association afin de composer une polychimiothérapie optimale.

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Chiropractic Management of a Patient With Chronic Fatigue: A Case Report
2016, Journal of Chiropractic Medicine
Citation Excerpt :
The polytherapy described in this case included general nutritional support, targeted supplementation, dietary changes, and lifestyle modifications; the patient declined the endocrinologist referral. Polytherapy has been widely described in clinical pharmaceutical literature44-46; however, polytherapy studies in nutritional medicine have been performed only on a small scale,47 even though the use of nutritional medicine polytherapy has lower side effects. This research phenomenon may have resulted from researchers wanting to see the effects of a single nutritional entity.
The purpose of this case report was to describe the examination and management of a patient with chronic fatigue.
A 34-year-old woman presented to a chiropractic clinic with complaints of fatigue and inability to lose weight for 2 years. When tested, she was found to have high serum thyroglobulin antibodies, low serum vitamin D₃, low saliva dehydroepiandrosterone-sulfate, and low saliva total and diurnal cortisol.
The patient was placed on an anti-inflammatory ancestral diet and given recommendations to decrease the aerobic intensity of her exercise routine. On the basis of the result of conventional and functional laboratory tests, she was prescribed a treatment plan of targeted supplementation. After 12 weeks of application of dietary, lifestyle, and supplementation recommendations, the patient reported experiencing increased energy and weight loss of 15 pounds. Her thyroglobulin antibodies returned within reference range, salivary cortisol increased and closely followed the proper circadian rhythm, and dehydroepiandrosterone-sulfate increased.
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2013, Canadian Journal of Cardiology
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Revising knowledge translation and key messages to direct clinicians' attention to the care gaps in elderly women and systolic blood pressure should be considered. Past evaluation of appropriate combinations of antihypertensive medications should be updated19,20 and, if required, new programs should be introduced to better inform clinicians on how to combine antihypertensive drugs. The use of electronic medical and health records that guide clinicians in selection of pharmacotherapy and blood pressure targets and that calculate and track total cardiovascular risk may also assist.
Blood pressure surveillance, monitoring, and evaluation of programs to prevent and control hypertension are critical because increased blood pressure is a leading risk for premature death and disability. Since 2003, the Hypertension Outcomes Research Task Force has existed in Canada, with members who assist in the development and revision of surveys and conduct analyses that help guide hypertension programs. Although the Task Force has tracked a 5-fold increase in the control of hypertension (from 13% in 1985-1992 to 65% in 2007-2009), surveillance data also indicate that many “care gaps” remain. Fifty-four percent of people with diabetes and 34% of those without diabetes have blood pressure readings greater than their target. Treatment rates are high in those who are diagnosed (95%), but 17% of people with hypertension remain undiagnosed. Younger men (more so than women) are too often unaware of having hypertension. Although they are more likely to be aware of their diagnosis, older women are 2 times more likely to have uncontrolled hypertension than men; systolic blood pressure is high in over 80% of those with uncontrolled blood pressure (90% in women); and often people with hypertension are not provided comprehensive advice on healthy behaviours, or assisted in developing plans to control their blood pressure. Many current surveys do not have adequate statistical power to assess vulnerable populations; surveys of Aboriginal populations do not usually assess blood pressure, such that the burden of hypertension in these high risk populations cannot be assessed.
La surveillance et le monitorage de la pression artérielle, et l'évaluation des programmes pour prévenir et maîtriser l'hypertension sont très importants puisqu'une pression artérielle élevée est le principal facteur de risque de mortalité prématurée et d'incapacité. Depuis 2003, le groupe de travail responsable de la recherche des effets de l'hypertension sur la santé (Hypertension Outcomes Research Task Force) existe au Canada par l'intermédiaire de membres qui aident à l'élaboration et à la révision d'enquêtes, et mènent des analyses aidant à orienter les programmes sur l'hypertension. Même si le groupe de travail a découvert que la maîtrise de l'hypertension s'est améliorée de 5 fois (de 13 % de 1985 à 1992 à 65 % de 2007 à 2009), la surveillance des données indique aussi que plusieurs « lacunes en matière de soins » demeurent. Cinquante-quatre pour cent (54 %) des diabétiques et 34 % des non diabétiques ont des mesures de pression artérielle plus grande que leur valeur cible. Les taux de traitements sont élevés chez ceux qui sont diagnostiqué (95 %), mais 17 % des personnes hypertendues ne sont pas diagnostiquées. Aussi, les plus jeunes hommes (plus que de femmes) ignorent souvent qu'il souffre d'hypertension. Même si elles sont plus susceptibles de ne pas ignorer leur diagnostic, les femmes plus âgées sont 2 fois plus susceptibles que les hommes de souffrir d'une hypertension non maîtrisée. La pression artérielle systolique est élevée chez plus de 80 % de ceux ayant une pression artérielle non maîtrisée (90 % chez les femmes) et, souvent, les personnes hypertendues ne reçoivent pas de conseils exhaustifs sur les comportements favorables à la santé ou ne reçoivent pas d'aide dans l'élaboration de plans pour maîtriser leur pression artérielle. Plusieurs enquêtes actuelles n'ont pas la puissance statistique adéquate pour évaluer les populations vulnérables. Les enquêtes des populations autochtones n'évaluent habituellement pas la pression artérielle, de telle sorte que le fardeau de l'hypertension chez ces populations exposées à un risque élevé ne peut pas être évalué.
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Table 4 summarizes the validation studies of the primary outcome measure derived from these databases. Secondary outcome measures include mortality due to CVD and coronary artery disease (CAD), and all-cause mortality; hospitalisations for stroke and CAD; differences in rates of initiation of antihypertensive drug therapy (Tu et al., 2002); differences in rates of hypertension drug treatment (one antihypertensive drug versus polytherapy) (Campbell et al., 2007); and health service utilisation and cost-benefit analysis (Drummond et al., 2005). The sample size was fixed, as there were only 39 Ontario communities of 10,000 to 60,000 residents that met our eligibility criteria.
High blood pressure is an important and modifiable cardiovascular disease risk factor that remains under-detected and under-treated. Community-level interventions that address high blood pressure and other modifiable risk factors are a promising strategy to improve cardiovascular health in populations. The present study is a community cluster-randomised trial testing the effectiveness of CHAP (Cardiovascular Health Awareness Program) on the cardiovascular health of older adults.
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Trends in antihypertensive drug prescriptions and physician visits in Canada between 1996 and 2006
2008, Canadian Journal of Cardiology
In 1999, the Canadian Hypertension Education Program (CHEP) was launched to develop and implement evidence-based hypertension guidelines.
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Longitudinal drug data (Intercontinental Medical Statistics [IMS] CompuScript database; IMS Health Canada) were used to examine prescriptions over an 11-year period (1996 to 2006) for five major cardiovascular drug classes. The IMS Canadian Disease and Therapeutic Index database was used to determine trends in physician office visits for hypertension.
Prescriptions for antihypertensive agents increased significantly over the 11-year period (4054% for angiotensin receptor blockers, 127% for thiazide diuretics, 108% for angiotensin-converting enzyme inhibitors, 87% for beta-blockers and 55% for calcium channel blockers). Time series analyses demonstrated increases in the growth rate for all drug classes, with the greatest annual change in prescriptions occurring during the 1999 to 2002 time period (except in angiotensin receptor blockers). An increase in prescriptions for fixed-dose combination products occurred, which was temporally related to the change in CHEP recommendations encouraging their use in 2001. The proportion of physician office visits for hypertension increased significantly from 4.9% in 1995 to 6.8% in 2005 (P < 0.001).
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En 1999, le Programme éducatif canadien sur l’hypertension (PECH) était créé pour élaborer et implanter des lignes directrices probantes sur l’hypertension.
Déterminer les tendances temporelles de prescription d’antihypertenseurs et de consultations chez les médecins au Canada et les corréler avec les recommandations du PECH.
Les données longitudinales sur les médicaments (bases de données CompuScript d’IMS, IMS Health Canada) ont permis d’examiner les prescriptions sur une période de 11 ans (de 1996 à 2006) à l’égard de cinq grandes catégories de médicaments cardiovasculaires. La base de données de l’IMS Canadian Disease and Therapeutic Index a été utilisée pour déterminer les tendances des consultations au cabinet du médecin en raison de l’hypertension.
Les prescriptions d’antihypertenseurs ont augmenté considérablement au cours de la période de 11 ans (4 054% pour les antagonistes des récepteurs de l’angiotensine, 127% pour les diurétiques thiazidiques, 108% pour les inhibiteurs de l’enzyme de conversion de l’angiotensine, 87% pour les bétabloquants et 55% pour les inhibiteurs calciques). Des analyses de séries chronologiques ont démontré des augmentations du taux de croissance de toutes les classes de médicaments, le changement annuel le plus important en matière de prescription s’étant observé entre 1999 et 2002 (sauf pour les antagonistes des récepteurs de l’angiotensine). On a constaté une augmentation des prescriptions de polythérapies à dose fixe, reliée dans le temps à la modification des recommandations du PECH favorisant leur utilisation en 2001. La proportion de consultations au cabinet du médecin en raison de l’hypertension a connu une hausse significative de 4,9% en 1995 à 6,8% en 2005 (P < 0,001).
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Citation Excerpt :
Our study addresses limitations of previous studies, including having relevant comparison groups, time-varying cumulative exposure variables, large sample size and standardized measurement of cumulative dose. We also adjusted for concomitant use of other antihypertensive medications55 and adjusted for treatment selection bias by including a binary ever or never use variable for each antihypertensive class.38 We assessed 3 different outcomes for 5 separate antihypertensive drug cohorts, and the multiple comparisons could have inflated the chance of a false-positive result.
The risk of skin cancer associated with antihypertensive medication use is unclear, although thiazides have been implicated in regulatory safety warnings. We aimed to assess whether use of thiazides and other antihypertensives is associated with increased rates of keratinocyte carcinoma and melanoma.
We conducted a population-based inception cohort study using linked administrative health data from Ontario, 1998–2017. We matched adults aged ≥ 66 years with a first prescription for an antihypertensive medication (thiazides, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, β-blockers) by age and sex to 2 unexposed adults who were prescribed a non-antihypertensive medication within 30 days of the index date. We evaluated each antihypertensive class in a separate cohort study. Our primary exposure was the cumulative dose within each class, standardized according to the World Health Organization’s Defined Daily Dose. Outcomes were time to first keratinocyte carcinoma, advanced keratinocyte carcinoma and melanoma.
The inception cohorts included a total of 302 634 adults prescribed an antihypertensive medication and 605 268 unexposed adults. Increasing thiazide exposure was associated with an increased rate of incident keratinocyte carcinoma (adjusted hazard ratios [HRs] per 1 Defined Annual Dose unit 1.08, 95% confidence interval [CI] 1.03–1.14), advanced keratinocyte carcinoma (adjusted HR 1.07, 95% CI 0.93–1.23) and melanoma (adjusted HR 1.34, 95% CI 1.01–1.78). We found no consistent evidence of association between other antihypertensive classes and keratinocyte carcinoma or melanoma.
Higher cumulative exposure to thiazides was associated with increased rates of incident skin cancer in people aged 66 years and older. Consideration of other antihypertensive treatments in patients at high risk of skin cancer may be warranted.
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Polytherapy with two or more antihypertensive drugs to lower blood pressure in elderly Ontarians. Room for improvementPolychimiothérapie composée d’au moins deux antihypertenseurs pour abaisser la pression artérielle chez les personnes âgées en Ontario : Place à l’amélioration

Background

Objective

Methods

Results

Conclusions

Contexte

But

Méthode

Résultats

Conclusions

Lancet

Lancet

Lancet

Lancet

Lancet

Lancet

Am J Hypertens

Effects of different blood pressurelowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: Results of prospectively designed overviews of randomized trials

Arch Intern Med

Health outcomes associated with various antihypertensive therapies used as first-line agents: A network meta-analysis

JAMA

JAMA

2003 European Society of Hypertension- European Society of Cardiology guidelines for the management of arterial hypertension

J Hypertens

Canadian Hypertension Education Program. The 2005 Canadian Hypertension Education Program recommendations for the management of hypertension: Part II – therapy

Can J Cardiol

Hypertension management in the elderly has improved: Ontario prescribing trends, 1994 to 2002

Hypertension

Is it time to move to multidrug combinations?

Am J Hypertens

Success and predictors of blood pressure control in diverse North American settings: The antihypertensive and lipidlowering treatment to prevent heart attack trial (ALLHAT)

J Clin Hypertens

BMJ

British Hypertension Society. Guidelines for management of hypertension: Report of the fourth working party of the British Hypertension Society, 2004-BHS IV

J Hum Hypertens

2001 Canadian hypertension recommendations. What has changed?

Can Fam Physician

Resistant hypertension and the Birmingham Hypertension Square

Curr Hypertens Rep

The ‘Birmingham Hypertension Square’ for the optimum choice of add-in drugs in the management of resistant hypertension

J Hum Hypertens

Value of low dose combination treatment with blood pressure lowering drugs: Analysis of 354 randomised trials

BMJ

Canadian Drug Reference for Health Professionals

Physician's Desk Reference

Comparison of antihypertensive effects of an angiotensinconverting enzyme inhibitor, a calcium antagonist and a diuretic in patients with hypertension not controlled by angiotensin receptor blocker monotherapy

J Hypertens

Lack of effect of a diuretic added to diltiazem

J Hum Hypertens

The effects of bendroflumethiazide added to nifedipine in patients with hypertension

J Clin Pharmacol