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To update the evidence-based recommendations for the prevention and management of hypertension in adults.
For lifestyle and pharmacological interventions, evidence was preferentially reviewed from randomized controlled trials and systematic reviews of trials. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease.
A Cochrane collaboration librarian conducted an independent MEDLINE search from 2006 to August 2007 to update the 2007 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by content and methodological experts using prespecified levels of evidence.
For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium intake to less than 100 mmol/day (and 65 mmol/day to 100 mmol/day in hypertensive patients); perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (smaller than 102 cm for men and smaller than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a diet that is reduced in saturated fat and cholesterol, and one that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on by the patient’s global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (in nonblack patients), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered for initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. Other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine CCBs or ARBs. In patients with angina, recent myocardial infarction or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with protein-uric nondiabetic chronic kidney disease, ACE inhibitors are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension but who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered.
All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.
Mettre à jour les recommandations probantes pour la prévention et la prise en charge de l’hypertension chez les adultes.
Dans le cadre d’interventions pharmacologiques et touchant le mode de vie, les auteurs ont procédé à une analyse préférentielle des données tirées d’essais aléatoires et contrôlés et d’analyses systématiques d’essais. Tandis que des modifications à la morbidité et à la mortalité cardiovasculaires constituaient les principales issues d’intérêt, dans le cas des interventions touchant le mode de vie, la diminution de la tension artérielle était acceptée comme issue primaire en raison de l’absence de données à long terme sur la morbidité et la mortalité dans ce secteur. Dans le cas des patients atteints d’une néphropathie chronique, l’aggravation du dysfonctionnement rénal constituait également une issue primaire pertinente d’un point de vue clinique.
Un bibliothécaire de Collaboration Cochrane a effectué une recherche indépendante dans la base de données MEDLINE entre 2006 et août 2007, afin de mettre les recommandations de 2007 à jour. On a également dépouillé les listes de référence et communiqué avec des experts pour repérer d’autres études publiées. Tous les articles pertinents ont été analysés et évalués de manière indépendante par des experts du contenu et de la méthodologie, au moyen de qualités des preuves préétablies.
Les modifications au mode de vie pour prévenir ou traiter l’hypertension consistent à réduire la quantité de sel d’origine alimentaire à moins de 100 mmol/jour (et à entre 65 mmol/jour et 100 mmol/jour pour les hypertendus), à pratiquer des activités aérobiques de 30 à 60 min quatre à sept jours par semaine, à maintenir un poids santé (indice de masse corporelle de 18,5 kg/m2 à 24,9 kg/m2) et un tour de taille sain (inférieur à 102 cm chez les hommes à 88 cm chez les femmes), à limiter la consommation d’alcool à 14 unités par semaine chez les hommes et à neuf unités par semaine chez les femmes, à respecter un régime alimentaire pauvre en gras saturés et en cholestérol et riche en fruits et légumes, en produits laitiers à faible teneur en matières grasses, en fibres alimentaires et solubles ainsi qu’en grains entiers et en protéines d’origine végétale, et à envisager des techniques de maîtrise du stress pour certaines personnes hypertendues. Pour ce qui est de la prise en charge pharmacologique de l’hypertension, les valeurs seuils et les valeurs cibles de traitement doivent dépendre du risque athéroscléreux global du patient, de l’atteinte des organes cibles et des pathologies comorbides. Il faut abaisser la tension artérielle à moins de 140/90 mm Hg chez tous les patients et à moins de 130/80 mm Hg chez les patients diabétiques ou atteints d’une néphropathie chronique. La plupart des patients adultes devront prendre plus d’un médicament pour parvenir aux valeurs cibles. Chez les adultes qui ne sont pas tenus de prendre d’autres agents, le traitement initial devrait inclure des diurétiques thiazidiques. D’autres médicaments conviennent au traitement de première intention de l’hypertension diastolique associée ou non à une hypertension systolique, soit les inhibiteurs de l’enzyme de conversion de l’angiotensine (ECA, sauf chez les patients noirs), les inhibiteurs calciques (IC) à action prolongée, les antagonistes des récepteurs de l’angiotensine (ARA) et les bétabloquants (chez les personnes de moins de 60 ans). On peut également envisager deux médicaments de première intention pour le traitement initial de l’hypertension si la tension artérielle systolique dépasse la cible d’au moins 20 mm Hg ou si la tension artérielle diastolique la dépasse d’au moins 10 mm Hg. D’autres médicaments conviennent au traitement de première intention de l’hypertension systolique isolée, y compris les IC dihydropyridines à action prolongée ou les ARA. Aussi, chez les patients angineux, ayant récemment subi un infarctus du myocarde ou atteints d’une insuffisance cardiaque, des bétabloquants et des inhibiteurs de l’ECA sont recommandés en première intention. Chez les patients atteints d’une maladie vasculaire cérébrale, l’association d’un inhibiteur de l’ECA et d’un diurétique est à privilégier, tandis que chez les patients atteints d’une néphropathie chronique non diabétique avec protéinurie, les inhibiteurs de l’ECA sont recommandés et chez les diabétiques, les inhibiteurs de l’ECA ou les ARA (ou, chez les patients ne présentant pas d’albuminurie, les thiazidiques ou les IC dihydropyridines) conviennent en première intention. Tous les patients hypertendus dyslipidémiques doivent être traités selon les seuils, les valeurs cibles et les médicaments proposés dans le document de principes de la Société canadienne de cardiologie (recommandations sur le diagnostic et le traitement de la dyslipidémie et la prévention des maladies cardiovasculaires). D’après ce document, certains patients hypertendus très vulnérables qui n’atteignent pas les seuils leur donnant droit à un traitement aux statines devraient tout de même recevoir ce traitement. Un traitement à l’acide acétylsalicylique pourra être envisagé une fois la tension artérielle stabilisée.
Toutes les recommandations ont été classées selon la solidité des données probantes, et les 57 membres du groupe de travail des recommandations du Programme éducatif canadien sur l’hypertension ont exercé leur vote à leur égard. Toutes les recommandations publiées ont obtenu un consensus d’au moins 95 %. Ces lignes directrices continueront d’être mises à jour chaque année.
Hypertension is one of the most important modifiable risk factors for preventing cardiovascular disease and death (1–3). Care of the hypertensive patient is constantly evolving in response to new data published each year. To ensure that patients receive timely benefit from important new advances in hypertension research, the Canadian Hypertension Education Program (CHEP) Recommendations Task Force conducts an annual review of recently published hypertension treatment studies. These data are translated into practical, updated, evidence-based recommendations for primary care providers on the management of adults with hypertension. In the present report, we provide the complete 2008 recommendations for lifestyle and pharmacological management of hypertension, as well as the evidence and rationale supporting all new recommendations. Summary documents of these recommendations, along with a freely downloadable slide kit, are available on the Canadian Hypertension Society Web site (www.hypertension.ca).
For 2008, there have been several important developments, including expanding the role of combination therapy in the initial treatment of hypertension based on the recent publication of the Action in Diabetes and Vascular disease: preterAx and diamicronN-MR Controlled Evaluation (ADVANCE) trial (4), and review of the Felodipine Event Reduction (FEVER) trial (5), the Heart Outcomes Prevention Evaluation (HOPE) (6) and the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) (7), as well as clarifying the optimal antihypertensive dosages for patients with heart failure. We also review findings from a post hoc analysis of the PROGRESS trial (8) evaluating the associations of achieved follow-up blood pressure levels with stroke risk.
Although we mention individual antihypertensive agents when discussing hypertension trials, the reader may assume that all drug-specific recommendations are applicable to the entire drug class in question, unless otherwise specified. Finally, while these recommendations are based on best evidence, health care providers must also use their own clinical judgement and consider patient preferences when applying these recommendations to their patients.
A Cochrane collaboration librarian conducted a MEDLINE search using a highly sensitive search strategy for randomized trials and systematic reviews published from 2006 to August 2007. To ensure that all relevant studies were included, bibliographies of identified articles were hand-searched. (Details of search strategies and retrieved articles are available on request.)
Each subgroup, consisting of national and international hypertension experts (see Appendix), reviewed all identified articles relevant to their topic area. Members of the Canadian Diabetes Association Guidelines Committee and Canadian Society of Nephrology collaborated with CHEP subgroup members for the 2008 recommendations process. The subgroups appraised the quality of relevant studies using a standardized algorithm developed by CHEP (9). Subsequently, the central review committee, consisting of clinical epidemiologists (see Appendix), reviewed the draft recommendations from each subgroup and, in an iterative process, helped to refine and standardize all recommendations and their grading across subgroups (see Table 1).
The draft recommendations from each subgroup were then formally vetted at the 2007 consensus conference held in Quebec City, Quebec, by task force committee members, as well as members from the Canadian Diabetes Association Guidelines Committee and the Canadian Society of Nephrology. Based on the deliberations at the consensus conference, the 2008 recommendations were finalized and submitted to all 57 voting members of the CHEP Evidence-Based Recommendations Task Force for approval. Members with conflicts of interest for certain recommendations were recused from voting. As in previous years, only those recommendations approved by more than 70% of the task force were included in the final recommendations presented here.
Lifestyle modifications are a critical part of the prevention and treatment of hypertension. Regular physical activity is independently associated with reductions in blood pressure (10), type 2 diabetes (11), cardiovascular events and all-cause mortality (12). Because these benefits of physical activity appear to be dose-related (13,14), and to be consistent with the American Heart Association (15) and American College of Sports Medicine exercise guidelines (16), CHEP has clarified that the recommended exercise prescription is in addition to the routine activities of daily living (grade D).
There is a large and compelling body of literature demonstrating that antihypertensive drug therapy is associated with a 20% to 25% reduction in cardiovascular events and a 10% reduction in mortality (20). The majority of these studies were based on step-up titration schemes, in which a single agent was initiated and doses were titrated upward or other antihypertensive agents were added until target blood pressure was achieved. These studies form the foundation for the grades A and B monotherapy recommendations, and represent the primary strategy for initiating antihypertensive drug therapy. However, because many patients require more than one drug to achieve blood pressure targets, hypertension trials are now evaluating the safety and efficacy of initial combination therapy on reduction of cardiovascular end points. On review of these trials, CHEP included a grade C recommendation supporting combination therapy for initial treatment. In the FEVER trial (5), 9711 hypertensive patients from China 50 to 79 years of age were initiated on low-dose hydrochlorothiazide and then randomly assigned to additional low-dose felodipine or placebo. After a mean follow-up of 3.3 years, those assigned to combination felodipine plus hydrochlorothiazide had lower blood pressure and a significantly lower risk of fatal or nonfatal stroke (hazard ratio [HR] 0.73; 95% CI 0.60 to 0.89), cardiovascular events (HR 0.73; 95% CI 0.61 to 0.86) and total mortality (HR 0.69; 95% CI 0.54 to 0.89). In addition, the PROGRESS trial (7) demonstrated a greater blood pressure lowering effect and a significant reduction in stroke incidence (RR 0.57; 95% CI 0.46 to 0.70; P<0.001) in patients allocated to combination therapy (indapamide plus perindopril) compared with placebo among 6105 patients with a history of stroke or transient ischemic attack. However, single drug therapy was not associated with a reduction in stroke. The results from PROGRESS need to be interpreted with caution because allocation to combination therapy compared with monotherapy was determined by the physician rather than through random assignment. In the blood pressure-lowering arm of the ADVANCE trial (4), 11,140 patients aged 55 years or older with type 2 diabetes and a history of major vascular disease or vascular risk factors were randomly assigned to perindopril plus indapamide versus placebo, in addition to their current antihypertensive therapy. After a mean follow-up of 4.3 years, combination therapy was associated with a 5.6/2.2 mmHg greater reduction in blood pressure compared with placebo. However, there were no significant differences in the macrovascular or microvascular primary end points between combination therapy and placebo. Although the HR favoured perindopril plus indapamide therapy when these major end points were combined, the CI included 1.0, indicating that no difference between the treatment groups was still possible. In the secondary end point analysis, however, combination therapy was associated with a significant reduction in cardiovascular death (HR 0.82; 95% CI 0.68 to 0.98; P=0.03) and total mortality (HR 0.86; 95% CI 0.75 to 0.98; P=0.03) compared with placebo. This study was given a grade C rating because the benefits of combination therapy were largely found in the secondary end point evaluation, where multiple secondary end points were tested, and because of the need to extrapolate from a diabetic population. Despite the limitations of these studies, the findings collectively support a greater blood pressure-lowering effect with combination therapy compared with monotherapy and a reduction in cardiovascular end points. Given the significantly greater blood pressure reductions associated with combination therapy, CHEP added the proviso that a combination of two first-line agents should be used in patients with a significant elevation in blood pressure, and caution should be exercised in patients in whom a substantial fall in blood pressure is more likely to occur or is more poorly tolerated (eg, elderly patients).
Because there has not been a significant change in the evidence base, these recommendations are unchanged (21).
Because there has not been a substantive change in the evidence base, these recommendations are unchanged from previous recommendations (19).
Because there has not been a substantial change in the evidence base this year, these recommendations remain unchanged from previous iterations (19). Please also note that while ACE inhibitors reduce cardiovascular events among most patients with coronary artery disease, these benefits do not appear to extend to coronary artery disease patients with low cardiovascular risk (ie, those with normal ejection fraction, adequate coronary revascularization and well-controlled atherosclerotic risk factors). It should also to be noted that CHEP guidelines recommend that blood pressure be lowered to 140/90 mmHg or lower, but they do not specify aggressively lowering blood pressure in patients with ischemic heart disease because of the unanswered question about whether excess lowering of blood pressure in patients with coronary artery disease accentuates myocardial ischemia. This position is similar to the one taken by the American Heart Association and American College of Cardiology in recent recommendations (22).
ACE inhibitors and ARBs are associated with significant reductions in cardiovascular events among patients with heart failure (23,24). Consistent with the Canadian Cardiovascular Society recommendations on heart failure (25), CHEP has clarified that the dosages of ACE inhibitors and ARBs should be titrated to those dosages found to be effective in the clinical trials unless adverse effects arise. The remaining recommendations are unchanged from previous iterations (19,21).
Although antihypertensive therapy is well established in the secondary prevention of stroke, it is unclear whether lowering blood pressure beyond 140/90 mmHg would provide additional benefits. Benefits of aggressive blood pressure lowering would have to be weighed against the risk of inducing cerebral hypotension and iatrogenic stroke. In a post hoc analysis of the PROGRESS trial (8), investigators determined the effects of achieved follow-up blood pressure levels on stroke risk among 6105 normotensive and hypertensive individuals with previous stroke or transient ischemic attack. Stroke incidence declined with no evidence of a J curve, with progressively lower achieved follow-up systolic blood pressure throughout the range of blood pressures (112 mmHg to 168 mmHg). While this analysis reassures that lowering blood pressure in a heterogeneous stroke population may not precipitate stroke in the recommended target of lower than 140/90 mmHg, optimal blood pressure levels cannot be determined until data from randomized trials are available. The remaining recommendations are unchanged from 2007 (21).
These recommendations are unchanged from 2007 (21).
Because there has not been a substantial change in the evidence base, these recommendations are unchanged this year (19).
This year, there are no changes to the recommendations for patients with diabetes (21,26). The ADVANCE trial (4) is using a 2×2 factorial design to test the effects of blood pressure lowering with perindopril plus indapamide and intensive glucose control using a sulphonylurea on micro- and macrovascular complications in patients with type 2 diabetes. Full assessment of this trial will be considered pending the publication of the intensive glucose control arm to assess for a possible interaction between the two treatment strategies (blood pressure control and intensive glucose control) on risk for developing micro- and macrovascular complications.
Because there has been no substantive change in the evidence base this past year, the recommendations for this section are unchanged (27).
Because there has been no substantive change in the evidence base this past year, the recommendations for this section are unchanged.
The present paper represents the ninth iteration of the annually updated CHEP recommendations for the management of hypertension. A summary of the considerations for selecting antihypertensive therapy is presented in Table 8. We will continue to conduct yearly systematic reviews of clinical trial evidence to annually update our recommendations for therapy.
|Steering Committee: N Campbell (Chair), S Tobe, R Lewanczuk, M Lebel, D Drouin, J Onysko, R Petrella, V Gopalkrishnan, S Samis, L Vardy, J Kaczorowski, S Matheson, L Poirier|
|Executive Committee: N Campbell (Chair), S Tobe, R Lewanczuk, M Lebel, D Drouin, J Onysko, J Kaczorowski|
|Recommendations Task Force: S Tobe (Chair), M Lebel (Vice-Chair)|
|Central Review Committee: B Hemmelgarn (Chair), C Bell, M Hill, J Mahon, N Khan, F McAlister, R Padwal|
|Accurate Measurement of Blood Pressure: C Abbott (Chair), K Mann, L Cloutier|
|Follow-up of Blood Pressure: P Bolli (Chair), G Tremblay|
|Risk Assessment: S Grover (Chair), G Tremblay, A Milot|
|Self-measurement of Blood Pressure: D McKay (Chair), A Chockalingam|
|Ambulatory Blood Pressure Monitoring: M Myers (Chair), M Dawes|
|Routine Laboratory Testing: T Wilson (Chair), B Penner, E Burgess|
|Echocardiography: G Honos (Chair)|
|Lifestyle Modification: R Touyz (Chair), N Campbell, R Petrella, L Trudeau, P Katzmarzyk|
|Pharmacotherapy of Hypertension in Patients Without Other Compelling Indications: R Herman (Chair), G Carruthers, J DeChamplain, G Fodor, P Hamet, R Lewanczuk, G Pylypchuk|
|Pharmacotherapy for Hypertension in Patients with Cardiovascular Disease: S Rabkin (Chair), M Arnold, G Moe, JM Boulanger, J Howlett|
|Diabetes: P Larochelle (Chair), L Leiter, R Ogilvie, C Jones, S Tobe, V Woo, P McFarlane|
|Renal and Renovascular Hypertension: S Tobe (Chair), K Burns, M Ruzicka, M Vallée|
|Endocrine Forms of Hypertension: E Schiffrin (Chair)|
|Vascular Protection: E Schiffrin (Chair), R Hegele, P McFarlane, R Feldman|
|Adherence Strategies for Patients: T Campbell (Chair), A Milot, J Stone, R Feldman|
FUNDING: The CHEP process is sponsored by the Canadian Hypertension Society, Blood Pressure Canada, the Public Health Agency of Canada, The College of Family Physicians of Canada, the Canadian Pharmacy Association, the Canadian Council of Cardiovascular Nurses, and the Heart and Stroke Foundation of Canada.