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To update the evidence-based recommendations for the prevention and management of hypertension in adults for 2009.
For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was preferentially reviewed. 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 2007 to August 2008 to update the 2008 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence.
For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to less than 2300 mg (100 mmol)/day (and 1500 mg to 2300 mg [65 mmol 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 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. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). 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 patients who are not black), 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 as the initial treatment of hypertension if the systolic blood pressure is 20 mmHg above the target or if the diastolic blood pressure is 10 mmHg above the target. The combination of ACE inhibitors and ARBs should not be used. 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 proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to 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 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 en 2009.
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 insuffisance rénale 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 2007 et août 2008 afin de mettre les recommandations de 2008 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 2 300 mg (100 mmol)/jour (et à entre 1 500 mg et 2 300 mg [entre 65 mmol/jour et 100 mmol]/jour pour les hypertendus), à pratiquer des activités aérobiques de 30 à 60 minutes 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 mmHg chez tous les patients et à moins de 130/80 mmHg chez les patients diabétiques ou atteints d’une insuffisance rénale chronique. La plupart des patients adultes devront prendre plus d’un médicament pour parvenir aux valeurs cibles. Il faut envisager la prescription d’antihypertensifs chez tous les patients adultes, quel que soit leur âge (en faisant preuve de prudence chez les patients âgés fragiles). Dans le cas des adultes chez qui il n’y pas d’indication impérieuse d’administrer d’autres médicaments, 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 mmHg ou si la tension artérielle diastolique la dépasse de 10 mmHg. Il faut éviter d’associer des inhibiteurs de l’ECA à des ARA. 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 insuffisance rénale chronique non diabétique avec protéinurie, les inhibiteurs de l’ECA ou les ARA (en cas d’intolérance aux 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. Une fois la tension artérielle stabilisée, un traitement à l’acide acétylsalicylique pourra être envisagé.
Toutes les recommandations sont classées selon la solidité des données probantes, et les 57 membres du groupe de travail des recommandations probantes du Programme éducatif canadien sur l’hypertension ont exercé leur vote à leur égard. Toutes les recommandations ont obtenu un consensus d’au moins 95 %. Les présentes lignes directrices continueront d’être mises à jour chaque année.
Hypertension affects one in five Canadian adults and the majority of these patients will require pharmacological therapy to control their blood pressure (1,2). Each year, the Canadian Hypertension Education Program (CHEP) Recommendations Task Force reviews recently published hypertension pharmacological and nonpharmacological treatment studies in an effort to alert primary care providers to new clinical advances in the management of hypertension. Equally important is the review of studies that indicate the potential harm of certain therapies for hypertension patients.
This year, recent publication of the landmark study, HYpertension in the Very Elderly Trial (HYVET) (3) resulted in new recommendations on treatment of hypertension in the very old, and the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) studies (4,5) demonstrate harm associated with combination angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor antagonist (ARB) therapy. We also discuss other key hypertension trials – the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) trial (6), the Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease (TRANSCEND) (7), and the Prevention Regimen For Effectively Avoiding Second Strokes (PRoFESS) trial (8) – as well as current evidence on the risk of new-onset atrial fibrillation (AF) with antihypertensive therapy.
The present scientific report outlines the complete 2009 recommendations on the 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).
Although we mention individual antihypertensive agents when discussing hypertension trials, the CHEP makes the assumption that the benefits are generalized 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.
A Cochrane collaboration librarian conducted a MEDLINE search using a highly sensitive search strategy for randomized trials and systematic reviews published from 2007 to August 2008. 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 the Canadian Society of Nephrology collaborated with the CHEP subgroup members for the 2009 recommendations process. The subgroups appraised the quality of relevant studies using a standardized algorithm developed by the CHEP (9). Subsequently, the central review committee, constisting 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 (Table 1).
The draft recommendations from each subgroup were then formally vetted at the 2008 consensus conference held in Toronto, Ontario, by task force committee members. Based on the deliberations at the consensus conference, the 2009 recommendations were finalized and then 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 the mainstay interventions to prevent or delay the onset of hypertension and are an essential concomitant therapy for those who require pharmacological drug treatment for hypertension. Smoking and smokeless tobacco increase the incidence of hypertension (10,11). Furthermore, smoking and hypertension together substantially increase the risk of mortality and confer a greater than additive risk (12). Therefore, smoking cessation counselling and treatment should be provided to all hypertensive patients who smoke.
Randomized trials of antihypertensive therapy demonstrate clear benefit across many subgroups of hypertensive patients (15). However, very elderly patients were largely excluded from these trials. Observational studies raise concern that blood pressure lowering in patients 80 years of age or older may be poorly tolerated and associated with increased mortality (16,17). This year, the landmark HYVET randomized placebo-controlled trial (3) examined the efficacy and safety of antihypertensive therapy in this very elderly population. Hypertensive patients 80 years of age or older, predominantly from Europe and China, without a history of heart failure, dementia, chronic kidney disease or a requirement for nursing home care, were enrolled. A total of 3845 patients with a mean baseline blood pressure of 173/90.8 mmHg were randomly assigned to receive indapamide or a placebo. The indapamide group had a greater mean reduction in blood pressure (−15.0/−6.1 mmHg) than the placebo group. After a median 1.8 years of follow-up, the trial was terminated early with a 30% RR reduction in the primary end point, fatal or nonfatal stroke (95% CI −1% to 51%; P=0.06), a 39% reduction in fatal stroke (95% CI 1% to 62%; P=0.05) and a 21% reduction in the total mortality (95% CI 4% to 35%; P=0.02) in the indapamide group compared with the placebo group. The rate of serious adverse events was higher in the placebo group than the indapamide group. HYVET clearly demonstrates the beneficial effects of antihypertensive therapy in reducing the risk of stroke and death in very elderly patients; these results form the basis of the new recommendation to prescribe antihypertensive therapy regardless of age. However, it is important to note that the selected patients enrolled in HYVET were healthier than the general Canadian population 80 years of age and older (18); therefore, these results may not be extrapolated to elderly patients who require nursing home care or who are frail.
Evidence for potential benefits of antihypertensive therapy must be weighed against potential harms when applying trial results to clinical practice. However, clinical trial evidence on harm is published less often or is poorly reported (20). The Consolidated Standards of Reporting Trials (CONSORT) statement (21) has extended their recommendations to help improve the reporting of harm-related evidence. This year, the CHEP has added a grade A recommendation to avoid dual renin angiotensin system (RAS) blockade with ACE inhibitor and ARB based on evidence of harm from the ONTARGET study (4). The ONTARGET study was a large, randomized double-blind trial comparing the effects of the ACE inhibitor ramipril 10 mg/day and the ARB telmisartan 80 mg/day, separately and in combination, in patients who were at least 55 years of age who had established vascular disease or diabetes with organ damage. Among the 25,620 patients randomized and after a median follow-up period of 56 months, the telmisartan (−0.9/−0.6 mmHg) and combination therapy groups (−2.4/−1.4 mmHg) had significantly lower blood pressures than the ramipril monotherapy group. There was no significant difference in the primary outcome (cardiovascular death, myocardial infarction, stroke or hospitalization for congestive heart failure) between the ramipril and telmisartan monotherapy groups or the combination therapy group compared with the ramipril monotherapy group. However, combination therapy was associated with significantly higher rates of discontinuation due to syncope (0.3% versus 0.2%) and renal impairment (13.5% versus 10.2%) compared with ramipril. From the prespecified secondary end point analysis (5), combination therapy was associated with a significantly increased risk of dialysis, doubling of serum creatinine or death compared with ramipril monotherapy (hazard ratio [HR] 1.09, 95% CI 1.01 to 1.18; P=0.037). The findings of this high-quality trial demonstrate that combining full doses of telmisartan and ramipril does not provide additional cardiovascular benefits compared with monotherapy with either agent alone, but does significantly increase the adverse event rate. It is unclear whether less than full doses of these agents in combination causes worsening renal impairment or hypotension. However, randomized trials of heart failure patients also report an increased rate of adverse events from renal impairment with combination ACE inhibitor and ARB at various dosages (22,23). Additionally, the potential benefits or harms of dual RAS therapy that includes novel direct renin inhibitors with ACE inhibitor or ARB are unknown.
First-line antihypertensive agents such as thiazide diuretics and ACE inhibitors have been shown to be similar across large randomized clinical trials for end points such as cardiac mortality, myocardial infarction and stroke (24). There is some evidence suggesting that RAS blockade may have additional pleiotropic benefits in reducing other end points including new-onset AF. AF affects approximately 1% of the general population and 5% of patients 65 years of age and older (25), with rates reported to be higher among patients with hypertension (25,26). New-onset AF also connotes a worse prognosis, with increased rates of cardiovascular events and all-cause mortality (27–29). RAS inhibition may have a favourable effect on the incidence of new-onset AF because of reduced atrial stretch, lowered end-diastolic left ventricular pressure and prevention of atrial fibrosis (26,30,31). A meta-analysis of the Losartan Intervention For End point reduction in hypertension (LIFE) trial (32), the Captopril Prevention Project (CAPPP) (33) and the Swedish Trial in Old Patients with hypertension-2 (STOP2) trial (34), as well as the the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study (29), showed that RAS blockade with either ACE inhibitors or ARB therapy was associated with a lower risk of new-onset AF compared with either beta-blockers or CCBs (27). However, the incidence of AF was similar in diuretic and placebo groups in the the Systolic Hypertension in the Elderly Program (SHEP) study analysis (28). To date, these analyses from large trials were derived from studies that did not examine new-onset AF as the primary end point. Furthermore, it is still unclear whether the reduced incidence of AF associated with RAS therapy yields a net reduction in cardiovascular events. In the LIFE study (32), in which 18,044 patients with left ventricular hypertrophy were randomly assigned to receive either losartan or atenolol, there was a significant reduction in composite cardiovascular end points (HR 0.60, 95% CI 0.38 to 0.94; P=0.03) and stroke (HR 0.49, 95% CI 0.29 to 0.86; P=0.01) among those with new-onset AF treated with losartan compared with atenolol. However, in the VALUE study (29), the reduced incidence of new-onset AF associated with valsartan compared with amlodipine did not translate into a reduction in the primary end point. There are ongoing studies, namely Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto (GISSI)-AF (35), that will examine AF as the primary end point. Until the results of these studies are published or until further data emerge to support a specific antihypertensive agent to reduce overall cardiovascular events by reducing the risk of new-onset AF, the CHEP cannot make any conclusive recommendations at this time. We will continue to monitor this area. The remaining recommendations are unchanged this year and the supporting evidence was discussed in previous recommendations documents (19,36).
Because there has not been a significant change in the evidence base, these recommendations are unchanged (36).
Because there has not been a substantial change in the evidence base, these recommendations are unchanged from our previous recommendations (19).
This year, there is a new grade B recommendation to avoid dual RAS inhibition with combination ACE inhibitor and ARB therapy in patients with coronary artery disease, but without coexisting systolic heart failure. This recommendation is based on extrapolation of evidence of harm from the ONTARGET study (4,5). The ONTARGET study population was a high vascular risk group, with 74% of patients having a history of stable coronary artery disease and 49% having a history of previous myocardial infarction at baseline. Patients with heart failure were excluded from the study; of note, several randomized trials (22,23) demonstrated a reduction in congestive heart failure hospitalizations or mortality with combination ACE inhibitor and ARB therapy.
The CHEP also reviewed TRANSCEND (7), the smaller sister study to ONTARGET. This trial studied 5926 patients with cardiovascular disease or high-risk diabetes who were intolerant of ACE inhibitors. The patients were randomly assigned to receive telmisartan or placebo. Despite a greater blood pressure reduction in the telmisartan group (−3.2/−1.3 mmHg) over a mean of 2.5 years, there was no difference in the primary composite outcome of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure (HR 0.92, 95% CI 0.81 to 1.05; P=0.2). There was a modest difference in the prespecified composite secondary outcome of cardiovascular death, myocardial infarction and stroke in the telmisartan group (13.0%) compared with the placebo group (14.8%) (HR 0.87; P=0.048). However, this difference became nonsignificant after statistical adjustments were made for multiple comparisons (P=0.068). These results from TRANSCEND do not alter the CHEP recommendations for ischemic heart disease, and ACE inhibitors should continue to be used as first-line agents. The remaining recommendations are unchanged from 2008.
Following an ischemic stroke, the risk of recurrent stroke, transient ischemic attack or cardiac event ranges from 5% to 15% per year (37). An ACE inhibitor/diuretic combination was found to be neuroprotective in this population and it was thought that there may be a greater benefit exerted with an ARB (38). The Morbidity and Mortality After Stroke, Eprosartan Compared With Nitrendipine for Secondary Prevention (MOSES) study (39) found that the ARB, eprosartan, reduced the risk of the composite outcome of total mortality, and cardiovascular and cerebrovascular events compared with nitrendipine in patients with a previous stroke. The recent PRoFESS study (8), a 2×2 factorial randomized controlled trial, evaluated combination antiplatelet agents and telmisartan versus placebo in 20,332 patients with a recent ischemic stroke. After a mean follow-up period of 2.5 years, the telmisartan group had a lower blood pressure (−3.8/−2.0 mmHg) compared with the placebo group. However, there was no significant difference between the telmisartan (8.7%) and placebo groups (9.2%) for risk of the primary end point, recurrent stroke, or for the secondary end point, composite cardiovascular events. The negative results of PRoFESS may be due, in part, to an insufficient follow-up period because the telmisartan group appeared to have significantly fewer recurrent strokes after a minimum of six months on therapy. Presently, there are insufficient data to provide any conclusive recommendations on ARB monotherapy for the treatment of hypertension in patients with cerebrovascular disease. The ONTARGET study (4) provided an opportunity to evaluate the role of an ACE inhibitor and ARB combination in the cerebrovascular disease population because approximately 20% of the ONTARGET study population had a previous stroke. As discussed earlier, there was no benefit from an ARB and ACE inhibitor combination over ACE inhibitor alone, and combination therapy was further associated with a greater risk for hypotension and renal impairment. Thus, the CHEP has a grade B recommendation to avoid this combination in patients with previous stroke or transient ischemic attack. The remaining recommendations are unchanged from 2008 (36).
These recommendations are unchanged from 2008 (36).
The ONTARGET study investigators conducted a prespecified analysis of a composite renal end point of dialysis, doubling of serum creatinine or death (5). Approximately 20% of the ONTARGET population had chronic kidney disease with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or lower at baseline. However, it is uncertain what proportion of these patients had nondiabetic chronic kidney disease. Risk of the composite renal end point was similar in the telmisartan (13.4%) and ramipril (14.5%) groups (HR 1.00, 95% CI 0.92 to 1.09). These results were consistent across subgroups of patients with and without diabetic nephropathy, micro-and macroalbuminuria, and patients with an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or lower. Extrapolating the finding of noninferiority of ACE inhibitors and ARBs to patients with nondiabetic chronic kidney disease, the CHEP has upgraded the recommendation for the use of an ARB to grade B if there is intolerance to an ACE inhibitor.
Dual RAS inhibition has been shown to significantly reduce proteinuria (40), a surrogate end point for cardiovascular disease and renal impairment, in patients with chronic kidney disease. The Combination Treatment of Angiotensin-II Receptor Blocker and Angiotensin-converting Enzyme Inhibitor in Non-diabetic Renal Disease (COOPERATE) trial (41) found a reduced risk of dialysis with combination therapy compared with monotherapy; however, serious inconsistencies among the data since publication have raised concerns about the validity of the results. The ONTARGET study similarly found greater blood pressure reduction and reduced proteinuria with combination therapy. However, likely through a mechanism independent of proteinuria, full doses of combination therapy were associated with an increased risk of doubling of serum creatinine, dialysis or death compared with ramipril monotherapy. Thus, the CHEP has also recommended that this combination should not be used in patients with nonproteinuric chronic kidney disease.
The number of individuals with end-stage renal disease treated by transplantation and dialysis is expected to double by 2010 (42). Kidney transplant recipients have a high prevalence of hypertension that may either pre-exist from chronic native kidney disease or occur de novo post-transplantion. Dialysis patients also carry a high prevalence of hypertension and other cardiac risk factors, placing them at higher risk for developing cardiovascular disease. Cardiovascular mortality is 10 to 30 times higher in dialysis patients than in the general population (43). Control of hypertension is therefore paramount in these high-risk patients. Care providers should refer to the Canadian Society of Nephrology practice guidelines for managing hypertension in dialysis patients (44). The CHEP recommendations task force is actively working with the Canadian Society of Nephrology to develop future recommendations for these patient populations. The remaining recommendations remain unchanged from previous years (19,36,45).
Because there has not been a substantial change in the evidence base, these recommendations are unchanged this year (19).
The antihypertensive therapy recommendations for diabetic patients are largely based on trials that use monotherapy with an up-titration of agents to achieve targets. However, there are an increasing number of trials evaluating combination antihypertensive therapy, which is particularly relevant given that two or more antihypertensive agents are often required to achieve target blood pressures. This year, based on the efficacy and safety findings from the ADVANCE trial in diabetic patients (6), and extrapolating from other nondiabetic studies (38,46,47), we have added the new recommendation that combination therapy using two first-line agents is a reasonable option in the initial management of hypertension in diabetic patients. In the blood pressure-lowering arm of the ADVANCE trial, 11,140 patients with type 2 diabetes who were older than 55 years of age, with a history of major vascular disease or vascular risk factors, were randomly assigned to receive perindopril/indapamide versus placebo in addition to current antihypertensive therapy. After a mean follow-up period of 4.3 years, combination therapy was associated with a 5.6/2.2 mmHg greater reduction in blood pressure compared with placebo. There were no significant differences in the macrovascular or microvascular primary end points between combination therapy and placebo. 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. Rates of serious adverse events and permanent discontinuation for hypotension or dizziness were similarly low in combination and placebo groups. Several trials in nondiabetic patients also found combination therapy to be associated with greater blood pressure lowering, reduced rates of cardiovascular end points and low rates of adverse events (38,46). Given the significantly greater blood pressure reductions associated with combination therapy, the CHEP added the proviso that a combination of two first-line agents should be used in patients with significant elevations 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, the elderly and patients with autonomic neuropathy).
Combination or add-on agents used to achieve blood pressure targets should be selected from first-line choices. However, the combination of an ACE inhibitor and ARB should not be used in diabetic patients with normal urinary albumin levels. This new grade B recommendation is based on extrapolation of the ONTARGET studies in which 38% of enrolled patients were diabetic. The remaining recommendations are unchanged from previous recommendations (36,45).
1. Adherence to an antihypertensive prescription can be improved by a multipronged approach (Table 5).
Because there has been no substantial change in the evidence base this year, the recommendations for this section are unchanged (47).
Because there has been no substantive change in the evidence base this year, the recommendations for this section are unchanged.
The present paper (see Table 8 for the summary) represents the 10th iteration of the annually updated CHEP recommendations for the management of hypertension and we will continue to conduct yearly systematic reviews of the clinical trial evidence to update our recommendations for therapy.
|Steering Committee: N Campbell (Chair), S Tobe, M Lebel, R Lewanczuk, J Kaczorowski, O Baclic, F McAlister, L Vardy, R Touyz, M Godwin, S Matheson, L Poirier, M Lum-Kwong|
|Executive Committee: N Campbell (Chair), S Tobe, M Lebel, R Lewanczuk, J Kaczorowski, O Baclic, F McAlister|
|Recommendations Task Force Co-Chairs: S Tobe, M Lebel|
|Central Review Committee: B Hemmelgarn (Chair), M Hill, J Mahon, N Khan, F McAlister, R Padwal, C Bell|
|Recommendations Task Force subgroups|
|Ambulatory Blood Pressure Monitoring: M Myers (Chair), M Dawes|
|Lifestyle Modification in Hypertension: R Touyz (Chair), N Campbell, L Trudeau, S Bacon, R Petrella|
|Adherence Strategies for Patients: T Campbell (Chair), R Feldman, A Milot, J Stone|
|Accurate Measurement of blood Pressure: C Abbott (Chair), K Mann, L Cloutier|
|Cardiovascular Risk assessment: S Grover (Chair), G Tremblay, A Milot|
|Pharmacotherapy for Hypertensive Patients with CVD: S Rabkin (Chair), M Arnold, G Moe, J-M Boulanger, J Howlett|
|Echocardiography: G Honos (Chair)|
|Pharmacotherapy for Hypertensive Patients Without Compelling|
|Indications: R Herman, P Hamet, G Fodor, G Carruthers, J deChamplain, G Pylypchuk, P Lindsay|
|Endocrinological Forms of Hypertension: E Schiffrin (Chair)|
|Renal and Renovascular Hypertension: S Tobe (Chair), K Burns, M Ruzicka, M Vallée, R Prasad|
|Follow-up on Patients with Hypertension: P Bolli (Chair), G Tremblay|
|Routine laboratory Tests: T Wilson (Chair), B Penner, E Burgess|
|Hypertension and Diabetes: P Larochelle (Chair), L Leiter, C Jones, R Ogilvie, S Tobe, V Woo, R Gilbert|
|Self Measurement of blood Pressure: D McKay (Chair), A Chockalingam|
|Vascular Protection: E Schiffrin (Chair), R Feldman, R Hegele, P McFarlane|
|Implementation Task Force Co-Chairs: J Kaczorowski, R Lewanczuk|
|Implementation Task Force subgroups|
|Nurses: L Cloutier, D McLean, C Bolton, J Costello, S Matheson, T Green|
|Pharmacists: A Thompson, R Tsuyuki, L Poirier, W Semchuk|
|Family Physicians: M Dawes, M Gelfer, J Hickey|
|Members at large: R Feldman, N Campbell, S Tobe, A Milot, G Tremblay, A Gupta, D Drouin, O Baclic, F Jhandir, R Ward|
SPONSORS: 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 Pharmacists Association, the Canadian Council of Cardiovascular Nurses, and the Heart and Stroke Foundation of Canada.