2009 Scientific Summary
2009 marks the tenth consecutive year that the Canadian Hypertension Education Program (CHEP) has had updated recommendations for the management of hypertension. CHEP is a program of the Canadian Hypertension Society, Blood Pressure Canada, the Public Health Agency of Canada, the Heart and Stroke Foundation of Canada, the Canadian Council of Cardiovascular Nurses, the Canadian Pharmacists Association and the College of Family Physicians of Canada. CHEP makes substantive efforts to harmonize recommendations for the management of hypertension with other organizations that also produce guidelines that include blood pressure lowering therapy. In particular the 2009 CHEP recommendations are harmonized with those of the Canadian Diabetes Association, the Canadian Society of Nephrology and the Canadian Stroke Network.
CHEP’s leadership in guidelines processes is characterized by the routine cycles of surveillance, evaluation of care gaps, and development of programs and educational resources to address the care gaps. In 2008, CHEP was aided by data that allowed identification both of successes that could be attributed to the program but also important clinical care gaps that continue to exist. A survey (ONBP) conducted by the Heart and Stroke Foundation found that while Ontario had a low prevalence of hypertension (21%) relative to other developed countries it had the worlds highest published rates of awareness, treatment and control of hypertension 1, 2. Nevertheless, the survey found that two thirds of Ontarians with hypertension and diabetes have uncontrolled blood pressure (1/2 the control rate of those without diabetes). A national survey also demonstrated a care gap in that only ½ of younger people with hypertension were treated with medications and the rate of treatment did not increase with increasing number of concomitant cardiovascular risk factors 3. In fact hypertensive people who smoked were less likely to be treated and those with five additional cardiovascular risk factors were no more likely to be treated than those with hypertension alone. The CHEP recommendations continue to emphasize the importance of patient self-efficacy by promoting lifestyle change to prevent and control hypertension and by home measurement of blood pressure. In a prospective national cohort survey there was little indication that a diagnosis of hypertension triggered overall healthy lifestyle change for most people 4. After being diagnosed with hypertension there was a slight increase in smoking cessation, and an increase in physical activity however body mass index (BMI) increased and there was no change in excess alcohol consumption. Those who were not prescribed medications were not more likely to make lifestyle changes. CHEP will make efforts to develop resources and tools to improve care in these areas.
There were several major hypertension clinical trials in 2008 as well as new information from trials published in 2007. The major changes in the evidence have resulted in new CHEP recommendations to specifically not combine an ACE inhibitor with a angiotensin receptor blocker in people with uncomplicated hypertension, ischemic heart disease in the absence of heart failure, past stroke, non-proteinuric chronic kidney disease or diabetes without nephropathy (albuminuria, see table 1 ). The HYVET trial supported a previous CHEP recommendation to treat hypertension in those over age 80. The same cautions as indicated in the past need to be exercised when prescribing antihypertensive therapy in those who are risk for adverse effects of blood pressure lowering (e.g. the frail elderly). The recent publication of the ADVANCE trial has resulted in CHEP recommending consideration of initial therapy with 2 antihypertensive drugs for people with diabetes and blood pressures >150/90 mmHg 5, 6.
This is a short scientific summary of the new clinical hypertension evidence and the 2009 CHEP recommendations as well as the opinions of the CHEP executive regarding important issues in hypertension management in Canada. The full CHEP recommendations are available at www.hypertension.ca and will be published in the May 2009 issue of the Canadian Journal of Cardiology. Tables 2, and 3 contain the target values for treating hypertension, and recommended lifestyle respectively.
New evidence has allowed CHEP to address additional clinical questions in the management of hypertension for the 2009 recommendations.
Why should I treat people with diabetes and hypertension to a target of less than 130/80 mmHg?
In 2008, the ONBP survey found two thirds of people with diabetes and hypertension had blood pressure that was 130/80 mmHg or above. Up to 80% of people with diabetes die of cardiovascular complications and up to three quarters of specific diabetic complications can be attributed to high blood pressure 7. In people with diabetes and hypertension reducing blood pressure results in a large reduction in death and disability 6, 8-12. In the Syst Eur trial of isolated systolic hypertension, hypertensive therapy in people with diabetes reduced total mortality by 55%, cardiovascular mortality by 76%, and all cardiovascular events by 67% 13. In the HOT trial, people with diabetes who had more intensive treatment of diastolic blood pressure had a 66% reduction in death from heart disease and stroke even though the difference in diastolic blood pressure was only 4 mmHg at the end of the trial 14. In a meta analysis of randomized controlled trials, more vs. less intensive lowering of blood pressure reduced total mortality by 24% and major cardiovascular events by 25% 15. The use of an ACE inhibitor or angiotensin receptor blocker based therapeutic regime to lower blood pressure has additional advantages in people with proteinuric chronic kidney disease 15. CHEP recommends treating systolic blood pressure to <130 mmHg and diastolic to <80 mmHg. Economic analysis indicates that more intensive reduction in blood pressure in people with diabetes is one of the few medical interventions that may reduce overall health costs 16.
What are the implications of new clinical trials for treating people with hypertension?
Should I prescribe the combination of an ACE inhibitor with an angiotensin receptor blocker in my patients?
The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint
Trial (ONTARGET) was a large, randomized double-blinded trial to determine if telmisartan was non-inferior to ramipril at full doses and whether the combination of telmisartan and ramipril was superior to ramipril alone 17, 18. People were enrolled into the study if they were aged 55 years and older and had evidence of vascular disease or diabetes with target organ damage. 25,620 people were randomized to either telmisartan 80 mg/day, ramipril 10 mg/day, or a combination of telmisartan 80 mg/day and ramipril 10 mg/day. After a median follow-up of 56 months, the telmisartan (-0.9/-0.6 mmHg) and the combination therapy groups (-2.4/-1.4 mmHg) had significantly lower blood pressures compared to the ramipril monotherapy group. There was no significant difference in the primary outcome (cardiovascular death, myocardial infarction, stroke or hospitalisation for congestive heart failure) between the ramipril and telmisartan monotherapy groups as well as the combination therapy group compared with the ramipril monotherapy group. However, combination therapy was associated with significantly higher rates of discontinuation due to syncope and renal impairment compared with ramipril. Specifically, combination therapy was associated with a significantly increased rate of dialysis, and doubling of serum creatinine compared to ramipril monotherapy (HR: 1.09; 95%CI: 1.01-1.18, p=0.037). The findings of this study provide evidence that telmisartan is equally effective as ramipril for people with cardiovascular disease or diabetes with target organ damage. The findings also demonstrate that the combination of telmisartan and ramipril do not provide additional cardiovascular benefits above and beyond either therapy alone but does increase the adverse event rate in the ONTARGET population. The COOPERATE trial has been used as evidence in favour of prescribing the combination of an ACE inhibitor with an angiotensin receptor blocker 19. In 2008 serious concerns have been raised regarding several data inconsistencies in the study 20. To date the only data supporting improved patient related outcomes from prescribing the combination of an ACE inhibitor with an angiotensin receptor blocker have been from secondary outcome analysis of heart failure trials 21, 22. There are ongoing trials in proteinuric people with substantive chronic kidney disease. In the absence of evidence there is no recommendation to use the combination aside from in people with heart failure. CHEP recommends specifically to not prescribe the combination of an ACE inhibitor with an angiotensin receptor blocker in people with uncomplicated hypertension, ischemic heart disease in the absence of heart failure, past stroke, non-proteinuric chronic kidney disease or diabetes without albuminuria.
Should I prescribe an angiotensin receptor blocker in people who have had a stroke?
The PROFESS study was large randomized 2×2 factorial trial of angiotensin receptor blocker (ARB) based blood pressure lowering therapy and antiplatelet therapy to prevent recurrent strokes 23. Over twenty thousand patients aged 50 or older with a prior ischemic stroke were randomized to telmisartan vs. placebo regardless of their pre-treatment blood pressure. No statistically significant interaction effect between antiplatelet and telmisartan arms was observed. In the latter arm, the blood pressure was 3.8/2.0 mmHg lower than placebo, with a mean follow-up of 2.5 years. The ARB therapy did not reduce the primary endpoint of recurrent stroke (HR 0.95 (0.86-1.04, p=0.23)) nor the secondary outcome of major cardiovascular events (stroke, MI, vascular death, worsening CHF), HR: 0.94 (0.87-1.01, p=0.11)). Exploratory analyses suggested that a difference in outcome in favour of telmisartan began to emerge after the first 6 months of therapy. Although the absolute risk increase was small (~3%), adverse events, principally hypotensive symptoms, syncope and atrial fibrillation were more common in the telmisartan group compared to placebo. It is possible that the modest reduction in blood pressure in a PROFESS study population and the relatively low entry blood pressure (144/84 mmHg) may be the reason for the negative results. CHEP recommendations currently support a target blood pressure of <140/90 mmHg in post stroke patients hence many of the PROFESS trial patients would have been within CHEP targets at the start of the trial. Taken within the context of a previous large randomized controlled trial (PROGRESS with a combination of a diuretic (indapamide) and ACE inhibitor (perindopril)) and meta analyses of blood pressure lowering trials showing a reduction in recurrent stroke 24, 25, the PROFESS trial has not impacted the CHEP recommendations. The PROGRESS trial entered people with an average blood pressure of 147/86mmHg. In the PROGRESS people who received ACE inhibitor therapy only, the reduction in stroke was not significant (post hoc analysis) but a large reduction in stroke was seen in the trial overall and in particular in those who received the ACE inhibitor with the diuretic indapamide. CHEP recommends strong consideration should be given to the initiation of antihypertensive therapy and preferably an ACE inhibitor plus diuretic combination after the acute phase of a stroke or transient ischemic attack.
In people who are intolerant to an ACE inhibitor and who have cardiovascular disease or diabetes should I prescribe an angiotensin receptor blocker?
The TRANSCEND study randomized 5926 people with coronary disease, prior stroke or diabetes mellitus with end-organ damage and who were intolerant of ACE inhibitors to telmisartan or placebo with an average blood pressure at baseline of 141/69 mmHg 26. The mean blood pressure difference was 3.2/1.3 mmHg lower at study end in the telmisartan group. Over a median follow-up of just over 2.5 years, the telmisartan therapy did not reduce the primary outcome (composite of cardiovascular death, myocardial infarction, stroke or hospitalization for heart failure, HR 0.92 (0.81-1.05, p=0.216)). The study does not exclude a small therapeutic benefit and a secondary endpoint of cardiovascular death, myocardial infarction or stroke was close to conventional significance level: HR 0.87 (0.76-1.00, p=0.068). Syncopal spells were more common in the telmisartan group but the absolute risk difference was small (0.44%) and overall adverse events were not different between the two groups. The TRANSCEND trial has not changed the CHEP recommendation to prescribe an ACE inhibitor for most people with hypertension and documented coronary artery disease based on the HOPE, EUROPA and PEACE studies 27-29.
Should I start people with diabetes and hypertension on a combination of two antihypertensive drugs?The ADVANCE trial was a randomized controlled trial that included 11,140 people with type 2 diabetes and at least another cardiovascular risk factor 6. The ADVANCE trial used a factorial design to assess both the effects of an intensive glucose lowering regimen and antihypertensive treatment. In the hypertension aspect of the trial people were randomized to a fixed combination tablet consisting of perindopril (an ACE inhibitor) and indapamide (a diuretic) or placebo. The treatment reduced both cardiovascular death (HR 0.82; 95% CI 0.68 – 0.98) and total mortality (HR 0.86; 95% CI 0.75 – 0.98). In 2008 it was established that there was no interaction between the glucose lowering and blood pressure lowering therapies; hence CHEP recommends consideration of initial therapy with a combination of first line drugs in people with diabetes if blood pressure is 150/90 mmHg or higher 5, 6. Caution is required in people where a substantial fall in blood pressure is more likely or would be poorly tolerated (e.g. those with postural hypotension).
How do I optimally reduce cardiovascular risk in my patients?
Although it remains important to stay up to date with new evidence and recommendations much of what is important to improve patient outcomes remains unchanged.
Because most Canadians will develop hypertension during their lives routine assessment of blood pressure is recommended in all people at all appropriate visits. Most people with high normal blood pressure (130-139 systolic or 85-89 mmHg) will develop hypertension in the next 2-4 years and require annual assessment of blood pressure. To encourage self-efficacy, people with hypertension are recommended to measure their blood pressure at home.
Nine in ten Canadians with hypertension will have other risks for cardiovascular disease. Hence optimum management of hypertension requires assessment of overall cardiovascular risk. This includes identifying and managing these other risks (e.g. smoking, dyslipidemia, dysglycemia (e.g. impaired fasting glucose, diabetes)), abdominal obesity, unhealthy diet, physical inactivity,. A comprehensive approach to cardiovascular risk reduction can more than double cardiovascular risk reduction compared to blood pressure management alone.
To optimally reduce cardiovascular risk, blood pressure should be lowered to less than 140/90 mmHg in most people and in those with diabetes or chronic kidney disease, to less than 130/80 mmHg. Although it is usually more difficult to lower systolic than diastolic blood pressure, the risk reduction from lowering the systolic blood pressure is as large if not larger than the diastolic blood pressure. Combinations of both lifestyle and drug therapies are generally necessary to achieve target blood pressures. Most people require more than one antihypertensive drug and many with diabetes or chronic kidney disease may require three or more drugs. People whose blood pressure is above target should be monitored at least every 2 months and the intensity of treatment increased until the targets are achieved.
Lack of adherence to therapy is an important cause of poor blood pressure control and poor outcomes. Patient adherence to therapy should be assessed on each visit and interventions to improve adherence should be a part of clinical routine.
What lifestyle changes are effective in preventing hypertension, treating people with hypertension and in reducing blood pressure?
High blood pressure as well as other cardiovascular risk factors can be prevented or reduced through simple sustained lifestyle changes. Lifestyle interventions can have a similar reduction in blood pressure to single antihypertensive drugs. A healthy diet, regular physical activity, moderation in alcohol consumption, reductions in dietary sodium, and a smoke free environment are the cornerstone of prevention and management of hypertension. In selected people, stress reduction including behaviour modification is helpful.
A recent meta-analysis found decreasing dietary sodium intake by 1860mg/day reduced blood pressure 5.1/2.7 mmHg 30. In Canada it has been estimated that a 1860mg/day decrease in dietary sodium would cause a substantive reduction in prevalence of hypertension, health costs and cardiovascular complications 31, 32. In the DASH trial, a diet rich in fruits, vegetables and low-fat dairy products with reduced saturated and total fat decreased blood pressure 5.5/3.0 mmHg overall and by 11.4/5.5 mmHg in those with hypertension 33. A meta-analysis on the effects of regular aerobic exercise showed physical activity reduced blood pressure 3.8/2.6 mmHg in people who were previously inactive 34. The TOHP study found a decrease in weight of 4.4 kg led to a blood pressure reduction of 4.0/2.8 mmHg 35.
Brief clinical interventions increase the probability of a patient adhering to lifestyle changes even for addictive behaviours such as smoking and problem alcohol consumption 36, 37 and more comprehensive interdisciplinary care approaches are more effective 33, 38-41. Because few Canadians change their lifestyle after a diagnosis of hypertension it is important that health professionals assist people in implementing lifestyle interventions 4. For this reason Blood Pressure Canada, the Heart and Stroke Foundation and CHEP have developed a variety of patient resources including paper copies, videos and web based interactive monitoring systems to assist people making lifestyle changes 4. These resources can be found at www.hypertension.ca and www.heartandstroke.ca/bp.
Comments from the CHEP executive
The CHEP believes that reliable up to date evidence based recommendations that are broadly disseminated in easy to use formats are important to the care of Canadians with hypertension. The CHEP program has taken a number of steps to reduce personal and commercial bias (table 4). CHEP also supports regular evaluation of the impact of its program to identify ongoing clinical issues where care needs to improve. Further CHEP monitors ongoing changes in the health care system that will change the way hypertension will be managed in the future and is actively developing new partnerships, educational resources and dissemination strategies. Important to the prevention and control of hypertension is active involvement of people in their care. CHEP partners with Blood Pressure Canada, the Heart and Stroke Foundation of Canada, the Public Health Agency of Canada and other organizations to develop resources to assist people become more informed about hypertension and more engaged in their care (table 5). Recently the increase in treatment of hypertension has been found to be strongly associated with reductions in death and hospitalization of major cardiovascular events in Canada 42.
In 2010 the results of a national survey on hypertension prevalence treatment and control will be released by Statistics Canada. The survey results will allow CHEP to more carefully assess the hypertension care gaps that remain. Further in 2010 the results of another survey that assesses patient knowledge, attitudes and barriers to care will be released that will allow much more focused patient education programs to be developed. The development of a comprehensive hypertension evaluation program in Canada with ongoing assessment of care gaps and subsequent development of tailored intervention programs is expected to result in further reductions in cardiovascular disease.