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Analysis of the Canadian hypertension guidelines and the impact on upcoming recommendations
Recommendations may serve as preview for US hypertension guidelines.
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The ideal target and/or threshold for the treatment of BP has been the subject of much debate since the controversial U.S. Evidence-Based Guideline for the Management of High Blood Pressure in Adults report from the panel members appointed to the Eighth Joint National Committee, or JNC 8, which was published in 2014 in JAMA. Relaxing the BP goal to less than 150/90 mm Hg was endorsed in this guideline for patients aged 60 years and older. Adding to the debate, results of the large NIH-funded SPRINT trial were subsequently presented at the American Heart Association Scientific Sessions in 2015 and simultaneously published in The New England Journal of Medicine, showing a benefit from intensive BP lowering. Exactly how these results will be incorporated into clinical guidelines has been a subject of intense speculation.
While the American College of Cardiology and AHA guideline committee is expected to release its recommendations within the next year, the 2016 Canadian Hypertension Education Program (CHEP) Guidelines for Blood Pressure Management, Diagnosis, Assessment of Risk, Prevention and Treatment of Hypertension, published in the Canadian Journal of Cardiology in May, now provide us with a first look at how this evidence will be interpreted for clinical use and what we can potentially expect to see in the upcoming ACC/AHA guidelines.
New recommendations
Overall, there are four new recommendations and two revisions of the prior CHEP recommendations. There are three recommendations for the treatment of hypertension including:
- a target of 120 mm Hg for high-risk patients fitting the SPRINT inclusion criteria;
- dietary potassium supplementation for patients who are not at risk for hyperkalemia; and
- the use of either a beta-blocker or calcium channel blocker in patients with stable angina.
The three other recommendations are for the measurement and diagnosis of hypertension:
- the preference for BP measurement using an automated office BP (AOBP) system without the presence of a health care provider;
- the use of either fasting or non-fasting lipid panels for risk stratification; and
- the assessment of laterality for patients with secondary hypertension due to primary hyperaldosteronism.
Impact of SPRINT, other recent research
Among these changes, the incorporation of the treatment recommendation to systolic BP 120 mm Hg for high-risk patients according to the SPRINT inclusion criteria will undoubtedly have the largest impact on patient care.
In the SPRINT trial, patients aged 50 years and older with increased CV risk were treated to a goal systolic BP 120 mm Hg in the intensive-treatment group compared with a goal of 140 mm Hg in the control group. Those in the intensive-treatment group achieved a mean systolic BP of 121 mm Hg vs. 134 mm Hg in the control group. This significant separation in systolic BP was achieved with the average addition of only one extra BP medication (mean, 2.8 medications in intensive-treatment group vs. 1.8 medications in control group). CV outcomes were significantly better in the intensive-treatment group (see Table). The overall rate of adverse events was similar between groups, although there was a small increase in hypotension, syncope, electrolyte abnormalities and acute kidney injury in the intensive-treatment group, but no difference in injurious falls. There was a threefold increase in participants whose estimated glomerular filtration rate (eGFR) declined by 30% or more to less than 60 mL/min/1.73 m2, although the clinical significance of this reduction remains unclear.
Adding support to this evidence were two subsequent meta-analyses. The first meta-analysis of 19 randomized controlled trials demonstrated a 14% reduction in major CVD events for patients treated to a mean systolic BP of 133 mm Hg vs. 140 mm Hg in the control groups (HR = 0.86; 95% CI, 0.78-0.96). The second meta-analysis included more than 600,000 participants and showed that for every 10-mm Hg reduction in systolic BP, there was an overall 20% reduction in major CV events (HR = 0.8; 95% CI, 0.77-0.83). Moreover, among participants with a systolic BP < 130 mm Hg, there was a 37% reduction in major CV events (HR = 0.5-0.8) and a 47% reduction in all-cause mortality (HR = 0.53; 95% CI, 0.37-0.76) for every 10-mm Hg reduction in systolic BP.
It is important to note that the intensive treatment target in CHEP is recommended only for high-risk individuals, who are defined to match the inclusion criteria for SPRINT as patients with:
- clinical or subclinical CVD;
- an estimated 10-year global CVD risk 15% by the Framingham risk score;
- age 75 years and older; or
- chronic kidney disease (eGFR, 20-59 mL/min/1.73 m2, <1 g per day proteinuria or non-diabetic nephropathy).
However, the CHEP guideline committee cautions that meeting these criteria should not automatically trigger treatment to a more intensive target and that the risks and benefits should be weighed as part of the decision-making process. The committee noted that evidence for intensive treatment is inconclusive among patients fulfilling the above criteria who also have diabetes, prior stroke or an eGFR < 20 mL/min/1.73 m2. The committee also emphasized that patients must be involved in this process and that an increase in BP-lowering intensity also has an associated increase in clinical encounters and the number of medications required to achieve these BP goals.
Management of elderly patients
While patients aged 75 years and older are one of the high-risk groups indicated for intensive therapy based on the SPRINT trial, the CHEP guidelines keep their prior recommendations of a systolic BP goal of < 150 mm Hg for the very elderly (80 years and older). The guidelines also keep the treatment goals of < 140 mm Hg systolic and < 90 mm Hg diastolic for adults who do not meet SPRINT eligibility criteria.
In a separate publication reviewing their guideline decisions, a group of three of the CHEP authors discuss that a more detailed review of BP management in the very elderly will be undertaken with the next CHEP guidelines. However, in the meantime, they state that intensive BP lowering to < 120 mm Hg for patients aged 80 years and older is endorsed by CHEP for patients in whom clinicians believe to be appropriate candidates based on SPRINT criteria. For all other very elderly patients, they continue with their prior recommendations for now.
Definition, measurement techniques
The CHEP guidelines do not change their definition of hypertension, which is still defined as a systolic BP 140 mm Hg or a diastolic BP 90 mm Hg when measured manually by a trained health care provider. However, they now recommend that the preferred measurement technique is through the use of an automated office BP device without health care provider interaction. When using this measurement technique, hypertension is defined as 135/ 85 mm Hg due to the fact that automated BP measurement is characterized by slightly lower readings than manual readings.
The recommendation for the use of automated BP measurement serves the two separate purposes: attempting to delineate white-coat hypertension from true hypertension and to remove operator-induced error. This recommendation is also prompted by the fact that the majority of clinical trials now use automated BP measurements. However, in SPRINT, the average of three sequential automated BP measurements after 5 minutes of quiet resting were used for treatment decisions. Single, non-averaged BP measurement or non-resting BP measurements may result in higher values and, if used for treatment decisions, could result in the overtreatment of patients.
Optimal target for diabetes
One area of BP management that remains unanswered by SPRINT and other recent publications is the optimal BP target for patients with diabetes. Patients with diabetes were excluded from SPRINT, as the ACCORD trial was already ongoing and the subsequent results from ACCORD did not support intensive BP lowering to < 120 mm Hg systolic among patients with diabetes. The BP results from ACCORD have been discussed in detail elsewhere and we will not review them in detail here. However, the results were impacted by the trial’s factorial design, lower than expected event rate leading to an underpowering of the BP arm, lack of inclusion of HF as an endpoint and younger mean patient age than in the SPRINT trial (mean age, 62 years vs. 68 years).
While the results from ACCORDION, a long-term follow-up of ACCORD, suggest that participants in the standard glucose and intensive BP-lowering arm may have some benefit, the CHEP task force did not feel that the currently available data justify extending the results from SPRINT to patients with diabetes. Therefore, the CHEP committee did not adjust the recommendations for BP lowering among patients with diabetes. Whether a future trial will be conducted to definitively answer this question remains to be seen.
SPRINT vs. HOPE-3
Not considered in the 2016 CHEP BP guidelines are results of the HOPE-3 trial, which were published in the weeks leading up to the release of the CHEP update. HOPE-3 was a factorial-designed trial with a BP arm and a lipid-lowering arm using fixed doses of medications similar to that which could be used in a polypill. In the BP arm, there was no significant reduction in major CVD (CV death, nonfatal MI or nonfatal stroke) during a median follow-up of 5.6 years, although for the prespecified subgroup of participants in the upper tertile of systolic BP treatment (mean baseline, 154 mm Hg) that resulted in a mean systolic BP of 148 mm Hg resulted in a significant reduction in major CV events (HR = 0.73; 95% CI, 0.56-0.94).
However, there are important differences in the design and participant characteristics that can account for the differences observed in HOPE-3 compared with SPRINT.
First, both trials set out to answer different questions. SPRINT aimed to determine CVD and mortality risk reduction with intensive BP treatment in high-risk patients. On the other hand, HOPE-3 aimed to answer the same question in intermediate-risk patients with an eye toward the use of a BP-lowering agent as part of a polypill.
Second, participants in SPRINT were treated much more aggressively than participants in HOPE-3. The average separation in systolic BP was 13 mm Hg in SPRINT vs. 6 mm Hg in HOPE-3.
Third, SPRINT participants were more commonly treated with chlorthalidone than with hydrochlorothiazide. Chlorthalidone is not only a longer-acting diuretic, but is more potent than hydrochlorothiazide. Therefore, the differences in results between SPRINT and HOPE-3 were more attributable to differences in CV risk, degree of BP reduction and/or pharmaceutical mechanisms.
Insight for upcoming guidelines
Overall, the new 2016 CHEP BP guidelines endorse intensive BP lowering for high-risk patients meeting criteria for entry into SPRINT. The guidelines advise that caution should be taken in extending the SPRINT results to groups with limited evidence in whom the generalizability of the SPRINT results is uncertain, such as patients with diabetes or prior stroke. The guidelines emphasize the importance of patient participation through a willingness to take additional medication(s), attend more clinic visits while their BP medications are titrated to achieve a more intensive goal, and the overall small risk for possible side effects.
Moreover, the new CHEP recommendations for use of AOBP and decisions based on mean BP measurement as implemented in most trials including SPRINT should be equally strongly emphasized, as the use of single measurements can lead to overtreatment. Furthermore, the CHEP guidelines reiterate that the use of long-acting antihypertensive medications such as chlorthalidone is imperative.
The CHEP guidelines, which had a focus on incorporation of the SPRINT results, provide some insight as what we are likely to see from the upcoming ACC/AHA BP guidelines with respect to patients meeting the SPRINT criteria. However, whether guideline committees will generalize the results of SPRINT to patients beyond the inclusion criteria remains to be seen.
- References:
- Cushman WC, et al. Long-term cardiovascular effects of 4.9 years of intensive blood pressure control in type 2 diabetes mellitus: The Action to Control Cardiovascular Risk in Diabetes Follow-on Blood Pressure Study. Presented at: American Heart Association Scientific Sessions; Nov. 7-11, 2015; Orlando, Fla.
- Ettehad D, et al. Lancet. 2016;doi:10.1016/S0140-6736(15)01225-8.
- James PA, et al. JAMA. 2014;doi:10.1001/jama.2013.284427.
- Leung AA, et al. Can J Cardiol. 2016;doi:10.1016/j.cjca.02.066.
- Lonn EM, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1600175.
- Padwal R, et al. Hypertension. 2016;doi:10.1161/HYPERTENSIONAHA.116.07573.
- Pareek AK, et al. J Am Coll Cardiol. 2016;doi:10.1016/j.jacc.2015.10.083.
- The SPRINT Research Group. N Engl J Med. 2015;doi:10.1056/NEJMoa1511939.
- Xie X, et al. Lancet. 2016;10.1016/S0140-6736(15)00805-3.
- For more information:
- Seamus P. Whelton, MD, MPH, and Haitham M. Ahmed, MD, MPH, are clinical fellows at the Johns Hopkins Ciccarone Center for the Prevention of Heart Disease and are members of the Cardiology Today Fellows Advisory Board. Roger S. Blumenthal, MD, is director of the Ciccarone Center for the Prevention of Heart Disease and is the CHD and Prevention Section Editor of Cardiology Today. J. William McEvoy, MB BCh, BAO, MRCP, is an assistant professor of medicine in the division of cardiology and the department of medicine at Johns Hopkins University School of Medicine.
Disclosures: The authors report no relevant financial disclosures.