II. Indications for Drug Therapy for Adults with Hypertension Without Compelling Indications for Specific Agents

Prevention and Treatment

Subgroup Members: George K. Dresser, MD, PhD; Robert J. Herman, MD; Pavel Hamet, MD, PhD; Ellen Burgess, MD; Richard Lewanczuk, MD, PhD; Jean C. Gregoire, MD;Luc Poirier, BPharm, MSc
Central Review Committee: Stella S. Daskalopoulou, MD, PhD; Kaberi Dasgupta, MD, MSc; Kelly B. Zarnke, MD, MSc; Kara Nerenberg, MD, MSc; Alexander A. Leung, MD, MPH; Kevin C. Harris, MD, MHSc; Kerry McBrien, MD, MPH; Sonia Butalia, BSc, MD; Meranda Nakhla, MD, MSc
Chair: Doreen M. Rabi, MD, MSc
This information is based on the Hypertension Canada guidelines published in Leung, Alexander A. et al. Hypertension Canada’s 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. Can J Cardiol 2017; 33(5): 557-576.

Guidelines

  1. Antihypertensive therapy should be prescribed for average DBP measurements of ≥100 mmHg (Grade A) or average SBP measurements of ≥160 mmHg (Grade A) in patients without macrovascular target organ damage or other cardiovascular risk factors.
  2. Antihypertensive therapy should be strongly considered for average DBP readings ≥90 mmHg (Grade A) or for average SBP readings ≥140 mmHg (Grade B for 140-160 mmHg; Grade A for >160 mmHg; revised guideline) in the presence of macrovascular target organ damage or other independent cardiovascular risk factors.

Background

1. Antihypertensive therapy should be prescribed for average DBP measurements of ≥100 mmHg (Grade A) or average SBP measurements of ≥160 mmHg (Grade A) in patients without macrovascular target organ damage or other cardiovascular risk factors.

Population-based epidemiological studies establish clearly that risk of cardiovascular events, including stroke, myocardial infarction and heart failure, increases in a log-linear fashion with increased BP (1–4). (Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903-1913.) Further, numerous trials show antihypertensive therapy reduces relative risk of cardiovascular events by approximately 25% to 30%, irrespective of pre-treatment BP, (at least for diastolic BPs in excess of 90 mm Hg) — of course, Early trials generally enrolled patients with diastolic blood pressures in excess of 90 mm Hg and later trials enrolled patients with elevated systolic blood pressure (often greater than 160 mmHg) (5-8).

Recommendations for hypertension management emphasize the importance of cardiovascular risk assessment when making treatment decisions. It is well known the risk of cardiovascular disease in hypertensive patients with identical blood pressure (BP) readings can vary more than 10-fold, depending on presence of other cardiovascular risk factors, hypertension-related complications, cardiovascular diseases or other illnesses (3,12,13). Patients with Stage II hypertension (≥160/100 mmHg), those with known cardiovascular disease, and those with multiple risk factors are at highest risk.

2. Antihypertensive therapy should be strongly considered for average DBP readings ≥90 mmHg (Grade A) or for average SBP readings ≥140 mmHg (Grade B for 140-160 mmHg; Grade A for >160 mmHg; revised guideline) in the presence of macrovascular target organ damage or other independent cardiovascular risk factors.

The meta-analytic data cited above supports this recommendation. Many of the early trials in the field of hypertension were based upon the randomization of subjects with elevated diastolic blood pressure. The Hypertension Detection and Follow-up Program (HDFP), a 5-year pragmatic randomized trial comparing an intensive antihypertensive treatment program with usual care, is a notable example. This trial reported a statistically significant 17% reduction in total mortality in the overall trial (14). Mortality was also reduced (5.9% with active treatment vs. 7.4% for usual care; P < 0.01) in the subgroup of 7825 patients with DBP levels between 90 and 104 mm Hg (10). Relative risk reductions were similar across BP strata (90–94, 95–99, and 100–104 mm Hg respectively).

The Grade B recommendation is to initiate pharmacotherapy for those patients with systolic BPs of 140 mm Hg to 159 mm Hg with concurrent macrovascular target organ damage. This recommendation to lower treatment threshold for high-risk patients derives from observational data and extrapolation from the Heart Outcomes Prevention Evaluation (HOPE) study (23) and from the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS) (24). A meta-analysis of 61 prospective observational studies (12.7 million person-years) demonstrated for every 20 mm Hg increment in usual systolic BP (SBP), an associated two-fold difference occurs in stroke and cardiovascular death rate (25). Large cohort studies demonstrate consistently SBP has a strong, continuous, and graded association with cardiovascular morbidity and mortality, and there is no clear threshold value that distinguishes those patients at increased risk (25).

In the HOPE study (23), 9297 patients (≥ 55 years of age) with evidence of macrovascular target organ damage or diabetes, plus one other cardiovascular risk factor, who had a mean BP at entry of 139/79 mm Hg, were randomly assigned to ramipril or to placebo therapy. Study results showed a significant risk reduction in incidence of myocardial infarction (MI), stroke and cardiovascular death with ramipril use compared with placebo (RR 0.78; 95%CI 0.70 to 0.86; P<0.001). Those with SBPs above and below 138 mm Hg had similar benefits with use of ramipril (26). PROGRESS randomly assigned 6105 patients with a history of stroke or transient ischemic attack to perindopril, with or without indapamide or placebo. With a mean BP at study entry of 157/89 mm Hg, active treatment lowered BP by 9/4 mm Hg and conferred a reduction in total vascular events of 26% (24).

No recommendation has been made for the treatment of Stage 1 hypertension (BP 140–159/90–99 mm Hg) and no cardiovascular disease and, therefore, this is a gap within the CHEP treatment guidelines. Meta-analytic data do support the premise that the treatment of patients with Stage 1 hypertension (BP 140–159/90–99 mm Hg) and no cardiovascular disease is beneficial; however, the accumulated data are not as compelling as those supporting drug treatment of higher levels of BP or higher risk individuals and NNTs are higher (25).

With respect to the treatment of Stage 1 hypertension, two points deserve emphasis: First, non-pharmacological management should be instituted in all patients and, if successful, can potentially normalize BP levels without need for drug therapy. Second, the decision to initiate pharmacological treatment and timing of initiation should be guided by individual global cardiovascular risk assessment. In low-risk patients, including those without other cardiovascular risk factors or target organ damage, an extended interval of non-pharmacological management alone, with appropriate monitoring of BP levels, can be used. However, if non-pharmacological management is unsuccessful or if patients progress to Stage II hypertension, antihypertensive drug therapy should be considered.

References

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