VII. Treatment of Hypertension in Association With Heart Failure

Prevention and Treatment

Subgroup Members: Simon W. Rabkin, MD; Gordon W. Moe, MD, MSc; Jonathan G. Howlett, MD
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. In patients with systolic dysfunction (ejection fraction <40%), ACE inhibitors (Grade A) and β-blockers (Grade A) are recommended for initial therapy. Aldosterone antagonists (mineralocorticoid receptor antagonists) might be added for patients with a recent cardiovascular hospitalization, acute myocardial infarction, elevated B-type natriuretic peptide or N-terminal (NT) pro-B-type natriuretic peptide level, or New York Heart Association Class II–IV symptoms (Grade A). Careful monitoring for hyperkalemia is recommended when adding an aldosterone antagonist to ACE inhibitor or ARB. Other diuretics are recommended as additional therapy if needed (Grade B for thiazide/thiazide-like diuretics for BP control, Grade D for loop diuretics for volume control). Beyond considerations of BP control, doses of ACE inhibitors or ARBs should be titrated to those found to be effective in trials unless adverse effects become manifest (Grade B).
  2. An ARB is recommended if ACE inhibitors are not tolerated (Grade A).
  3. A combination of hydralazine and isosorbide dinitrate is recommended if ACE inhibitors and ARBs are contraindicated or not tolerated (Grade B).
  4. For hypertensive patients whose BP is not controlled, an ARB may be added to an ACE inhibitor and other antihypertensive drug treatment (Grade A). Careful monitoring should be used if combining an ACE inhibitor and an ARB because of potential adverse effects such as hypotension, hyperkalemia, and worsening renal function (Grade C). Additional therapies might also include dihydropyridine CCBs (Grade C).

Background

1. In patients with systolic dysfunction (ejection fraction <40%), ACE inhibitors (Grade A) and β-blockers (Grade A) are recommended for initial therapy. Aldosterone antagonists (mineralocorticoid receptor antagonists) might be added for patients with a recent cardiovascular hospitalization, acute myocardial infarction, elevated B-type natriuretic peptide or N-terminal (NT) pro-B-type natriuretic peptide level, or New York Heart Association Class II–IV symptoms (Grade A). Careful monitoring for hyperkalemia is recommended when adding an aldosterone antagonist to ACE inhibitor or ARB. Other diuretics are recommended as additional therapy if needed (Grade B for thiazide/thiazide-like diuretics for BP control, Grade D for loop diuretics for volume control). Beyond considerations of BP control, doses of ACE inhibitors or ARBs should be titrated to those found to be effective in trials unless adverse effects become manifest (Grade B).

Hypertension persisting after development of heart failure is associated with more frequent adverse outcomes such as hospitalization (1). As outlined below, hypertension treatment regimens in patients with heart failure (HF) should generally include ACE inhibitors (or ARBs), beta-blockers and MRAs in selected patients.  Consistent with the Canadian Cardiovascular Society (CCS) recommendations on heart failure (21), dosages of ACE inhibitors and ARBs should be titrated to those dosages found to be effective in clinical trials unless adverse effects arise.  Loop diuretics provide symptomatic relief for fluid retention and volume overload.

The recommendation supporting ACE inhibitors as first-line therapy is derived from RCT and  meta-analytic data, including a quantitative review of of nearly 13,000 patients with systolic dysfunction showing substantial reductions in mortality, heart failure hospitalizations and MI in both hypertensive and nonhypertensive patients (2,4,5). (19)

β-blockers have been shown to improve survival in patients with hypertension, systolic dysfunction, and New York Heart Association (NYHA) functional class II–IV symptomatology (6–12).

The recommendation  for mineralocorticoid receptor antagonists (MRAs) is based on several RCTs including RALES (13), EPHESUS (14) and EMPHASIS-HF trial (15).

Caution should be exercised in combining an ACE inhibitor with an ARB, particularly in patients who are also taking an MRA, given the potential risk of hyperkalemia. Should clinicians choose to use this combination, they should closely monitor serum potassium and creatinine (16).

In reference to thiazides, in the absence of placebo-controlled trials testing thiazides in patients with hypertension who have systolic dysfunction, the recommendation supporting use of thiazides was based on extrapolation from multiple thiazide-based antihypertensive trials showing reductions in stroke, MI and death rates (and thus Grade B) (17,18).

2. An ARB is recommended if ACE inhibitors are not tolerated (Grade A).

Data from a meta-analysis of RCTs supports the use of ARBs in heart failure (20).  Seminal studies include the CHARM series of trials as well as the Val-HeFT trial (25–29).

3. A combination of hydralazine and isosorbide dinitrate is recommended if ACE inhibitors and ARBs are contraindicated or not tolerated (Grade B).

Hydralazine, combined with isosorbide dinitrate, improves survival in patients with heart failure, and the recommendation supporting their use as alternative first- line agents is derived by extrapolation from the Vasodilator in Heart Failure (V-HeFT) I trial (with 40% of the patients having hypertension), thus, Grade B (32). The V-HeFT II trial provides Grade B evidence that angiotensin-converting enzyme inhibitors are superior to hydralazine and/or isosorbide dinitrate (positive study, but we are extrapolating from overall results to the 50% of enrolled patients with hypertension) (33).

4. For hypertensive patients whose BP is not controlled, an ARB may be added to an ACE inhibitor and other antihypertensive drug treatment (Grade A). Careful monitoring should be used if combining an ACE inhibitor and an ARB because of potential adverse effects such as hypotension, hyperkalemia, and worsening renal function (Grade C). Additional therapies might also include dihydropyridine CCBs (Grade C).

Although there is evidence of benefit in combining an ARB and ACE inhibitor in selected patients with heart failure (27,35), a caution was added to use of this combination and careful monitoring is recommended due to concerns over increased risks of hypotension, hyperkalemia (particularly in patients who are concomitantly taking MRAs) and worsening renal function.

There is a limited role for CCBs in heart failure, particularly given the results of two meta-analyses suggesting increased risk of heart failure in at-risk patients treated with CCBs (RR, 1.12; 95%CI, 0.95 to 1.33) (36,37). Post hoc subgroup analysis of the Prospective Randomized Amlodipine Survival Trial revealed a statistically significant reduction in mortality in heart failure patients with hypertension treated with amlodipine compared with placebo (thus, a Grade C recommendation) (38).

References

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