Management of Hypertension in Chronic Heart Failure

Saraswathy Manickavasagam; Ramanna Merla; Michael M Koerner; Ken Fujise; Sanjay Kunapuli; Salvatore Rosanio; Alejandro Barbagelata

Disclosures

Expert Rev Cardiovasc Ther. 2009;7(4):423-433. 

In This Article

Expert Commentary & Five-year View

In clinical practice we encounter a spectrum of hypertensive patients, ranging from those at risk of developing HF, to those with end-stage HF. We recommend treatment of HTN according to the stage of HF. Reducing the systolic and diastolic blood pressures of those at risk may prevent HF; diuretics do this in a wide range of target populations.[36] ACE inhibitors also prevent HF, making them good add-on drugs but, when used alone, their ability to reduce cardiovascular outcomes is not superior to other antihypertensive drugs.[19] Calcium channel and α-blockers are less effective in preventing HF.[19]

When treating HTN in a patient at risk of or already with HF, factors such as LV function and nature of dysfunction, whether systolic or diastolic, should be taken into consideration. A patient with stage B HF has structural abnormalities but no symptoms of failure. Many such patients have had a myocardial infarction with or without evidence of ventricular remodeling, and are at considerable risk of developing HF.[80,81] ACE inhibition is preferred for these patients, followed by β-receptor blockade. Combining these drugs is especially helpful.[82] Angiotensin receptor blockade is used in patients intolerant to ACE inhibitors.

Stage C HF patients currently have or have had HF symptoms. All these patients should take both an ACE inhibitor and β-receptor blocker at the highest doses tolerated. These agents reduce the mortality and hospitalization rates of these patients. Spironolactone, nitrates and hydralazine are added if HTN remains uncontrolled in advanced HF, and diuretics are reserved for patients with volume overload. Amlodipine may be considered but in general, calcium channel blockade is not indicated for routine treatment of HTN in HF patients with reduced systolic function, unless there is a need after target dose. The other evidence-based treatments fail to control the blood pressure.

Stage D patients are end stage when hypotension is more likely than HTN. These patients respond favorably to ACE inhibition and β-adrenergic blockade (similarly to those with mild-to-moderate disease) but it is not clear if angiotensin receptor blockade is as effective as ACE inhibition in this group.[19] Spironolactone prolongs the life and reduces the hospitalization frequency of NYMA III and IV patients and is another good choice for treating their HTN. Nitrates and hydralazine are good add-on agents and preferred if ACE inhibition, angiotensin receptor blockade and β-adrenergic blockade are not tolerated ( Table 2 ).

Although HFNEF is increasing rapidly, especially in elderly individuals, we have little evidence-based data to guide our pharmacologic management of this condition. ARBs, ACE inhibition, and β-receptor and calcium channel blockade play an important role in controlling blood pressure, while diuretics are reserved for patients with volume overload. There is little doubt that ongoing trials, such as TOPCAT, will provide information that will help us treat the HTN that coexists with HFNEF.

In the next 5 years, we expect newer drugs being approved for treatment of HTN in HF. Several agents currently under investigation include nebivolol, a third-generation, highly selective β1-receptor blocker that also promotes endothelial nitric oxide production.[83] HF patients with HTN tolerate this drug well. In patients with symptomatic HF and reduced systolic function, its hemodynamic effects are similar to carvedilol. A large trial showed that nebivolol reduced the composite end point of mortality and hospitalization in HF patients.[84] Europe has approved the drug for mild-to-moderate, uncomplicated HTN and mild-to-moderate HF and, in the USA, the drug is now under FDA review. In the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors With Heart Failure (SENIORS) trial, nebivolol significantly reduced the composite end point of death and cardiovascular hospitalizations in patients aged at least 70 years whose ejection fractions were reduced or preserved.[84]

Aliskiren, a direct renin inhibitor, is another novel agent whose dose-dependent reductions in blood pressure are comparable to an ARB, but aliskiren blocks the renin-angiotensin-aldosterone system more completely than other downstream inhibitors and prevents the increase in plasma renin that follows diuretic therapy, ACE inhibition, calcium channel and angiotensin receptor blockade. The US FDA-approved aliskiren for HTN in 2007.[85,86,87] It can effectively treat hypertensive African-American patients who typically do not respond well to β-receptor blockade. The agent may also help HF patients and, although not approved for HF, it appears promising. In the Aliskiren Observation of Heart Failure Treatment (ALOFT) study, favorable neurohormonal changes occurred in HF patients after combining aliskiren with ACE inhibition or angiotensin receptor blockade and a β-receptor blocker.[88]

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