American College of Cardiology/American Heart Association (ACC/AHA) guidelines for treatment of hypertension were last published in 2018. Treatment of hypertensive urgencies and emergencies is not discussed here.

Among patients with chronic heart failure, those with a left ventricular ejection fraction (LVEF) ≤40% are considered to have heart failure with reduced ejection fraction (HFrEF). Patients with a LVEF ≥50% are considered to have heart failure with preserved ejection fraction (HFpEF). Those with a LVEF of 41-49% are an intermediate group more similar to patients with HFpEF.

View the Comparison Table: Some Drugs for HFrEF

Drugs available for treatment of chronic hypertension and their dosages, adverse effects, and costs are listed in the tables. Treatment of hypertensive urgencies and emergencies is not discussed here.

Patients with a left ventricular ejection fraction (LVEF) ≤40% are considered to have heart failure with reduced ejection fraction (HFrEF). Patients with a LVEF ≤50% and symptoms of heart failure are considered to have heart failure with preserved ejection fraction (HFpEF). There is little evidence that drug treatment improves clinical outcomes in patients with HFpEF.

View the Expanded Table: Some Drugs for HFrEF

in the US and their dosages, adverse effects, and costs are listed in the tables. Treatment of hypertensive urgencies and emergencies is not discussed here.

The FDA has approved Entresto (Novartis), an oral fixed-dose combination of the neprilysin inhibitor sacubitril and the angiotensin receptor blocker (ARB) valsartan, to reduce the risk of cardiovascular death and heart failure hospitalization in patients with heart failure with reduced ejection fraction. Sacubitril is the first neprilysin inhibitor to become available in the US.

Heart failure is usually associated with left ventricular dysfunction. According to recent guidelines, patients with a left ventricular ejection fraction (LVEF) ≤40% are considered to have heart failure with reduced ejection fraction (HFrEF) or systolic heart failure. Patients with a LVEF ≥50% and symptoms of heart failure are considered to have heart failure with preserved ejection fraction (HFpEF) or diastolic heart failure; there is little evidence that drug treatment improves clinical outcomes in these patients. The treatment of acute heart failure is not included here.

Chronic systolic heart failure is usually associated with a left ventricular ejection fraction (LVEF) of ≤40%. Many patients with symptoms of heart failure have higher ejection fractions, but there is no evidence that drug treatment of heart failure with preserved systolic function (LVEF >40%) improves clinical outcomes. Some of the drugs commonly used now for treatment of chronic heart failure are listed in the table on page 71.

A randomized, placebo-controlled trial evaluating the addition of the direct renin inhibitor aliskiren (Tekturna – Novartis) to an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) in 8606 patients with type 2 diabetes and renal impairment (ALTITUDE) was terminated prematurely by the manufacturer because the combined incidence of cardiovascular and renal events was higher in patients who received aliskiren than in those who received placebo.1

Combining two different types of drugs that block the renin angiotensin system in patients at high-risk for cardiovascular and renal events has been studied previously. Use of both the ACE inhibitor ramipril (Altace, and others) and the ARB telmisartan (Micardis) in hypertensive patients with diabetes or vascular disease (ONTARGET) did not improve cardiovascular or renal outcomes compared to use of either drug alone, and patients treated with both drugs had more hypotensive symptoms, syncope and renal dysfunction.2

Aliskiren is available alone (Tekturna) and in fixed-dose combinations with hydrochlorothiazide (Tekturna HCT), the calcium channel blocker amlodipine (Tekamlo), both hydrochorothiazide and amlodipine (Amturnide) and the ARB valsartan (Valturna) for treatment of hypertension.3 None of these products has been shown to improve clinical outcomes. Novartis is advising prescribers not to use aliskiren-containing products with an ACE inhibitor or an ARB in patients with diabetes.

1. Novartis.Novartis announces termination of ALTITUDE study with Rasilez/Tekturna in high-risk patients with diabetes and renal impairment. Available at www.novartis.com/newsroom/rasileztekturna-information-center/index.shtml. Accessed January 17, 2012.

2. S Yusuf et al. Telmisartan, ramipril, or both in patients at high risk for vascular events. N Engl J Med 2008; 358:1547.

3. Aliskiren/valsartan (Valturna) for hypertension. Med Lett Drugs Ther 2009; 51:94.

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Drugs available in the US for treatment of chronic hypertension, with their dosages and adverse effects, are listed in the tables that begin on page 2. Combination products are listed on page 8. Drugs for treatment of hypertensive emergencies are not discussed here. They were reviewed previously.

The range of drugs for treatment of chronic heart failure continues to expand. Some of those commonly used now are listed in the table on page 55. Mechanical therapies for the treatment of heart failure such as cardiac resynchronization, implanted cardiac defibrillators (ICDs), ventricular assist devices and ultrafiltration for the relief of congestion will not be reviewed here.

Drugs available in the US for treatment of chronic hypertension, with their dosages, adverse effects and costs, are listed in the tables that begin on page 2. Combination products are listed on page 9. Drugs for treatment of hypertensive emergencies are not discussed here. They were reviewed in Treatment Guidelines (volume 1, page 19, December 2002) and in The Medical Letter (volume 50, page 73, September 22, 2008).

The choice of drugs for treatment of chronic heart failure continues to evolve. Those most commonly used now are listed in the table on page 3. The use of implanted cardiac defibrillators (ICDs) to reduce the incidence of sudden death in patients with heart failure and the treatment of decompensated heart failure were discussed in previous issues.

Drugs available in the US for treatment of chronic hypertension, with their dosages, adverse effects and costs, are listed in the tables that begin on page 40. Combination products are listed on page 47. Drugs for treatment of hypertensive emergencies are not discussed here.

The importance of adequate control of hypertension in preventing organ damage and death is well established, but the choice of drugs is still controversial. Three recent drug trials, one supporting initial therapy with a diuretic, the second favoring an angiotensin converting enzyme (ACE) inhibitor, and the third showing equivalence between a calcium-channel blocker and an angiotensin-receptor blocker (ARB) have intensified the debate.

Management of intermittent claudication, the most common symptom of peripheral arterial disease (PAD), involves both risk factor modification and symptomatic treatment (WR Hiatt, N Engl J Med 2001; 344:1608; RM Schainfeld, J Am Board Fam Pract 2001; 14:443).

The choice of drugs for treatment of chronic heart failure continues to evolve. It has become increasingly recognized that drugs used in heart failure produce beneficial effects through neurohormonal as well as hemodynamic mechanisms. The treatment of decompensated heart failure is not discussed here; drugs used for this indication were reviewed in Cardiovascular Drugs in the ICU, Treatment Guidelines from The Medical Letter 2002; 1:19.

Drugs available in the US for treatment of chronic hypertension, with their dosages, adverse effects and costs, are listed in the table that begins on page 35. Combination products are listed on page 39. Drugs for treatment of hypertensive emergencies were discussed in Treatment Guidelines volume 1, issue 4, page 19, December 2002.

Drugs available in the USA for treatment of chronic hypertension, their dosages and adverse affects are listed in the table and discussed in the text.

Perindopril, the tenth angiotensin converting enzyme (ACE) inhibitor to be marketed in the USA, and telmisartan and eprosartan, the fifth and sixth angiotensin receptor blockers, have recently become available for treatment of hypertension.

Drugs available in the USA for treatment of chronic hypertension, their dosages and adverse affects are listed in the table and discussed in the text.

Irbesartan (Avapro - Sanofi/Bristol-Myers Squibb) is the third angiotensin II receptor antagonist to become available in the USA for oral treatment of hypertension. Losartan (Cozaar) and valsartan (Diovan) were marketed earlier. Eprosartan (Teveten - SmithKline Beecham) has been approved by the FDA but not marketed.

Valsartan (Diovan - Novartis), a non-peptide tetrazole, is the second angiotensin II receptor antagonist approved for oral treatment of hypertension by the US Food and Drug Administration. The first was losartan (Cozaar - Medical Letter, 37:57, 1995).

Trandolapril (tran doe la pril; Mavik - Knoll) has become the ninth angiotensin-converting- enzyme (ACE) inhibitor to be approved by the US Food and Drug Administration (FDA) for treatment of hypertension.

Cardiologist now emphasize the importance of neurohormonal as well as hemodynamic factors in the pathophysiology of chronic heart failure (JN Cohn, N Engl J Med, 335:490, August 15, 1996). Drugs that act on different mechanisms are commonly used together.

Losartan potassium (Cozaar - Merck), the first angiotensin II receptor antagonist, has been approved for oral treatment of hypertension by the US Food and Drug Administration. It will be marketed both alone and in a fixed-dose combination with the diuretic hydrochlorothiazide (Hyzaar).

The US Food and Drug Administration has approved use of the angiotensin-converting enzyme (ACE) inhibitor captopril (Capoten) for patients with left ventricular dysfunction after a myocardial infarction. ACE inhibitors, widely used for treatment of hypertension, in recent years have also been used for treatment of heart failure (Medical Letter, 35:40, 1993).

Quinapril (Accupril - Parke-Davis), an angiotensin-converting enzyme (ACE) inhibitor, has been approved by the US Food and Drug Administration (FDA) for treatment of hypertension. ACE inhibitors are now widely used for this indication (Medical Letter, 33:33, 1991).

Benazepril (Lotensin - Ciba-Geigy), fosinopril (Monopril - Mead Johnson), and - Hoechst, Upjohn) are new angiotensin-converting enzyme (ACE) inhibitors recently approved by the US Food and Drug Administration (FDA) for once-a-day treatment of hypertension. Three other ACE inhibitors, captopril (Capoten), enalapril (Vasotec), and lisinopril (Prinivil, Zestril) were previously available in the USA for this indication. Captopril and enalapril have also been approved by the FDA for treatment of congestive heart failure.