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.

In our Drugs for Chronic Heart Failure article,1 our description of the PARADIGM-HF trial comparing the combination of the ARB valsartan and the neprilysin inhibitor sacubitril (Entresto) with the ACE inhibitor enalapril for treatment of heart failure with reduced ejection fraction (HFrEF) characterized the dosage of enalapril as "suboptimal". Some readers have objected to that characterization.

The FDA-approved dosage of enalapril for treatment of HFrEF is 2.5-20 mg twice daily. In PARADIGM-HF, the dosage was capped at 10 mg twice daily, a widely used dosage that has been shown to reduce mortality in patients with HFrEF.2 In the trial, the rate of death from cardiovascular causes or hospitalization for heart failure was significantly lower with the combination of valsartan and sacubitril than with enalapril 10 mg twice daily (21.8% vs 26.5%). Whether allowing titration to 20 mg twice daily would have changed that result is a reasonable question, but there is no direct evidence that the higher dosage is more effective for this indication.3 We have removed the word "suboptimal" from the article as it appears online.

1. Med Lett Drugs Ther 2019; 61:49.
2. JJ McMurray et al. N Engl J Med 2014; 371:993.
3. N Bartell and WH Frishman. Cardiol Rev 2017; 25:315.

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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.

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).

Aliskiren (Tekturna - Novartis), the first direct renin inhibitor for treatment of hypertension, has been approved for use in a fixed-dose combination with the diuretic hydrochlorothiazide (Tekturna HCT - Novartis). Many angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are also available in fixed-dose combinations with hydrochlorothiazide (HCTZ).

Nebivolol (Bystolic - Forest) is a new beta-blocker that has been approved by the FDA for treatment of hypertension. It has been marketed in Europe since 1999 for treatment of hypertension and heart failure.

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.

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.

Candesartan cilexetil (Atacand - Astra) is the fourth angiotensin II receptor antagonist to become available in the USA for oral treatment of hypertension.

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.

Carvedilol (Coreg - SmithKline Beecham and Boehringer-Mannheim), a betaadrenergic and alpha-adrenergic blocker approved by the FDA for treatment of hypertension in 1995, but not marketed at that time, has now been approved and marketed for treatment of mild or moderate (NYHA class II or III) heart failure stabilized on other drugs. It is being promoted as an add-on drug that reduces the morbidity and mortality of the disease.

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.

Moexipril hydrochloride (Univasc - Schwarz Pharma), an angiotensin-converting enzyme (ACE) inhibitor, was recently approved by the US Food and Drug Administration (FDA) for treatment of. It is the eighth ACE inhibitor to be marketed in the USA.

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).

Chronic heart failure results from an iterplay between hemodynamic and neurohormonal factors (M Packer, Lancet, 340:88, 92, 1992). For patients with heart failure due to left ventricular dysfunction, drugs that decrease cardicac preload and afterload and those that increase contractility are commonly used together.

Flosequinan (Manoplax - Boots), a fluoroquinolone derivative, is now available in the USA for treatment of congestive heart failure. Labeling approved by the US Food and Drug Administration recommends the drug only for patients who cannot tolerate or have not responded adequately to an angiotensin-converting enzyme (ACE) inhibitor.

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.

Doxazosin (mesylate - Roerig), an alpha1-adrenergic receptor blocker similar to prazosin (Minipress, and others) and terazosin (Hytrin), was recently approved by the US Food and Drug Administration for treatment of hypertension.

Some commonly used systemic drugs that may cause pulmonary toxicity are listed in the table below. These adverse effects may sometimes be difficult to distinguish from the underlying disease (JAD Cooper, Jr et al, Am Rev Respir Dis, 133:321, 488, 1986). Pulmonary effects that are part of a generalized reaction or are indirect effects of drugs - on respiratory muscles, for example, or on the immune system - are not included here.

The angiotensin-converting enzyme (ACE) inhibitors captopril (Capoten - Squibb) and enalapril (Vasotec - Merck) are now widely used to treat chronic congestive heart failure that has not responded adequately to digitalis and diuretics (Medical Letter, 30:13, Jan 29, 1988). Recently, some cardiologists have debated whether ACE inhibitors should also be used as first-line agents for treatment of this condition (WW Parmley et al, J Am Coll Cardiol, 12:265, July 1988).

- Merck; Zestril - Stuart), a new angiotensin-converting enzyme (ACE) inhibitor, was recently approved by the US Food and Drug Administration (FDA) for once-daily treatment of . Two other ACE inhibitors, captopril (Capoten - Squibb) and e

Vasodilators are widely used for treatment of congestive heart failure (CHF) that has not responded adequately to diuretics and digitalis. Vasodilator drugs redistribute blood volume in patients with heart failure, lowering pressure and reducing volume in the failing left ventricle, which leads to increased cardiac output, decreased pulmonary capillary wedge pressure, and improved exercise tolerance. Since the last Medical Letter review of this subject (Volume 26, page 115, 1984), some additional data have become available.