Isosorbide mononitrate (ISMN; Ismo - Wyeth-Ayerst), an oral nitrate long available in Europe, was recently approved by the US Food and Drug Administration for prophylactic use in patients with chronic stable angina. ISMN is the major active metabolite of isosorbide dinitrate (ISDN; Isordil, and others).

BiDil (NitroMed), a fixed-dose combination of isosorbide dinitrate and hydralazine, was approved by the FDA for adjunctive use in the treatment of heart failure in black patients.Both drugs are oral vasodilators that have been used together off-label for many years to treat heart failure in patients not responding to other drugs.

Isosorbide mononitrate, the major active metabolite of isosorbide dinitrate, was first approved in the USA for oral use in patients with chronic stable angina in 1992 (Medical Letter, 34:61, 1992). Now an extended-release formulation of isosorbide mononitrate (Imdur -Key) has been approved by the US Food and Drug Administration.

Many nitrates, beta-blockers, and calcium-channel blockers have now been approved by the US Food and Drug Administration for treatment of stable angina pectoris. The table beginning on page 112 lists the individual drugs, their dosage, and their cost.

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.

Transdermal nitroglycerin products commercially available in the USA are listed in the table below. These patches, which look like adhesive bandages, are often applied over the precordium, but they can be attached to any hairless area of the skin, except distal parts of the extremities. Individual patients vary in their absorption of nitroglycerin from the skin; the amounts delivered (the doses) are average figures.

Pharmacologic management of chronic heart failure (HF) is primarily determined by the patient's left ventricular ejection fraction (LVEF) and severity of symptoms. Patients with chronic HF who have an LVEF ≤40% are considered to have heart failure with reduced ejection fraction (HFrEF) and those with an LVEF ≥50% are considered to have heart failure with preserved ejection fraction (HFpEF). Patients with an LVEF of 41-49% have heart failure with mildly reduced or mid-range ejection fraction.

The FDA has approved vericiguat (Verquvo – Merck), an oral soluble guanylate cyclase (sGC) stimulator, to reduce the risk of hospitalization for heart failure and cardiovascular (CV) death following a worsening heart failure event (hospitalization for heart failure or treatment with IV diuretics as an outpatient) in patients with symptomatic chronic heart failure and left ventricular ejection fraction (LVEF) <45%. Vericiguat is the second sGC stimulator to be marketed in the US. Riociguat (Adempas), which is FDA-approved for treatment of pulmonary arterial hypertension...

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.

View the Comparison Chart: Some Drugs for HFrEF