The FDA has approved the dual endothelin receptor antagonist aprocitentan (Tryvio – Idorsia) for use in combination with other antihypertensive drugs to treat hypertension in adults whose blood pressure is not adequately controlled on other drugs. Three other dual endothelin receptor antagonists, ambrisentan (Volibris, and generics), bosentan (Tracleer, and generics), and macitentan (Opsumit), are available in the US for treatment of pulmonary arterial hypertension.

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.

Recently published guidelines from the American Diabetes Association (ADA) and the Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group recommend addition of the oral nonsteroidal mineralocorticoid receptor antagonist (MRA) finerenone (Kerendia) to standard treatment in patients with type 2 diabetes and chronic kidney disease (CKD).

The FDA has approved Tarpeyo (Calliditas), a delayed-release capsule formulation of the corticosteroid budesonide, to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN; also called Berger's disease) who are at risk of rapid disease progression. It is the fi rst drug to be approved in the US for this indication. Oral formulations of budesonide have been available for years for treatment of inflammatory bowel disease.

A synthetic form of the protein apoaequorin is the active ingredient in the over-the-counter dietary supplement Prevagen (Quincy Bioscience), which is heavily marketed to improve memory.

Finerenone (Kerendia – Bayer), an oral nonsteroidal mineralocorticoid receptor antagonist (MRA), has been approved by the FDA to reduce the risk of sustained eGFR decline, end-stage renal disease, nonfatal MI, hospitalization for heart failure (HF), and cardiovascular death in adults with chronic kidney disease (CKD) associated with type 2 diabetes. It is the first nonsteroidal MRA to be approved in the US.

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.

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 and chronic thromboembolic pulmonary hypertension, was the first.

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.

The severity and rapid spread of COVID-19 (caused by SARS-CoV-2) have raised questions about the use of some drugs in patients with the disease and whether currently available drugs could be effective in treating it. Definitive answers are lacking, but some recommendations can be made. For additional information on specific drugs, see our table Some Drugs Being Considered for Treatment of COVID-19.

View the Table: Treatments Considered for COVID-19

The severity and rapid spread of COVID-19 (caused by SARS-CoV-2) have raised questions about the use of some drugs in patients with the disease and whether currently available drugs could be effective in treating it. Definitive answers are lacking, but some recommendations can be made. For additional information on specific drugs, see our table Some Drugs Being Considered for Treatment of COVID-19.

Consensi (Coeptis/Burke), a fixed-dose combination of the calcium channel blocker amlodipine (Norvasc, and others) and the COX-2 selective NSAID celecoxib (Celebrex, and generics), has been approved by the FDA for treatment of patients who have hypertension and osteoarthritis.

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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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.

An oral nonopioid analgesic may be sufficient for treatment of mild to moderate migraine without severe nausea or vomiting. A triptan is the drug of choice for treatment of moderate to severe migraine. Use of a triptan early in an attack when pain is still mild to moderate in intensity improves headache response and reduces recurrence rates.

View the Comparison Table: Some Drugs for Migraine Prevention in Adults

The FDA has approved patiromer (Veltassa – Relypsa), an oral potassium binder, for treatment of hyperkalemia. It is the first drug to be approved for this indication since the cation-exchange resin sodium polystyrene sulfonate (Kayexalate, and others) in 1958. Patiromer is not indicated for emergency correction of life-threatening hyperkalemia. Sodium zirconium cyclosilicate, another oral potassium binder, is currently being reviewed by the FDA; a decision on its approval is expected in May 2016.

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.

The FDA has approved a fixed-dose combination of the angiotensin receptor blocker (ARB) azilsartan and the thiazide-like diuretic chlorthalidone as Edarbyclor (Takeda) for treatment of hypertension

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.

Drugs for treatment of migraine are listed in Table 2 on page 9. Drugs for prevention of migraine are listed in Table 3 on page 10. Treatment of migraine in the emergency room, which may involve use of intravenous drugs, is not included here.

Many patients with hypertension require more than one drug to control their blood pressure. Tribenzor (Daiichi Sankyo), recently approved by the FDA for treatment of hypertension, combines the calcium channel blocker amlodipine (Norvasc, and others), the angiotensin receptor blocker (ARB) olmesartan (Benicar)and the most commonly prescribed diuretic, hydrochlorothiazide (HCTZ). Tribenzor is not approved for initial therapy, but is recommended for patients not adequately controlled on any 2-drug combination of a calcium channel blocker, an ARB or a diuretic.

The FDA has approved Twynsta (Boehringer Ingelheim), a fixed-dose combination of the calcium-channel blocker (CCB) amlodipine and the angiotensin receptor blocker (ARB) telmisartan, for treatment of hypertension.

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.

Most patients with hypertension require more than one drug to control their blood pressure. Exforge HCT (Novartis) is a new 3-drug fixed-dose combination tablet approved by the FDA for treatment of hypertension. It combines the calcium-channel blocker amlodipine (Norvasc, and others) and the angiotensin receptor blocker (ARB) valsartan (Diovan), which are already available in a combination tablet (Exforge), with the most commonly prescribed diuretic hydrochlorothiazide (HCTZ). Exforge HCT is not approved for initial treatment of hypertension, but rather for patients not adequately controlled on a 2-drug combination of a calcium-channel blocker, an ARB or a diuretic. It can also be substituted for amlodipine, valsartan and HCTZ in patients already taking all 3 of these drugs.

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).

Some drugs for treatment of migraine attacks are listed in table 2 on page 18. Drugs for prevention of migraine are listed in table 3 on page 20. Treatment of migraine in the emergency room, which may involve use of intravenous drugs, is not included here.

Aliskiren (ah LIS ker in; Tekturna - Novartis), the first direct renin inhibitor, has been approved by the FDA for treatment of hypertension. It is indicated for oral use either as monotherapy or in combination with other antihypertensive agents.

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.

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.

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.

Angiotensin receptor blockers (ARBs) are widely used as an alternative to angiotensin converting enzyme (ACE) inhibitors for treatment of hypertension because they lower blood pressure without inducing a cough. It has not been established that they provide the same cardiac benefits as ACE inhibitors. Recently, an editorial in the British Medical Journal suggested that ARBs may increase the risk of myocardial infarction.

Drugs for treatment of migraine attacks are listed in the table on page 64. All of the oral drugs are most effective if taken early in an attack when the pain is mild (H Christoph-Diener et al, Neurology 2004; 63:520). Drugs for prevention of migraine are listed in the table on page 65. Treatment of migraine in the emergency room, which may involve use of intravenous drugs, is not included 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.

Eplerenone (e pler' en one; Inspra - Pharmacia), an aldosterone receptor antagonist similar to spironolactone (Aldactone, and others), has been approved by the FDA, but not yet marketed, for treatment of hypertension. It has also been tried for treatment of heart failure.

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.

Olmesartan medoxomil (Benicar - Sankyo), a substituted imidazole, is the seventh oral angiotensin II receptor blocker (ARB) approved by the FDA for treatment of hypertension.