Adults with a body mass index (BMI) between 25 and 29.9 kg/m² are considered overweight. Those with a BMI ≥30 are considered obese. The initial recommendation for any weight loss effort is to achieve a 5-10% reduction in weight, which has been associated with a reduction in the risk of developing type 2 diabetes, hypertension, and dyslipidemia. Diet, exercise, and behavior modification are the preferred methods for losing weight, but long-term weight maintenance can be difficult. Several drugs and devices are FDA-approved for weight reduction and maintenance of weight loss.

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.

The once-monthly, subcutaneously injected calcitonin gene-related peptide (CGRP) receptor antagonist erenumab-aooe (Aimovig) was approved by the FDA in 2018 for preventive treatment of migraine in adults. Now the FDA has added a new warning to its labeling about a risk of new-onset hypertension and worsening of preexisting hypertension associated with use of the drug. CGRP is a potent microvascular vasodilator; blocking or deleting it has produced hypertensive effects in animals.

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.

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.

A reader asked whether healthcare providers should avoid prescribing the angiotensin receptor blocker (ARB) olmesartan medoxomil (Benicar, and others) because it can cause severe GI adverse effects.

In 2013, the FDA warned that olmesartan can cause sprue-like enteropathy, a condition characterized by intestinal villous atrophy, severe chronic diarrhea, and significant unintended weight loss. The warning was based on 23 cases of serious sprue-like enteropathy associated with use of olmesartan, some occurring years after starting the drug. All patients improved after stopping olmesartan; 10 had a positive rechallenge.1 A case series describing 22 patients reported similar observations.2

Duodenal biopsies in patients with olmesartan-associated enteropathy have shown elevated CD8+ T cell counts and overexpression of interleukin-15 by epithelial cells, biomarkers similar to those seen after gluten exposure in patients with celiac disease. Mucosal recovery and lower levels of inflammatory biomarkers were observed in biopsies obtained after stopping olmesartan.3

In an observational cohort study including about 4.5 million patients in France who started ARB or angiotensin converting enzyme (ACE) inhibitor therapy over a 6-year period, exposure to olmesartan for >2 years was associated with one additional hospitalization for intestinal malabsorption per 12,550 patients, compared with exposure to another ARB or ACE inhibitor; this difference was statistically significant.4

Isolated cases of enteropathy have been reported with use of other ARBs.5-8

The absolute risk of sprue-like enteropathy with olmesartan is very low, and the effect is reversible. Patients without GI risk factors whose hypertension is well controlled on olmesartan could probably continue taking it. For patients starting antihypertensive therapy and those with GI risk factors, any of the several other ACE inhibitors or ARBs available generically9 might be a better choice. Patients taking any ARB should notify their healthcare provider if they develop severe diarrhea.

1. FDA Drug Safety Communication: FDA approves label changes to include intestinal problems (sprue-like enteropathy) linked to blood pressure medicine olmesartan medoxomil. Available at: www.fda.gov. Accessed January 18, 2018.
2. A Rubio-Tapia et al. Severe spruelike enteropathy associated with olmesartan. Mayo Clin Proc 2012; 87:732.
3. EV Marietta et al. Immunopathogenesis of olmesartan-associated enteropathy. Aliment Pharmacol Ther 2015; 42:1303.
4. M Basson et al. Severe intestinal malabsorption associated with olmesartan: a French nationwide observational cohort study. Gut 2016; 65:1664.
5. A Negro et al. A case of moderate sprue-like enteropathy associated with telmisartan. J Clin Med Res 2017; 9:1022.
6. HS Mandavdhare et al. Telmisartan-induced sprue-like enteropathy: a case report and a review of patients using non-olmesartan angiotensin receptor blockers. Intest Res 2017; 15:419.
7. ML Herman et al. A case of severe sprue-like enteropathy associated with valsartan. ACG Case Rep J 2015; 2:92.
8. EY Choi and BJ McKenna. Olmesartan-associated enteropathy: a review of clinical and histologic findings. Arch Pathol Lab Med 2015; 139:1242.
9. Drugs for hypertension. Med Lett Drugs Ther 2017; 59:41.

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New US guidelines for the treatment of hypertension have recently been published.1

Probably the most important change from previous guidelines2 is that use of blood pressure-lowering medication is now recommended for secondary prevention in patients with cardiovascular disease and an average systolic blood pressure (SBP) ≥130 mm Hg or diastolic blood pressure (DBP) ≥80 mm Hg, and for primary prevention in adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk3 of ≥10% and an average SBP ≥130 mm Hg or DBP ≥80 mm Hg.

For patients with no history of cardiovascular disease and an estimated 10-year ASCVD risk of <10%, blood pressure-lowering medication is recommended for those with an average SBP ≥140 mm Hg or an average DBP ≥90 mm Hg.

A blood pressure target of <130/80 mm Hg is recommended for patients with markers for increased risk and may be reasonable, according to the new guideline, even for those with no markers for increased risk.

1. PK Whelton et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2017 November 7 (epub).
2. Drugs for hypertension. Med Lett Drugs Ther 2017; 59:41.
3. American College of Cardiology. ASCVD risk estimator plus. Available at: http://tools.acc.org. Accessed November 21, 2017.

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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.

The FDA has approved Byvalson (Allergan), a fixed-dose combination of the beta blocker nebivolol (Bystolic) and the angiotensin receptor blocker (ARB) valsartan (Diovan, and generics), for treatment of hypertension. It is the only combination product that contains nebivolol, and the first to combine a beta blocker with an ARB.

The FDA has approved Prestalia (Symplmed), an oral fixed-dose combination of the dihydropyridine calcium channel blocker amlodipine (Norvasc, and generics) and a new salt form of the angiotensin-converting enzyme (ACE) inhibitor perindopril, for treatment of hypertension in patients not adequately controlled on monotherapy or already taking both drugs, and in those just starting therapy who are likely to need multiple drugs to control their blood pressure. The new salt form (perindopril arginine) is more stable and has a longer shelf-life than perindopril erbumine (Aceon, and generics). Two other ACE inhibitor/calcium channel blocker combinations, benazepril/amlodipine (Lotrel, and generics) and trandolapril/verapamil ER (Tarka, and generics), have been available in the US for many years.

Our July 9, 2012 article (Med Lett Drugs Ther 2012; 54:55) on renal sympathetic denervation for multiple-drug resistant hypertension concluded that the catheter-based procedure (Symplicity Catheter System – Medtronic) can lower blood pressure in most patients with hypertension resistant to ≥3 antihypertensive drugs. That conclusion was based on the results of 2 studies. SYMPLICITY HTN-1 compared outcomes to baseline blood pressures. SYMPLICITY HTN-2 randomized patients to renal denervation or usual care.

Medtronic has issued a press release (January 9, 2014) announcing that SYMPLICITY HTN-3, a double-blind trial with sham controls, failed to meet its primary efficacy endpoint, the change in office blood pressure from baseline to 6 months (www.medtronic.com).

No quantitative results have been published to date. In all 3 trials, there were no serious complications of the procedure.

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Renal sympathetic denervation is under investigation as a therapeutic option for hypertension that has not responded to ≥3 antihypertensive drugs (resistant hypertension).

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

The average daily intake of sodium in the US is about 3400 mg. Dietary guidelines recommend reducing it to <2300 mg/day in general, and to 1500 mg for African Americans, persons with hypertension, diabetes or chronic renal disease, and for all those >50 years old. Salt reduction lowers blood pressure, and lowering blood pressure reduces the risk of myocardial infarction, stroke and death.

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 angiotensin receptor blocker (ARB) azilsartan medoxomil (Edarbi – Takeda) was recently approved by the FDA for oral treatment of hypertension, either alone or combined with other drugs. It is the eighth ARB approved for this indication.

The FDA has approved aliskiren/amlodipine/hydrochlorothiazide (Amturnide) for treatment of hypertension, with no restrictions except that it should not be used for initial therapy. A combination of the direct renin inhibitor aliskiren and the calcium channel blocker amlodipine (Tekamlo) was approved earlier for initial treatment.1

Use of combination tablets is, of course, more convenient than taking the components separately, and as long as all the same doses are available and the cost is no greater, there is no reason not to use them.

Aliskiren alone or in combination has not been shown to improve clinical outcomes.2 Whether it offers any advantage over the angiotensin receptor blockers (ARBs), which are also available in various antihypertensive combinations, remains to be determined.

1. Aliskiren/amlodipine (Tekamlo): another combination tablet for hypertension. Med Lett Drugs Ther 2010; 52:94.

2. Drugs for hypertension. Treat Guidel Med Lett 2009; 7:1.

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The FDA has approved Tekamlo (Novartis), an oral fixed-dose combination of the direct renin inhibitor aliskiren (Tekturna) and the calcium channel blocker amlodipine (Norvasc, and others), for treatment of hypertension in patients not adequately controlled on monotherapy or already taking both drugs, and as initial therapy in those likely to need multiple drugs to control their blood pressure (BP). Both aliskiren and amlodipine are available in combinations with other antihypertensive agents.

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 treatment of atrial fibrillation includes ventricular rate control, anticoagulation, conversion to normal sinus rhythm and maintenance of sinus rhythm. The choice of therapies that can achieve these goals is discussed in the text that follows. Some drugs are recommended here for indications that have not been approved by the FDA.

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 FDA has approved the use of aliskiren (Tekturna), a direct renin inhibitor, with valsartan (Diovan), an angiotensin-receptor blocker (ARB), in a fixed-dose combination as Valturna (Novartis) for treatment of hypertension in patients already taking both drugs or not adequately controlled on monotherapy, and as initial therapy in those likely to need multiple drugs to control their blood pressure.

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.

Effective treatment of hypertension can prevent organ damage and death. The choice of drugs for initial treatment continues to be controversial.

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).

Clevidipine (Cleviprex - The Medicines Company), a dihydropyridine calcium channel blocker (CCB), has been approved by the FDA for intravenous (IV) use in lowering high blood pressure. It is the second IV CCB to be marketed in the US; nicardipine has been available in an IV formulation (Cardene IV) for more than 10 years. Like IV nicardipine, clevidipine will probably be used mainly for urgent treatment of hypertension in intensive care units, operating rooms and emergency departments.

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 FDA has approved Exforge (Novartis) and Azor (Daiichi Sankyo), the first combinations of a calcium channel blocker (CCB) with an angiotensin receptor blocker (ARB) for treatment of hypertension. Amlodipine is the CCB in both products. The ARBs are valsartan in Exforge and olmesartan in Azor. All 3 of these drugs are available in fixed-dose combinations with other antihypertensive drugs.

The FDA has approved the marketing of Resperate (InterCure), a device that helps patients breathe slowly, as an adjunct for treatment of hypertension. The FDA does not require proof of effectiveness for approval of devices with minimal potential for harm, such as this one.

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.

Coenzyme Q10, a fat-soluble antioxidant also known as ubidecarenone, ubiquinone and CoQ10, is marketed as a dietary supplement in the US, both as a single ingredient and in various combination products.

The Medical Letter reported last year that sildenafil (Viagra - Pfizer) appeared to be effective for idiopathic pulmonary arterial hypertension (PAH), but confirmation from a controlled trial was needed. Now the results of such a study are about to be published, and the drug has been approved by the FDA for this indication under the trade name Revatio.

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.

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.

Caduet (Pfizer), a combination of the calcium-channel blocker amlodipine (Norvasc - Pfizer) and the HMG-CoA reductase inhibitor (statin) atorvastatin (Lipitor - Pfizer), is now available in the US. It was approved by the FDA for use in patients with indications for treatment with both amlodipine, which is used to treat hypertension and/or angina pectoris, and atorvastatin, which is used to treat dyslipidemia. The combination is bioequivalent to the 2 components taken separately.

Several recent case reports suggest that oral sildenafil may be effective for treatment of pulmonary arterial hypertension (PAH). Sildenafil is currently marketed as Viagra for treatment of erectile dysfunction (Medical Letter 1998; 40:51).

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).

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.

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.

Ever-increasing specialization has made it difficult for many physicians to keep up with therapeutic standards in intensive-care units (ICUs). This issue of Treatment Guidelines offers current recommendations for use of cardiovascular drugs in the ICU for treatment of hypertensive emergencies; shock, cardiac arrest or decompensated heart failure; and ventricular arrhythmias.

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

Some classes of drugs include so many agents that hospital formulary committees, managed care organizations and individual practitioners may find it difficult to choose among them. Fifteen beta-adrenergic receptor antagonists (beta-blockers) are now marketed for systemic use in the USA. One or more have been approved by the FDA for use in hypertension and eight other indications.

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.

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.

Nisoldipine (Sular -Zeneca), a dihydropyridine calcium-channel blocker structurally similar to nifedipine, has been approved for marketing by the US Food and Drug Administration. It is available in an oral extended-release formulation for treatment of hypertension.

Epoprostenol sodium (Flolan - Glaxo Wellcome), also known as prostacyclin, has been approved by the US Food and Drug Administration for continuous intravenous treatment of primary pulmonary hypertension.

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).

Drugs available in the USA for treatment of chronic hypertension, their dosages and adverse effects are listed in the table below and discussed in the text beginning on page 47. Drugs for treatment of hypertensive emergencies are not discussed here.

Torsemide, a new loop diuretic similar in action to bumetanide (Bumex) and furosemide, was recently approved by the US Food and Drug Administration for treatment of edema due to congestive heart failure, renal disease, or hepatic disease and also for treatment of hypertension. It is available for both oral and intravenous use.

Amlodipine (am loe' di peen) besylate (Norvasc - Pfizer), a dihydropyridine calcium-channel blocker, has been approved by the US Food and Drug Administration for once-daily oral treatment of hypertension, chronic stable angina, and vasospastic (Prinzmetal's) angina.

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).

Felodipine (Plendil - Merck), an extended-release preparation of a dihydropyridine calcium-channel blocker was recently marketed in the USA for oral treatment of hypertension. An immediate-release formulation is available in some other countries.

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.

Isradipine (DynaCirc - Sandoz), a dihydropyridine calcium-channel blocker chemically related to nicardipine (Cardene) and nifedipine (Procardia, and others), was recently approved by the US Food and Drug Administration for oral treatment of hypertension.

The treatment of hypertension continues to change; many new drugs have become available, and use of non-pharmacologic treatment has decreased dosage requirements for some hypertensive patients. Proven non-pharmacologic methods of decreasing blood pressure, which may add to effects of drug treatment, include weight loss, limited alcohol consumption, and decreased soudium intake; less well-proven approaches include aerobic exercise and increasing dietary potassium (A Chockalingam et al, Can Med Assoc J, 142:1397, 1990). Drugs available in the USA for treatment of chronic hypertension, their dosages, and adverse effects, are listed in the table beginning on page 35.

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.

Betaxolol (Kerlone - Searle), an oral beta-adrenergic blocker, was recently approved by the US Food and Drug Administration for once-daily treatment of hypertension. The new drug is beta 1 (cardio)-selective with no intrinsic sympathomimetic (partial agonist) activity. It is also available in a topical formulation for treatment of glaucoma (Betoptic - Medical Letter, 28:45, 1986). Beta-blockers currently available in the USA for treatment of hypertension are listed in the table below.

Drugs available in the USA for treatment of chronic hypertension, their dosages and adverse effects are listed in the table beginning on page 27. A thiazide-type diuretic or a beta-adrenergic blocker has traditionally been the first drug used for treatment of hypertension, but many clinicians now start with an angiotensin-converting exzyme (ACE) inhibitor or a calcium-entry blocker (1988 Joint National committee, Arch Intern Med, 148:1023, 1988). If the drug is ineffective or poorly tolerated, another type of drug can be substituted. If more than one drug is necessary and a diurectic was not used initially, most clinicians would add a diuretic.

Microx (Pennwalt), a new low-dosage formulation of the thiazide-type diuretic metolazone (Zaroxolyn; Diulo), was recently marketed in the USA. The manufacturer claims that the low dose of controls hypertension with less potassium loss, making it safer than other diuretics and as effective as combination drugs, such as Dyazide, that include both a thiazide and a potassium-sparing diuretic. Medical Letter consultants generally do not recommend Dyazide or other fixed-dose combinations for treatment of hypertension.

- 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