Treatment of hypertension in asthma and COPD

INTRODUCTION — 

The management of hypertension in a patient with asthma or chronic obstructive pulmonary disease (COPD) is a common problem owing to the high prevalence of each condition in the adult population [1,2]. Indications for the treatment of hypertension and the use of nonpharmacologic approaches are similar in patients with or without either of these conditions. (See "Overview of hypertension in adults".)

Pharmacologic treatment of hypertension in patients with asthma or COPD may be complicated by the respiratory effects of some antihypertensives [1-3]. For example, angiotensin-converting enzyme inhibitors, among the most widely used antihypertensive drugs, can induce a bothersome cough. Although not damaging to the lungs, this symptom is easily confused with cough due to underlying pulmonary diseases. Beta blockers may increase airway reactivity and interfere with the activity of beta agonists, which can have serious consequences for patients with chronic asthma, acute allergic or exercise-induced bronchospasm, or asthma-COPD overlap syndrome. Each category of antihypertensives is discussed in further detail in the context of asthma and COPD, as below.

ANGIOTENSIN-CONVERTING ENZYME INHIBITORS — 

Although angiotensin-converting enzyme (ACE) inhibitors are among the first-line agents for the treatment of hypertension, we prioritize other agents as first-line therapy in patients with COPD or asthma, especially in patients with ongoing cough symptoms. ACE inhibitors increase the likelihood of cough, which may be confused with an exacerbation of COPD or asthma. Rarely, patients with asthma treated with ACE inhibitors have also experienced increased airflow obstruction.

Cough is the most common side effect of therapy with ACE inhibitors, developing in 3 to 20 percent of patients [4]. It is typically dry, irritative, and persistent but rarely productive. When this cough occurs in a patient with either asthma or COPD, it can be confused with an increase in symptoms related to underlying airway disease. There are conflicting data on whether patients with underlying asthma are more likely than nonasthmatics to develop cough after ACE inhibition [4,5].

There is no evidence of adverse effects of ACE inhibitors on the course of COPD [6]. However, in asthmatic patients, some cases of worsening asthma with ACE inhibitors have been described. In one study examining adverse respiratory effects of ACE inhibitors, reactions diagnosed as asthma, bronchospasm, or dyspnea were reported at one-tenth the frequency of cough, with several cases of bronchospasm occurring in patients with known asthma [7]. In addition, the possibility that ACE inhibitor cough may represent an asthma equivalent has been suggested by the demonstration of bronchial hyperresponsiveness in some affected patients [8,9]. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers", section on 'Cough'.)

Angiotensin II receptor blockers are an alternative antihypertensive without cough complications in patients for whom blockade of the renin-angiotensin system is desired. (See 'Angiotensin II receptor blockers' below and "Renin-angiotensin system inhibition in the treatment of hypertension".)

ANGIOTENSIN II RECEPTOR BLOCKERS — 

Angiotensin II receptor blockers (ARBs) do not appear to induce cough and may be used safely in patients with asthma or COPD. In one small trial including hypertensive patients with asthma, there was no increase in cough or bronchial hyperreactivity with an ARB, and it was as well tolerated as calcium channel blockers [10].

BETA BLOCKERS — 

Beta blockers may induce bronchoconstriction and block beta agonist-induced bronchodilation. While they are generally safe for use in most patients with COPD, we use them with caution in patients with asthma, as detailed below.

●Chronic obstructive pulmonary disease – Beta blockers, particularly beta-1 selective beta blockers (table 1), appear to be safe in most patients with COPD [11-14]. In a systematic review of 20 randomized trials, single-dose and longer-term administration of a beta-1 selective beta blocker did not affect the forced expiratory volume in the first second (FEV₁) treatment response to inhaled beta agonists in patients with COPD [11]. In an earlier meta-analysis, short-term selective beta-blocker therapy did not increase respiratory symptoms or change baseline FEV₁ [14].

Observational studies suggest that beta blockers may reduce mortality and exacerbations of respiratory symptoms in patients with COPD [12,13]. However, in some studies, these findings vary based on the presence of a cardiovascular indication (eg, post-myocardial infarction, heart failure with reduced ejection fraction, atrial fibrillation, or refractory hypertension) [15]. Furthermore, these findings have not been confirmed in randomized trials. In one randomized trial of 532 patients with moderate to severe COPD and no primary cardiovascular indication for beta blockers, metoprolol did not affect the time until the first COPD exacerbation or the overall rate of exacerbations, although it did increase the risk of a severe COPD exacerbation leading to hospitalization (hazard ratio 1.91, 95% CI 1.29-2.83) [16]. In the largest observational study, which included over 1300 patients with COPD, cardioselective beta blockers were associated with a reduced risk of COPD exacerbations only among those who had a cardiovascular indication for the use of a beta blocker but not in those without a cardiovascular indication [15].

The use of beta blockers in patients with primary cardiovascular indications for beta blockers is discussed in detail separately. (See "Management of the patient with COPD and heart disease", section on 'Approach to beta blocker use in COPD'.)

●Asthma – We prefer not to use beta blockers in patients with asthma. Beta blockers can increase bronchial obstruction, airway reactivity, and resistance to the effects of inhaled or oral beta-receptor agonists (such as albuterol or terbutaline) [1,17,18]. Even topical ophthalmic administration of nonselective beta blockers for the treatment of glaucoma has led to asthmatic exacerbations [19]. Although the precise mechanism of beta blocker-induced bronchoconstriction is unknown, parasympathetic pathways of airway control may be involved since the anticholinergic drug oxitropium bromide can inhibit the effect of inhaled propranolol [20].

Although beta-1 selective blockers are safer than nonselective beta blockers (table 1), they should still be used with caution in patients with asthma, particularly in those with severe obstruction or markedly reduced pulmonary function at baseline [2]. As an example, in a meta-analysis of 32 randomized trials including over 1300 patients with asthma, nonselective beta blockers caused a greater reduction in FEV₁ compared with beta-1 selective beta blockers (a reduction of 10 versus 7 percent), but one in eight patients on beta-1 selective blockers had a 20 percent or larger decrease in FEV₁. Nonselective beta blockers compared with beta-1 selective blockers also resulted in greater attenuation of the bronchodilator response to inhaled beta agonists (20 versus 10 percent reduction) [17].

THIAZIDE DIURETICS — 

Thiazide diuretics are generally safe to use in patients with either asthma or COPD [21]. However, there may be potential issues related to thiazide-induced hypokalemia and/or metabolic alkalosis, especially when superimposed upon metabolic side effects of beta agonists or glucocorticoids:

●Among patients with COPD and chronic hypercapnia, diuretics can also induce a metabolic alkalosis, which can suppress ventilatory drive, raise partial pressure of carbon dioxide, and potentially exacerbate hypoxemia [22,23].

●Inhaled beta agonists can drive potassium into the cells, acutely lowering the plasma potassium concentration by as much as 0.5 to 1 mEq/L [24]. Glucocorticoids may also lower serum potassium by mildly enhancing urinary potassium excretion [24,25]. Thiazide diuretics also reduce serum potassium, and therefore, concomitant use of these agents with beta agonists or glucocorticoids can exacerbate hypokalemia [23]. (See "Causes of hypokalemia in adults".)

Thus, it is safest to administer only low thiazide doses (eg, 12.5 to 25 mg of hydrochlorothiazide once daily) to nonedematous hypertensive patients with asthma or COPD. Low-dose therapy may be effective and less likely to produce unwanted side effects such as metabolic alkalosis and hypokalemia. (See "Use of thiazide diuretics in patients with primary (essential) hypertension".)

CALCIUM CHANNEL BLOCKERS — 

The calcium channel blockers (especially those of the dihydropyridine group, such as nifedipine and nicardipine) are excellent agents for the treatment of hypertension in asthma [23,26]. (See "Major side effects and safety of calcium channel blockers".)

In addition to effectively lowering the blood pressure, calcium channel blockers also have the theoretical advantages of opposing muscle contraction in tracheobronchial smooth muscle, inhibiting mast cell degranulation, and possibly reinforcing the bronchodilator effect of beta agonists. Nifedipine, for example, can antagonize the bronchoconstricting effects of antigen, histamine, or cold air challenge [27]. Although some studies have shown a mild improvement in airway function [27], most studies have demonstrated no effect of calcium antagonists on asthma [28,29].

OTHER ANTIHYPERTENSIVES

Sympathetic blockers — Clonidine and other alpha-2 receptor agonists (methyldopa, guanabenz) should be used with caution in asthmatics. Oral doses of these agents do not change baseline air flow in asthmatics, but they do increase bronchial reactivity to inhaled histamine [30].

Additives to drug preparations — Little specific information is available for the remaining antihypertensive agents, including hydralazine. However, if asthma occurs with these or other drugs, one should always consider the possibility that the tartrazine dye or other pseudoallergen within the drug preparation may be the culprit [31].

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in adults".)

SUMMARY

●Overview – Indications for the treatment of hypertension and the use of nonpharmacologic approaches are similar in patients with or without asthma or chronic obstructive pulmonary disease (COPD). The pharmacologic management of hypertension in a patient with either of these conditions may be complicated by the potential airway and metabolic effects of some antihypertensive drugs. (See 'Introduction' above.)

●Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) – Although ACE inhibitors are among the first-line agents for the treatment of hypertension, we prioritize other agents as first-line therapy in patients with COPD or asthma, especially in patients with ongoing cough symptoms. ACE inhibitors increase the likelihood of cough, which may be confused with an exacerbation of COPD or asthma. Rarely, patients with asthma treated with ACE inhibitors have also experienced increased airflow obstruction. (See 'Angiotensin-converting enzyme inhibitors' above.)

ARBs are an alternative antihypertensive without cough complications in patients for whom blockade of the renin-angiotensin system is desired. (See 'Angiotensin II receptor blockers' above.)

●Beta blockers – Beta blockers, particularly beta-1 selective beta blockers (table 1), appear to be safe in most patients with COPD. However, we prefer not to use them in patients with asthma. Beta blockers can cause increased bronchial obstruction and airway reactivity and resistance to the effects of inhaled or oral beta-receptor agonists (such as albuterol or terbutaline).

Although the clinical effects of more beta-1 selective beta blockers on pulmonary function appear to be less severe, they should still be used with caution in patients with asthma, particularly in those with severe obstruction or markedly reduced pulmonary function at baseline (table 1). (See 'Beta blockers' above.)

●Thiazide diuretics – Thiazide diuretics are generally safe to use in patients with either asthma or COPD. However, there may be potential issues related to thiazide-induced hypokalemia and/or metabolic alkalosis, especially when superimposed upon metabolic side effects of beta agonists or glucocorticoids. It is safest to administer only low thiazide doses (12.5 to 25 mg of hydrochlorothiazide once daily) to nonedematous hypertensive patients with asthma or COPD. (See 'Thiazide diuretics' above.)

●Calcium channel blockers – The calcium channel blockers (especially those of the dihydropyridine group, such as nifedipine and nicardipine) are excellent agents for the treatment of hypertension in asthma. In addition to effectively lowering blood pressure, they also have the theoretical advantages of opposing muscle contraction in tracheobronchial smooth muscle, inhibiting mast cell degranulation, and possibly reinforcing the bronchodilator effect of beta agonists. (See 'Calcium channel blockers' above.)

ACKNOWLEDGMENTS

The UpToDate editorial staff acknowledges Norman Kaplan, MD, who contributed to earlier versions of this topic review.

We are saddened by the death of George Bakris, MD, who passed away in June 2024. UpToDate acknowledges Dr. Bakris's past work as a section editor for this topic.