Version July 2025
INTRODUCTION —
Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) occur in similar demographic groups and share tobacco abuse as a major risk factor. Heart disease is a leading cause of death among patients with COPD.
This topic will review the epidemiology and impact of concurrent COPD and heart disease (including coronary artery disease [CAD] and heart failure [HF]), comanagement of these diseases, and alterations in treatment strategies necessitated by cotreatment.
Related issues, including the impact of COPD on cardiac arrhythmias and development of pulmonary hypertension, are discussed separately:
●(See "Arrhythmias in COPD".)
The general diagnosis and management of COPD, coronary artery disease, and heart failure are also discussed separately.
●(See "Chronic obstructive pulmonary disease: Diagnosis and staging" and "Stable COPD: Overview of management" and "Stable COPD: Initial pharmacologic management" and "Stable COPD: Follow-up pharmacologic management" and "Management of refractory chronic obstructive pulmonary disease".)
●(See "Chronic coronary syndrome: Overview of care" and "Overview of the acute management of ST-elevation myocardial infarction" and "Overview of the nonacute management of ST-elevation myocardial infarction" and "Overview of the acute management of non-ST-elevation acute coronary syndromes" and "Overview of the nonacute management of unstable angina and non-ST-elevation myocardial infarction".)
●(See "Overview of the management of heart failure with reduced ejection fraction in adults" and "Treatment and prognosis of heart failure with preserved ejection fraction".)
CLINICAL EPIDEMIOLOGY —
COPD and heart disease frequently coexist, have overlapping symptoms, and the presence of one can affect outcomes in the other [1].
Frequency of concurrent disease — Numerous studies have identified high frequencies of concurrent cardiovascular disease (CVD) and COPD [2-6]. In a meta-analysis of 29 datasets, patients with COPD were more likely to be diagnosed with CVD (odds ration [OR] 2.5, 95% CI 2.0-3.0) than patients without COPD [6]. The CVDs included ischemic heart disease, cardiac arrhythmia, heart failure (HF), diseases of the pulmonary circulation, and diseases of the systemic arteries.
As an example, a study from a large United Kingdom database of more than 1.2 million patients over age 35 years identified almost 30,000 patients with COPD; these patients were nearly five times more likely to have CVD and stroke than those without COPD [2].
The prevalence of particular cardiac diseases in patients with COPD has also been examined:
●Coronary artery disease – In a study of 322 patients with advanced COPD undergoing evaluation for lung transplantation, coronary angiography identified coronary artery disease in 60 percent, and coronary artery disease was occult in 53 percent [3].
●Chronic heart failure – HF is common among patients with COPD [7], with reported prevalences ranging from 7 to 21 percent [8-10]. The prevalence of COPD among patients in HF registries is also high (eg, 10 to 40 percent) [7,8].
Impact on mortality and cardiovascular outcomes — Many observational studies have found that patients with concurrent COPD and CVD have increased mortality and worse cardiovascular outcomes [11-16].
COPD as a risk factor for CVD — Patients with COPD may have increased risk for CVD and mortality independent of known cardiovascular disease risk factors [15,17]. The cause of increased cardiovascular risk in patients with COPD beyond the traditional risk factors is uncertain.
In a large population-based cohort study of 5.8 million individuals age ≥40 years without known CVD, of whom approximately 150,000 had a diagnosis of COPD, rates of acute myocardial infarction (MI), stroke, or cardiovascular death over the following eight years were 3.3 times higher in patients with, compared with those without, COPD [15]. The rate of these major cardiovascular outcomes remained 25 percent higher in COPD patients (hazard ratio [HR] 1.25, 95% CI 1.23-1.37) even after adjusting for age, sex, smoking, sociodemographic characteristics, comorbidities, health care utilization, and laboratory testing typically used in robust cardiovascular risk models.
A similar increased risk for major cardiovascular events was associated with the diagnosis of COPD in a population-based cohort of 496,056 individuals with known CVD (4.5 versus 2.9 events per 100 person-years, adjusted HR 1.24, 95% CI 1.21-1.26) after adjustment for sociodemographic characteristics, comorbidities, and other cardiovascular risk factors [18].
Large database studies have suggested that the increased cardiovascular risk associated with COPD is dose-dependent, with an approximately 20 to 30 percent relative increase in cardiovascular events and mortality for each fall in forced expiratory volume in one second (FEV1) by 10 percent [13].
Individual patients with COPD most likely to have coincident CVD demonstrate the typical cardiac risk factors. In one study of over 1000 patients with COPD from the National Health and Nutrition Examination, factors associated with an increased risk of CVD included male sex, older age, smoking history, being overweight, history of blood transfusions, heart disease in close relatives, and higher leukocyte or monocyte counts [16].
Outcomes after COPD exacerbation — Risk for cardiovascular events appears to be acutely elevated following COPD exacerbations:
●In a study of over 200,000 patients with COPD followed for a median of 2.4 years, the rate of nonfatal cardiovascular events (acute coronary syndrome, arrhythmia, HF, ischemic stroke, or pulmonary hypertension) in those with moderate or severe COPD exacerbations was much higher than for those who did not experience exacerbations (7.8 and 16 versus 3.7 events per 100 person-years, respectively) [19]. Risk for cardiovascular events was highest early after any exacerbation (1 to 14 days; adjusted HR 3.2, 95% CI 2.7–3.8) but remained elevated after one year (adjusted HR 1.84, 95% CI 1.78–1.91) even after adjusting for age, sex, smoking history, hypertension, and other confounders. The most common cardiovascular events seen early after exacerbations were arrhythmia and HF. The incidence of these early cardiovascular complications is much higher after severe COPD exacerbations when compared with moderate COPD exacerbations [19,20].
●In a separate study of 5696 patients with COPD, severe and moderate exacerbations led to similarly increased risk of MI in the first 90 days after the exacerbation (incidence rate ratio [IRR] 2.6 95% CI 2.3-3.0 and 1.6 [95% CI 1.5-1.7], respectively) [11].
Outcomes after MI or PCI — Patients with COPD and coronary artery disease (CAD) are at increased risk for adverse outcomes [21-24] following MI or percutaneous coronary interventions (PCI) as illustrated by the following studies:
●Myocardial infarction – In a study of 3249 patients with an acute ST-elevation MI, COPD was an independent predictor of the composite end-point of in-hospital death or cardiogenic shock (adjusted OR 1.8, 95% CI 1.2-2.8) [21].
●Percutaneous coronary interventions – COPD is also an independent predictor of adverse outcomes in patients undergoing PCI [22,23].
For example, among 14,346 patients who underwent PCI at a single center, COPD was a significant independent risk factor for overall mortality, cardiac mortality, and MI [22].
Similarly, in a study of patients undergoing PCI, patients with COPD (n = 860) had a higher mortality rate (10.7 versus 4.2 percent; adjusted HR 1.3, 95% CI 1.0-1.7) and rate of repeat revascularization (18.2 versus 15.3 percent; adjusted HR 1.2, 95% CI 1.0-1.5) at one year compared with patients without COPD (n = 10,048) [23]. At discharge, patients with COPD were less likely to be prescribed aspirin, beta blockers, and statins. The patients with COPD also had a slightly lower mean left ventricular ejection fraction (49 versus 53 percent) and a slightly greater number of significant coronary lesions (3.2 versus 3.0).
Heart failure outcomes — Patients with COPD and HF (HF with reduced ejection fraction [HFrEF] or HF with preserved ejection fraction [HFpEF]) have higher rates of cardiovascular risk factors and may have worse prognosis than patients with HF without COPD [8], as illustrated by the following studies:
●Acute HFrEF – A retrospective study of 20,118 patients hospitalized with HFrEF found that 25 percent of patients had concomitant COPD; these patients had higher rates of cardiovascular risk factors (such as smoking, hyperlipidemia, and kidney disease) than the 75 percent of patients who did not have COPD [25]. Patients with COPD had increased in-hospital mortality (4.5 versus 3.7 percent; adjusted OR 1.7; 95% CI 1.1-2.4). Patients with COPD were also less likely to receive beta blocker or angiotensin-converting enzyme inhibitor during hospitalization and at discharge.
However, in a cohort of 2682 patients hospitalized with HFrEF, who were followed after discharge, 60-day mortality was similar in patients with and without COPD (6.2 versus 6.0 percent), suggesting intermediate outcomes may not differ greatly.
●Chronic HFpEF – In a subanalysis of the PARAGON-HF trial of 4791 patients with HFpEF, 14 percent were found to have concurrent COPD; their clinical characteristics and outcomes were evaluated in comparison with the rest of the cohort [26]. Patients with COPD were more likely to be male, had worse New York Heart Association functional class, worse Kansas City Cardiomyopathy Questionnaire Clinical Summary scores, and more frequent history of hospitalization for HF. After adjustment for these and other clinical factors, COPD remained associated with higher rates of mortality (adjusted HR 1.5, 95% CI 1.3-1.8), cardiovascular death (adjusted HR 1.4, 95% CI 1.1-1.8), and HF hospitalization (adjusted HR 1.5, 95% CI 1.2-1.9).
DIAGNOSIS OF HEART DISEASE IN PATIENTS WITH COPD —
Given the frequency of concomitant disease and overlapping symptoms (dyspnea, wheezing, and chest tightness), differentiating the relative contributions of heart disease and COPD to a given patient’s presentation can be challenging. Clinicians caring for patients with COPD should have a low threshold for performing additional diagnostic testing for timely diagnosis and evaluation of coronary artery disease (CAD) and/or heart failure (HF).
Myocardial ischemia — Because both COPD exacerbations and CAD may be associated with dyspnea and chest tightness, further testing with electrocardiography, cardiac enzymes, or stress testing may be required to evaluate for myocardial ischemia. The presence of the full constellation of symptoms of a COPD flare (eg, dyspnea, cough, wheezing, and change in sputum) suggests a pulmonary exacerbation, but in some cases both organ systems may be involved, and their relative contributions may be difficult to discern. (See "Approach to the adult with dyspnea in the emergency department" and "Troponin testing: Clinical use".)
●Anginal symptoms at rest – Clinicians should consider the possibility of an acute coronary syndrome (ACS; which includes myocardial infarction [MI] or unstable angina) in adults presenting with chest discomfort or dyspnea at rest. The evaluation of suspected ACS includes obtaining serial electrocardiograms and serum cardiac biomarkers (preferably high-sensitivity troponin), as discussed separately. (See "Initial evaluation and management of suspected acute coronary syndrome (myocardial infarction, unstable angina) in the emergency department".)
For patients with COPD presenting to the hospital with dyspnea, an elevated serum cardiac troponin frequently, but not always, indicates the presence of CAD, as illustrated by a prospective study of patients presenting with acute COPD exacerbation and elevated high-sensitivity troponin (cardiac troponin I >0.05 ng/mL) [27]. All patients underwent coronary angiography within 72 hours. CAD (defined as coronary stenosis ≥50 percent) was identified in 67 percent, while 39 percent had an indication for percutaneous coronary intervention (PCI). There were no differences in troponin values or trend between patients with or without an indication for coronary intervention. More ST depressions were seen in the PCI group (21 versus 7 percent), but these electrocardiographic findings were present in a minority of patients.
●Exertional symptoms – For ambulatory patients with COPD and exertional symptoms that could be attributable to myocardial ischemia, we typically perform a baseline 12-lead electrocardiogram and dobutamine stress imaging (dobutamine stress radionuclide myocardial perfusion imaging or dobutamine stress echocardiography), as exercise limitations may preclude exercise stress testing, and potential bronchoconstriction is often a contraindication to vasodilator radionuclide myocardial perfusion imaging. (See "Approach to the patient with suspected angina pectoris" and "Selecting the optimal cardiac stress test" and "Stress testing for the diagnosis of obstructive coronary artery disease".)
Heart failure — Symptoms of HF and COPD can be difficult to distinguish. We have a low threshold to obtain a serum B-type natriuretic peptide (BNP; or N-terminal pro-BNP [NT-proBNP]) level and an echocardiogram in patients with a COPD exacerbation to make sure HF is not overlooked. However, BNP/NT-proBNP results should be carefully interpreted in patients with severe COPD, as pulmonary hypertension can also lead to an elevated BNP. Although chest radiograph characteristics can also frequently identify HF, bullous emphysema can lead to atypical radiographic features and subsequent underdiagnosis. (See "Natriuretic peptide measurement in heart failure" and "COPD exacerbations: Clinical manifestations and evaluation", section on 'Differential diagnosis'.)
In one study of 148 patients admitted to the intensive care unit with suspected acute exacerbation of COPD, acute left heart dysfunction was judged to be present in 31 percent of patients [28]. NT-proBNP showed good accuracy for identifying those with and without left heart dysfunction.
Chronic heart failure is also likely underdiagnosed in the ambulatory population with COPD. In one cross-sectional study of 244 older adults with COPD, previously unrecognized HF was identified in 21 percent, and ischemic heart disease was judged to be the most common cause of HF [29]. (See "Chronic obstructive pulmonary disease: Diagnosis and staging", section on 'Differential diagnosis'.)
PHARMACOLOGIC TREATMENT OF CARDIOVASCULAR DISEASE IN PATIENTS WITH COPD
Role of beta blocker therapy — Patients with COPD commonly have cardiovascular indications for beta blocker therapy (such as heart failure with reduced ejection fraction [HFrEF], post-myocardial infarction [post-MI], atrial fibrillation, hypertension, chronic coronary artery disease (CAD), and arrhythmias including atrial fibrillation). However, patients with moderate to severe COPD are frequently not given these agents out of concern for possible bronchoconstrictive (beta-2 antagonist) effects. Evidence suggests that cardioselective beta blockers are safe and likely beneficial in those with cardiac indications.
Approach to beta blocker use in COPD — For patients with COPD and a cardiovascular indication for beta blocker therapy (post-MI, HFrEF, angina, refractory hypertension, or atrial fibrillation), we suggest using a cardioselective (beta-1 selective) beta blocker (table 1) rather than a nonselective beta blocker. The use of beta blockers to treat cardiovascular disease (CVD) in patients with COPD is otherwise generally the same as for patients without COPD [30]. We avoid nonselective beta blockers in patients with COPD due to concerns that nonselective agents may induce clinically important bronchoconstriction and increase exacerbation risk [31,32].
The preferred cardioselective beta blocker (and the availability of alternatives to beta blocker therapy) varies among the CVD indications for beta blocker use (algorithm 1).
●As an example, specific beta blocker agents are a cornerstone for treatment of HFrEF because specific beta blockers have an established mortality benefit. Patients with HFrEF and COPD are treated with one of two cardioselective beta blocker agents (metoprolol succinate or bisoprolol). These agents are preferred to carvedilol, which is a noncardioselective beta blocker and an alpha blocker. (See 'Effect on lung function' below.)
●In contrast, non-beta blocker drugs are recommended for initial pharmacologic therapy of hypertension. In the management of hypertension, beta blocker use is generally reserved for refractory hypertension; in this setting, cardioselective blockers that also have vasodilatory properties (eg, nebivolol) are preferred. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker' and "Hypertension in adults: Initial drug therapy".)
When initiating a cardioselective beta-blocker for a cardiovascular indication in a patient with COPD, patients and their caregivers should be provided with careful guidance regarding which new or worsening symptoms (eg, dyspnea, exercise intolerance, cough) or changes in medication use patterns (eg, increased need for a beta-agonist inhaler) should prompt reevaluation. Highly cardioselective beta blockers, such as bisoprolol, may be safest in those with a history of severe COPD exacerbations.
Effect on lung function — While nonselective beta blockade can precipitate bronchospasm in those who are predisposed, cardioselective beta-1 blockers (eg, atenolol, bisoprolol, or metoprolol) are generally safe in patients with COPD, even when there is a bronchospastic component [30,33-37]. In large trials of long-acting bronchodilator therapies, concomitant cardioselective beta blocker therapy did not appear to reduce the respiratory benefits of inhaled long-acting beta-agonists [38,39]. Data regarding the effects of combined beta- and alpha-adrenergic blockade (eg, carvedilol, labetalol) in patients with COPD are limited.
●Cardioselective beta blockers – The effect of cardioselective beta blockers was assessed in a meta-analysis of randomized trials in which single-dose or long-term cardioselective beta blockers were administered to nearly 400 patients with either asthma or COPD and reversible bronchoconstriction (>15 percent improvement in forced expiratory volume in one second [FEV1] following bronchodilator treatment) [40]. The following results were noted:
•Single-dose use was associated with an 8 percent decrease in FEV1, but a 5 to 9 percent increase in bronchodilator response
•Sustained use was not associated with a significant change in baseline FEV1
•Long-term therapy did not increase respiratory symptoms or the use of inhaled beta-agonists
In a study of methacholine inhalation challenge in patients with COPD, propranolol (80 mg/day) caused a reduction in FEV1 and in the bronchodilating effect of formoterol in addition to an increase in airway hyperresponsiveness to methacholine [41]. In contrast, metoprolol (100 mg/day) did not affect FEV1 or responsiveness to formoterol but did increase airway hyperresponsiveness.
●Combined beta and alpha blockers – Combined beta and alpha blockers are sometimes indicated for patients with HFrEF, CAD, or hypertension (table 1). Although limited data are somewhat reassuring in patients with mild to moderate COPD [42], further study is needed. (See "Primary pharmacologic therapy for heart failure with reduced ejection fraction", section on 'Beta blocker' and "Beta blockers in the management of chronic coronary syndrome", section on 'Agents with alpha blocking activity'.)
Limited data regarding the effects of combined nonselective beta- and alpha-adrenergic blockade (eg, carvedilol, labetalol) include the following:
•The effect of carvedilol on lung function was compared with the selective beta blockers metoprolol and bisoprolol in 35 patients with COPD and heart failure (HF) [43]. FEV1 was lowest with carvedilol and highest with bisoprolol (carvedilol 1.85 L [95% CI, 1.67-2.03]; metoprolol 1.94 L [95% CI, 1.73-2.14]; bisoprolol 2.0 L [95% CI, 1.79-2.22]), but the six-minute walk distance was not different between groups. In a separate report of 14 patients with COPD treated with carvedilol 25 mg orally twice daily for HF, no changes were noted in FEV1, vital capacity, or peak oxygen consumption with exercise [44].
•In a small series of 11 patients with COPD and hypertension, labetalol up to 1200 mg/day caused no significant changes in FEV1 or forced expiratory flow [45].
Effect on outcomes — Observational data suggest that in patients with COPD with a cardiovascular indication for beta blocker therapy, cardioselective beta blocker therapy does not worsen the risk of COPD exacerbations, and some studies suggest a clinical benefit of beta blocker therapy in reducing risk of mortality and/or COPD exacerbations [31,37,46-50]. Although the data in aggregate suggest a possible protective effect of beta blockade in patients with COPD and CVD, there may have been selection bias in observational studies based on patient selection for beta blocker use.
By contrast, randomized trials of beta blocker therapy in those without cardiovascular indications have not shown a benefit [51,52].
Those with cardiovascular indications
●Post myocardial infarction – Observational studies in patients with COPD suggest that post-MI beta blocker therapy does not increase risk for COPD exacerbations but may reduce risk of COPD exacerbations, as illustrated by the following studies. Indications for beta blocker therapy after acute MI are discussed separately. (See "Acute myocardial infarction: Role of beta blocker therapy".)
•In an observational study of 10,884 patients with COPD discharged from Danish hospitals after an acute MI, beta blocker use was associated with a lower risk of acute exacerbation of COPD over at least a year of follow-up (multivariable-adjusted hazard ratio [HR] 0.78, 95% CI 0.74-0.83) independent of COPD severity or exacerbation history [50].
•In a smaller multicenter observational study in the United States, 502 of 579 patients (86.7 percent) with COPD received a beta blocker upon discharge after acute MI [53]. After adjustments to reduce confounding, those who did and did not receive beta blockers had similar risks for a composite of death, hospitalization, or revascularization, as well as composite cardiovascular or respiratory events.
●With various indications for beta blocker use – Retrospective studies of patients with COPD have found that those treated with beta blockers (apparently for cardiovascular indications) had lower mortality rates than those not treated with beta blocker therapy. These studies were summarized in a systematic review and meta-analysis of nine retrospective studies (three in patients with COPD and prior MI, one in patients with COPD and HF, one in patients with COPD and vascular disease). Beta blocker use was associated with reduced mortality rate in each of the nine studies. The pooled relative risk of COPD-related mortality secondary to beta blocker use (dominated by two large studies of patients with prior MI) was 0.69 (95% CI 0.62-0.78).
One illustrative study included in the meta-analysis was an observational cohort study of 2230 patients with COPD (most with CVD, hypertension, or diabetes). Beta blocker use was associated with lower HRs for both mortality (HR 0.68, 95% CI 0.56-0.83) and exacerbations of COPD (HR 0.71, 95% CI 0.60-0.83) [37]. A limitation of this study (and most of the studies in the meta-analysis) is that the observed association between beta blocker therapy and mortality was not stratified by indication for beta blocker therapy.
Those without cardiovascular indications — In patients with COPD without a cardiovascular indication for beta blocker use, randomized trials have found no evidence of benefit from beta blocker therapy [51,52]:
●In one multicenter trial, 532 patients with moderate to severe COPD, at least one exacerbation in the past year or prescription for home supplemental oxygen, and no established indication for beta blocker therapy were randomly assigned to receive extended-release metoprolol or placebo [51]. The metoprolol group experienced an increased risk of COPD exacerbation leading to hospitalization during nearly one year of follow-up (92 versus 58 hospitalizations, rate ratio 1.6, 95% CI 1.1-2.4), leading to early termination of the trial. This severe exacerbation risk was not mediated by changes in lung function or bronchodilator responsiveness in the metoprolol group [54]. Those taking metoprolol had a similar time until first exacerbation of 202 days, versus 222 days among those not receiving metoprolol (HR 1.05; 95% CI, 0.8-1.3) [51].
●In a separate multicenter trial, 515 patients with moderate to severe COPD and frequent exacerbations (≥2 per year) were randomly assigned to receive bisoprolol or placebo [52]. Patient-reported moderate to severe exacerbations were nearly identical (2.03 versus 2.01 exacerbations per year), as were COPD hospitalizations (adjusted incidence rate ratio [IRR] 1.0). Time to first exacerbations was 96 days with bisoprolol and 70 with placebo (HR 0.94). There was a possible, statistically borderline, increase in dyspnea but not in COPD symptoms overall. Serious adverse events were similar in the two groups.
Differences between these trials include the agents administered (ie, bisoprolol is more beta-1 selective) and recruited populations (the metoprolol study population comprised more patients with severe COPD and fewer patients on triple inhaled therapy). Any potential harm is most likely to be seen in those with very severe disease and high exacerbation risk.
Effect of statins on COPD exacerbations — Nearly all patients with known CVD should be treated with a statin. (See "Prevention of cardiovascular disease events in those with established disease (secondary prevention)".)
While statins have been postulated to have an additional benefit of reducing COPD exacerbations, the evidence is conflicting and subject to bias [55-58]. (See "COPD exacerbations: Prognosis, discharge planning, and prevention", section on 'Ineffective interventions'.)
REVASCULARIZATION IN PATIENTS WITH COPD —
The presence of COPD impacts decision making in patients with indications for coronary artery revascularization (coronary artery bypass grafting [CABG] or percutaneous coronary intervention [PCI]) because of concerns about elevated risk of periprocedural morbidity and mortality in patients with COPD [59-62]. However, patients with significant COPD who survive the early postoperative period after CABG appear to have improved quality of life [63].
Periprocedural risk — Risk calculators for cardiac surgery (including CABG) such as The Society of Thoracic Surgeons Adult Cardiac Surgery Database (STS ACSD) Operative Risk Calculator (for operative mortality and morbidity) and The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II (for operative mortality) include chronic lung disease as a risk factor.
Both CABG and PCI are associated with elevated risk for morbidity and mortality in patients with COPD, as illustrated by the following studies:
●Coronary artery bypass graft surgery
•Elevated mortality (with severe COPD) – Expected post-CABG mortality ranges from 2 to 4 percent for all patients and is about 1 percent for those at lowest risk. In a retrospective study of 11,217 patients who underwent CABG, increasing severity of COPD based on impairment in forced expiratory volume in one second (FEV1) correlated with an increasing frequency of postoperative complications, and severe COPD was associated with increased early mortality, (5.7 versus 1.4 percent; adjusted odds ratio [OR] 2.3, 95% CI 1.2-4.4) [59].
In contrast to patients with severe COPD, post-CABG mortality for patients with mild or moderate COPD is similar to the rate among those without COPD [64]. (See "Early cardiac complications of coronary artery bypass graft surgery" and "Early noncardiac complications of coronary artery bypass graft surgery".)
•Elevated morbidity (with COPD) – Patients with COPD who undergo CABG are at increased risk of perioperative morbidity, particularly pulmonary complications that result from sternotomy and use of cardiopulmonary bypass [59,63]. In a database study from Taiwan of 706 individuals with COPD and almost 15,000 without, COPD did not increase the risk of mortality, but did increase the risk of postoperative pneumonia and acute respiratory failure [61]. (See "Early noncardiac complications of coronary artery bypass graft surgery".)
●Percutaneous coronary intervention – Compared with those having coronary artery disease (CAD) alone, patients with CAD and COPD undergoing PCI (balloon angioplasty or stent placement) demonstrate increased mortality and rates of repeat revascularization within one year, as illustrated by the following studies:
•Using the National Heart, Lung, and Blood Institute Dynamic Registry, the outcomes following PCI were compared in patients with (860) or without (10,048) COPD [23]. Patients with COPD had a significantly increased risk of death (2.2 versus 1.1 percent; adjusted hazard ratio [HR] 1.3, 95% CI 1.0-1.7). Of note, patients with COPD were also significantly less likely to be prescribed beta blockers at discharge.
•In an analysis of over 4600 cases comparing bare-metal stents with drug-eluting stents, patients with COPD had higher rates of major adverse cardiac events (15.2 versus 8.1 percent), all-cause death (11.7 versus 2.4 percent), cardiac death (5.7 versus 1.2 percent), myocardial infarction (MI; 3.5 versus 1.9 percent), stent thrombosis (2.5 versus 0.9 percent), and major bleeding (4.2 versus 2.1 percent) after two years of follow-up [65].
In all instances, the drug-eluding stent patients had better outcomes than the bare-metal patients, suggesting that drug-eluting stents are superior in patients with COPD (as for most patients). (See "Intracoronary stents: Stent types".)
Procedural considerations — For patients who require elective coronary revascularization, preprocedural optimization of pulmonary function may be helpful. For all patients undergoing revascularization procedures, we advise postprocedure pulmonary evaluation as well as careful monitoring for rhythm disturbances.
For patients with an indication for coronary revascularization, the choice between PCI and CABG is based upon multiple factors including coronary artery lesion complexity and procedural risks. (See "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention".)
Although outcomes after PCI or CABG have not been directly compared in patients with COPD, PCI may be a reasonable alternative for selected patients with COPD who would otherwise receive a recommendation for CABG. Off-pump or minimally invasive CABG may represent other therapeutic alternatives to standard high-risk CABG, although published experience in patients with COPD is limited [66]. We suggest that the decision to choose one revascularization therapy be made after the patient has been fully informed of the relative benefits and risks of each approach.
●(See "Anesthesia for patients with chronic obstructive pulmonary disease".)
●(See "Strategies to reduce postoperative pulmonary complications in adults".)
●(See "Coronary artery bypass surgery: Perioperative medical management".)
●(See "Off-pump and minimally invasive direct coronary artery bypass graft surgery: Clinical use".)
●(See "Early cardiac complications of coronary artery bypass graft surgery", section on 'Arrhythmias'.)
CARDIOVASCULAR EFFECTS OF COPD TREATMENTS —
The mainstays of treatment for COPD include the inhaled anticholinergic agents, inhaled selective beta-2 agonists, and inhaled glucocorticoids; roflumilast, chronic azithromycin, and theophylline are less commonly used. For most patients with cardiovascular disease (CVD), we treat symptomatic COPD with the same agents and doses that we would for someone without CVD despite some concerns about increased cardiac risks as noted below. (See "Stable COPD: Initial pharmacologic management" and "Stable COPD: Follow-up pharmacologic management".)
Inhaled anticholinergic medications — An inhaled short-acting anticholinergic (muscarinic) antagonist (SAMA; eg, ipratropium) is sometimes used as an alternative to inhaled short-acting beta-agonists (SABAs) or in combination with a SABA for acute symptoms of COPD. Long-acting muscarinic antagonists (LAMAs; eg, aclidinium, glycopyrronium, tiotropium, umeclidinium) are recommended, regardless of underlying heart disease, for most patients with COPD [1]. (See "Stable COPD: Initial pharmacologic management".)
Older systematic reviews and a case-cohort study suggested possible adverse cardiovascular effects of inhaled muscarinic antagonist therapy [67,68]. However, long-term, randomized controlled trials have not identified any significant safety issues or increased risk of cardiovascular events in patients with COPD, including those with known CVD [69-73].
●One trial randomly assigned 5993 patients to either tiotropium or placebo in addition to other, unrestricted respiratory medications for four years. A significantly lower rate of cardiac adverse events was found in the tiotropium group (risk ratio [RR] 0.84, 95% CI 0.73-0.98) [69]. Cardiac mortality was also decreased in the tiotropium group (hazard ratio [HR] 0.86, 95% CI 0.75-0.99) [72].
●In a separate randomized controlled trial that included 3589 subjects with moderate to very severe COPD and a history of CVD or two atherothrombotic risk factors, the risk of a major adverse cardiovascular event during the three years of the trial was not significantly different between the aclidinium and placebo groups (3.9 versus 4.2 percent, HR 0.89, one-sided 97.5% CI 0-1.23) [70]. Approximately 60 percent of subjects were taking an inhaled glucocorticoid and a long-acting beta-agonist (LABA).
●The risk of cardiovascular events was further examined using the clinical trial safety database for tiotropium, which monitored 19,545 patients with moderate to severe COPD who were randomly assigned to tiotropium or placebo in a total of 30 trials [73]. No increase in all-cause mortality, cardiovascular mortality, or cardiovascular events was found in the tiotropium group.
Similarly, two systematic reviews and meta-analyses raised concerns that tiotropium, when administered by soft mist inhaler (SMI; eg, Spiriva Respimat), might be associated with increased mortality [74,75]. However, a subsequent large randomized trial with over 17,000 patients demonstrated no difference in mortality between those receiving tiotropium by SMI compared with dry powder inhaler (DPI) [71]. Patients with cardiac arrhythmia and coronary heart disease were included in this trial, although those with unstable cardiovascular conditions (class III or IV heart failure [HF], myocardial infarction [MI] in the prior six months, unstable or life-threatening arrhythmias that required an intervention or change in drug therapy within 12 months) were excluded.
Beta-2 agonists — The inhaled beta-2 agonists (eg, albuterol, terbutaline, formoterol, indacaterol, olodaterol, salmeterol, vilanterol) are relatively selective for beta-2 adrenergic receptors. However, the possibility has been raised that mild beta-1 activity associated with these agents might cause the following adverse effects in patients with COPD and heart disease:
●The possible induction of arrhythmias by stimulation of cardiac beta-adrenoreceptors
●Reflex activation of adrenergic mechanisms by causing peripheral vasodilation
●Downregulation of myocardial beta-2 receptors, potentially worsening HF associated with left ventricular systolic dysfunction
●Provocation of hypokalemia by intracellular translocation of potassium or hypoxemia through worsened matching of ventilation and perfusion
Short-acting beta-agonists — SABAs (eg, albuterol, levalbuterol) are the preferred bronchodilators for treatment of acute symptoms of COPD based on their rapid onset of action. This choice is unaffected by the presence of coronary artery disease (CAD). It is reassuring that among 12,090 patients aged 55 years or older with COPD, SABAs did not increase the risk of fatal or nonfatal MI [76]. The management of acute exacerbations of COPD is discussed separately. (See "COPD exacerbations: Management", section on 'Initiate short-acting bronchodilators (inpatient)'.)
Long-acting beta-agonists — Inhaled LABAs are widely used for treatment of COPD; data are generally reassuring regarding their safety in patients with CVD [77,78]. Several studies have specifically evaluated the cardiovascular effects of LABAs.
●Cardiovascular events – The Toward a Revolution in COPD Health (TORCH) trial compared salmeterol alone, fluticasone alone, salmeterol plus fluticasone, and placebo in 6112 patients with COPD over three years [79]. The frequency of cardiovascular events was not increased in the salmeterol alone group or the salmeterol plus fluticasone group [80].
In contrast, a nested case-control study found an increased risk of cardiovascular events (ie, emergency department visit or hospitalization for coronary heart disease, cardiac arrhythmia, HF, or ischemic stroke) among 37,719 patients with COPD and new use of a LABA (adjusted odds ratio [OR] 1.5, 95% CI 1.4-1.7), while prevalent use was associated with a 9 percent decrease in risk [81]. Similarly, a large database study of over 180,000 patients found that initiation of LABA, SABA, or inhaled corticosteroid (ICS)/LABA in patients with COPD was associated with increased risk for cardiovascular events compared with patients with COPD initiated on SAMAs, but not compared with those initiated on LAMAs [82].
There are some important limitations to these studies. The TORCH trial may not be widely generalizable due to exclusion of patients with underlying CVD. In addition, the case-control and database designs are limited by potential confounding. Therefore, we advise caution when prescribing beta-agonists to people with severe and/or symptomatic CAD. Thorough patient characterization and risk stratification prior to the use of LABAs may reduce the risk of cardiovascular events in patients with CAD.
●Heart failure – Some but not all studies have suggested that beta-2 agonists may have an adverse effect in patients with left ventricular systolic dysfunction. In a review of 1529 patients with left ventricular systolic dysfunction (by echocardiography or radionuclide ventriculography), the relative risk of hospitalization for HF followed a dose-response relationship with the use of inhaled beta-agonists [83]. However, a retrospective study of 1294 subjects attending a HF disease management program did not find an increase in mortality associated with beta-2 agonist use (HR 1.0, 95% CI 0.8-1.4) after adjusting for age, sex, smoking, medications, and severity of comorbidities [84].
●Arrhythmias – While beta-2 adrenergic agonists have the potential to increase heart rate and may increase cardiac arrhythmias via nonselective beta-adrenergic effects, a number of studies have shown a very low to no increased risk of serious arrhythmias with these medications. This is discussed in detail separately. (See "Arrhythmias in COPD", section on 'Beta-adrenergic agonists'.)
Combination LAMA-LABA — The combination of LAMA plus a LABA is suggested as an initial regimen for patients with COPD with exacerbations or burdensome respiratory symptoms (algorithm 2). Data regarding cardiovascular safety of the individual agents are mixed, but largely reassuring [1,73,80], as described above. (See 'Inhaled anticholinergic medications' above and 'Long-acting beta-agonists' above.)
Data from clinical trials and systematic reviews of combination bronchodilator inhalers are more limited and not entirely consistent, suggesting heterogeneous effects in different trial populations:
●A systematic review comparing the combination of a LABA plus tiotropium with a LABA or tiotropium alone found no significant increase in serious adverse events with the combination inhaler, although separate data on cardiovascular outcomes were not provided [85].
●In a systematic review of trials comparing LAMA-LABA and LABA-glucocorticoid inhalers for stable COPD (11 studies, 9839 participants), a nonsignificant decrease in serious adverse events was noted in the LAMA-LABA group [86].
●However, another large systemic review (42 studies, over 71,000 patients with stable COPD) found that while dual LAMA-LABA therapy did not demonstrate increased risk for major adverse cardiovascular events compared with LAMA alone, LABA alone, or placebo, there was a small increased risk compared with combined LABA and inhaled glucocorticoid (1.6 versus 1.3 percent, RR 1.4, 95% CI 1.1-1.8) [87].
Combination LAMA or LABA plus glucocorticoid — The evidence suggests that the addition of inhaled glucocorticoids to LABAs or dual bronchodilator therapy is safe [79,80,87-92] and may possibly have a small benefit compared with bronchodilators alone [87].
●In the three-year Study to Understand Mortality and MorbidITy (SUMMIT), the effect of fluticasone furoate-vilanterol (100 mcg-25 mcg) combination was compared with the individual components and placebo in 16,590 patients with moderate COPD (forced expiratory volume in one second [FEV1] between 50 and 70 percent of predicted) and risk factors for or known CVD [90]. Relative to placebo, the combination inhaler did not affect all-cause mortality (HR 0.9, 95% CI 0.7-1.0) or composite cardiovascular events (HR 0.9, 95% CI 0.75-1.1).
●In a meta-analysis (10 studies, 10,680 participants) that compared combination inhaled LABA plus glucocorticoid with inhaled LABA alone in COPD, there was no significant difference in mortality (OR 0.9, 95% CI 0.8-1.1) [88]. However, underlying CVD was an exclusion criterion for participation, and the rate of cardiovascular events was not examined.
●In the IMPACT and ETHOS trials of combination LAMA, LABA, and inhaled glucocorticoids in patients with stable COPD, there was reduced all-cause mortality in the groups receiving triple therapy compared with dual bronchodilator therapy alone [91,92]. (See "Stable COPD: Follow-up pharmacologic management", section on 'Exacerbations on LAMA-LABA therapy'.)
Although not statistically significant, there was also a trend towards reductions in cardiovascular mortality in the triple therapy compared with dual therapy arm in both trials (0.5 versus 1.4 percent in ETHOS; 0.6 versus 1.0 percent in IMPACT). Similarly, there were numerically fewer major adverse cardiac events (MACE) in the ETHOS trial over one year in patients who received triple therapy compared with LAMA-LABA alone (1.4 versus 2.1 percent), although this was not statistically significant in all groups [93].
●In a systematic review and meta-analysis, there was a similar risk of major adverse cardiovascular events in patients receiving triple therapy with LAMA-LABA-glucocorticoid compared with those receiving dual LAMA-LABA therapy (1.6 versus 1.8 percent, RR 0.8, 95% CI 0.6-1.2) based on three studies of nearly 14,000 patients [87]. However, patients receiving LAMA-LABA-glucocorticoid combination therapy did have slightly increased rates of cardiovascular events compared with LABA-glucocorticoid alone (1.6 versus 1.4 percent, RR 1.3, 95% CI 1.0-1.7) in nine studies of 21,000 patients.
The roles of combined LABA-glucocorticoid and LAMA-LABA-glucocorticoid inhaled medications in COPD are discussed separately. (See "Stable COPD: Initial pharmacologic management", section on 'Alternative approaches' and "Stable COPD: Follow-up pharmacologic management", section on 'Persistent exacerbations with or without dyspnea'.)
Ensifentrine — Ensifentrine is an inhaled selective dual phosphodiesterase-3 (PDE3) and phosphodiesterase-4 (PDE4) inhibitor approved in the summer of 2024 in the United States for the treatment of stable COPD. In the phase 3 trials, adverse events, including prominent gastrointestinal side effects often seen with oral PDE4 inhibitors, were minimal [94]. Available limited data do not suggest a significant association between ensifentrine and cardiovascular risk; postapproval monitoring of patients with COPD and CVD using ensifentrine will better answer this question. (See "Stable COPD: Follow-up pharmacologic management", section on 'Dyspnea on LAMA-LABA'.)
Roflumilast — Roflumilast is a PDE4 inhibitor that is approved for use in patients with refractory COPD and frequent exacerbations (algorithm 3). It provides a modest improvement in pulmonary function. Initial studies suggest that roflumilast does not substantially increase cardiovascular outcomes of death and nonfatal MI but may increase the frequency of atrial fibrillation. As examples:
●In a pooled analysis of 14 trials lasting from 12 to 52 weeks, the composite endpoint of cardiovascular death, nonfatal MI, and stroke was lower among patients receiving roflumilast compared with placebo (HR 0.65, 95% CI 0.45-0.9), although none of the individual components reached statistical significance [95].
●In a meta-analysis of eight trials (8696 patients), atrial fibrillation was more frequent in patients on roflumilast than placebo (0.4 versus 0.2 percent) [96]. Atrial fibrillation and other supraventricular arrhythmias occurred in less than 2 percent of patients in previous clinical trials with roflumilast, but these trials may not have included patients with known CVD.
●Concomitant administration of roflumilast and formoterol to healthy men did not result in adverse cardiovascular effects [97].
The use of roflumilast in refractory COPD is discussed separately. (See "Management of refractory chronic obstructive pulmonary disease", section on 'Oral phosphodiesterase-4 inhibitors (roflumilast)'.)
Azithromycin — Azithromycin is a macrolide antibiotic that is often prescribed acutely for moderate or severe COPD exacerbations as well as chronically for those with frequent exacerbations despite maximal inhaled therapy (algorithm 3). (See "Management of refractory chronic obstructive pulmonary disease", section on 'Azithromycin and other long-term antibiotic therapy'.)
Macrolide antibiotics, including azithromycin, are associated with QT interval prolongation. Those with a family history of long QT syndrome or receiving additional QT-prolonging medications may be better suited for alternative agents. We obtain an electrocardiogram to assess the QT interval in those on chronic therapy. Additional discussion of arrhythmogenic risks associated with azithromycin may be found separately. (See "Arrhythmias in COPD", section on 'Azithromycin' and "Azithromycin and clarithromycin", section on 'QT interval prolongation and cardiovascular events'.)
Theophylline — Theophylline is generally avoided in patients with CAD. While very occasionally used in patients with COPD for its mild bronchodilating effects and a possible improvement in exercise performance, it has a narrow therapeutic index and is associated with tachycardia and arrhythmias. Administration of theophylline is plagued by an appreciable incidence of side effects, even when serum drug concentrations are in the low therapeutic range. These adverse effects include tachycardia and palpitations in addition to gastrointestinal upset and headaches. (See "Theophylline poisoning".)
Evidence of an adverse effect of theophylline in patients with CVD is largely indirect, but suggests an increased risk of dose-related atrial and ventricular arrhythmias [98-100]. The contribution of theophylline to the development of arrhythmias in patients with COPD is discussed separately. (See "Arrhythmias in COPD", section on 'Theophylline'.)
SHARED SUPPORTIVE THERAPIES —
Several supportive therapies may help reduce symptoms and improve quality of life in patients with concomitant COPD and cardiovascular disease (CVD). These interventions have been evaluated in patients with either COPD or CVD but have not been examined extensively when both diseases are present.
●Smoking cessation – Smoking cessation is essential to improving outcomes in patients with comorbid COPD and CVD. Behavioral and pharmacologic interventions (eg, nicotine replacement therapy, bupropion, varenicline) to help patients with smoking cessation are discussed separately. (See "Overview of smoking cessation management in adults" and "Behavioral approaches to smoking cessation" and "Pharmacotherapy for smoking cessation in adults".)
Nicotine replacement therapy is indicated for ambulatory patients with COPD despite the presence of CVD. The risk of coronary events (eg, cardiac arrest, myocardial infarction [MI], admission to the hospital for CVD events) is lower among users of nicotine replacement than placebo. The use of nicotine replacement in patients with coronary artery disease (CAD) or acute MI is discussed separately. (See "Cardiovascular effects of nicotine", section on 'Safety of nicotine replacement therapy' and "Overview of the nonacute management of ST-elevation myocardial infarction", section on 'Smoking cessation'.)
●Cardiopulmonary rehabilitation – A number of studies and systematic reviews have demonstrated the benefits of exercise training in patients with either COPD or CVD, but data are more limited regarding the benefit of exercise training in patients with comorbid COPD and CAD [101]. Observational studies have yielded conflicting results regarding the effect of comorbid CAD on the response to pulmonary rehabilitation. These studies are described in greater detail separately. (See "Pulmonary rehabilitation", section on 'Effect of comorbidities'.)
We typically refer patients to a pulmonary rehabilitation program, unless chest pain or myocardial ischemia is noted on an exercise pretest. These patients are referred for cardiac evaluation and possibly a cardiac rehabilitation program. (See "Pulmonary rehabilitation" and "Cardiac rehabilitation programs" and "Cardiac rehabilitation: Indications, efficacy, and safety in patients with coronary artery disease" and "Cardiac rehabilitation in patients with heart failure".)
●Vaccination – Annual vaccination against influenza, severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and pneumococcal pneumonia is indicated for patients with COPD and/or CVD. Older adults with COPD over the age of 60 years may also benefit from vaccination for the prevention of respiratory syncytial virus and shingles. (See "Stable COPD: Overview of management", section on 'Vaccination' and "Prevention of cardiovascular disease events in those with established disease (secondary prevention)", section on 'COVID-19 and influenza vaccination'.)
●Oxygen therapy – Treatment of resting hypoxemia (eg, pulse oxygen saturation ≤88 percent) with supplemental oxygen in patients with COPD improves mortality and may also protect against myocardial ischemia. Decreased left ventricular work due to augmented systemic delivery of oxygen may be a primary reason that oxygen supplementation improves survival [102-104]. The presence of known heart disease does not alter indications for supplemental oxygen. The details of prescribing long-term oxygen therapy to prevent hypoxemia are provided separately. (See "Long-term supplemental oxygen therapy" and "Long-term supplemental oxygen therapy", section on 'Prescribing oxygen'.)
The duration and extent of hypoxemia necessary to produce ischemic changes resulting from coronary lesions is unknown. Mild or brief hypoxemia appears to be unimportant. This was illustrated in a study of 38 patients with ST depression on cardiac stress testing in whom three minutes of breathing a hypoxic mixture to produce an arterial oxygen saturation of 85 percent did not amplify the electrocardiographic signs of ischemia [105]. Myocardial ischemia appears more likely to worsen when the duration of hypoxemia is longer than five minutes or the degree of hypoxemia is severe (pulse oxygen saturation [SpO2] <85 percent) [106].
Hypoxemia may also increase the risk of cardiac arrhythmia. A high incidence of ventricular and supraventricular arrhythmia, particularly multifocal atrial tachycardia (MAT), has been described in patients with COPD with either stable disease or an acute exacerbation [107,108]. Arrhythmias in COPD are discussed separately. (See "Multifocal atrial tachycardia" and "Arrhythmias in COPD".)
●Noninvasive positive pressure ventilation – Noninvasive positive pressure ventilation (NPPV) can provide temporary ventilatory support in selected patients with acute cardiogenic pulmonary edema or acute hypercapnic respiratory failure due to a COPD exacerbation. It is an attractive option for patients who have severe dyspnea that may be due to COPD or CVD, buying additional time for diagnostic studies (eg, to determine whether symptoms are due to COPD, CVD, or both) and empiric therapy. (See "Noninvasive ventilation in adults with acute respiratory failure: Benefits and contraindications".)
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: Chronic obstructive pulmonary disease".)
SUMMARY AND RECOMMENDATIONS
●Epidemiology – COPD and cardiovascular disease (CVD; including coronary artery disease [CAD] and heart failure [HF]) frequently coexist, have overlapping symptoms, and the presence of one can affect outcomes of the other. (See 'Clinical epidemiology' above.)
●General approach – In general, the pharmacologic management of comorbid COPD and CVD is the same as for patients without comorbid disease. (See 'Cardiovascular effects of COPD Treatments' above and 'Pharmacologic treatment of cardiovascular disease in patients with COPD' above.)
●Diagnosis of heart disease in patients with COPD – Physicians caring for patients with COPD should have a low threshold for performing additional diagnostic testing for CAD and/or HF due to the overlapping symptoms and frequency of coexistent disease. (See 'Diagnosis of heart disease in patients with COPD' above.)
●Use of beta blockers in patients with COPD
•Those with cardiovascular indications – For patients with COPD and a cardiovascular indication for beta blocker therapy (post-MI, heart failure with reduced ejection fraction [HFrEF], angina, hypertension, or atrial fibrillation), we suggest using a cardioselective (beta-1 selective) beta blocker (table 1) rather than a nonselective beta blocker (Grade 2C). The preference to avoid nonselective beta blockers is based on the potential for increased risk of bronchoconstriction and exacerbation with these agents; there is some observational evidence to support this effect. (See 'Approach to beta blocker use in COPD' above.)
The choice of cardioselective beta blocker is based on the cardiovascular indication for beta blocker therapy (algorithm 1).
When initiating a cardioselective beta blocker in a patient with COPD, patients and their caregivers should be counseled regarding the small risk of worsening airway obstruction with beta blocker use. However, observational data do not show any harm and suggest potential benefit for use of beta blockers in this setting.
•Those without cardiovascular indications – There is no role for beta blocker therapy in patients with COPD without an established cardiovascular indication. In these patients, randomized trials have found no evidence of benefit with beta blocker use. (See 'Those without cardiovascular indications' above.)
●Coronary revascularization in patients with COPD - The presence of COPD elevates risk of periprocedural morbidity and mortality in patients with COPD. (See 'Revascularization in patients with COPD' above.)
•For patients who require elective coronary revascularization, preprocedural optimization of pulmonary function may be helpful. For all patients undergoing revascularization procedures, we perform postprocedure pulmonary evaluation as well as careful monitoring for rhythm disturbances.
•For patients with an indication for coronary revascularization, the choice between percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) surgery is based upon multiple factors including coronary artery lesion complexity and procedural risks (see "Revascularization in patients with stable coronary artery disease: Coronary artery bypass graft surgery versus percutaneous coronary intervention"). For patients with severe COPD who require coronary revascularization, potential alternatives to high-risk standard CABG surgery may include PCI, off-pump CABG, or minimally invasive CABG.
●Cardiovascular effects of COPD treatments – Cardiovascular effects of common medications for COPD have been studied and may occasionally affect treatment decisions:
•Inhaled bronchodilators and glucocorticoids – Extensive study of inhaled bronchodilators and glucocorticoids has generally been reassuring in terms of cardiovascular safety. (See 'Inhaled anticholinergic medications' above and 'Beta-2 agonists' above and 'Combination LAMA-LABA' above and 'Combination LAMA or LABA plus glucocorticoid' above.)
•Roflumilast and ensifentrine – Initial studies suggest that roflumilast does not substantially affect most cardiovascular outcomes but may increase the frequency of atrial fibrillation. Ensifentrine use was not associated with adverse cardiovascular events in initial trials, but real-world use has been very limited. (See 'Roflumilast' above and 'Ensifentrine' above.)
•Azithromycin – Macrolide antibiotics, including azithromycin, are associated with QT interval prolongation. Caution or an alternative agent should be used for those with a family history of long QT syndrome or receiving additional QT-prolonging medications. Obtaining an electrocardiogram to assess the QT interval is appropriate for those on chronic therapy. (See 'Azithromycin' above and "Acquired long QT syndrome: Clinical manifestations, diagnosis, and management".)
•Theophylline – Theophylline is a rarely used oral bronchodilator that has a narrow therapeutic window; toxicity includes tachycardia and palpitations. Theophylline is not recommended for patients with CVD. (See 'Theophylline' above.)
●Shared supportive therapies – Several supportive therapies (eg, smoking cessation, cardiopulmonary rehabilitation) are known to be helpful for COPD but may have additional benefit in those with concomitant heart disease. (See 'Shared supportive therapies' above.)
