Clinical trial NCT02516332: Exercise and Pharmacotherapy for Anxiety in Cardiac Patients
Official title: Exercise and Pharmacotherapy for Anxiety in Cardiac Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Anxiety
Cardiovascular Disease
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2015-08-05
Enrollment: 128
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Coronary heart disease (CHD) is the leading cause of death in the United States; more than 600,000 Americans suffer a fatal cardiac event each year. Traditional CHD risk factors such as high blood pressure, smoking, and elevated cholesterol do not fully account for the timing and occurrence of CHD events and individuals with elevated levels of anxiety appear to have a greater risk of cardiovascular events. The present study will examine the impact of aerobic exercise and Lexapro in the treatment of anxiety and cardiovascular biomarkers among individuals with CHD.

Detailed description: Coronary heart disease (CHD) is the leading cause of death in the United States; more than 600,000 Americans suffer a fatal cardiac event each year. Traditional CHD risk factors such as high blood pressure, smoking, and elevated cholesterol do not fully account for the timing and occurrence of CHD events. The term "cardiovascular vulnerable patient" has been used to describe patients susceptible to acute coronary events based upon plaque, blood, or myocardial characteristics. Psychosocial factors also have been shown to be associated with increased adverse health outcomes and increased cardiovascular vulnerability. For example, clinical depression and elevated depressive symptoms are associated with increased morbidity and mortality, and as a result, the American Heart Association has recommended that clinicians should routinely assess depression in CHD patients. Although much research and clinical recommendations have focused on depression, the significance of anxiety has been largely ignored, despite the fact that anxiety disorders are as prevalent as depression in the general population and are associated with similar levels of disability.

Despite the prevalence and prognostic significance of anxiety in CHD populations, there have been few randomized clinical trials (RCTs) specifically targeting anxious CHD patients. Anxiolytic medications, including selective serotonin reuptake inhibitors (SSRIs), have been shown to be effective in treating anxiety. SSRIs have been evaluated for the treatment of clinical depression in cardiac patients, with equivocal results. Surprisingly, to our knowledge, there have been no RCTs examining the efficacy of medications for treating anxiety in CHD patients. Moreover, because many cardiac patients are reluctant to take additional medications and psychotropic medications may not be effective for everyone or may produce unwanted side effects, there continue to be a need to identify alternative approaches for treating anxiety in cardiac patients. The investigators believe that exercise may be one such approach.

The purpose of this study is to evaluate the following hypotheses in a population of CHD patients with elevated symptoms of anxiety. The present study will examine the impact of a 3-month intervention of either exercise, Lexapro, or placebo on anxiety symptoms and CHD biomarkers among individuals with cardiac disease and elevated anxiety. The investigators hypothesize that: (1) Both exercise training and medication will reduce anxiety symptoms to a greater extent than placebo; (2) Exercise training will improve CHD biomarkers of risk including autonomic regulation, vascular endothelial function, and inflammation more than either medication or placebo; and (3) Improvements in CHD biomarkers will be mediated by reductions in symptoms of anxiety. The investigators also will explore potential moderators of treatment (e.g., anxiety diagnoses, CHD severity) as well as the longer-term benefits of treatment by documenting medical events and health care costs over a follow-up period of up to 4 years.

Eligibility criteria: Inclusion Criteria:

* Men and women with documented CHD (i.e., a prior MI, coronary revascularization procedure, or \>70% stenosis in at least one coronary artery)
* Age \> 39 years
* Patients also will have an anxiety symptom severity score of at least 8 on the Hospital Anxiety and Depression-Anxiety scale (HADS-A) or a DSM-5 diagnosis of an Anxiety Disorder, such as General Anxiety, Social Anxiety, or Panic Disorder.

The study team plans to actively recruit women and minorities, with at least 50% women and 25% minorities.

Exclusion Criteria:

* An MI or coronary revascularization procedure (i.e., CABG or percutaneous coronary intervention) within the last 3 months
* Unstable angina
* Severe left ventricular dysfunction (ejection fraction \<30%) or decompensated heart failure
* Unrevascularized left main coronary artery stenosis \>50%
* Complete Pacemaker dependence
* Resting BP \>200/120 mm Hg
* Conditions that would preclude randomization to either the drug (e.g., prolonged QT interval, known allergy to or intolerance of escitalopram) or exercise (e.g., musculoskeletal problems or abnormal cardiac response to exercise)
* Patients with a primary psychiatric diagnosis other than Anxiety Disorder will be excluded, including patients with PTSD, OCD, or any of the following DSM-5 diagnoses:

  1. Dementia, delirium;
  2. Schizophrenia, Schizoaffective, or other psychotic disorder;
  3. Psychotic features including any delusions or hallucinations; or
  4. Current alcohol or other substance abuse disorder.
* Similarly, patients who pose an acute suicide or homicide risk or who, during the course of the study, would likely require treatment with additional psychopharmacologic agents will not be enrolled.
* Patients will also be excluded if they are taking other medications that would preclude assignment to either drug or exercise conditions (e.g., clonidine, dicumarol, anticonvulsants, and MAO inhibitors) or are taking herbal supplements with purported mood effects (e.g., St. John's Wort, valerian, ginkgo).
* Patients already engaged in regular exercise (at least 30 minutes \>1x/week) will not be enrolled.
* Finally, pregnant women will be excluded from participation.

Primary outcomes:
measure: Change in Hospital Anxiety and Depression Scale (HADS), Anxiety
timeFrame: Baseline, 3 months
Secondary outcomes:
measure: Change in Heart Rate Variability, SDNN (Msec)
timeFrame: Baseline, 3 months
measure: Change in Baroreflex Sensitivity, ms/mm Hg
timeFrame: Baseline, 3 months
measure: Change in Vascular Endothelial Function, Percentage of Dilation
timeFrame: Baseline, 3 months
measure: Change in Inflammation (C-Reactive Protein, ug/ml)
timeFrame: Baseline, 3 months
measure: Change in Urinary Catecholamines (Epinephrine and Norepinephrine, Unit-weighted Z-score)
timeFrame: Baseline, 3 months
measure: Change in Lipids - Total Cholesterol, LDL (Low-density Lipoprotein), and HDL (High-density Lipoprotein); mg/dL
timeFrame: Baseline, 3 months
Other outcomes:
measure: Change in Hospital Anxiety and Depression Scale, Total Score
timeFrame: 9 months, 15 months
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
References:
citation: Blumenthal JA, Smith PJ, Jiang W, Hinderliter A, Watkins LL, Hoffman BM, Kraus WE, Liao L, Davidson J, Sherwood A. Effect of Exercise, Escitalopram, or Placebo on Anxiety in Patients With Coronary Heart Disease: The Understanding the Benefits of Exercise and Escitalopram in Anxious Patients With Coronary Heart Disease (UNWIND) Randomized Clinical Trial. JAMA Psychiatry. 2021 Nov 1;78(11):1270-1278. doi: 10.1001/jamapsychiatry.2021.2236.
citation: Blumenthal JA, Feger BJ, Smith PJ, Watkins LL, Jiang W, Davidson J, Hoffman BM, Ashworth M, Mabe SK, Babyak MA, Kraus WE, Hinderliter A, Sherwood A. Treatment of anxiety in patients with coronary heart disease: Rationale and design of the UNderstanding the benefits of exercise and escitalopram in anxious patients WIth coroNary heart Disease (UNWIND) randomized clinical trial. Am Heart J. 2016 Jun;176:53-62. doi: 10.1016/j.ahj.2016.03.003. Epub 2016 Mar 12.