Statin therapy is borderline significantly associated with depression and physical functioning in implantable cardiac defibrillator patients

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Madelein T Hoogwegt, Center of Research on Psychology in Somatic diseases (CoRPS), Tilburg University and Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands, and others have found that there is a borderline significant association between statin therapy and depression and statin therapy and physical functioning in patients with an implantable cardioverter defibrillator (ICD).

However, the researchers did not find any association between statins and anxiety. The study has been published in the online edition of the American Journal of Cardiology.

“The effect of statin therapy on psychological functioning in patients with cardiovascular disease is inconclusive,” the authors wrote. Some studies have looked into the influence of statin therapy on the well-being and health status of cardiac patients, but, according to Hoogwegt et al, “No studies to date have examined the association between statin therapy and psychological functioning in ICD patients and the potential influence of statin type on these outcomes.”

With the absence of such studies, Hoogwegt et al aimed to investigate the association between statin use and psychological functioning in terms of anxiety and depression, and ICD patients’ health status throughout the 12 months after implantation. The researchers also set out to evaluate the effect of specific types and dosages of statins on psychological functioning.

In the study, a consecutive cohort of 448 patients implanted with a first time ICD were enrolled in the MIDAS study (Mood and personality as precipitants of arrhythmia in patients with an implantable cardioverter defibrillator: A prospective study) at the Erasmus Medical Center from August 2003 to February 2010. The authors clarified that this study was part of a wider objective that aims “to create a more complete picture of the interrelation between ICD patients’ psychological functioning and clinical risk profile.”

Four hundred and nine patients (78.2% men, mean age 59 ± 12 years) out of the 448 enrolled completed the Hospital Anxiety and Depression Scale and the Medical Outcomes Short Form 36-item Health Survey that taps into eight health status domains [Physical functioning, Role limitations–physical, Bodily pain, Social functioning, Mental health, Role limitations–emotional, Vitality, and General health] at baseline and three, six and 12 months after implantation.

In total, 246 (60%) of the 409 patients were prescribed statins. The median equivalent dosage was 160 mg/day. Hoogwegt et al found that statin therapy was associated with impaired health status on three of the eight health status domains of the 36-item Health Survey. Statin use was independently associated with poorer Role limitations physical (p=0.001), Social functioning (p=0.007), and Role limitations emotional (p=0.006) during the 12 months after implantation, with these findings being independent of statin type, dosage and other potential confounders including ICD shocks .

However, after adjusted analysis, the authors found a borderline significant association between statin therapy and depressive symptoms (p=0.06) and statin therapy and Physical functioning (p=0.05) but no association with anxiety (p >0.05). (See Table 1)

Table 1. Longitudinal association between statin therapy and anxiety, depression, and health status (adjusted analysis)*

Variable

Estimate

t

p-value

95% CI

Psychological distress

Anxiety

-0.81

-1.60

0.11

-1.80 to 0.18

Depression

-0.97

-1.87

0.06

-1.99 to 0.05

Medical Outcomes Study Short Form 36-item Health Survey domains

Physical functioning

6.42

1.93

0.05

-0.11 to 12.94

Role limitations – physical

18.02

3.33

0.001

7.40 to 28.64

Bodily pain

4.31

1.34

0.18

-2.03 to 10.65

Social functioning

8.11

2.68

0.008

2.16 to 14.07

Mental health

2.36

0.96

0.34

-2.46 to 7.19

Role limitations – emotional

14.26

2.87

0.004

4.49 to 24.03

Vitality

4.81

1.74

0.08

-0.64 to 10.25

General health

4.06

1.34

0.18

-1.89 to 10.01

CI = confidence interval.

* Statin users were the reference group; adjusted for gender, age, educational level, indication for ICD therapy, occurrence of shocks (both appropriate and inappropriate) during 12 months after implantation, coronary artery disease, symptomatic heart failure, atrial fibrillation, diabetes mellitus, peripheral arterial disease, smoking, and the use of amiodarone, b-blockers, and psychotropic

After studying five different types of statin therapy [Pravastatin, Rosuvastatin, Simvastatin, Atorvastatin and Fluvastatin] the researchers did not find any significant relation between statin type and psychological functioning.

The authors concluded that further research including a larger sample size and comparing the influence of statin types matched according to a daily equivalent dosage is needed. “In the clinical management and care of ICD patients, it is important to be aware of the potential influence of statin therapy on health status and to discuss this with patients, because decreased psychological functioning is negatively associated with medication adherence,” the authors wrote.

Susanne S Pedersen (CoRPS, Tilburg University; Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands; Department of Cardiology, Odense University Hospital, Denmark; and Institute of Psychology, University of Southern Denmark), senior author of the study, spoke to Cardiac Rhythm News on the subject:

1. Why is it important to study the effect of statin therapy in ICD patients?


Attention to the impact of drug therapy on patients’ well being is important as their functioning may be impaired due to side-effects, which in turn may lead to non compliance with medication. In addition, ICD patients are often prescribed antiarrhythmic agents, such as amiodarone, together with statins. These drugs may interact with each other, increasing the risk of severe or hampering side effects. Examination of patients’ tolerance for specific types and dosages and closer monitoring of drug effects during follow-up might reduce the possible burden that patients experience. Attention should also be paid to discussing possible side-effects with patients and screening patients for psychological distress both at the time of implantation but also during follow-up visits, as poor psychological functioning not only influences medication adherence but also increases the risk of ventricular tachyarrhythmias and mortality, as we and others have shown previously.


2. What should be considered to get more definite results in this area?

Future research should include larger sample sizes, and compare the influence of statin type matched by means of a daily equivalent dosage, as we have not been able to demonstrate a significant relationship between type and psychological functioning, probably due to the small number of patients using pravastatin, rosuvastatin and fluvastatin. In addition, future research should focus on a broader spectrum of psychological measures, as depression has been the main focus of investigation to date. Further attention should also be given to the studying of the mechanisms that may explain the relationship between statin therapy and psychological functioning, as these mechanisms could provide us with insight into treatment strategies that may lead to more patient-tailored care.

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