Adverse Effects of β-Blocker Therapy for Patients With Heart Failure

Ko, Dennis T.; Hebert, Patricia R.; Coffey, Christopher S.; Curtis, Jeptha P.; Foody, JoAnne M.; Sedrakyan, Artyom; Krumholz, Harlan M.

doi:10.1001/archinte.164.13.1389

Cited by 139 publications

(38 citation statements)

References 36 publications

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“…6–9,36,37 Regarding harms, little is known about the impact of beta blockers on functional status. However, these agents increase risk of fatigue (particularly first-generation agents such as propranolol) 12 and have been associated with increased rates of dizziness 38,39 and decreased subjective sense of well-being, 40,41 although no consistent effect has been found on rates of depression 12 or falls. 13,42 …”

Section: Discussionmentioning

confidence: 99%

Association of β-Blockers With Functional Outcomes, Death, and Rehospitalization in Older Nursing Home Residents After Acute Myocardial Infarction

et al. 2017

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IMPORTANCE Although β-blockers are a mainstay of treatment after acute myocardial infarction (AMI), these medications are commonly not prescribed for older nursing home residents after AMI, in part owing to concerns about potential functional harms and uncertainty of benefit. OBJECTIVE To study the association of β-blockers after AMI with functional decline, mortality, and rehospitalization among long-stay nursing home residents 65 years or older. DESIGN, SETTING, AND PARTICIPANTSThis cohort study of nursing home residents with AMI from May 1, 2007, to March 31, 2010, used national data from the Minimum Data Set, version 2.0, and Medicare Parts A and D. Individuals with β-blocker use before AMI were excluded. Propensity score-based methods were used to compare outcomes in people who did vs did not initiate β-blocker therapy after AMI hospitalization.MAIN OUTCOMES AND MEASURES Functional decline, death, and rehospitalization in the first 90 days after AMI. Functional status was measured using the Morris scale of independence in activities of daily living. RESULTS The initial cohort of 15 720 patients (11 140 women [70.9%] and 4580 men [29.1%]; mean [SD] age, 83 [8] years) included 8953 new β-blocker users and 6767 nonusers. The propensity-matched cohort included 5496 new users of β-blockers and an equal number of nonusers for a total cohort of 10 992 participants (7788 women [70.9%]; 3204 men [29.1%]; mean [SD] age, 84 [8] years). Users of β-blockers were more likely than nonusers to experience functional decline (odds ratio [OR], 1.14; 95% CI, 1.02-1.28), with a number needed to harm of 52 (95% CI, 32-141). Conversely, β-blocker users were less likely than nonusers to die (hazard ratio [HR], 0.74; 95% CI, 0.67-0.83) and had similar rates of rehospitalization (HR, 1.06; 95% CI, 0.98-1.14). Nursing home residents with moderate or severe cognitive impairment or severe functional dependency were particularly likely to experience functional decline from β-blockers (OR, 1.34; 95% CI, 1.11-1.61 and OR, 1.32; 95% CI, 1.10-1.59, respectively). In contrast, little evidence of functional decline due to β-blockers was found in participants with intact cognition or mild dementia (OR, 1.03; 95% CI, 0.89-1.20; P = .03 for effect modification) or in those in the best (OR, 0.99; 95% CI, 0.77-1.26) and intermediate (OR, 1.05; 95% CI, 0.86-1.27) tertiles of functional independence (P = .06 for effect modification). Mortality benefits of β-blockers were similar across all subgroups.CONCLUSIONS AND RELEVANCE Use of β-blockers after AMI is associated with functional decline in older nursing home residents with substantial cognitive or functional impairment, but not in those with relatively preserved mental and functional abilities. Use of β-blockers yielded a considerable mortality benefit in all groups.

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Section: Discussionmentioning

confidence: 99%

Association of β-Blockers With Functional Outcomes, Death, and Rehospitalization in Older Nursing Home Residents After Acute Myocardial Infarction

et al. 2017

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“…However, the concentrations of carvedilol required to suppress SOICR (0.3-1 μM) are much higher than those for beta-blockade (~1 nM) 46 . Therefore, strong SOICR inhibition would require high doses of carvedilol, which could produce excessive beta-blockade and the accompanying adverse effects such as bradycardia 47 . In other words, carvedilol’s anti-SOICR benefit is dose limited by the drugs beta-blocking activity.…”

Section: Discussionmentioning

confidence: 99%

Carvedilol and its new analogs suppress arrhythmogenic store overload–induced Ca2+ release

Zhou

Xiao

Jiang

et al. 2011

Nat Med

223

257

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Carvedilol is one of the most effective beta-blockers for preventing ventricular tachyarrhythmias (VTs) in heart failure (HF), but the mechanisms underlying its favorable anti-arrhythmic benefits remain unclear. Spontaneous Ca2+ waves, also termed store-overload-induced Ca2+ release (SOICR), are known to evoke VTs in patients with HF. Here we show that carvedilol is the only beta-blocker that effectively suppresses SOICR by directly reducing the open duration of the cardiac ryanodine receptor (RyR2). This unique anti-SOICR activity of carvedilol combined with its beta-blocking activity likely contributes to its favorable anti-arrhythmic effect. To allow individual and optimal titration of these beneficial activities, we developed a novel SOICR-inhibiting, minimally-beta-blocking carvedilol analogue VK-II-86. We found that VK-II-86 alone prevented stress-induced VTs in RyR2 mutant mice, and was more effective when combined with a selective beta-blocker metoprolol or bisoprolol. Thus, SOICR inhibition combined with optimal beta-blockade presents a new, promising and potentially patient-tailorable anti-arrhythmic approach.

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“…For example, in HF studies fatigue did not correlate with age 3,4 or with ejection fraction (EF), 3-5 and in a meta-analysis of randomized clinical trials, fatigue was not related to β-blocker therapy. 6 Researchers of other chronic disease populations have implicated pro-inflammatory cytokines in the etiology of fatigue. 7-11 Increased plasma cytokine levels have been found in patients with HF.…”

Section: Introductionmentioning

confidence: 99%

Fatigue, Inflammation, and Projected Mortality in Heart Failure

Fink

Gonzalez

Lisowski

et al. 2012

Journal of Cardiac Failure

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Background Fatigue is a prominent and poorly understood symptom of heart failure with reduced ejection fraction (HFrEF). The purpose of this study was to determine whether fatigue correlated with immune biomarkers and prognosis. Methods/Results In patients with HFrEF (N = 59) and healthy controls (N = 25), we prospectively measured fatigue (Profile of Mood States), depressive symptoms (Patient Health Questionnaire-8), sleep quality (Pittsburgh Sleep Quality Index), and immune biomarkers (plasma C-reactive protein [CRP], tumor necrosis factor-α [TNFα], and interleukins [IL-6 and IL-10]). Seattle Heart Failure Model (SHFM) mortality risk scores were determined. Patients with HFrEF had significantly greater fatigue and depressive symptoms and poorer sleep quality compared to control subjects. When controlling for depressive symptoms, however, fatigue did not differ significantly between patients with HFrEF and controls. Patients with HFrEF had significantly lower levels of IL-10 compared to controls. Cytokines did not correlate significantly with fatigue, but fatigue was significantly associated with higher SHFM scores. Conclusions Depressive symptoms were an important covariate of fatigue in patients with HFrEF. Our study findings were the first to show a positive association between fatigue and the SHFM score, indicating that fatigue was associated with poorer prognosis.

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Adverse Effects of β-Blocker Therapy for Patients With Heart Failure

Cited by 139 publications

References 36 publications

Association of β-Blockers With Functional Outcomes, Death, and Rehospitalization in Older Nursing Home Residents After Acute Myocardial Infarction

Association of β-Blockers With Functional Outcomes, Death, and Rehospitalization in Older Nursing Home Residents After Acute Myocardial Infarction

Carvedilol and its new analogs suppress arrhythmogenic store overload–induced Ca2+ release

Fatigue, Inflammation, and Projected Mortality in Heart Failure

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