Beta Blocker vs Calcium Channel Blocker for Stable Angina
(LIVEBETTER Trial)
Recruiting in Palo Alto (17 mi)
+10 other locations
Age: 65+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 4
Recruiting
Sponsor: Yale University
Must not be taking: Beta-blockers, Calcium channel blockers
Disqualifiers: Hypotension, AV block, Bradycardia, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
To establish the effectiveness and tolerability of standard of care anti-anginal treatment (beta-blocker and calcium channel blocker medications) in older adults with symptomatic Stable Ischemic Heart Disease (SIHD) and multiple chronic conditions (MCC).
Will I have to stop taking my current medications?
If you are currently taking beta-blockers or calcium channel blockers, you cannot participate in this trial. The trial does not specify about other medications, so it's best to discuss with the trial team.
What evidence supports the effectiveness of beta blockers for treating stable angina?
Research shows that beta blockers like carvedilol, metoprolol, and bisoprolol improve survival and symptoms in heart failure patients, suggesting they may also help with stable angina. These drugs have additional benefits like reducing blood pressure and improving heart function, which can be beneficial for angina.12345
Are beta blockers and calcium channel blockers generally safe for humans?
Beta blockers like metoprolol, bisoprolol, and carvedilol are generally safe with a low risk of serious side effects if used correctly, though they can cause issues like slow heart rate or breathing problems in some cases. Calcium channel blockers are not specifically mentioned in the provided research, but beta blockers have been shown to be safe in large studies for conditions like heart failure.16789
What makes the drug for stable angina unique?
The drug for stable angina is unique because it compares beta blockers, which can have additional benefits like vasodilation and antioxidant properties, with calcium channel blockers. Some beta blockers, like nebivolol, also improve blood vessel function by releasing nitric oxide, which can be beneficial for heart health.35101112
Eligibility Criteria
This trial is for older adults aged 75 and above with stable angina, heart disease, and at least two other chronic conditions. They must be planning to start medical therapy for their heart condition but can't have severe reactions to beta-blockers or calcium channel blockers, nor plans for immediate complete revascularization.Inclusion Criteria
I am 75 years old or older.
I am an older adult with stable ischemic heart disease and multiple chronic conditions.
I am 18 years old or older.
See 4 more
Exclusion Criteria
You cannot participate if you have certain heart or lung conditions, are at high risk for heart disease, need certain medications, or have specific medical history or treatment plans.
I am currently taking a beta-blocker or calcium channel blocker.
Professional caregiver (i.e. not a relative or close friend of the participant), Primary language other than English or Spanish, Inability to complete follow-up, Previously enrolled in LIVEBETTER, Refused informed consent
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either Beta-Blocker or Calcium Channel Blocker therapy as part of the study medication
12 months
4 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including cognitive assessments
12 months
4 visits (in-person)
Ancillary Neurocognitive Study
Extended follow-up to assess cognitive decline and incidence of mild cognitive impairment and probable dementia
12 months
Treatment Details
Interventions
- Beta blocker (Beta Blocker)
- Calcium channel blocker (Calcium Channel Blocker)
Trial OverviewThe study tests the effectiveness of standard anti-anginal medications (beta-blockers and calcium channel blockers) in managing symptoms of Stable Ischemic Heart Disease in seniors with multiple health issues. The choice of medication is left to the clinician's discretion.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: Calcium Channel Blockers (CCB) TherapyExperimental Treatment2 Interventions
Participants randomized to this arm will be given a calcium channel blocker. Specific and appropriate drug selection from the class of calcium channel blockers (i.e. type of CCB, dosing, and escalation of dose) will be left to the site clinician in accordance with clinical guidelines. All CCB will be administered orally (i.e. pills).
Group II: Beta-Blockers (BB) TherapyExperimental Treatment2 Interventions
Participants randomized to this arm will be given a beta-blocker. Specific and appropriate drug selection from the class of beta blockers (i.e. type of BB, dosing, and escalation of dose) will be left to the site clinician in accordance with clinical guidelines. All BB will be administered orally (i.e. pills).
Beta blocker is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:
🇪🇺 Approved in European Union as Beta blockers for:
- Hypertension
- Heart failure
- Angina
- Arrhythmias
- Migraine
- Glaucoma
- Anxiety disorders
🇺🇸 Approved in United States as Beta blockers for:
- Hypertension
- Heart failure
- Angina
- Arrhythmias
- Migraine
- Glaucoma
- Anxiety disorders
🇨🇦 Approved in Canada as Beta blockers for:
- Hypertension
- Heart failure
- Angina
- Arrhythmias
- Migraine
- Glaucoma
- Anxiety disorders
🇯🇵 Approved in Japan as Beta blockers for:
- Hypertension
- Heart failure
- Angina
- Arrhythmias
- Migraine
- Glaucoma
- Anxiety disorders
🇨🇳 Approved in China as Beta blockers for:
- Hypertension
- Heart failure
- Angina
- Arrhythmias
- Migraine
- Glaucoma
- Anxiety disorders
🇨🇭 Approved in Switzerland as Beta blockers for:
- Hypertension
- Heart failure
- Angina
- Arrhythmias
- Migraine
- Glaucoma
- Anxiety disorders
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Nirvana Integrative MedicineNew York, NY
Rush University Medical CenterChicago, IL
Wellstar Research InstituteMarietta, GA
Cook County HealthChicago, IL
More Trial Locations
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Who Is Running the Clinical Trial?
Yale UniversityLead Sponsor
References
Replacement of carvedilol for propranolol in patients with heart failure. [2019]Large clinical trials using the betablockers carvedilol, metoprolol, bisoprolol and nebivolol have demonstrated improvement of survival and symptoms in patients with heart failure. Despite the lack of scientific evidence, it is plausible that their beneficial effects are extensible to other betablockers.
Are all beta-blockers the same for chronic heart failure? [2019]beta-Adrenergic receptor blockade has been conclusively proven to increase survival and morbidity in patients with heart failure. Hospitalization rate decreases and patients feel better after receiving beta-blockers. Furthermore, this benefit is observed in a wide range of patients. The beta-blockers bisoprolol, metoprolol, and carvedilol have been extensively evaluated in heart failure patients. These drugs all show marked benefit. Bucindolol, an investigational beta-blocker, showed only mild improvement in survival in patients with heart failure. The beta-blockers differ regarding beta-selectivity, vasodilation properties, and perhaps other ancillary properties. At present, the importance and consequences of these differences are unknown.
The effects of newer beta-adrenoceptor antagonists on vascular function in cardiovascular disease. [2019]This review provides a systematic overview of the influence of the third generation beta-adrenoceptor antagonists on vascular and/or endothelial function at a cellular level as well as of the advantages of their application in hypertension, heart failure and coronary artery disease. Drugs antagonizing the beta-adrenoceptors have been in use for the treatment of hypertension for decades. In systolic heart failure and post-myocardial infarction, beta-adrenoceptor antagonists were proven to be effective in decreasing the number of deaths and improving morbidity. However, betaadrenoceptor antagonists are a heterogeneous drug group, consisting of agents with different selectivity for adrenoceptors and/or additional effects in heart and peripheral circulation. Beta-adrenoceptor antagonists comprise a multitude of different agents, which may have additional properties exceeding the pure receptor blockade. These features may provide additional benefit in the treatment of hypertension. The third generation drug nebivolol exerts a nitric oxide-mediated vasodilating activity which has positive effects on intima and media thickness and arterial rigidity, a major risk factor in cardiovascular disease. Moreover, anti-proliferative, anti-inflammatory, and anti-oxidative properties have been detected for carvedilol and nebivolol, contributing to their additional value in treatment of hypertension and heart failure.
Beta-blockade in heart failure: selective versus nonselective agents. [2018]Controlled clinical trials performed in more than 13 000 patients have, to date, consistently shown the beneficial effects of long term beta-adrenoceptor antagonist (beta-blocker) therapy in patients with chronic heart failure. It is not clear whether this represents a class effect or whether it is specific only to some agents. Beneficial effects on the prognosis of patients with mild to moderate heart failure have been shown with metoprolol, bisoprolol, and carvedilol. These beta-blockers, however, differ in their pharmacologic characteristics. Metoprolol and bisoprolol are selective for beta(1)-adrenergic receptors and are devoid of ancillary properties. Carvedilol, at a dosage of 50 mg/day, blocks all beta(1)-, beta(2)-, and alpha(1)-adrenergic receptors, and it has associated antiproliferative and antioxidant activities. These differences cause a varied acute hemodynamic response, with a reduction in cardiac output and a tendency toward a rise in pulmonary wedge pressure with selective agents and no change in cardiac output and a slight decrease in pulmonary pressures with carvedilol. Accordingly, when the therapy is started, the most frequent adverse effects are worsening heart failure with metoprolol and bisoprolol, and hypotension and dizziness with carvedilol. It remains controversial whether these differences also influence the long term effects of therapy. Carvedilol may provide a more comprehensive blockade of the cardiac adrenergic drive than selective beta-blockers because it does not upregulate beta(1)-adrenergic receptors, blocks all adrenergic receptors and decreases cardiac norepinephrine release. These properties may lead to a larger increase in left ventricular function and a lack of improvement in maximal exercise capacity with carvedilol, compared with selective beta-blockers. It is, however, unclear whether these differences also influence patient outcome. The long term effects of different beta-blockers on prognosis are currently being compared in the Carvedilol or Metoprolol European Trial (COMET) in which more than 3000 patients with chronic heart failure have been randomized in a 1 : 1 ratio to receive metoprolol or carvedilol.
Beta-blockers in heart failure: are pharmacological differences clinically important? [2018]Beta-blockers are not an homogeneous group of agents. Only three beta-blockers, carvedilol, bisoprolol and metoprolol succinate, have had favorable effects on prognosis in controlled clinical trials in the patients with chronic heart failure. However, pharmacological differences exist between them. Metoprolol and bisoprolol are selective for beta(1)-adrenergic receptors while carvedilol blocks also beta(2)-, and alpha(1)- adrenergic receptors, and has associated antioxidant, anti-endothelin and antiproliferative properties. In COMET carvedilol was associated with a significant reduction in mortality compared to metoprolol tartrate further showing that different beta-blockers may have different effects on the outcome. These differences may be related to the ancillary properties of carvedilol or to its broader antiadrenergic profile. However, also more effective and prolonged blockade of beta1 adrenergic receptors may occur with carvedilol compared to metoprolol.
[Differential therapy with beta blockers. What is their value, what are the risks?]. [2017]The selective beta blockers metoprolol, bisoprolol and atenolol, but also the non-selective beta blocker carvedilol, are drugs with individually specific properties that are widely prescribed for a wide range of indications. Modern beta blockers are safe drugs with a low profile of side effects, which, applied with proper consideration being given to contraindications, rarely produce serious side effects such as bradyarrhythmia, bronchial obstruction, or aggravation of heart failure. Their prognostic benefit, for example, in the treatment of post-myocardial infarction patients, or in cardiac insufficiency, has been demonstrated in large randomized clinical trials.
[Endothelial dysfunction: role of vasodilating betablockers in hypertension and chronic heart failure]. [2010]The beneficial effects of beta blocking drugs in hypertension and heart failure are well known. However, this class of drugs is pharmacologically heterogeneous. In contrast to the non vasodilator betablockers like propranolol, atenolol or metoprolol which, in hypertension do not decrease intima media thinckness both in arterioles and large arteries, do not decrease arterial rigidity and can induce diabetes mellitus, the betablockers with vasodilating properties are beneficial on these parameters. Moreover, in heart failure, they more markedly decrease left ventricular workload than betablockers without any vascular relaxing effect and the results of SENIOR with nebivolol could suggest the beneficial role of NO on left ventricular dysfunction. Finally, the third generation betablockers, represented by celiprolol, carvedilol and nebivolol, have antioxidant properties which are probably implicated in their endothelial protective effects and in their absence of deleterious metabolic effects, effects which are probably of interest in term of protection of target organs during chronic treatment of hypertensive patients.
Beta-adrenoceptor antagonists in elderly patients with chronic heart failure: therapeutic potential of third-generation agents. [2018]Chronic heart failure (CHF) is a common and disabling condition with an incidence and prevalence that increase sharply with age. The median age of presentation of new heart failure cases is > 75 years. Effective treatments, including beta-adrenoceptor antagonists, have been proven in randomised, controlled trials. The average age in these placebo-controlled mortality and morbidity studies of beta-adrenoceptor antagonists in heart failure has, however, been or = 40% were excluded. This lack of a representative sample of elderly patients with heart failure has raised concerns about extrapolating the available evidence for beta-adrenoceptor antagonists to a more elderly heart failure population. Beta-adrenoceptor antagonists may have a less beneficial effect or even an adverse effect in elderly heart failure patients. There is evidence that beta-adrenoceptor antagonists are less frequently prescribed in elderly CHF patients, and that this lack of treatment is associated with impaired outcomes. Establishing which beta-adrenoceptor antagonists, if any, are effective in elderly CHF is therefore of extreme importance. The elderly have a reduced cardiovascular reserve and may be less tolerant of the introduction of a vasoconstricting beta-adrenoceptor antagonist. In addition, the higher proportion of elderly CHF patients with relatively preserved systolic function (for which no treatment has been proven to reduce mortality and morbidity) means that we cannot say with certainty that beta-adrenoceptor antagonists have been proven to be effective in a general elderly CHF population. Third-generation beta-adrenoceptor antagonists with vasodilating actions in addition to their beta-adrenoceptor antagonist effects may offer several theoretical advantages over earlier beta-adrenoceptor antagonists for elderly CHF patients. Three of this class (carvedilol, bucindolol and nebivolol) have been evaluated with respect to their efficacy in reducing mortality and morbidity in CHF, and only two of these (carvedilol and nebivolol) had a proven outcome benefit in a properly powered randomised, controlled trial. Only the Study of the Effects of Nebivolol Intervention on Outcomes and Rehospitalisation in Seniors with Heart Failure (which used the vasodilating third-generation beta-adrenoceptor antagonist nebivolol) has prospectively investigated the treatment of CHF in elderly patients, including those with preserved systolic function, and demonstrated a significant reduction in the risk of death or cardiovascular hospitalisation. In conclusion, prescribers are advised that nebivolol should be preferred in elderly patients with CHF, because of its proven efficacy in a representative group of elderly CHF patients.
The large-scale placebo-controlled beta-blocker studies in systolic heart failure revisited: results from CIBIS-II, COPERNICUS and SENIORS-SHF compared with stratified subsets from MERIT-HF. [2022]The four pivotal beta-blocker trials in heart failure (HF) had different inclusion criteria, making comparison difficult without patient stratifying. The aim of this study was to compare, in similar patients, the effects of bisoprolol, metoprolol controlled release/extended release (CR/XL), carvedilol and nebivolol on (i) total mortality, (ii) all-cause mortality or hospitalization due to cardiovascular causes (time to first event), (iii) all-cause mortality or hospitalization because of HF and (iv) tolerability, defined as discontinuation of randomized treatment.
Pharmacokinetics and pharmacodynamics of beta blockers in heart failure. [2018]Although beta-blockers have been used for nearly three decades in the management of heart failure, only recent randomized clinical trials have demonstrated substantial benefit in reducing morbidity and mortality. Carvedilol, metoprolol succinate and bisprolol have evidence supporting their use in heart failure while other beta blockers either lack evidence supporting their use or have not been shown to be useful in heart failure. The only currently approved beta-blockers in the U.S. for heart failure are metoprolol succinate and carvedilol.Beta-blockers differ in their pharmacokinetic and pharmacodynamic properties. It should not be assumed that potential benefit in heart failure is a class effect since differences in the half-life, volume of distribution, protein binding, and route of elimination may give rise to differences in duration of beta blockade and potential drug interactions. Furthermore, pharmacodynamic differences exist because of selectivity for beta(1), beta(2) or alpha(1) adrenoreceptor blockade among the beta-blockers. Receptor kinetics also differ among the beta-blockers and this may influence the extent and duration of beta and alpha blockade across the category. Carvedilol is an inherently long-acting beta-blocker while the duration of beta blockade for metoprolol is dependent on the salt and formulation, which is used. Metoprolol tartrate is a short-acting form of metoprolol while metoprolol succinate is a longer acting salt and the commercially available product is designed as a once daily formulation. A recently published trial, the Carvedilol or Metoprolol European Trial (COMET) tested carvedilol given twice daily versus metoprolol tartrate given twice daily in patients with chronic heart failure. Although carvedilol reduced all cause mortality when compared with metoprolol tartrate, extrapolation to similar findings with metoprolol succinate are not possible since the pharmacokinetic and pharmacodynamic effects of these two formulations are different. Furthermore, the dosing of metoprolol tartrate in COMET may have been inadequate based on prior studies. Additional studies are needed to compare carvedilol directly to metoprolol succinate before concluding inequivalency exists for these two beta-blockers in heart failure.
The role of nitric oxide in improving endothelial function and cardiovascular health: focus on nebivolol. [2015]Although beta-blockers have been endorsed by guidelines committees for the treatment of patients with hypertension, particularly those with significant CVD and high CVD risk, there are concerns about conventional beta-blockers related to poorer clinical outcomes compared with other classes of antihypertensive agents, as well as deleterious effects on quality of life and lipid and carbohydrate metabolism. beta-Blockers comprise a heterogeneous group of antihypertensive agents, including nonselective agents, cardioselective, nonvasodilating agents, and vasodilating agents that either combine beta-nonselectivity with alpha-blockade or possess cardioselectivity without alpha-blockade. The pharmacologic, mechanistic, and hemodynamic differences between conventional, nonvasodilating beta-blockers and vasodilating beta-blockers are discussed in this review, with a focus on the cardioselective vasodilating beta-blocker nebivolol. These differences may have important clinical implications, particularly in the treatment of complicated hypertension, such as that associated with patients with diabetes or the cardiometabolic syndrome, elderly patients, and African American patients, suggesting that mechanism of action may be an important consideration when choosing a beta-blocker.
Celiprolol in angina pectoris. [2019]Celiprolol, a long-acting beta1-selective adrenergic-blocking drug with peripheral beta2-stimulatory and peripheral a2-inhibitory activities, has a unique vasodilator beta-blocker pharmacologic profile. The efficacy and safety of celiprolol in angina pectoris have been demonstrated in multiple studies that highlight its different hemodynamic properties compared with traditional beta-blockers. Celiprolol was found to be an effective antianginal agent compared with placebo. In addition, in angina and ischemia its efficacy was comparable to that of propranolol and atenolol.