Low-dose Β-blocker Research Articles

Impact of Diabetes Mellitus on Benefit of β-Blocker Therapy After Myocardial Infarction

Beta blockers are uniformly recommended for all patients after myocardial infarction (MI), including those with diabetes mellitus (DM). This study assesses the impact of β-blocker type and dosing on survival in patients with DM after MI. A cohort of 6,682 patients in the Outcomes ofBeta-blockerTherapyAfter MyocardialINfarction registry were discharged after MI. In this cohort, 2,137 patients had DM (32%). Beta-blocker dose was indexed to the target daily dose used in randomized clinical trials and reported as percentage. Dosage groups were: no β blocker, >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of the target dose. The overall mean discharge β-blocker dose in patients with DM was 42.7 ± 34.1% versus 35.9 ± 27.4% in patients without DM (p <0.0001). Patients with DM were prescribed carvedilol at a higher rate than those without DM (27.8% vs 19.6%). The 3-year mortality estimates were 24.4% and 12.8% for patients with DM versus without DM (p <0.0001), respectively, with an unadjusted hazard ratio=1.820 (confidence interval 1.587 to 2.086, p <0.0001). Patients with DM in the >12.5% to 25% dose category had the highest survival rates, whereas patients in the >50% dose had the lowest survival rate among patients discharged on β blockers (p <0.0001). In the multivariable analysis among patients with DM after MI, all β-blocker dose categories demonstrated lower mortality than no therapy; however, only the >12.5% to 25% dose had a statistically significant hazard ratio 0.450 (95% confidence interval 0.224 to 0.907, p=0.025). In patients with DM, there was no statistically significant difference in 3-year mortality among those treated with metoprolol versus carvedilol. In conclusion, our analysis in patients with DM after MI suggested a survival benefit from β-blocker therapy, with no apparent advantage to high- versus low-dose β-blocker therapy; although, physicians tended to prescribe higher doses in patients with DM. There was no survival benefit for carvedilol over metoprolol in patients with DM.

Optimal Dose and Type of β-blockers in Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

The clinical benefit of β-blockers in modern reperfusion era is not well determined. We investigated the impact of β-blockers in acute coronary syndrome (ACS) after percutaneous coronary intervention. From the Grand-DES registry, a patient-level pooled registry consisting of 5 Korean multicenter prospective drug-eluting stent registries, a total of 6,690 ACS patients were included. Prescription records of dose and type of β-blockers were investigated trimonthly from discharge. Patients were categorized by the mean value of doses during the follow-up (≥50% [high-dose], ≥25% to <50% [medium-dose], and <25% [low-dose] of the full dose that was used in each randomized clinical trial) and vasodilating property of β-blockers. Three-year cumulative risk of all-cause death, cardiac death, and myocardial infarction were assessed. Patients receiving β-blockers were associated with a lower risk of all-cause and cardiac death compared with those not receiving β-blockers (adjusted hazard ratio [aHR] 0.29, 95% confidence interval [CI] 0.24 to 0.35 for all-cause death; aHR 0.27, 95% CI 0.21 to 0.34 for cardiac death). Medium-dose β-blocker group was associated with a lower risk of cardiac death compared with high- and low-dose β-blocker groups (aHR 0.49, 95% CI 0.25 to 0.96, for high-dose; aHR 0.46, 95% CI 0.29 to 0.74, for low-dose). Patients receiving vasodilating β-blockers were associated with a lower risk of cardiac death compared with those receiving conventional β-blockers (aHR 0.58, 95% CI 0.40 to 0.84). In conclusion, β-blocker therapy was associated with better clinical outcomes in patients with ACS, especially with medium-dose and vasodilating β-blockers.

Effect of Metoprolol Succinate in Patients with Stable Angina and Elevated Heart Rate Receiving Low-Dose β-Blocker Therapy.

Aims: β-blockers are underused in Chinese patients with coronary heart disease. The prescribed dose is often low. The aim of this study was to investigate the effect of metoprolol succinate doses of 95 mg and 190 mg on heart rate (HR) control, as well as drug tolerance, in Chinese patients with stable angina, low-dose β-blocker use and unsatisfactory HR control.Methods: This was a multicenter, randomized, open-label, parallel-group trial in 15 clinical sites. Patients with stable angina, taking low-dose β-blockers (equivalent to metoprolol succinate 23.75-47.5 mg/day), and having a resting HR of ≥ 65 bpm were enrolled and randomized to either the metoprolol 95-mg group or the 190-mg group. The change in 24-h average HR from baseline recorded by Holter monitoring and the percentages of patients with resting HR controlled to ≤ 60 bpm were compared between the two groups.Results: Two hundred thirty-one patients entered the intent-to-treat population for the main analysis. The change in 24-h average HR from baseline was -0.62 ± 0.66 bpm in the 95 mg group and -2.99 ± 0.62 bpm in the 190 mg group (p = 0.0077) after 8 weeks of treatment. The percentages of patients with resting HR controlled to ≤ 60 bpm were 24.1% (95% CI: 16.35%, 31.93%) and 40.0% (95% CI: 31.05%, 48.95%), respectively (p = 0.0019). Only 4 and 2 of the patients, respectively, discontinued the study drugs because of hypotension or bradycardia.Conclusions: The metoprolol succinate dose of 190 mg is superior to the 95 mg dose in terms of HR control, in Chinese patients with stable angina, low-dose β-blocker use and unsatisfactory HR control. Both doses were well tolerated.

Triple antianginal combinations in the treatment of elderly and senile patients with stable angina

To compare the efficiency and safety of antianginal therapy (AAT) using a combination of bisoprolol, ivabradine, and trimetazidine or ranolazine in elderly and senile patients with stable angina. The study enrolled 107 patients aged 60 to 79 years with coronary heart disease and Functional Class II and III angina. When the patients taking bisoprolol 1.25-2.5 mg once daily and ivabradine 2.5-7.5 mg twice daily continued to have angina and/or silent myocardial ischemia, after randomization 54 patients received an additional 35 mg of trimetazidine twice a day and 53 patients had ranolazine 500 mg twice daily. A comprehensive clinical and instrumental study was conducted prior to randomization and after 6 months of triple AAT. The patients tolerated well both treatments that substantially improved the results of a treadmill exercise test. Trimetazidine reduced to a greater extent the duration of silent ST-segment depression, as evidenced by Holter monitoring. Trimetazidine and ranolazine comparably improved left ventricular systolic and diastolic function, large arterial structure and function, and quality of life in the patients. The combinations of the low-dose β-blocker with ivabradine and trimetazidine or ranolazine may be used to treat refractory stable angina in elderly and senile patients. Trimetazidine is preferred due to its higher efficacy in treating silent myocardial ischemia and to its lower cost.

β-blocker dosage and outcomes after acute coronary syndrome

Although β-blockers increase survival in acute coronary syndrome (ACS) patients, the doses used in trials were higher than doses used in practice, and recent data do not support an advantage of higher doses. We hypothesized that rates of major adverse cardiac events (MACE), all-cause death, myocardial infarction, and stroke are equivalent for patients on low-dose and high-dose β-blocker. Patients admitted to Intermountain Healthcare with ACS and diagnosed with ≥70% coronary stenosis between 1994 and 2013 were studied (N = 7,834). We classified low dose as ≤25% and high dose as ≥50% of an equivalent daily dose of 200 mg of metoprolol. Multivariate analyses were used to test association between low-dose versus high-dose β-blocker dosage and MACE at 0-6 months and 6-24 months. A total of 5,287 ACS subjects were discharged on β-blockers (87% low dose, 12% high dose, and 1% intermediate dose). The 6-month MACE outcomes rates for the β-blocker dosage (low versus high) were not equivalent (P = .18) (hazard ratio [HR] = 0.76; 95% CI, 0.52-1.10). However, subjects on low-dose β-blocker therapy did have a significantly decreased risk of myocardial infarction for 0-6 months (HR = 0.53; 95% CI, 0.33-0.86). The rates of MACE events during the 6-24 months after presentation with ACS were equivalent for the 2 doses (P = .009; HR = 1.03 [95% CI, 0.70-1.50]). In ACS patients, rates of MACE for high-dose and low-dose β-blocker doses are similar. These findings question the importance of achieving a high dose of β-blocker in ACS patients and highlight the need for further investigation of this clinical question.

Abstract 17846: Prognosis of High Sinus Heart Rate After Catheter Ablation for Atrial Fibrillation

Introduction: Although radiofrequency catheter ablation (RFCA) for atrial fibrillation (AF) increases a sinus heart rate (HR) after rhythm control, its mechanism and prognosis have not yet been clearly elucidated. Hypothesis: We hypothesized that post-procedural high sinus HR is associated with better clinical outcome of AF ablation without hemodynamic adverse effects. Methods: We included 991 AF patients (75% male, 58 ± 11 years old, 70% paroxysmal AF [PAF]) who had analyzable HR variability (HRV) at 3-months and 1-year after RFCA, and pre- and post-1-year echocardiogram. Average HR measured by 24-hour Holter greater than 2SD (≥92bpm) was defined as post-ablation high sinus HR. Results: 1. Average heart rate was increased significantly (68.8±13.1 to 71.4±10.7bpm, p&lt;0.001), and high sinus HR (≥92bpm) was observed in 28 patients (2.8%) at 3-months after AF ablation. All of them tolerated well, 21% (6/28) were taking low dose β-blocker, and 36% (10/28) kept average HR≥92bpm at 1-year after RFCA. 2. High sinus HR was independently associated with pre-procedural high average HR (OR 1.097; 95% CI 1.029 to 1.169, p=0.005), high left atrial (LA) voltage (OR 3.545; 95% CI 1.183 to 10.618, p=0.024), and reduced rMSSD at 3-months HRV (OR 0.959; 95% CI 0.919 to 0.999, p=0.047). 3. At 1-year follow-up echocardiogram, LA reverse remodeling (ΔLA; -1.1±3.7 vs. -3.0±4.6mm, p=0.055) and the improvement of ejection fraction (ΔEF; 0.7±8.4 vs. 1.7±7.7%, p=0.529) were not significantly different between the patients with high sinus HR and those without. 4. During 27±17 months of follow-up, the patients with high sinus HR at 3-months after RFCA showed significantly lower clinical recurrence than those without (log rank, p=0.020). Conclusions: High sinus HR 3-months after AF ablation is observed in patients with less remodeled LA with significant post-procedure vagal modulation. High sinus HR after AF ablation did not show hemodynamic adverse effect and was associated with lower clinical recurrence rate of AF after RFCA.

GW26-e2438 Efficacy and safety of low-dose β-blocker for the treatment of vasovagal syncope

GW26-e2438 Efficacy and safety of low-dose β-blocker for the treatment of vasovagal syncope

The Effect of Low-Dose β-Blocker on Heart Rate and Heart Rate Variability in Healthy Subjects with a Resting Heart Rate of Less than 65 Beats per Minute: Effect on the Image Quality of Prospective Electrocardiography-Gated Coronary CT Angiography

The Effect of Low-Dose β-Blocker on Heart Rate and Heart Rate Variability in Healthy Subjects with a Resting Heart Rate of Less than 65 Beats per Minute: Effect on the Image Quality of Prospective Electrocardiography-Gated Coronary CT Angiography

Low-Dose β-Blocker in Combination With Milrinone Safely Improves Cardiac Function and Eliminates Pulsus Alternans in Patients With Acute Decompensated Heart Failure

The purpose of this study was to determine whether a low-dose β-blocker, in combination with milrinone, improves cardiac function in acute decompensated heart failure (ADHF) with tachycardia. Twenty ADHF patients (New York Heart Association classification III, n=1, and IV, n=19; heart rate [HR], 107±12 beats/min; left ventricular ejection fraction, 24±7%; cardiac index [CI], 2.2±0.6 L·min(-1)·m(-2); pulmonary capillary wedge pressure [PCWP], 26±8 mmHg) were enrolled in this study. The patients first underwent conventional therapy with milrinone, vasodilators and diuretics; landiolol (1.5-6.0 µg·kg(-1)·min(-1); i.v.), which is an ultra-short-acting β(1)-selective blocker, was then added to the treatment regimen to study its effect on hemodynamics. Low-dose landiolol (1.5 µg·kg(-1)·min(-1)) significantly reduced HR by 11% without changing blood pressure (BP) and CI, whereas higher doses (≥3.0 µg·kg(-1)·min(-1)) tended to decrease BP and CI while increasing PCWP and systemic vascular resistance. After treatment with landiolol (1.5 µg·kg(-1)·min(-1)), hemodynamic parameters such as PCWP, stroke volume index, SvO(2), rate pressure product, filling time/RR, E/e', and Tei index were significantly improved. A low-dose β-blocker in combination with milrinone improved cardiac function in ADHF patients with tachycardia; therefore, it may be considered as an adjunct therapy for use when standard therapy with milrinone is not effective at slowing HR.

A Novel Mutation in the RYR2 Gene Leading to Catecholaminergic Polymorphic Ventricular Tachycardia and Paroxysmal Atrial Fibrillation: Dose-Dependent Arrhythmia-Event Suppression by β-Blocker Therapy

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a genetic condition that presents with exercise-induced polymorphic arrhythmias. We describe a case report of a 25-year-old woman who had a cardiac arrest due to ventricular fibrillation. Genetic analysis revealed a novel missense mutation in exon 90 of the ryanodine receptor (RyR2) gene resulting in substitution of arginine for serine at residue 4153 (S4153R). The patient received an implantable cardioverter-defibrillator and low-dose β-blocker therapy. She had recurrent polymorphic ventricular arrhythmias treated with appropriate cardioverter-defibrillator shocks and paroxysmal atrial fibrillation. Titration of β-blocker to a much higher dose suppressed further episodes of ventricular arrhythmia and paroxysmal atrial fibrillation, resulting in reduction in device therapies.

When the Worst Headache Becomes the Worst Heartache!

Although a great deal of literature has been generated regarding left ventricular wall abnormalities, ECG changes and cardiac enzyme leaks associated with subarachnoid hemorrhage (SAH), there have been only a few reports of true transient left ventricular apical ballooning syndrome in patients with SAH. Several pathophysiological mechanisms have been proposed to explain the unusual features of this syndrome, such as multivessel coronary vasospasm, abnormalities in coronary microvascular function, and catecholamine-mediated cardiotoxicity. Summary of Case- A previously healthy 64-year-old woman with no history of vascular disease was found unresponsive at home. She was taken to the emergency room where a CT head revealed an SAH due to a ruptured aneurysm of the posterior communicating artery. On admission, an ECG showed deeply inverted T-waves and QT prolongation, typical of SAH. Cardiac troponin was measured at 1.2 ng/mL, and later increased to 3.7 ng/mL. A transthoracic echocardiogram on the next day revealed a large left ventricular wall abnormality, characteristic of apical ballooning with an ejection fraction of 25% to 30%. The patient remained hemodynamically stable and was started on low dose beta-blocker and angiotensin-converting enzyme inhibitor. She had an uneventful cardiac recovery within 5 days at which time a repeat transthoracic echocardiogram revealed a normal ejection fraction with no wall motion abnormality. This report adds to the growing list of "stressors" for Takotsubo cardiomyopathy. Clinicians should be aware of the existence and the typical clinical manifestations of this syndrome, which is increasingly recognized in various populations. In particular, neurologists should consider this syndrome in the differential diagnosis of ECG changes and apical wall motion abnormalities in patients with SAH. Prognosis is generally very good with full recovery in most patients; however, there may be increased morbidity associated in patients with SAH.

Rate of heart failure and 1-year survival for older people receiving low-dose β-blocker therapy after myocardial infarction

Many older people do not receive beta-blocker therapy after myocardial infarction or receive doses lower than those tested in trials, perhaps because physicians fear that beta-blockers may precipitate heart failure. We examined the relation between use of beta-blockers, the dose used, and hospital admission for heart failure and 1-year survival in a cohort of all older patients surviving myocardial infarction in Ontario, Canada. We collected data on a cohort of 13,623 patients aged 66 years or older who were discharged from hospital after a myocardial infarction and who did not receive beta-blocker therapy or received low, standard, or high doses. We used Cox's proportional-hazards models to study the association of dose with admission for heart failure and survival with adjustment for factors including age, sex, and comorbidity. Among 8232 patients with no previous history of heart failure, dispensing of beta-blocker therapy was associated with a 43% reduction in subsequent admission for heart failure (adjusted risk ratio 0.57 [95% CI 0.48-0.69]) compared with patients not dispensed this therapy. Among the 4681 patients prescribed beta-blockers, the risk of admission was greater in the high-dose than in the low-dose group (1.53 [1.01-2.31]). Among all 13,623 patients in the cohort, 2326 (17.1%) died by 1 year. Compared with those not dispensed beta-blocker therapy, the adjusted risk ratio for mortality was lower for all three doses (low 0.40 [0.34-0.47], standard 0.36 [0.31-0.42], high 0.43 [0.33-0.56]). Compared with high-dose beta-blocker therapy, low-dose treatment is associated with a lower rate of hospital admission for heart failure and has a similar 1-year survival benefit. Our findings support the need for a randomised controlled trial comparing doses of beta-blocker therapy in elderly patients.