Use and adherence to beta‐blockers for secondary prevention of myocardial infarction: who is not getting the treatment?

PURPOSE: To characterise those who receive beta-blocker therapy after MI and to estimate the effect of adherence to beta-blocker use on subsequent mortality and recurrent MI. METHODS: A community-based observational cohort study was done using a record linkage database. Patients were those discharged from hospitals after their first MI between January 1994 and December 1995 and who also survived for at least 1 year. The outcome was all cause mortality and recurrent MI. Results were adjusted for age, sex, social deprivation, airways disease, peripheral vascular disease (PVD), diabetes mellitus, cardiovascular drug use, steroid use and hospitalisation for cardiovascular disease using a logistic regression model and a Cox regression model. RESULTS: A total of 865 patients were included in this study. 386 (44.6%) were on beta-blocker treatment during the year after MI. Beta-blocker use was lower amongst high-risk patients (older patients, patients with obstructive airway disease, PVD and those with a previous hospitalisation for heart failure). Mortality was lower in patients treated with beta-blockers compared with those untreated. Good adherence (>or=80%) was associated with a lower adjusted relative risk of mortality compared with unexposed patients (0.49, 95%CI 0.30-0.80, p < 0.01). Within the high-risk subgroup of patients, the adjusted relative risk of mortality with good adherence was 0.40 (0.17-0.93, p = 0.03). CONCLUSIONS: Beta-blocker use was lower in older patients, patients with airways disease, PVD and heart failure, but these patients appeared to have the greatest benefit from beta-blockers. Good adherence to beta-blocker treatment after MI was associated with a lower risk of mortality.     

No risk of drug-associated liver injury with alpha1-adrenoreceptor blocking agents in men with BPH: results from an observational study using the GPRD

PURPOSE: To compare the risk of liver injury in men treated with alpha1-blockers against that in a similar non-exposed population. METHODS: Using a study population registered on the UK General Practice Research Database (GPRD) we performed (a) a retrospective cohort analysis amongst men with lower urinary tract symptoms (LUTS) indicative of benign prostatic hypertrophy (BPH) comparing the incidence of liver injury in men exposed to alpha1-blockers with the incidence in those not exposed, and (b) two nested case-control studies looking at risk factors associated with the development of liver injury compared with age- or practice-matched controls. RESULTS: Amongst 45,851 men with LUTS/BPH, 9666 were exposed to an alpha1-blocker and 154 were identified with drug-induced/idiopathic liver injury. The crude incidence of liver injury in men with LUTS/BPH exposed to an alpha1-blocker was not statistically significantly different from that in the unexposed population (13.9 vs. 11.0 cases per 10,000 exposed years: incidence rate ratio (IRR) 1.28 [95% confidence interval (CI): 0.64, 2.31]). In the case-control analyses, the adjusted odds ratio (OR) of liver injury associated with exposure to alpha1-blockers compared with no use was not statistically significant (age-matched OR 0.92 [95%CI: 0.43, 1.97]; practice-matched OR 0.98 [95%CI: 0.45, 2.16]). Our analyses confirmed an association between liver injury and alcohol consumption as well as exposure to various classes of drugs known to be potentially hepatotoxic. CONCLUSIONS: This study could not offer any evidence to support an association between exposure to alpha1-blockers and liver injury in men with LUTS/BPH.     

Studies of the mechanisms involved in the production of stress and stress-atropine ulcers in rats

The mechanism of the production of gastric ulcers induced in atropinized rats under stress was investigated and compared with that of stress-induced ulcers (S-ulcer). The etiology of the stress-atropine ulcer (A-ulcer) was found to be mainly due to the participation of adrenergic nerves since the ulceration was inhibited by ganglion blockers, adrenergic blockers, and reserpine, though vagotomy also inhibited the formation of A-ulcer. On the other hand, S-ulcer was inhibited by certain nervous system depressants, ganglion blockres, vagotomy and atropine; therefore, a certrally mediated cholinergic factor was suggested to be the main factor in the ulceration.     

糖尿病合并高血压的可能机制和降压药选择策略

糖尿病合并高血压使患者心、脑血管事件和终末期肾病的发病危险明显增加。本文简述了糖尿病合并高血压的可能机制,并对糖尿病合并高血压患者的降压药选择进行了复习。目前的总体认识为：血管紧张素转换酶抑制剂、血管紧张素Ⅱ受体阻滞剂、钙通道阻滞剂对糖代谢和糖尿病本身的作用为中性,甚至可产生一定的有益作用;而利尿剂、β受体阻滞剂则可能对糖代谢产生不利影响,特别是当两者合用时,但现有的研究资料尚不能明确证实某一类型降压药具有明显的优越性,因此,无论使用何种药物,使患者的血压迅速、稳定地控制在130/80mmHg以下才是最重要的目标。     

Antihypertensive treatment and blood pressure control in patients with hypertension in daily clinical practice: a cross-sectional,multicenter, observational study in Egypt

Objective: Management of hypertension in Egypt is difficult because of various reasons. This real-life study was conducted to determine BP control rate, treatment modalities, factors influencing the choice of antihypertensive drugs, physicians’ satisfaction with the treatment, and demographics of patients with uncontrolled BP who were treated for hypertension in daily clinical practice in Egypt.

Methods: This was a cross-sectional, multicenter, observational study conducted in patients treated for hypertension in out-patient private clinics in Egypt, during October 2011 to June 2012.

Results: Of 4139 patients with hypertension, 1509 (36.5%) had controlled BP and 2630 (63.5%) had uncontrolled BP. In BP controlled vs. uncontrolled groups, respectively, beta-blockers (41.7% vs. 41.0%) were the most frequently used antihypertensive agents, followed by diuretics (40% vs. 37.8%), angiotensin-converting enzyme inhibitors (35.3% vs. 34.9%), angiotensin receptor blockers (31.1% vs.19.4%), and calcium channel blockers (21.3% vs. 19.4%); the factors influencing the choice of antihypertensive therapy were “add-on therapy” (1.5% vs. 32.4%) and “change the current medication” (9.3% vs. 50.8%); physicians’ satisfaction with treatment was rated as “excellent” (31.6% vs. 3.2%) and “poor” (1.6% vs. 58%).

Conclusion: The majority of patients from Egypt had uncontrolled hypertension even after receiving treatment. This might increase awareness among physicians and enable them to prescribe appropriate treatment to patients with uncontrolled BP.

Key limitations: The questionnaire used in the study for the evaluation of patient/physician satisfaction level was not standardized and was based on the choice and practice of the physicians     

The Road to Eleusis: Unveiling the Secret of the Mysteries

Abstract

Vivid imagery and hallucinations are occasionally reported by patients on beta-adrenergic blocking agents. The authors document this side effect with drawings by a well-known commercial artist.     

Cardiotoxic Overdose Treated with Intravenous Fat Emulsion and High-Dose Insulin in the Setting of Hypertrophic Cardiomyopathy

High-dose insulin (HDI) and intravenous fat emulsion (IFE) are used in overdoses, although rarely combined. To our knowledge, IFE therapy has not been reported in overdoses of diltiazem, metoprolol and amiodarone. We report a severe overdose of these drugs treated with HDI and IFE in a patient with hypertrophic cardiomyopathy (HCM). We also discuss the potential clinical implications of the inotropic effects of HDI in the setting of HCM and the use and efficacy of IFE in this overdose.     

Diastolic dysfunction in pulmonary artery hypertension: Creatine kinase and the potential therapeutic benefit of beta‐blockers

Passive properties of the myocardium influence diastolic filling and cardiac output. In heart failure, changes in contributors to the passive properties of the ventricle, such as titin and collagen, and loss of the metabolic enzyme creatine kinase, increase resistance to filling resulting in diastolic dysfunction. Pulmonary artery hypertension (PAH) arises from interactions between the pulmonary vasculature and the right ventricle (RV) which ultimately leads to RV failure. Beta1‐adrenergic receptor blockers (BB) act on the myocardium and are beneficial in left heart failure but are not used in PAH. We investigated whether BB improved survival and RV function in a rat model of PAH. Rats were injected with monocrotaline (60 mg/kg) to induce PAH and RV failure, or saline as controls (CON). When PAH was established, rats were treated with metoprolol (10 mg/kg per day) (MCT+BB) or vehicle (sucrose) (MCT); CON were treated with vehicle. In vivo measurement of RV compliance using pressure–volume catheter, indicated diastolic dysfunction in the RV of MCT rats was improved with BB treatment. Expression of creatine kinase protein and mRNA was lower in MCT rats compared to CON, with a trend for reversion by BB treatment. Isolated CON RV myocytes had a positive contraction response to faster pacing, whereas it was negative in MCT. MCT+BB cells had an intermediate response, indicating improved ability to respond to increased demand. BB improved diastolic function, partially restored metabolic enzymes and augmented contractility in PAH. These data support the hypothesis that BB may be beneficial in PAH by supporting RV function.     

The importance of a central adrenergic mechanism in the cardiovascular responses to ouabain

Central administration of ouabain in the ventricular system of vagotomized dogs and cats elicited increases in blood pressure, cardiac contractile force and cardiac rate followed by ventricular arrhythmia. Spinal transection (C₂) or hexamethonium treatment abolished the central effects of ouabain. Bilateral stellate ganglionectomy prevented the tachycardia and reduced the pressor response to the lower dose (15 μg) of ouabain; bilateral adrenalectomy only reduced the pressor effect. Neither of the procedures alone was adequate to inhibit the cardiovascular responses following a higher dose (90 μg) of ouabain whereas a combination of both procedures blocked these responses completely.Tachyphylaxis to the cardiovascular effects of very high doses of intracerebroventricularly (i.c.v.)-administered ouabain was shown to be of central origin. Prior depletion of brain catecholamines by Ro 4-1284 or 6-hydroxydopamine, and central adrenergic neuron blockade by bretylium prevented the centrogennic effects of ouabain. Similarly, central α- or β-adrenoceptor blockade also prevented the responses to i.c.v. ouabain. The results suggest that oubain causes the release of adrenergic mediator (noradrenaline) in the brain, probably by a depolarization of a primary neuron(s), and that the central adrenergic mechanism is responsible for the genesis of the cardiovascular effects. Both α- and β-adrenoceptors seem to be important in the central control of cardiovascular function. The most sensitive site for ouabain action was found to be the posterior hypothalamus in the vicinity of the third ventricle.     

Effect of prophylactic bisoprolol plus magnesium on the incidence of atrial fibrillation after coronary bypass surgery: results of a randomized controlled trial

ABSTRACT

Objective: Bisoprolol, a highly cardioselective β₁‐blockers, is widely used to treat elderly patients with hypertension, coronary artery disease and heart failure. The current literature lacks evidence regarding its potency to prevent atrial fibrillation (AF) following cardiac surgery. Therefore the aim of this study was to evaluate the efficacy of bisoprolol plus magnesium (Mg) in the prophylaxis of AF after coronary artery bypass graft (CABG) surgery.

Research design and methods: A total of 100 consecutive patients subjected to elective on-pump CABG (84 men, age 65 ± 8 [SD] years), with no prior AF history, were randomly assigned to the prophylaxis group (?n = 50) receiving after surgery bisoprolol (5?mg/day) plus Mg (intravenous infusion of 2?g of Mg on arrival in the intensive care unit, followed by oral Mg at 1800?mg/day for 1 week), or to the control group (?n = 50), receiving no combined study medication but remaining on their preoperative drugs, including β‐blockers. All patients were continuously monitored to identify the onset of AF.

Results: In the prophylaxis group the incidence of postoperative AF was significantly lower, with 20% (10 / 50) compared to 42% (21 / 50) among controls (?p = 0.030, 95% confidence interval [CI] for absolute risk reduction [ARR], 2–42%). Particularly in the elderly, bisoprolol plus Mg was effective in preventing AF; in the prophylaxis group only six of 36 (17%) patients ≥ 65 years of age developed AF, compared to 13 of 20 (65%) in the control group (?p < 0.001, 95% CI for ARR, 17–65%). This was associated with significantly (?p = 0.022) shorter hospital stays in the prophylaxis group (median of 7 vs. 9 days, 95% CI for difference in medians, 0–3 days).

Conclusions: The combination of bisoprolol plus Mg effectively reduces the incidence of postoperative AF following on-pump CABG, particularly in elderly patients, and is associated with a shorter hospital length of stay.     

Metoprolol monotherapy in the treatment of mild hypertension

Metoprolol tartrate (MT) as monotherapy was administered orally in 17 patients with mild hypertension. All other drugs were discontinued 2 weeks prior to MT therapy. The present study group consisted of 10 men and 7 women within the age range of 42 to 71 years (mean ± S.D. = 55.8 ± 8). MT was administered at an initial dose of 50 mg twice daily. Subsequently, the dose of MT was titrated on a biweekly basis for a period of 12 weeks until the diastolic blood pressure was < 90 mmHg or a maximum daily dose of 300 mg was administered. The blood-pressure-lowering effect of MT was found to be clinically satisfactory and statistically significant (P < 0.05). Mild fatigue and swelling of the extremities were seen in two patients each. Mild headache, transient diarrhea, and mild cloudiness of mind were seen in one patient. From this study it is concluded that MT is a safe and effective first-step antihypertensive agent. The long-term effect of MT as a monotherapy in the treatment of mild hypertension needs further clinical evaluation.     

Current treatment of hypertension in patients with coronary artery disease recommended by different guidelines

Introduction: It is important to know how to treat hypertension in patients with coronary artery disease (CAD). The reason for the review was to update this treatment and to discuss the 2015 American Heart Association/American College of Cardiology/American Society of Hypertension 2015 guidelines of treatment of hypertension in patients with CAD.

Areas covered: Studies between 1968 and 2015 were reviewed on treatment of hypertension in patients with CAD using a Medline search, and studies between 1977 and 2015 were reported. Hypertension should be treated with beta blockers and ACE inhibitors or angiotensin receptor blockers (ARBs). Long-acting nitrates are effective antianginal and anti-ischemic drugs. Calcium-channel blockers (CCBs) may be added if angina persists despite beta blockers and long-acting nitrates. The 2015 guidelines recommend that the blood pressure should be < 140/90 mm Hg in patients aged ≤ 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.

Expert opinion: Hypertension in patients with CAD should be treated with beta blockers and ACE inhibitors or ARBs. Long-acting nitrates are effective antianginal and anti-ischemic drugs. CCBs may be added if angina persists despite beta blockers and long-acting nitrates. The blood pressure should be < 140/90 mm Hg in patients aged < 80 years and the systolic blood pressure < 150 mm Hg if they are ≥ 80 years.