Beta-adrenoceptor Blocking Research Articles

Cost analysis of different brands of antianginal drugs available in India

Background: Ischemic heart disease is the most common cardiovascular disease in developed countries such as United States and Angina pectoris is the most frequent among them. If not managed adequately angina results in significant morbidity and mortality too due to the complications. Antianginal therapy is lifelong. Therefore, analysis of the price of drugs used in ischemic heart disease will help to improve patient compliance. Methods: Prices of various antianginal drugs of different strengths and combinations marketed by different companies was obtained from current index of medical stores. The variation between highest and lowest price of the same medication manufactured by various pharma companies and percentage variation in price for ten tablets was calculated. Results: In India, percentage variation in price for antianginal drugs was found to be: tablet isosorbide dinitrate (5 mg) 250%, glyceryltrinitrate (6.4 mg) 24.44%. In calcium channel blockers group, tablet amlodipine 10 mg shows maximum price variation of 1045%, closely followed by 5 mg of amlodipine with a variation of 1040%, while 120 mg of diltiazem shows the least variation of 262%. In betaadrenergic receptor blockers group, tablet atenolol 50 mg shows maximum price variation of 563%, whereas 100 mg of extended release metoprolol shows the least variation of 42%. Conclusions: To increase the benefit to the patient and reduce drug in compliance, doctors should be trained to be familiar from internship period itself about the brand names of cost-effective drugs with good safety profile for a long period.

Infantile haemangioma: a complicated disease.

Infantile haemangiomas (IH) are common benign vascular tumors of childhood. They are characterised by rapid growth during the first year of life and slow regression that is usually completed by 7-10 years of age. The underlying mechanism of action of IH is aberrant angiogenesis and vasculogenesis, and involves the mammalian target of rapamycin pathway and vascular endothelial growth factor pathway. IH become a challenge if they are part of a syndrome, are located in certain areas of the body, or if complications develop. The beta-adrenergic receptor blocker propranolol is a promising new candidate for first-line systemic therapy. This review focuses on the clinical characteristics, pathogenesis and management of IH.

A case of cardiac sarcoidosis with atrioventricular nodal dysfunction revealed by the administration of beta-receptor blocker

A case of cardiac sarcoidosis with atrioventricular nodal dysfunction revealed by the administration of beta-receptor blocker

Impact of alpha- and beta-adrenergic receptor blockers on fractional flow reserve and index of microvascular resistance.

We investigated the effect of β- and α-adrenergic blockers on fractional flow reserve (FFR) and index of microvascular resistance (IMR). In 43 patients (pts) with intermediate stenoses, we measured FFR and IMR before and after nonselective β-blocker propranolol (30 μg/kg, n = 20) and selective β1-blocker metoprolol (40 μg/kg, n = 23) IC; (b) In additional 21 pts after percutaneous coronary intervention (PCI), FFR and IMR were measured before and after α-blocker phentolamine (3 mg) IC. Neither propranolol nor metoprolol changed values of FFR and IMR. Phentolamine slightly decreased FFR (from 0.88 ± 0.05 to 0.87 ± 0.06, p = 0.025) but did not change IMR. FFR decreased from >0.80 to ≤0.80 in 3 pts (14%), but in none, the value decreased to <0.75. β-blockers do not affect FFR and IMR in intermediate stenoses. After PCI, a mild decrease in FFR occurs after α-blockers, though of limited clinical impact.

Histopathologic examination of the retina following intra-vitreal propranolol administration in rabbits

Propranolol is a nonselective, beta-adrenergic receptor blocker with anti-angiogenic and anti-inflammatory effects that could be used in the treatment and control of many vascular disorder-related retinopathies. In this pilot study, the effects and complications of an intra-vitreal injection of propranolol HCl on the rabbit retina were investigated by clinical and histopathological means as the first step to determination the viability of intra-vitreal propranolol administration. Group 1 (n = 8) had 15 μg of propranolol HCL given, via intra-vitreal injection, into the right eye. Group 2 (n = 8) had a matching volume of balanced saline solution also via intra-vitreal injection into the right eye. After 4 weeks, all rabbits were killed humanely and the right eyes from both groups enucleated for histopathological study. Clinical observations and histopathological findings suggest no difference between propranolol and control groups (P ≥ 0.05). As a result of handling, in some cases, the eyes had light inflammation, hyperaemia and oedema with acute degeneration changes. This study shows that 15 μg of propranolol does not cause any significant abnormalities and is not a toxic dose for intra-vitreal injection in rabbits.

PARADIGM-HF: Have we achieved a new paradigm in the treatment of heart failure?

PARADIGM-HF After several years of a disappointing series of negative clinical trials investigating novel therapies for systolic heart failure, the presentation of the landmark PARADIGM-HF [Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure] trial at the 2014 Congress of the European Society of Cardiology in Barcelona, with simultaneous publication in the New England Journal of Medicine, 1 has created considerable excitement and optimism. With knowledge that the trial had been halted prematurely by the independent data and safety monitoring committee (DSMB), the results were eagerly anticipated, and the trial results lived up to the expectations. PARADIGM-HF investigated the impact of LCZ696 (the novel combination of an angiotensin-receptor blocker (ARB) plus the neprilysin inhibitor sacubitril) compared to the angiotensin converting enzyme (ACE) inhibitor enalapril on outcomes of 8442 patients with heart failure and left ventricular systolic dysfunction (ejection fraction 40%). ACE inhibitors have been the cornerstone of treatment for heart failure with reduced ejection fraction for over two decades and are firmly embedded in U.S. and European guidelines for the management of heart failure. 2,3 Virtually all patients in the trial were receiving ACE inhibitors or ARBs prior to enrollment but had persistent left ventricular dysfunction. The trial randomly assigned 4187 patients to receive LCZ696 200 mg twice daily and 4212 to receive enalapril 10 mg twice daily. The 200 mg dose of LCZ696 includes the ARB equivalent of 160 mg of valsartan. Background therapy included beta adrenergic receptor blockers in 93% of patients and mineralocorticoid antagonists in 56%. The primary endpoint was cardiovascular death or hospitalization for heart failure, but PARADIGM-HF was also designed as a cardiovascular mortality trial with the power to detect a 15% reduction in mortality with LCZ696 compared to enalapril, which would represent a doubling of survival benefit relative to that of current inhibitors of the renin-angiotensin system. The DSMB was allowed to halt the trial prematurely only if there was a compelling effect on cardiovascular mortality. The DSMB stopped the trial after a median follow-up period of 27 months, because of evidence of significant benefit of LCZ696, with cardiovascular mortality rates of 13.3% in the LCZ696 group and 16.5% in the enalapril group (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.71 to 0.89; P , 0.001). At the time of trial termination, 21.8% of the LCZ696 group and 26.5% of the enalapril group had reached the primary combined endpoint (HR 0.80; 95% CI, 0.73 to 0.87; P , 0.001). LCZ696 was also associated with lower overall mortality 17.0% versus 19.8%; HR 0.84; 95% CI, 0.76 to 0.93; P , 0.001), reduced risk of hospitalization (21% decrease, P , 0.001) and reduced symptomatic limitation (P ¼ 0.001). Hypotension and non-serious angioedema occurred more frequently in the LCZ696 group, but renal impairment, hyperkalemia, and cough occurred more frequently in the enalapril group.

A nurse-led up-titration clinic improves chronic heart failure optimization of beta-adrenergic receptor blocking therapy--a randomized controlled trial.

BackgroundBeta-adrenergic blockade has been shown to improve left ventricular function, reduce hospital admissions and improve survival in chronic heart failure with reduced ejection fraction (HFrEF), with mortality reduction starting early after beta-adrenergic receptor blocker initiation and being dose-related. The aim of this pilot study was to determine the effectiveness of a nurse-led titration clinic in improving the time required for patients to reach optimal doses of the beta-adrenergic receptor blocking agents.MethodWe conducted a prospective pilot randomized controlled trial. Twenty eight patients with CHF were randomized to optimisation of beta-adrenergic receptor blocker therapy over six months by either a nurse-led titration (NLT) clinic, led by a nurse specialist with the support of a cardiologist in a CHF clinic, or by their primary care physician (usual care (UC)). The primary endpoint was time to maximal beta-adrenergic receptor blocker dose. The secondary end-point was the proportion of patients reaching the target dose of beta-adrenergic receptor blocker by six months.ResultsThe patients were predominantly men (72%), age 67 ± 16 years; New York Heart Association (NYHA) functional class I (32%), II (44%) and III (20%); baseline left ventricular ejection fraction 33 ± 10%, and a low mean Charlson co-morbidity score of 2.5 ± 1.4. The time to maximum dose was shorter in the NLT group compared to the UC group (90 ± 14 vs 166 ± 8 days, p < 0.0005). At six months, in the NLT group there were nine patients (82%) on high dose and one patient (9%) on low dose beta-adrenergic receptor blocker compared to the UC group with five (42%) patients reaching maximum dose and five (42%) patients on low dose (p = 0.04). The patients allocated to the NLT group also had significantly less worsening of depression between baseline and six months (p = 0.006).ConclusionA NLT clinic improves optimisation of beta-adrenergic receptor blocker therapy through increasing the proportion of patients reaching maximal dose and facilitating rapid up-titration of beta-adrenergic receptor blocker agents in patients with chronic HFrEF.Trial registrationAustralian Clinical Trials Registry (ACTRN012606000383561).

Bloqueadores beta en shock séptico: una revisión

In septic shock, high adrenergic stress is associated with cardiovascular and systemic adverse effects, which can negatively affect the results. Beta-adrenergic receptor block has been shown to be effective in controlling the disproportionate increase in heart rate, maintaining a favorable hemodynamic profile and apparently improving the efficiency of the cardiovascular system in order to maintain tissue perfusion. They have also been shown to modulate favorably catecholamine-induced immunosuppression and to decrease insulin resistance, protein catabolism, and proinflammatory cytokine expression associated with cardiovascular dysfunction. Selective beta-1 blockers appear to provide better results than non-selective blockers, even suggesting a positive impact on mortality. Future clinical trials are still needed to confirm these findings and define the scope of their benefits.

English

The role of adrenergic receptors in nicotine-induced hyperglycaemia has not been well studied in amphibians. Thus, this study investigates the effects of alpha and beta adrenergic receptor blockers in nicotine-induced hyperglycaemia in the common African toad Bufo regularis. Toads fasted for 24 h were anaesthetized with sodium pentobarbitone (3 mg/100 g body weight) intraperitoneally (i.p) and given intravenous (i.v) injection of 0.7% amphibian saline, or nicotine (50 &micro;g/kg), nicotine(50 &micro;g/kg i.v) 30 min after pretreatment with prazosin (0.2 mg/kg i.v), propranolol (0.5 mg/kg i.v) or combination of both prazosin (0.2 mg/kg i.v) and propranolol (0.5 mg/kg, i.v). Thereafter, blood samples were also collected from truncus arteriosus for estimation of blood glucose level using the modified glucose oxidase method. Nicotine caused significant increase (P&lt;0.01) in the levels of blood glucose in the common African toad. Pre-treatment of the toads with prazosin (0.2 mg/kg i.v) or propranolol (0.5 mg/kg, i.v) significantly (p &lt; 0.01) reduced the hyperglycaemia induced by nicotine (50 &micro;g/kg i.v). However, the combination of prazosin (0.2 mg/kg i.v) and propranolol (0.5 mg/kg, i.v) abolished the hyperglycaemic effect of nicotine (50 &micro;g/kg i.v). The above results on glucose metabolism suggests involvement of both alpha and beta adrenoceptors in nicotine-induced hyperglycaemia in common African toad B. regularis. &nbsp; Key words: Nicotine, hyperglycaemia, prazosin, propranolol, common African toad Bufo regularis.

Abstract 146: Biphasic Effect Of Cyclic Amp Axis On Cardiomyocyte Survival

Background: Persistent cardiac hypertrophy in response to pathological stimuli is results in maladaptive myocardial remodeling and cell death. Clinical evidence revealed that one of the most significantly beneficial medications for targeting heart failure with pathologic myocardial hypertrophy is beta1-adrenergic receptor (β1R) blockers. The molecular pathway of β1R is mediated by the second messenger cyclic AMP (cAMP). However, there are some debate regarding the role of cAMP in myocardial survival. We hypothesized whether there may be threshold concentration of cAMP in cell susceptibility to cardiomyocyte cell death. Methods: Male 14-week-old C57BL6 mice were subjected to the surgery of thoracic aortic constriction (TAC) to induce pressure overload. Changes in apoptosis were evaluated in each heart section and in vitro culture of neonatal cardiomyocytes using TUNEL. To elucidate the concentration-dependent distinct effect of cAMP on myocardial cell death, we tested the different concentration of cell-permeable cAMP (8-br-cAMP) at low (60 μM) and high concentration (6 mM), and receptor-mediated cAMP-stimulators (Ex4; exendin-4, ISO; isoproterenol). Results: In vitro analysis revealed that the high-cAMP and ISO exhibited marked increase in TUNEL-positivity (15.46%±3.09% for high-cAMP versus 6.71%±0.33% for ISO), which was reversed by Rp-cAMP (1.80%±0.17% and 2.05%±0.25%, respectively). Unexpectedly, the 8-p-Methoxyphenylthon-2-O-methyl-cAMP (pMe-cAMP, 50 μM), the specific activator of another cAMP-sensitive target Epac, reversed the high-cAMP-induced cell death even at a less extent compared to that observed by PKA-inhibitor Rp-cAMP (3.73%±0.70%). Serum depletion induced 3.22±0.24% of TUNEL-positive cell count of NRVM, which was reversed by pMe-cAMP, (50 μM) and Ex4 (1.74±0.18%, n=6, P&lt;0.01), which was insensitive to PKA inhibition by Rp-cAMP (100 μM). TAC increased myocardial apoptosis. TAC-CON heart exhibited 1.66-fold decrease in cardiac cAMP concentration compared to sham-CON. Ex4 ameliorated the TAC-induced cardiac dysfunction and apoptosis by increase in cAMP. Conclusions: The cAMP-related cell death was mediated by PKA activation, which were reversed by Epac activation.

An observational study of bimatoprost 0.01% in patients on prior intraocular pressure-lowering therapy: the Canadian Lumigan(®) RC Early Analysis Review (CLEAR) trial.

PurposeTo evaluate the ocular hyperemia and intraocular pressure (IOP)-lowering efficacy of bimatoprost 0.01% in subjects with elevated IOP due to primary open-angle glaucoma (POAG) or ocular hypertension (OHT) in a real-world clinical setting.Subjects and methodsThis open-label, 12-week, observational study was conducted at 67 centers in Canada. Subjects with elevated IOP due to POAG or OHT instilled bimatoprost 0.01% as monotherapy once daily. Ocular hyperemia was graded by the investigator at baseline, week 6, and week 12 using a standardized photographic 5-point grading scale. Change in IOP from baseline was also evaluated at these time points. This analysis includes the subgroup of 268 subjects who had been previously treated with latanoprost 0.005%, bimatoprost 0.03%, travoprost 0.004%, and travoprost 0.004% with SofZia™ or nonselective beta-adrenergic receptor blockers prior to the study.ResultsAfter 12 weeks of treatment with 0.01% bimatoprost, ocular hyperemia was graded as none-to-mild hyperemia (grades 0, +0.5, or +1) for 94.1% of subjects and as moderate-to-severe hyperemia (grades +2 or +3) for 5.9%. No statistically significant shifts in ocular hyperemia ratings were observed at week 12 for any of the prior IOP-lowering therapies except bimatoprost 0.03%, in which 20.8% of subjects experienced an improvement. The mean percentage change from baseline IOP at week 12 following the switch to bimatoprost 0.01% monotherapy ranged from −2.3%±17.3% to −26.3%±12.4%. Furthermore, the decreased mean percentage change from baseline IOP was statistically significant across all prior IOP-lowering medications, except for bimatoprost 0.03% at the 6- and 12-week visits and travoprost 0.004% at the 6-week visit.ConclusionThis observational study demonstrates that bimatoprost 0.01% was well tolerated among POAG and OHT subjects who switched from prior IOP-lowering medication. Furthermore, a switch in ocular hypertensive treatment to bimatoprost 0.01% was associated with an additional 10%–15% reduction in IOP.

Influence of Beta Blockers on Survival in Dogs with Severe Subaortic Stenosis

BackgroundSubaortic stenosis (SAS) is one of the most common congenital cardiac defects in dogs. Severe SAS frequently is treated with a beta adrenergic receptor blocker (beta blocker), but this approach largely is empirical.ObjectiveTo determine the influence of beta blocker treatment on survival time in dogs with severe SAS.MethodsRetrospective review of medical records of dogs diagnosed with severe, uncomplicated SAS (pressure gradient [PG] ≥80 mmHg) between 1999 and 2011.ResultsFifty dogs met the inclusion criteria. Twenty‐seven dogs were treated with a beta blocker and 23 received no treatment. Median age at diagnosis was significantly greater in the untreated group (1.2 versus 0.6 years, respectively; P = .03). Median PG at diagnosis did not differ between the treated and untreated groups (127 versus 121 mmHg, respectively; P = .2). Cox proportional hazards regression was used to identify the influence of PG at diagnosis, age at diagnosis, and beta blocker treatment on survival. In the all‐cause multivariate mortality analysis, only age at diagnosis (P = .02) and PG at diagnosis (P = .03) affected survival time. In the cardiac mortality analysis, only PG influenced survival time (P = .03). Treatment with a beta blocker did not influence survival time in either the all‐cause (P = .93) or cardiac‐cause (P = .97) mortality analyses.ConclusionsBeta blocker treatment did not influence survival in dogs with severe SAS in our study, and a higher PG at diagnosis was associated with increased risk of death.

Blood pressure lowering efficacy of nonselective beta-blockers for primary hypertension.

Beta-blockers are one of the classes of drugs frequently used to treat hypertension. Quantifying the blood pressure (BP) lowering effects of nonselective beta-blockers provides important information that aids clinical decision making. To quantify the dose-related effects of nonselective beta-adrenergic receptor blockers (beta-blockers) on systolic blood pressure (SBP) and diastolic blood pressure (DBP) as compared with placebo in people with primary hypertension. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and ClinicalTrials.gov for randomized controlled trials up to October 2013. Randomized, double-blind, placebo-controlled, parallel or cross-over trials. Studies had to contain a nonselective beta-blocker monotherapy arm with a fixed dose. Participants enrolled into the studies had to have primary hypertension at baseline. Duration of studies had to be between three and 12 weeks. Two review authors (GW and AL) independently confirmed the inclusion of studies and extracted the data. We included 25 RCTs that evaluated the BP lowering effects of seven nonselective beta-blockers in 1264 people with hypertension. Among the 25 RCTs, four were parallel studies and 21 were cross-over studies. Overall, nonselective beta-blockers lowered systolic BP and diastolic BP compared with placebo. Nonselective beta-blockers, in the recommended dose range, did not showed a convincing dose-response relationship by direct comparison. The once (1x) and twice (2x) starting dose subgroups contained the largest sample size. The estimate of BP lowering efficacy for nonselective beta-blockers by combining the 1x and 2x starting dose subgroup was -10 mmHg (95% CI -11 to -8) for systolic BP and -7 mmHg (95% CI -8 to -6) for diastolic BP (low-quality evidence). Nonselective beta-blockers starting at the 1x recommended starting doses lowered heart rate by 12 beats per minute (95% CI 10 to 13) (low-quality evidence). The dose-response relationship in heart rate was evident by both direct and indirect comparison. Due to imprecision, there was no clear evidence of an effect of nonselective beta-blockers on pulse pressure in any dose subgroups except for a small reduction with the 2x starting dose (-2.2 mmHg, 95% CI -3.7 to -0.7) (very low quality evidence). The point estimates in the 1x, four times (4x) and eight times (8x) starting dose subgroups were similar to the 2x starting dose subgroup. Therefore, it would appear that if nonselective beta-blockers do lower pulse pressure, the magnitude is likely to be about 2 mmHg. There were very limited data (two studies) on withdrawals due to adverse effects (risk ratio (RR) 0.84; 95% CI 0.38 to 1.82). In people with mild-to-moderate hypertension, nonselective beta-blockers lowered peak BP by a mean of -10/-7 mmHg (systolic/diastolic) and reduced heart rate by 12 beats per minute. Propranolol and penbutolol were the two drugs that contributed to most of the data for nonselective beta-blockers. This estimate is likely exaggerated due to the presence of extreme outliers and other sources of bias. If we removed the extreme outliers from the analysis, the estimate for non-selective beta-blockers was lower (-8/-5 mmHg (systolic/diastolic)). Nonselective beta-blockers did not show a convincing graded dose-response in the recommended dose range for systolic BP and diastolic BP, while higher dose nonselective beta-blockers provided greater reduction of heart rate. Using higher dose nonselective beta-blockers might cause more side effects, such as bradycardia, without producing an additional BP lowering effect. The effect of nonselective beta-blockers on pulse pressure was likely small, at about 2 mmHg.

Markers of Inflammation, Endothelial Activation, and Arterial Stiffness in Hypertensive Heart Disease and the Effects of Treatment

We assessed the contribution of blood pressure (BP), inflammation, and endothelial activation to the development of structural vascular and cardiac changes in hypertension. Furthermore, the effects of antihypertensive therapy were studied. We studied 114 patients with hypertension and left ventricular hypertrophy and 38 matched hypertensive subjects without cardiac hypertrophy and 38 normotensive subjects. The group with hypertension and cardiac hypertrophy were randomized to treatment with an angiotensin receptor blocker (irbesartan) or a beta-adrenergic receptor blocker (atenolol) for 48 weeks. Markers of inflammation (high-sensitive C-reactive protein, interleukin-6, leukocyte counts), vascular function (ambulatory aortic stiffness index, arterial compliance, and pulse pressure), and endothelial activation (E-selectin, intracellular adhesion molecule-1, vascular adhesion molecule-1) were assessed. Markers of inflammation and arterial stiffness were lowest in the normotensive group and highest in patients with hypertensive heart disease; endothelial markers were similar between groups. Inflammation was independently related to BP. Markers of arterial stiffness were independently related to BP and to a lesser extent to left ventricular mass. Antihypertensive treatment improved arterial compliance; inflammatory and endothelial markers remained unchanged. In conclusion, markers of inflammation and arterial stiffness are independently related to BP. Antihypertensive therapy seems to improve arterial stiffness, but effects on markers of inflammation and endothelial activation are small.

The beta-1 receptor blocker atenolol increases mortality in a mammal in association with its depressing effects on heart function only in very old individuals: agreement with meta-analyses in hypertensive human patients?

association with its depressing effects on heart function only in very old individuals: agreement with meta-analyses in hypertensive human patients? A. Gomez1, I. SanchezRoman1, J. Gomez1, C. Sanchez1 A. Naudi2, M. Portero-Otin2 ,R. Pamplona2 M. Lopez-Torres1 and G. Barja1 1Department of Animal Physiology-II, Complutense University of Madrid, Spain 2Department of Experimental Medicine, University of Lleida, Spain

Epidemiology and treatment of chronic heart failure; use of bisoprolol

The prevalence of chronic heart failure in Hungary is 1.6% in the adult population, but it occurs in 15-20% of subjects over 80 years of age. The base of treatment of heart failure is the blockade of the neuro-hormonal system, which includes the use of angiotensin converting enzyme inhibitors (angiotensin receptor blockers in case of angiotensin converting enzyme inhibitors intolerance), beta receptor blockers and mineralocorticoid receptor antagonists. Because of their negative inotropic effect, beta blockers were neglected for a long time from the treatment of heart failure. However, during the past decades several studies have demonstrated that beta blockers decrease mortality in patients with heart failure. The effectiveness of bisoprolol in reducing mortality has also also been documented in a number of studies.

Does Our “Flight and Fight” Response Have a Link With Cancer?

Does Our “Flight and Fight” Response Have a Link With Cancer?

Efficacy of beta blockers in the management of problem behaviours in people with intellectual disabilities: A systematic review

Both medication and non-medication based strategies are used in the management of problem behaviours in individuals with intellectual disabilities. Beta-adrenoceptor blocking medications are one group of drugs used for this purpose. However, despite its regular use, the evidence for the efficacy of these drugs for in this context is lacking. A systematic review was conducted to establish the research evidence for the efficacy of beta blockers in problem behaviours in adults and children with intellectual disabilities. Although the research identified supported the efficacy of beta blockers for this indication the overall quality of studies identified was poor and no randomised controlled trials were identified. There is a need for more robust research into the use of beta blockers for people with intellectual disabilities who show problem behaviours.

Selective atrial profibrotic signalling in mice and man

This editorial refers to ‘Molecular basis of selective atrial fibrosis due to overexpression of transforming growth factor-β1’ by D. Rahmutula et al. , pp. 769–779, this issue. Although oral anticoagulation can prevent the majority of strokes in patients with atrial fibrillation (AF) if used as recommended in treatment guidelines,1 patients with AF receiving optimal therapy still die prematurely, and are frequently hospitalized.2 Hence, we need a deeper understanding of the mechanisms behind AF in patients to develop better treatment. Most of the currently used treatments for AF were initially developed to treat ventricular heart disease, e.g. angiotensin-converting enzyme inhibitors, digitalis, beta-adrenoceptor blockers, spironolactone, and most antiarrhythmic drugs. Understanding electrophysiological differences between the atria and ventricles have allowed the recent development of atrial antiarrhythmic drugs (dronedarone, vernakalant), with others undergoing clinical development. Catheter ablation of AF also illustrates how the understanding of an atrial arrhythmia mechanism, i.e. focal firing in and around the pulmonary veins, helped develop a specific AF treatment. In this issue of Cardiovascular Research , Rahmutula et al. 3 characterize a molecular pathway leading to selective atrial fibrosis. By analysing human atrial and ventricular tissues, they identified an atrial preponderance of transforming growth factor-β (TGF-β) expression, and higher atrial TGF-β …

EVALUATION OF THE RELATIVE INCIDENCE OF ADVERSE EFFECTS LEADING TO TREATMENT DISCONTINUATION OF RECOMMENDED ANTIHYPERTENSIVE DRUGS

This study aimed at evaluating the incidence of adverse effects leading to treatment discontinuation of antihypertensive drugs within the same therapeutic class. Individual medical records were searched to identify those hypertensive patients who had been commenced on antihypertensive therapy during a 24 month period and who had subsequently for a reason (s) discontinued the therapy. The results showed variation in discontinuation rates for drugs within same class, and that might be related to the relative frequency of specific adverse effects. C ough was the reason cited for discontinuation of angiotensin converting enzyme inhibitor s , with linosopril appearing to be better tolerated than captopril ( 39% vs 48%) ; periphe ral oedema with calcium channel blockers, with amlodipine appearing to be better tolerated than nifedipine ( 29% vs 38 %) and bradycardia wit h beta adrenergic receptor blocker s , with propranolol better tolerated than atenolol (0% vs 48%) . Diuretics showed the lowest discontinuation rate ( 3.3%) mainly due to hypokalemia, with thiazide better tolerated than frusemide (11% vs 43%). Prescribers should verify their use of antihypertensive drugs to ensure that they prescribe drugs with lower adverse effect rate s , in order that patients with hypertension continue using the medication in the long term, thereby reducing the risk of developing cardiova scular complications associated with uncontrolled blood pressure .