Beta blockers after MI: safe for the few, still relevant for the many.

To evaluate the effect of current treatment with non-selective or cardioselective beta-blockers on the outcome of a first acute myocardial infarction in hypertensive patients. Peak aspartate aminotransferase was measured as an indirect estimate of infarct size, the occurrence of circulatory arrest from ventricular tachyarrhythmias and in-hospital mortality. A retrospective analysis was performed on data collected in a continuously operating register of all hospitalized acute myocardial infarctions in Malmö, Sweden. A total of 2114 hypertensive patients were admitted to hospital with a first acute myocardial infarction. Of these patients, 323 were treated with a non-selective beta-blocker on admission and 338 with a cardioselective beta-blocker. In patients given a non-selective beta-blocker the mean peak aspartate aminotransferase was 3.02 +/- 0.15 mukat/l, which was significantly lower than the peak (3.78 +/- 0.35 mukat/l) recorded in the patients given a cardioselective beta-blocker. In a multiple regression analysis, treatment with a non-selective beta-blocker was significantly and inversely related to peak aspartate aminotransferase after adjustment for several clinical characteristics. Age, anterior myocardial infarction, peak aspartate aminotransferase, serum potassium and treatment with a cardioselective beta-blocker were significantly and independently associated with the occurrence of circulatory arrest due to ventricular tachyarrhythmias. The relative risk of circulatory arrest in patients taking cardioselective beta-blockers was 1.73 (95% confidence interval 1.16-2.58) and in patients taking non-selective beta-blockers 1.02 (95% confidence interval 0.64-1.66). Advanced age, a history of diabetes mellitus, a history of stroke, anterior myocardial infarction, a high serum potassium level and a high peak aspartate aminotransferase level significantly predicted in-hospital mortality. The relative risk of in-hospital mortality in patients taking non-selective beta-blockers was 0.92 (95% confidence interval 0.64-1.30), and in patients taking cardioselective beta-blockers 0.84 (95% confidence interval 0.59-1.19). The study suggests that current treatment with non-selective beta-blockers may have reduced the enzymatically estimated infarct size and the occurrence of circulatory arrest due to ventricular tachyarrhythmias. Both non-selective and cardioselective beta-blockers may also have reduced the in-hospital mortality in this population of hypertensive patients suffering a first acute myocardial infarction. In a clinical study using with adrenaline infusions in healthy volunteers, we found that beta 2-receptor blockade improved potentially arrhythmogenic variables, such as hypokalemia and hypomagnesemia, but the adrenaline-induced reduction in diastolic blood pressure was reversed. Pretreatment with the new beta-blocker carvedilol preserved the beneficial electrolyte effects without increasing blood pressure during the adrenaline infusion.

Nonselective Beta-Blockers in Compensated Cirrhosis: Preventing Variceal Hemorrhage or Preventing Decompensation?

Prophylaxis with beta blockers as a performance measure of quality health care in cirrhosis

Compelling Indications Should be Listed for Individual Beta-Blockers (Due to Diversity), Not for the Whole Class.

Beta (ss) blockers are indicated for use in coronary artery disease (CAD). However, optimal therapy for people with CAD accompanied by intermittent claudication has been controversial due to the presumed peripheral haemodynamic consequences of beta blockers, leading to worsening symptoms of intermittent claudication. To quantify the potential harm of beta blockers on maximum walking distance, claudication distance, calf blood flow, calf vascular resistance, and skin temperature when used in patients with peripheral arterial disease (PAD). The Cochrane Peripheral Vascular Diseases (PVD) Group searched for publications describing randomised controlled trials (RCTs) of beta blockers in PAD in their Trials Register (last searched 6 May 2008) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008, Issue 2). We handsearched relevant journals and conference proceedings. Randomised controlled trials evaluating the role of both selective (beta1) and non-selective (beta1 and beta2) beta blockers compared with placebo. We excluded trials comparing different types of beta blockers. Primary outcome measures were claudication distance in metres, and the time to claudication in minutes, and maximum walking distance in metres and minutes (as assessed by treadmill).Secondary outcome measures were calf blood flow (ml/100 ml/min), calf vascular resistance, and skin temperature (degrees C). We included six RCTs fulfilling the above criteria, with a total of 119 patients. The beta blockers studied were atenolol, propranolol, pindolol, and metoprolol. None of the trials showed a statistically significant worsening effect of beta blockers on either the primary or secondary outcomes. There were no reports of any adverse events with the beta blockers studied. There is currently no evidence that beta blockers adversely affect walking distance in people with intermittent claudication. However, due to the lack of large published trials beta blockers should be used with caution if clinically indicated.

Beta (β) blockers are indicated for use in coronary artery disease (CAD). However, optimal therapy for people with CAD accompanied by intermittent claudication has been controversial because of the presumed peripheral haemodynamic consequences of beta blockers, leading to worsening symptoms of intermittent claudication. This is an update of a review first published in 2008. To quantify the potential harmful effects of beta blockers on maximum walking distance, claudication distance, calf blood flow, calf vascular resistance and skin temperature when used in patients with peripheral arterial disease (PAD). For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched March 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, 2013, Issue 2). Randomised controlled trials (RCTs) evaluating the role of both selective (β1) and non-selective (β1 and β2) beta blockers compared with placebo. We excluded trials that compared different types of beta blockers. Primary outcome measures were claudication distance in metres, time to claudication in minutes and maximum walking distance in metres and minutes (as assessed by treadmill).Secondary outcome measures included calf blood flow (mL/100 mL/min), calf vascular resistance and skin temperature (ºC). We included six RCTs that fulfilled the above criteria, with a total of 119 participants. The beta blockers studied were atenolol, propranolol, pindolol and metoprolol. All trials were of poor quality with the drugs administered over a short time (10 days to two months). None of the primary outcomes were reported by more than one study. Similarly, secondary outcome measures, with the exception of vascular resistance (as reported by three studies), were reported, each by only one study. Pooling of such results was deemed inappropriate. None of the trials showed a statistically significant worsening effect of beta blockers on time to claudication, claudication distance and maximal walking distance as measured on a treadmill, nor on calf blood flow, calf vascular resistance and skin temperature, when compared with placebo. No reports described adverse events associated with the beta blockers studied. Currently, no evidence suggests that beta blockers adversely affect walking distance, calf blood flow, calf vascular resistance and skin temperature in people with intermittent claudication. However, because of the lack of large published trials, beta blockers should be used with caution, if clinically indicated.

Initiation and Up-Titration of Beta Blockers Guided by B-Natriuretic Peptide in Patients With Systolic Heart Failure

The clinical importance of cardioselectivity and lipophilicity in beta blockers

See Article on Page 1304

The regulation of vascular resistance, cardiac output, and thus blood pressure can be influenced by antihypertensive drugs acting at central and peripheral adrenergic receptors. The results presented here are from acute or chronic studies in 205 patients with mild or moderately severe essential hypertension: beta blockers (N = 101); alpha blockers (N = 36); a separate alpha- + beta-blocker combination or the combination agent labetalol (N = 37); prizidilol, a beta-blocker/vasodilator (N = 14); and dilevalol, a beta blocker/beta 2-stimulator (N = 17). Beta blockers without strong intrinsic sympathomimetic activity reduce heart rate and cardiac output immediately, but due to a reflex increase in total peripheral resistance index, blood pressure is unchanged or only slightly reduced. During chronic use, total peripheral resistance drops towards pretreatment level and pressure falls. Beta blockers with strong intrinsic sympathomimetic activity do not reduce heart rate or cardiac output at rest when sympathetic tone is low. During exercise, heart rate and cardiac output are reduced, but less than with conventional beta blockers, and resistance is unchanged or slightly reduced. An acute and chronic reduction in blood pressure can be produced by alpha-adrenergic receptor blockers (prazosin, doxazosin, trimazosin), and in these cases the fall occurs via a reduction in total peripheral resistance index without reflex tachycardia. These drugs tend to increase exercise stroke volume and cardiac output during chronic treatment. Free combinations of beta and alpha blockers or the use of the fixed combination drug, labetalol, induce marked reductions in blood pressure at rest and during exercise, mainly through a reduction in total peripheral resistance index. During chronic treatment, exercise stroke volume and cardiac output are well maintained. In acute studies with dilevalol, systolic blood pressure, diastolic blood pressure, and mean arterial pressure were reduced (p less than 0.001) within 1 hour in 17 males with essential hypertension (WHO stage I) who received 200-400 mg oral dilevalol. The reduction in MAP was around 16-17% and was associated with an immediate fall in the total peripheral resistance index of the same magnitude (14%, p less than 0.001) after 1 hour at rest. There were no significant changes in heart rate or cardiac index.(ABSTRACT TRUNCATED AT 400 WORDS)

PP028. To assess maternal and neonatal outcomes of women on an antihypertensive agent with gestational hypertension, chronic hypertension or preeclampsia

Objectives: Rheumatoid arthritis (RA) is an independent nontraditional risk factor for incidence of myocardial infarction (MI) and post-MI outcome is impaired in the RA population. Use of beta-blockers improves the long-term survival after MI in the general population while the protective effect of beta-blockers in RA patients is not clear. We investigate the impact of beta-blockers on the long-term outcome of MI among RA patients.Methods: We identified RA subjects from the registries for catastrophic illness and myocardial infarction from 2003 to 2013. The enrolled subjects were divided into three groups according to the prescription of beta-blockers (non-user, non-selective, and β1-selective beta-blockers). The primary endpoint was all-cause mortality. We adjusted clinical variables and utilized propensity scores to balance confounding bias. Cox proportional hazards regression models were used to estimate the incidence of mortality in different groups.Results: A total of 1,292 RA patients with myocardial infarction were enrolled, where 424 (32.8%), 281 (21.7%), and 587 (45.5%) subjects used non-user, non-selective, and β1-selective beta-blockers, respectively. Use of beta-blockers was associated with lower risk of all-cause mortality after adjustment with comorbidities, medications (adjusted hazard ratio [HR] 0.871; 95% confidence interval [CI] 0.727–0.978), and propensity score (HR 0.882; 95% CI 0.724–0.982). Compared with β1-selective beta-blockers, treatment with non-selective beta-blockers (HR 0.856; 95% CI 0.702–0.984) was significantly related to lower risk of mortality. The protective effect of non-selective beta-blockers remained in different subgroups including sex and different anti-inflammatory drugs.Conclusion: Use of beta-blockers improved prognosis in post-MI patients with RA. Treatment with non-selective beta-blockers was significantly associated with reduced risk of mortality in RA patients after MI rather than β1-selective beta-blockers.

Improved Survival Outcomes in Non-small Cell Lung Cancer Patients With Incidental Concurrent Use of Beta-Blockers and Definitive Radiation Therapy

B-PO04-026 NON-SELECTIVE VERSUS Β1-SELECTIVE BETA-BLOCKERS IN THE TREATMENT OF SYMPTOMATIC CHILDREN WITH CATECHOLAMINERGIC POLYMORPHIC VENTRICULAR TACHYCARDIA

Background Heart failure (HF) is one of the major complications in atrial fibrillation (AF). We previously reported that not a few AF patients without pre-existing HF (defined as prior HF hospitalization, New York Heart Association functional class≥2, or left ventricular ejection fraction (LVEF)<40%) subsequently developed new-onset HF. Beta blockers are the established therapy for HF, but it remains unclear whether beta blockers prevent new-onset HF and improve outcomes in AF patients without preexisting HF. Methods In the Fushimi AF registry, 778 of 3,262 patients without pre-existing HF were receiving beta blockers at baseline. We investigated the incidence of new-onset HF defined as cardiac death or HF hospitalization, and all-cause death in a propensity-matched cohort (N=1,198; mean age, 71 years; 39% female; mean LVEF, 66%). Additionally, annual follow-up prescription data before the onset of events were collected in 294 of patients with beta blockers and 395 of those without beta blockers. We also investigated the association of starting or stopping beta blockers with the incidence of new-onset HF and all-cause death. Results During the median follow-up of 5.8 years, new-onset HF and all-cause death occurred in 77 (12.9%) and 118 (19.7%) of patients with beta blockers, and 70 (11.7%) and 131 (21.9%) of those without beta blockers, respectively. Incidence of new-onset HF was comparable between patients with and without beta blockers (Figure 1), and incidence of all-cause death was also comparable between the two groups (Figure 2). In exploratory subgroup analyses, there was no interaction in the association of beta blockers with the incidence of events, except for pulse rate for new-onset HF and left atrial size for all-cause death. Hazard ratio of beta blockers for new-onset HF tended to be lower in patients with higher pulse rates (>84 bpm) (Figure 1), and that for all-cause death was lower in those without left atrial enlargement (Figure 2). Of patients with follow-up prescription data, beta blockers were stopped in 55 (18.7%) and started in 97 (24.6%) patients, respectively. Patients with starting beta blockers had higher pulse rate (78.5±17.3 vs 74.9±13.9 bpm; p=0.03) and more symptomatic AF (58.8% vs 46.0%; p=0.03) compared to those without starting beta blockers, while there was no difference in baseline characteristics between those with and without stopping beta blockers. During the follow-up, the incidences of new-onset HF and all-cause death were also comparable between the patients with and without stopping beta blockers and those with and without starting beta blockers. Conclusion Beta blockers were not associated with the incidence of new-onset HF and all-cause death in AF patients without pre-existing HF. However, the exploratory subgroup analyses suggested the existence of subjects who may benefit from beta blockers. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Boehringer Ingelheim, Bayer Healthcare, Pfizer, Bristol-Myers Squibb, Astellas Pharma, AstraZeneca, Daiichi Sankyo, Novartis Pharma, MSD, Sanofi-Aventis, and Takeda Pharmaceutical.