Comparison of a chronotherapeutically administered beta blocker vs. a traditionally administered beta blocker in patients with hypertension

Increasing systolic blood pressure and heart rate during the early morning results in increased myocardial oxygen demand. The use of beta blockers during this period may decrease cardiac workload, particularly in beta-blocker sensitive patients. The impact of a new chronotherapeutic beta blocker was assessed in 44 hypertensive patients. Patients were randomized to delayed-release propranolol (INP) dosed at 10 p.m. or to traditionally dosed propranolol (ILA) dosed at 8 a.m. for 4 weeks, following which they were switched to the alternative formulation for 4 weeks. Thirty-four-hour ambulatory blood pressure monitoring and pharmacokinetic measurements were obtained. INP and ILA resulted in significant reductions in mean 24-hour blood pressure (-9.0/-6.9 mm Hg and -10.4/-7.7 mm Hg, respectively). The top 25% of responders to high-dose propranolol (sensitive patients) were compared on each formulation. Mean trough reductions were -8.0/-6.7 mm Hg and -7.6/-5.8 mm Hg, respectively. Mean blood pressure reductions in the beta-blocker sensitive patients (n = 11) between 6 a.m. and noon were -15.2/-11.9 mm Hg on INP and -8.0/-4.6 mm Hg on ILA. Heart rate reduction was -14.1 bpm and double product reduction was -3319 in the INP patients between 6 a.m. and 12 noon compared with -10.5 and -2209 in the ILA patients. This study suggests that INP and ILA are effective once-a-day beta blockers, but the use of delayed-release propanolol results in a greater reduction in double product between 6 a.m. and noon in beta-blocker sensitive patients than does traditionally dosed propranolol.     

Comparative Efficacy of Two Different β-Blockers on 24-Hour Blood Pressure Control

Atenolol and metoprolol succinate, dosed once daily, have different pharmacokinetic profiles. This study tests the hypothesis that differences that are especially noted in the early morning period, when cardiovascular risk is highest, in 24-hour blood pressure (BP) control exist between these 2 β-blockers. This was a small, randomized open-label study with blinded end point evaluation in 36 hypertensive patients. All participants received hydrochlorothiazide 12.5 mg for 2 weeks before randomization to either 50 mg atenolol or metoprolol succinate given every morning; both treatments were force-titrated to 100 mg/d at 4 weeks. The primary end point was the change in early morning ambulatory systolic BP. Early morning (12 am –6 am ) systolic BP differences were 3±14 mm Hg with atenolol vs −7±8 mm Hg with metoprolol succinate ( P =.03). The overall 24-hour changes in systolic BP were 1±15 mm Hg with atenolol vs −9±11 mm Hg with metoprolol ( P =.03). In conclusion, metoprolol succinate was more effective in sustaining 24-hour and early morning BP reductions compared with atenolol in a small group of hypertensive patients also treated with once-daily low-dose hydrochlorothiazide. It is possible that differences in outcome between atenolol-based and other therapies may be the result of inadequate dosing of atenolol, a medication that may not be effective for the entire 24-hour period.     

β-Blockers in Hypertension: A Reassessment of the Benefit of Combined α-/β-Blockade

β-Blockers have a long history of use in patients with high blood pressure, either alone or in combination with other classes of antihypertensive agents. Although β-blockers can lower blood pressure effectively, they have not been convincingly shown to reduce the likelihood of some cardiovascular complications from hypertension, and their utility for this purpose has been critically questioned of late. This growing distrust of β-blocker therapy, however, is misguided. Negative sentiments about one drug in a class, as has been the case for atenolol, often become unfairly disparaging of all drugs in a class. In the process of such lumping, the heterogeneity of the various compounds making up a drug class is often neglected. Such is the case for combined α-/β-blockade, which is to be distinguished from β-blockade alone because of differences in hemodynamic and metabolic effects. This should prompt a reappraisal of the role of selected agents, such as the combined α-/β-blocker carvedilol, in the long-term treatment of hypertension.     

Ophthalmically Administered β Blockers and Their Cardiopulmonary Effects

Early clinical studies revealed that timolol and other topical β blockers were effective in reducing intra-ocular pressure, without the side effects associated with other antiglaucoma agents. However, because persons with cardiovascular or respiratory diseases were generally excluded from many of these early studies, the risk of serious cardiovascular and respiratory side effects was seriously underestimated. Once these drugs were made available to the general population, reports of systemic side effects began to proliferate. Very quickly, adverse effects from topical β blockade became "old news." Despite this recognition, many treating physicians remained unaware of the potential for systemic β blockade from topically applied β blockers. A significant portion of a topically administered dose of a β blocker can be absorbed and thereby affect systemic β blockade. Sensitivity to systemic β blockade can be quite dramatic in certain highly susceptible patients, particularly those with either cardiac or pulmonary abnormalities. Careful review of patients' medications will generally lessen, but not completely eliminate, the risk of undesired complications attributable to topical P blockade.     

Oral Administration of Nipradilol and the Acute and Chronic Splanchnic Hemodynamic Effects of a New β-Blocker with Nitrovasodilating Properties in Patients with Liver Cirrhosis

Objectives: We studied the effects of nipradilol, which has both a nonselective β-blocker action and a vasodilating action similar to nitroglycerin, on portal hypertension. Methods: We measured hepatic venous pressure gradient and splanchnic and systemic hemodynamics before beginning therapy, 2 h after an oral dose of 6 mg, and after either 6 months of nipradilol 6 mg twice a day (n = 14) or of a placebo (n = 6) in 20 cirrbotic patients. Results: No significant changes were observed after the administration of the placebo. Oral nipradilol induced a significant reduction in the hepatic venous pressure gradient (base line: 14.8 ± 3.2 mm Hg vs 2 h: 12.3 ± 3.4 mm Hg, p < 0.01; 6 mo: 12.5 ± 3.2 mm Hg, p < 0.05) without a significant change in the free hepatic venous pressure. The hepatic vascular resistance decreased signifi-cantly (base line: 1811 ± 778 dyn. sec. cm^-5 vs 2 h: 1540 ± 701 dyn. scc. cm^-5, p < 0.05; 6 mo: 1564 ± 693 dyn. sec. cm^-5, p < 0.05) without a significant change in hepatic blood flow. A decrease in the hepatic venous pressure gradient greater than 10% was observed in nine patients (64%), defined as "responders," at 2 h and in 10 patients (71%) at 6 months. The reduction of mean heart rate and hepatic venous pressure gradient in these responders was 16.2% and 28.3% at 2 h and 15.1% and 27.1% at 6 months, respectively. Conclusions: We found that in some cirrhotic patients, at the doses used in this study, long term oral nipradilol administration produces a reduction in the hepatic venous pressure gradient with both a β-blocking and a nitrovasodilating action.     

Early Initiation of β Blockade in Heart Failure: Issues and Evidence

Despite clinical trials demonstrating that inhibitors of the renin-angiotensin and sympathetic nervous systems can reduce the mortality and morbidity risk associated with heart failure, these drugs have remained underutilized in general clinical practice. In particular, many patients with heart failure due to left ventricular systolic dysfunction fail to receive β blockers, although this class of drugs, as well as other antihypertensive agents such as angiotensinconverting enzyme inhibitors or angiotensin receptor blockers, are recommended as part of routine heart failure therapy by national expert consensus guidelines. In-hospital initiation of β-blocker therapy may improve long-term utilization by physicians and compliance by patients through obviating many of the misperceived dangers associated with β blockade. The following review of the clinical trial data from the Randomized Evaluation of Strategies for Left Ventricular Dysfunction (RESOLVD) trial, the Metoprolol Controlled-Release Randomized Intervention Trial in Heart Failure (MERIT-HF), the Cardiac Insufficiency Bisoprolol Study II (CIBIS-II), the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial, and the Initiation Management Predischarge Process for Assessment of Carvedilol Therapy for Heart Failure (IMPACT-HF) trial on the efficacy, safety, and tolerability of β blockers indicates that early initiation can be safely achieved and can improve patient outcomes.     

Five haplotypes in Black β-thalassaemia heterozygotes: three are associated with high and two with low Gγ values in fetal haemoglobin

Genotypes at seven different polymorphic restriction sites (5'to the ° gene, at the ^G γ, at the ^A γ, at the Ψβ , 3'to the Ψβ , at the β , and 3'to the β genes) were analysed by restriction endonuclease mapping of the DNA from 66 Black β -thalassaemia heterozygotes from Georgia and several of their normal relatives. Five different haplotypes were observed. Three of these were associated with high ^G γ values in the small amount of Hb F (0.8-8.3%) present in the blood of these patients and two with low ^G γ values. One haplotype [- + - ++++] that occurred on two of every three β thalassaemia chromosomes was associated with high ^G γ levels, and is the same as that found in some Black SS patients also having high ^G γ values (Gilman & Huisman, 1984). Two others [- ++ - + - +] and [−+−−+++] were also associated with high ^G γ, while two [−−−−+++] and [+−−−−++] were associated with low ^G γ. Variation in haematological data, mainly MCV and MCH values, was found to be caused in part by the type of β -thalassaemia (defined by its haplotype) and by the presence of an additional α-thalassaemia-2 heterozygosity or homozygosity.     

Polymorphisms of Interleukin-1β and β3-Adrenergic Receptor in Japanese Patients With Nonalcoholic Steatohepatitis

Background: Obesity, hypertriglyceridemia, and diabetes have been reported as frequent complications observed in patients with nonalcoholic steatohepatitis (NASH) in Western countries. The aim of this study was to investigate the genetic predisposition on NASH pathogenesis in the Japanese population.
Methods: Genotypes of two previously described functional polymorphisms—β3-adrenergic receptor 190 T/A polymorphism, which results in Trp64Arg (W64R) amino acid replacement, and interleukin-1β-511 T/C polymorphism in the promoter sequence—were determined in 63 Japanese NASH patients and 100 healthy volunteers using polymerase chain reaction and restriction fragment length polymorphism.
Results: β3-adrenergic receptor R allele frequency and the R/− (W/R and R/R) genotype frequency were significantly higher in NASH patients than those in control subjects. Interleukin-1β-511 T allele frequency and the T/T genotype frequency were significantly higher in NASH patients than those in control subjects. Obesity, hypertriglyceridemia, and hyperinsulinemia were associated with NASH patients with the R/− genotype, whereas an increase in fasting plasma glucose level and a decrease in insulinogenic index were associated with NASH patients with the W/W genotype.
Conclusion: This study confirmed the contribution of obesity, glucose intolerance, and hypertriglyceridemia to NASH development in the Japanese population. In addition to these factors, genetic predispositions to obesity and inflammation in the Japanese population were shown to contribute much to the development of NASH.     

α and β thalassaemia among Chinese children in Guangxi Province, P.R. China: molecular and haematological characterization

Summary We have studied nearly 100 patients with β thalassaemia major and 60 patients with Hb H disease who were attending the Haematology Clinic of Guangxi Medical College. Treatment of the patients was limited and only a few patients with β-thalassaemia major received blood transfusion(s). As a result, the severe anaemia has led to early death at 3–4 years for β⁺-thalassaemia homozygotes, and 8–12 years for β⁺-thalassaemia homozygotes. Four β-thalassaemia alleles are responsible for nearly 90% of all β-thalassaemia chromosomes. This information has resulted in the initiation of a prenatal testing programme at the local level. The patients with Hb H disease maintained a haemoglobin level of 6–10 g/dl and early death was infrequently observed. The ^SEA deletion was the major type of α-thalassemia-1, while three smaller deletions (−2.7, −3.7 and −4.2 kb) and two nondeletional α-thalassaemia determinants (Hbs Constant Spring and Quong Sze) were the α-thalassaemia-2 types.     

Heart Failure and Its Management With β-Blockade: Potential Applications of Once-Daily Therapy

Heart failure (HF) due to left ventricular (LV) systolic dysfunction is a progressive disease beginning with a primary injury that activates compensatory cardiovascular mechanisms including varying degrees of neurohormonal activation. Within the neurohormonal cascade, activation of the sympathetic nervous system is in part responsible for ongoing myocardial injury, progressive LV remodeling, and functional deterioration eventually leading to symptomatic HF. Large randomized clinical trials of certain β-blockers added to standard therapies have shown unequivocal benefits in patients with chronic systolic HF resulting in reduced remodeling, fewer total and cardiovascular deaths, and less risk of hospitalization for worsening HF. Evidence-based clinical guidelines recommend β-blockers as part of the regimen for patients with systolic HF as well as LV dysfunction following myocardial infarction. Based on published clinical trial results, bisoprolol, carvedilol, and sustained-release metoprolol succinate are recommended for systolic HF. Carvedilol, propranolol, and timolol are recommended for post-myocardial infarction LV dysfunction. Unfortunately, these evidence-based therapies are often underused in actual practice. Various strategies to increase β-blocker use in HF have been attempted, including in-hospital initiation of β-blocker therapy. Simplifying dosing regimens may also improve adherence to prescribed medications. Use of controlled-release carvedilol may encourage better adherence in patients with LV dysfunction and help overcome at least one barrier to optimal evidence-based care.     

Is a Shared Decision–Making Approach Effective in Improving Hypertension Management?

The authors assessed whether patient empowerment in the management of hypertension improved more with the practice of shared decision making (SDM) than by education programs. In a prospective controlled clinical study, 15 general practitioners in Nuremberg, Germany who were specially trained to conduct SDM consultations participated in a 12-month study. Hypertensive patients ( N =86) were included; N =40 were in the SDM group and N =46 were in the control group, if blood pressures were ≥135/85 mm Hg (self measurement) and patients had no signs of cardiovascular complications or severe hypertension. All participants in the SDM group and the control group were enrolled in an education program on hypertension in small groups. The SDM group participants also had 4 special consultations to share medical decisions. The main outcome measures were the effect of SDM on blood pressure control. After 1 year blood pressure had decreased in all participants: Δ−9.26±10.2 mm Hg/Δ−5.33±9.5 mm Hg in the SDM group ( P <0.001) compared to Δ−6.0±11.8 mm Hg/Δ−3.0±8.3 mm Hg in the control group. There was no significant difference between the 2 groups. The study group practiced more SDM than controls, but blood pressure control was not significantly better. Patient empowerment by means of an education program in small groups and creating awareness of hypertensive disease helps to improve the outcome of hypertension treatment. SDM, however, did not improve management when compared to an education program, which is much easier to implement in general practice.     

Do the Metabolic Effects of β Blockers Make Them Leading or Supporting Antihypertensive Agents in the Treatment of Hypertension?

Reduction of blood pressure to guideline goals (i.e., <130/80 mm Hg) in persons with diabetes is crucial to optimally reduce cardiovascular events and kidney disease progression. Since many patients will be >20/10 mm Hg above this goal, most guidelines recommend using agents that block the renin–angiotensin system in concert with a thiazide-like diuretic to achieve goal blood pressure. Meta-analyses of clinical trials indicate that while all classes of antihypertensive agents reduce cardiovascular risk, they exert different effects on glucose utilization and lipids and, hence, may affect morbidity. Specifically, β blockers, in general, worsen insulin resistance and increase triglycerides in a dose-dependent fashion. Moreover, they are not recommended as initial therapy for hypertension treatment in the absence of heart failure or recent myocardial infarction, especially in the elderly. Recent studies support the notion that newer β blockers with vasodilating effects have a better metabolic profile when compared with those that purely affect β receptors. Thus, vasodilating β blockers, by being neutral on glycemic and metabolic factors, are associated with less use of additional medication for lipid or glucose control and may provide a potentially greater cardiovascular risk reduction by virtue of these effects.     

Blood pressure lowering effects of β-blockers as add-on or combination therapy: A meta-analysis of randomized controlled trials

The authors performed a meta-analysis to assess the efficacy of non-atenolol β-blockers as add-on to monotherapy or as a component of combination antihypertensive therapy in patients with hypertension. The authors searched and identified relevant randomized controlled trials from PubMed until November 2021. Studies comparing blood pressure lowering effects of β-blockers with diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin receptor blockers (ARBs) were included. The analysis included 20 studies with 5544 participants. β-blockers add-on to monotherapy significantly reduced systolic and diastolic blood pressure as compared with non-β-blocker monotherapy (weighted mean difference in mm Hg [95% confidence interval]: −4.1 [−6.0, −2.2] and −3.7 [−4.6, −2.8], respectively). These results were consistent across the comparisons with diuretics (systolic pressure, −10.2 [−14.2, −6.2]; diastolic pressure, −5.4 [−8.2, −2.6]), CCBs (systolic pressure, −4.1 [−7.1, −1.0]; diastolic pressure, −2.8 [−4.1, −1.5]), and ACEIs/ARBs (systolic pressure, −2.9 [−4.3, −1.5]; diastolic pressure, −4.2 [−5.0, −3.4]). There was no significant difference in blood pressure lowering effects between combinations with and without a β-blocker (systolic pressure, −1.3 mm Hg [−5.8, 3.2]; diastolic pressure, −.3 mm Hg [−2.7, 2.1]). Metoprolol add-on or combination therapy had a significantly greater blood pressure reduction than non-β-blocker therapy (systolic pressure, −3.6 mm Hg [−5.9, −1.3]; diastolic pressure, −2.1 mm Hg [−3.5, −.7]). In conclusion, non-atenolol β-blockers are effective in lowering blood pressure as add-on to monotherapy or as a component of combination antihypertensive therapy. In line with the current hypertension guideline recommendations, β-blockers can and should be used in combination with other antihypertensive drugs.     

Propranolol compared with propranolol plus isosorbide-5-mononitrate for portal hypertension in cirrhosis. A randomized controlled study

OBJECTIVE: To investigate whether isosorbide-5-mononitrate (Is-5-Mn) given with propranolol reduces hepatic portal pressure more than does propranolol alone in patients with cirrhosis. DESIGN: A randomized controlled trial. PATIENTS: Fifty patients with cirrhosis and esophageal varices entered and 42 completed the study. INTERVENTION: Twenty-one patients received oral propranolol at increasing doses until their resting heart rate was reduced by 25%, and 21 patients received oral propranolol (on the same schedule) plus oral Is-5-Mn, 40 mg twice a day. MEASUREMENTS: Hepatic vein pressure gradient, liver function, and splanchnic and systemic hemodynamics before and after 3 months of continuous therapy. MAIN RESULTS: At 3 months, the hepatic venous pressure gradient decreased more (P less than 0.01) in patients given propranolol plus Is-5-Mn (19%, from 18.4 +/- 3.9 to 14.9 +/- 3.8 mm Hg; 95% CI, -2.4 to -4.5 mm Hg) than in those given propranolol alone (10%, from 18.2 +/- 3.5 to 16.3 +/- 3.1 mm Hg; CI, -1.1 to -2.7 mm Hg). The hepatic venous pressure gradient decreased by more than 20% of the baseline value in 10% of patients receiving propranolol, but in 50% of patients receiving combined therapy (P less than 0.02). There were statistically significant decreases in hepatic blood flow and the intrinsic clearance of indocyanine green after propranolol therapy, but not after combined therapy. The treatments caused similar reductions in azygos blood flow and cardiac output. CONCLUSIONS: The long-term combined administration of propranolol plus Is-5-Mn reduces portal pressure more than propranolol alone without adverse effects on hepatic perfusion and liver function. Whether this greater hemodynamic effect translates into better clinical efficacy should be determined in randomized controlled trials.     

Molecular analysis of the Turkish form of deletion-inversion (δβ)° thalassaemia

Two unrelated (δβ)°-thalassaemia patients from Southern Turkey are presented. DNA studies indicated that both of them are homozygous for the Turkish type of (δβ)°-thalassaemia characterized by one large deletion of 11.5 kb including the δ and β globin genes at the 5' end and one small deletion of 1.6 kb at the 3' end, which are separated by an inverted 7.6 kb long DNA segment that includes L1 repetitive sequence. In the present study a PCR-based method was performed to produce a unique deletion-specific product and subjected to sequence analysis for the determination of the breakpoint. DNA polymorphisms in the β-globin gene cluster of deletion-inversion type of (δβ)°-thalassaemia, IVS-I-6 and β-39 globin genes were examined. Analysis of sequence variations in regulatory regions including the 5' hypersensitive site-2 of the locus control region (LCR), the δ, ^Gγ and ^Aγ 5' flanking regions and the second intervening sequence (IVS-II) of ^Aγ and ^Gγ genes indicated the presence of close similarities between the chromosome carrying the Turkish form of deletion-inversion δβ)°-thalassaemia and the chromosome associated with β-39 nonsense mutation in haplotype II. These two chromosomes are characterized by the presence of a 4 base pair deletion in the ^Aγ^T globin gene promoter. A C → T alteration at position −199 5' to the δ gene was also found to be associated with the Turkish type of (δβ)°-thalassaemia and β-39 chromosome.     

Calcium entry blockers for systemic hypertension

Calcium entry blockers appear to be effective antihypertensive agents in both young and older patients. Studies comparing diltiazem and placebo, diltiazem and propranolol, and diltiazem and hydrochlorothiazide indicate that this calcium entry blocker is more effective than placebo, equally effective as the beta-adrenergic inhibitors at least in short-term studies, but not as effective in lowering systolic blood pressure (BP) when compared with hydrochlorothiazide (diastolic BP -11.5 mm Hg with diltiazem vs -12.2 mm Hg with hydrochlorothiazide; systolic BP -12.2 mm Hg with diltiazem vs -20.0 mm Hg with hydrochlorothiazide). Combination therapy with diltiazem and hydrochlorothiazide proved effective in a high percentage of mono-therapy nonresponders. The most common adverse reactions to diltiazem included headaches, dizziness and edema. The exact place of calcium entry blockers in therapy as initial or step-2 therapy with a diuretic in hypertension must be determined by additional long-term experience in large numbers of patients.     

Clinical responses to oxprenolol in the elderly

Data from 6 controlled clinical trials of oxprenolol carried out in the United States were reviewed to determine the efficacy and tolerability of oxprenolol in patients aged greater than or equal to 55 years. All study designs but 1 called for dosage to be increased to a maximum of 480 mg/day. In a 10-week trial of oxprenolol versus placebo given twice daily, oxprenolol reduced diastolic pressure by 8 mm Hg, while placebo reduced it by 3 mm Hg. A comparison of once-daily with twice-daily dosing showed similar results for both groups: -12/-6 mm Hg for once-daily and -9/-8 mm Hg for twice-daily. There were 2 short-term studies comparing oxprenolol and placebo, both given in addition to hydrochlorothiazide. In the first, the change in blood pressure with oxprenolol was -18/-14 mm Hg and with placebo was +6/-3 mm Hg; only 3 of 14 patients receiving oxprenolol received a maximal dosage. In the follow-up study, most of the dosages were titrated to maximum; reductions were -9/-9 mm Hg with oxprenolol treatment and 0/-12 mm Hg with placebo. Two long-term studies compared oxprenolol and propranolol, also as combination therapy with hydrochlorothiazide. In the 14-week study, the reduction in blood pressure was slightly better with oxprenolol: -15/-15 versus -12/-11 mm Hg. In the 27-week study, almost half of the patients in the oxprenolol group received the maximal dosage. Blood pressure was reduced 2 or 3 mm Hg less with oxprenolol than with propranolol. Oxprenolol was well tolerated in the elderly; it produced a low incidence of typical beta-blocker side effects even when given in a once-daily regimen.     

Should β Blockers Be Used in the Treatment of Hypertension in the Elderly?

The lack of benefit and the potential negative side effects of β blockers are overstated, especially in the elderly. This emphasis has led to recommendations by some investigators that these agents not be used in the management of hypertension in this age group. There are numerous reasons why these recommendations should not be followed. The use of β blockers in the elderly hypertensive has resulted in a reduction in strokes and congestive heart failure. In addition, it should be emphasized that elderly patients are more likely to have silent coronary artery disease or sustain myocardial infarctions. There is abundant evidence that β blockers are effective therapy in reducing mortality once a myocardial infarction has occurred. In fact, there is a clear reduction in sudden cardiac death. Furthermore, national statistics document that elderly patients have a prevalence of congestive heart failure that varies from 6%–10%. Multiple studies have now documented that β blockers are additive to angiotensin-converting enzyme inhibitors in reducing mortality for congestive heart failure. Thus, elderly hypertensive patients may benefit from the use of β blockers, especially if there is evidence of ischemic heart disease, cardiac arrhythmias, or congestive heart failure.     

Blood Pressure at 6 Months After Acute Myocardial Infarction and Outcomes at 2 Years: The Perils Associated With Excessively Low Blood Pressures

BackgroundThis study aimed to determine the association between achieved blood pressure at 6-month follow-up and cardiovascular outcomes at 2 years in patients treated with β-blockers and renin-angiotensin-aldosterone blockers after acute myocardial infarction (AMI).MethodsWe analyzed data from 5503 patients enrolled in the national AMI registry. Patients with myocardial reinfarction (MrI), rehospitalization for heart failure (rHHF), or stroke before 6-month follow-up were excluded. Achieved blood pressures were categorized into 10-mm Hg increments. The primary outcome was all-cause death. The secondary outcome was a composite of all-cause death, MrI, and rHHF. Hazard ratios (HRs) were estimated with multivariable-adjusted Cox hazards models using 125- to 134-mm Hg systolic blood pressure (SBP) and 75- to 84-mm Hg diastolic blood pressure (DBP) subgroups as reference.ResultsAfter a median follow-up of 2.1 years, SBP < 115 mm Hg was associated with increased risks for all-cause death (adjusted HR: 2.202 [1.158-4.188]) and for a composite outcome (HR: 1.682 [1.075-2.630]). Likewise, DBP < 75 mm Hg tended to be associated with an increase in all-cause death (HR: 2.078 [0.998-4.327] for DBP of 65 to 74 mm Hg; HR: 2.610 [1.256-5.423] for DBP < 65 mm Hg). Even in patients <75 years, the risk of a composite outcome was increased for DBP < 65 mm Hg (HR: 2.492 [1.401-4.434]).ConclusionsLow blood pressure achieved with β-blocker and renin-angiotensin-aldosterone blocker at 6 months was associated with an increased risk of all-cause mortality independently of confounding factors in patients with AMI. This finding suggests that caution should be taken for patients with AMI who use blood-pressure–lowering treatments.     

Carvedilol, a new nonselective beta-blocker with intrinsic anti- Alpha1-adrenergic activity, has a greater portal hypotensive effect than propranolol in patients with cirrhosis.

Only some patients show a substantial hepatic venous pressure gradient (HVPG) reduction after propranolol, which makes it desirable to investigate drugs with greater portal hypotensive effect. The aim of this study was to investigate whether carvedilol, a nonselective beta-blocker with anti-alpha1-adrenergic activity, may cause a greater HVPG reduction than propranolol. Thirty-five cirrhotic patients had hemodynamic measurements before and after the random administration of carvedilol (n = 14), propranolol (n = 14), or placebo (n = 7). Carvedilol markedly reduced HVPG, from 19.5 +/- 1.3 to 15.4 +/- 1 mm Hg (P <.0001). This HVPG reduction was greater than after propranolol (-20.4 +/- 2 vs. -12.7 +/- 2%, P <.05). Moreover, carvedilol decreased HVPG greater than 20% of baseline values or to 相似文献