Beta-blocker therapy cuts all-cause mortality in STEMI

19 jun 2014—For patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), beta-blocker therapy at discharge correlates with reduced all-cause mortality, according to a study published in the June issue of JACC: Cardiovascular Interventions.

Jeong Hoon Yang, M.D., from Samsung Medical Center in Seoul, South Korea, and colleagues examined the correlation of beta-blocker therapy at discharge with clinical outcomes using data from 8,510 patients with STEMI undergoing primary PCI. Patients were classified into a beta-blocker group (6,873 patients) and no-beta-blocker group (1,637 patients). Propensity-score matching analysis was conducted in 1,325 patient triplets. Patients were followed for a median of 367 days for the primary outcome of all-cause death.

The researchers found that all-cause death occurred in 2.1 percent of the beta-blocker group and 3.6 percent of the no-beta-blocker group (P < 0.001). Beta-blocker therapy correlated with lower incidence of all-cause death after 2:1 propensity-score matching (2.8 versus 4.1 percent; adjusted hazard ratio, 0.46; P = 0.004). In terms of all-cause death, the correlation of beta-blocker therapy with better outcomes was consistent across subgroups, including patients with relatively low-risk profiles such as ejection fraction >40 percent or single-vessel disease.

"Our results support the current American College of Cardiology/American Heart Association guidelines, which recommend long-term beta-blocker therapy in all patients with STEMI regardless of reperfusion therapy or risk profile," the authors write.

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Beta-blockers may increase adverse cardiac events, patients at risk during noncardiac surgical procedure

A recent study shows that patients given beta-blockers may actually be at increased risk of having an adverse cardiac event during a noncardiac surgical procedure. Risk of irregular heartbeat and worsening of symptoms in patients with existing heart disease also seemed to increase, but to a lesser degree. Beta-blockers are drugs commonly prescribed to treat high blood pressure and congestive heart failure. The study was presented during CHEST 2013, the annual meeting of the American College of Chest Physicians (ACCP), held October 26-31 in Chicago.

29 oct 2013--Researchers at State University of New York (SUNY)-Upstate Medical University Hospital analyzed 755 patients who had undergone noncardiac surgery in a single university-based center, with patients randomly chosen and subclassified according to gender, ethnicity, risk of surgery, and whether beta-blockers were used before, during, or after a noncardiac surgical procedure. Six different outcomes were investigated in the study: all-cause mortality, acute coronary syndrome (ACS), irregular heartbeat, cardiac event-related death, worsening of symptoms in a patient who has existing heart disease, and slower-than-normal heart rate. Three variables were used to predict these outcomes: beta-blocker administration, revised cardiac index score (RCRI)—a prediction of assessing risk of cardiac complications, and risk of surgery. Beta-blocker use was found to increase the odds of having an acute coronary event.

"The results from this study become especially important in view of the fact that beta-blockers are currently recommended by the American College of Cardiology/American Heart Association (ACC/AHA) 2011 guidelines regarding cardiac risk and management before, during and after surgery," said David D. Gutterman, MD, FCCP and past president of the ACCP.

Provided by American College of Chest Physicians

Beta-blocker use not associated with lower risk of cardiovascular events

Among patients with either coronary artery disease (CAD) risk factors only, known prior heart attack, or known CAD without heart attack, the use of beta-blockers was not associated with a lower risk of a composite of cardiovascular events that included cardiovascular death, nonfatal heart attack or nonfatal stroke, according to a study in the October 3 issue of JAMA.

04 oct 2012--"Treatment with beta-blockers remains the standard of care for patients with coronary artery disease, especially when they have had a myocardial infarction [MI; heart attack]. The evidence is derived from relatively old post-MI studies, most of which antedate modern reperfusion or medical therapy, and from heart failure trials, but has been widely extrapolated to patients with CAD and even to patients at high risk for but without established CAD. It is not known if these extrapolations are justified. Moreover, the long-term efficacy of these agents in patients treated with contemporary medical therapies is not known, even in patients with prior MI," according to background information in the article.

Sripal Bangalore, M.D., M.H.A., of the NYU School of Medicine, New York, and colleagues conducted a study to evaluate the association between beta-blocker use and long-term cardiovascular outcomes. The observational study included data from patients in the Reduction of Atherothrombosis for Continued Health (REACH) registry. From this registry, 44,708 patients met the study inclusion criteria of whom 14,043 patients (31 percent) had prior MI, 12,012 patients (27 percent) had documented CAD but without MI, and 18,653 patients (42 percent) had CAD risk factors only. The last follow-up data collection was April 2009. The primary outcome for this study was a composite of cardiovascular death, nonfatal MI, or nonfatal stroke. The secondary outcome was the primary outcome plus hospitalization for atherothrombotic events or a revascularization procedure. The overall median (midpoint) follow-up was 44 months. Among the 44,708 patients in the study, 21,860 were included in the propensity score-matched analysis.

The researchers found that in the prior MI group, the event rates were not significantly different among those with beta-blocker use (489 [16.93 percent]) vs. those without beta-blocker use (532 [18.60 percent]) for the primary outcome, or the secondary outcome (30.96 percent vs. 33.12 percent, respectively). In the CAD without MI cohort, the event rates were not different in those with beta-blocker use (391 [12.94 percent]) vs. those without p-blocker use (405 [13.55 percent]) for the primary outcome, for cardiovascular death, for stroke, and for MI. The event rates were higher in those with beta-blocker use (1,101 [30.59 percent] vs. those without beta-blocker use (1,002 [27.84 percent]) for the secondary outcome and for hospitalization in the propensity score-matched model.

In the risk factors alone group, the event rates were higher in those with beta-blocker use (467 [14.22 percent] vs. those without beta-blocker use (403 [12.11 percent]) for the primary outcome, for the secondary outcome (870 [22.01 percent] vs. 797 [20.17 percent], respectively) but not for MI or stroke. In the propensity score-matched model, there were similar event rates for cardiovascular death and for hospitalization.

The researchers also found that among patients with recent MI (one year or less), beta-blocker use was associated with a lower incidence of the secondary outcome.

"Among patients enrolled in the international REACH registry, beta-blocker use was not associated with a lower event rate of cardiovascular events at 44-month follow-up, even among patients with prior history of MI. Further research is warranted to identify subgroups that benefit from beta-blocker therapy and the optimal duration of beta-blocker therapy," the authors conclude.

More information: JAMA. 2012;308[13]:1340-1349. 

Provided by JAMA and Archives Journals

Beta-blockers and stroke -- new insights into their use for older people

Research conducted at Leicester reveals effects of blood pressure drugs on cardiovascular disease

30 aug 2009--A University of Leicester-led study may have uncovered the reason why Beta-blockers are less effective at preventing stroke in older people with high blood pressure, when compared to other drugs for high blood pressure.

The research, carried out by Bryan Williams, Professor of Medicine at the University of Leicester, and his colleague Dr. Peter Lacy, has been published in the prestigious Journal of the American College of Cardiology and has been cited on the MDLinx.com site as currently the world's number one leading finding in its field.

Professor Williams' research shows that lowering heart rate in older people, as Beta blockers do, can have a potentially detrimental effect on central aortic pressures (pressures in the large arteries close to the heart).

He commented: "Such findings can help define the template for optimal treatment strategies and highlight why new methods to estimate central aortic pressures are providing new insights into the pathogenesis of cardiovascular disease and how new drugs can be tailored to limit the damage.

"Leicester is acknowledged as one of the leading centres in the world in this field of research."

This study used analysis of the pulse wave measured at the wrist to estimate pressures in the large artery near to the heart, in people with high blood pressure. It shows that reducing heart rate in older people with high blood pressure can result in a higher than expected pressure in the large arteries.

This may be the reason why drugs such as Beta-blockers, a widely used drug to treat high blood pressure, have been shown to be less effective than other treatments at preventing stroke. In 2006, NICE recommended that Beta-blockers should no longer be used as a routine treatment for high blood pressure because they appeared somewhat less effective than other types of blood pressure lowering drugs at reducing the risk of stroke, especially in older people.

Professor Williams, who is also consultant physician with the University Hospitals of Leicester NHS Trust, suggests that the present study provides important insights into the mechanism. "There is no doubt that by better understanding of how modern drugs work in reducing the risk of stroke and heart disease, we will be able to continually refine treatments for the future," he said.

Should patients taking Beta-blockers stop them? Professor Williams emphasised: "No they should definitely not stop them. Beta-blockers are prescribed for a number of medical conditions, including angina and heart disease and in this context they are very beneficial.

"The new study is specifically exploring the reasons why Beta-blockers or other drugs that lower heart rate may be less effective at preventing stroke than some of the other drugs we use to lower blood pressure."

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The MDLinx.com website claims to include the world's most up-to-date index of articles of interest to physicians and healthcare professionals. Professor Williams' article, 'Impact of heart rate on central aortic pressures and hemodynamics: Analysis from the CAFE (Conduit Artery Function Evaluation Study: CAFE-Heart Rate' was on the HeartLinx site and can be seen on: http://www.mdlinx.com/heartlinx/news-article.cfm/2838447.

Perioperative Beta-blockers for Major Noncardiac Surgery: Primum Non Nocere

Vineet Chopra, MDa, Benjamin Plaisance, MDa, Erdal Cavusoglu, MDb, Scott A. Flanders, MDa, Kim A. Eagle, MDc

06 april 2009

Abstract

Recent studies have called into question the benefit of perioperative beta blockade, especially in patients at low to moderate risk of cardiac events. Once considered standard of care, the role of beta-blocker therapy now lies mired in conflicting data that are difficult to apply to the at-risk patient. We provide an overview of the evolution of perioperative beta blockade, beginning with the physiology of the adrenergic system, with emphasis on the biologic rationale for the perioperative implementation of beta-blockers. Although initial studies were small in size and statistically limited, early data showed cardiac benefit with the use of perioperative beta-blockers. However, larger, more recent studies now suggest a lack of benefit and potential harm from this practice. This paradigm holds true especially in those at low-to-moderate cardiovascular risk profiles. Potential explanations for these paradoxical results are discussed, stressing the key differences between earlier and current studies that may explain these divergent outcomes. We conclude by commenting on performance measures as they relate to perioperative beta-blockers and make recommendations for the continued safe implementation of this practice.

Keywords: Beta-blockers, Noncardiac surgery, Perioperative risk reduction, POISE

Beta-Blockers for Surgical Patients Linked to Increases in Stroke and Mortality

By Peggy Peck
HAMILTON, Ontario, 14 may 2008-- High-dose extended release metoprolol (Toprol XL) just before, shortly after, and for a month following non-cardiac surgery increased the risk of stroke and death within 30 days, researchers here reported.But the beta-blocker therapy reduced the number of non-fatal heart attacks and cardiac arrests, Philip J. Devereaux M.D., Ph.D., of McMaster University, and colleagues reported online in The Lancet.The investigators in the POISE (PeriOperative Ischemic Evaluation) trial said that their findings suggest the need to reconsider guidelines that currently recommend beta-blocker therapy for patients undergoing non-cardiac surgery.
Among patients with coronary artery disease, beta blockers are considered a cornerstone treatment that can improve survival in patients with angina, MI, peripheral arterial disease and heart failure, according to Lee A. Fleisher, M.D., of the University of Pennsylvania and Don Poldermans, M.D., Ph.D., of Erasmus Medical Center, Rotterdam, Holland.
In a commentary published with the POISE results, Drs. Fleisher and Poldermans suggested a reason for the troubling results could be the regimen -- 100 mg two to four hours before surgery followed by 100 mg within six hours after surgery, which meant that on the day of surgery a patient could have received as much as 200 mg of metoprolol, which is half of the maximum therapeutic dose.
By contrast, they wrote, in clinical practice the typical starting dose for heart failure patients is 12.5 mg to 25 mg and for hypertension the initial dose is usually 25 mg to 100 mg.
The trial randomized 8,351 surgery patients who had or were at risk for atherosclerosis to extended release metoprolol succinate or placebo. The mean age of patients was 69 and just over a third were women.
Patients were enrolled from October 2002 through July 2007 at 190 hospitals in 23 countries. Forty-two percent underwent vascular surgery, roughly 22% had intraperitoneal surgery, and about 21% had orthopedic surgery. Almost of half of the patients (47%) had general anesthesia.
The study drug was administered two to four hours before non-cardiac surgery, within six hours after surgery, and for 30 days thereafter. The primary endpoint was the composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal cardiac arrest.
Patients who received metoprolol were less likely than those given placebo to reach the primary endpoint (5.6% versus 6.9%, P=0.0399) and were also significantly less likely to have an MI (4.2% versus 5.7% P=0.0017).
Likewise, fewer metoprolol patients required revascularization (0.3% versus 0.6% P=0.00123) and they also were less likely to develop clinically significant atrial fibrillation (P=0.0435).
But mortality and stroke rates were significantly worse in the beta-blocker groups, with 129 deaths compared with 97 in the placebo group (P=0.0317), and 41 strokes versus 19 in the placebo arm (P=0.0053).
Moreover, most of the stroke patients "were left requiring help to do everyday activities or were incapacitated," the researchers wrote. By contrast, very few of the non-fatal MI patients developed congestive heart failure or were incapacitated at hospital discharge.
There were also significantly more cases of clinically significant hypotension (625 cases versus 404 P <0.0001) href="http://www.thelancet.com/journals/lancet/article/PIIS0140673608606017/abstract?isEOP=true" target="_blank">

AHA: Surgery with Beta-Blockers Onboard May Be Risky


ORLANDO, Nov. 7 -- Beta-blockers given before noncardiac surgery to prevent cardiovascular events in at-risk patients may be counterproductive, researchers found.
Action Points
Caution interested patients that although the study did not support the use of beta-blockade for prevention of perioperative events, it did not suggest that patients should stop taking the drug prescribed for other indications.
Note that this study was published as an abstract and presented orally at a conference. The data and conclusions should be considered to be preliminary until published in a peer-reviewed publication.
Perioperative metoprolol (Lopressor, Toprol-XL) started two to four hours before surgery prevented 15 MIs, three revascularizations, and seven atrial fibrillation events per 1,000 treated patients compared with placebo, according to a large prospective trial presented here at the American Heart Association meeting.
But this came at the expense of eight deaths, five severe strokes, 42 cases of significant bradycardia, and 53 significant hypotension events per 1,000 patients, reported P.J. Devereaux, M.D., of McMaster University in Hamilton, Ontario, and colleagues.
The "disturbing" increase in death and stroke recommends against routine use, commented Gordon F. Tomaselli, M.D., of Johns Hopkins University, who moderated a press conference at which the results were presented.
However, the drug should not be withdrawn for patients who come in for surgery and are already on beta-blockers for other indications, Dr. Tomaselli cautioned. "That's absolutely the wrong thing to do."
Perioperative beta-blockade for noncardiac surgery is a quality-of-care measure of the Physicians Consortium for Performance Improvement and the Surgical Care Project.
Likewise, joint guidelines from the AHA and the American College of Cardiology recommend perioperative beta-blockers for patients with heart disease or with risk factors, and suggest use can be considered for patients with low or intermediate risk as well. Neither recommendation had better than a moderate level of evidence.
"There's an enormous push to do this based on small trials," Dr. Devereaux said, which he compared to the situation that existed with hormone replacement therapy before the Women's Health Initiative linked it to breast cancer risk.
However, even the small trials have not consistently found a benefit.
So, Dr. Devereaux's group conducted the large Perioperative Ischemic Evaluation (POISE) trial. It included 8,351 patients 45 or older who were undergoing noncardiac surgery and had or were at risk for atherosclerotic disease.
Patients were randomized to receive a continuous-release formulation of metoprolol or placebo starting two to four hours before surgery and continuing for 30 days afterward.
Overall, 82% of patients had evidence of coronary artery or peripheral vascular disease before surgery. Treatment groups were balanced in risk factors and type of surgery.
Metoprolol reduced risk of the primary composite endpoint of cardiovascular death, nonfatal MI, and nonfatal cardiac arrest at 30 days compared with placebo (5.8% versus 6.9%, hazard ratio: 0.83, P=0.04).
This benefit was driven by a decrease in nonfatal MI (3.6% versus 5.1%, HR: 0.70, P=0.0007), which, although important, is typically less important to patients than risk of stroke, Dr. Devereaux said.
Stroke was more common after surgery among patients who received beta-blockers (1% versus 0.5%, HR: 2.17, P=0.005). And, total mortality was elevated with metoprolol compared with placebo (3.1% versus 2.3%, HR: 1.33, P=0.03).
Dr. Devereaux noted that these were not "benign strokes" and may have been caused by increases in other secondary outcomes, particularly hypotension and atrial fibrillation.
Among the other secondary findings, rates for metoprolol compared with placebo included:
Elevated for clinically significant hypotension (15% versus 9.7%, HR: 1.55, P0.0001).
Elevated for clinically significant bradycardia (6.6% versus 2.4%, HR: 2.71, P0.0001).
Reduced for atrial fibrillation (2.2% versus 2.9%, HR 0.76, P=0.04).
Slightly reduced for revascularization (0.3% versus 0.6%, HR: 0.41, P=0.01).
These findings were disappointing and leave surgeons with few options for prevention of ischemic events, Dr. Devereaux said.
"One of the reasons beta-blockers were pushed despite weak evidence is that we have nothing than we know works," he said.
Rather than studying other similar drugs for perioperative prevention, Dr. Devereaux suggested that the best strategy might simply be better monitoring after surgery to quickly identify and treat any events that do occur.
Nevertheless, the decision on whether to use perioperative beta-blockade will need to be decided with patients individually, he concluded.
The study was funded by AstraZeneca and national granting agencies in several countries.
The researchers made no declarations regarding financial conflicts of interest. Dr. Tomaselli reported no conflicts of interest.
Primary source: American Heart Association meetingSource reference: Devereaux PJ, et al "The Perioperative Ischemic Evaluation (POISE) Trial: A Randomized Controlled Trial of Metoprolol versus Placebo in Patients Undergoing Noncardiac Surgery" AHA meeting 2007; Abstract LBCT-20825.

Beta-Blockers May Exert Anti-Atherosclerotic Effects

CLEVELAND, July 3 -- Beta-blocker therapy can provide statistically significant regression of coronary artery plaque, found a review here of four intravascular ultrasound (IVUS) studies.
Atheroma volume decreased by an average of 2.4 mm3/y among beta blocker-treated patients, compared with 0.4 mm3/y among those who did not receive beta-blockers (P=0.034), reported Steven E. Nissen, M.D., of the Cleveland Clinic, and colleagues, in the July 3 issue of the Annals of Internal Medicine.
The volume of coronary plaque decreased significantly from baseline to the end of the evaluation period in patients who received beta-blockers (P<0.001) but not in patients whose therapy did not include beta-blockers (P=0.86).
"The analysis demonstrates that beta-blockers can slow progression of coronary atherosclerosis," concluded Dr. Nissen and colleagues. "The findings provide additional support for the current clinical guidelines advocating long-term use of beta-blockers to treat most forms of coronary artery disease."
The authors pointed out that beneficial effects on recurrent myocardial infarction, sudden cardiac death, and total mortality in MI patients emerged primarily from studies done two decades ago. Whether beta-blockers provide the same benefits in the current era of aggressive reperfusion for MI had not been clear.
To examine the effects of beta-blockers in contemporary patients, the investigators reviewed data from four clinical trials that used IVUS to evaluate the impact of medical interventions on coronary atherosclerosis volume. The four studies analyzed were:
REVERSAL, a randomized comparison of moderate versus aggressive lipid-lowering therapy with statin drugs
CAMELOT IVUS, a randomized comparison of a calcium-channel blocker and an ACE inhibitor
ACTIVATE, which evaluated lipid modification with a CoA-cholesterol acyltlransferase inhibitor
ASTEROID, a trial of high-intensity lipid-lowering therapy with a statin
The same IVUS technique was used in all four trials, and patients in each trial had IVUS at baseline and at the study's end.
The trials involved a total of 1,515 patients with coronary artery disease, including 1,154 who received beta-blockers as a component of their treatment. On average, patients treated with beta-blockers received the agents for 91% of the trials' duration. More patients in the beta-blocker group had a history of MI, angina, and hypertension.
Patients treated with beta-blockers had a significantly greater reduction in atheroma volume in a univariate analysis and a multivariate analysis that controlled for MI, angina, and hypertension. Adjustments for LDL-cholesterol level, concomitant medications, and clinical trial did not change the results.
The investigators said that antiatherosclerotic effects of beta-blockers have been demonstrated in multiple animal models but not in human coronary arteries. However, a meta-analysis of randomized controlled trials last year found that long-term beta-blocker therapy was associated with a significant slowing of carotid intima-media thickening in hypertensive patients with diabetes or coronary heart disease and asymptomatic carotid artery disease.
Dr. Nissen and colleagues pointed out that beta-blockers reduce heart rate and slow blood velocity, leading to less turbulent blood flow and less intramural stress. However, adjustment for average heart rate during therapy did not change the results. The investigators also cited evidence that beta-blockers may reduce the affinity of LDL cholesterol for vessel wall proteoglycans and blunt catecholamine-induced endothelial permeability to lipoproteins.
Limitations of the study include its nonrandomized nature and the imbalance between treated and untreated patients. Additionally, the authors acknowledge that IVUS findings are a surrogate endpoint for coronary artery disease. Whether IVUS-detected changes in atheroma volume predict cardiovascular outcomes is unknown.
The original IVUS-based studies were supported by Pfizer, Sankyo, and AstraZeneca. The study sponsors contributed to data collection for the pooled analysis but did not participate in the planning or conduct of the analysis. The authors reported multiple associations with the sponsors and with other companies unrelated to the study.Additional source: Annals of Internal MedicineSource reference: Sipahi I et al. "Beta-blockers and coronary atherosclerosis: Pooled analysis of 4 intravascular ultrasonography trials." Ann Intern Med. 2007;147:10-18. Additional source: StrokeSource reference: Wang JG, Staessen JA, Li Y, et al. "Carotid intima-media thickness and antihypertensive treatment: a meta-analysis of randomized controlled trials." Stroke 2006, 37:1933-49.