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Author: Dr. Hassan Gargoum

Clinical Professor of Medicine, University of Saskatchewan Consultant, Cardiovascular Diseases

FDA: Does Not Recommend Using Aspirin for Primary Prevention of Heart Attack or Stroke

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Aspirin should not be used to prevent a first heart attack or stroke in patients with no history of cardiovascular disease, according to the U.S. Food and Drug Administration (FDA).

In a statement released on May 5, 2014, the FDA said that its review of available data does not support the use of aspirin for primary prevention of a heart attack or stroke. Furthermore, the FDA pointed out that aspirin use is associated with “serious risks,” including increased risk of bleeding in the stomach and brain.

As for secondary prevention for people with cardiovascular disease or those who have had a previous heart attack or stroke, the available evidence continues to support aspirin use.  In patients who have had a cardiovascular event, the known benefits of aspirin for secondary prevention outweigh the risk of bleeding.

This development highlights the importance of patients having one-on-one discussions with their health care providers regarding the best treatment options for their individual circumstances.

Antibiotics Linked to Increased Risks for Arrhythmia and Mortality

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Azithromycin use has been associated with increased risk of death among patients at high baseline risk, but not for younger and middle-aged adults. The Food and Drug Administration issued a public warning on azithromycin, including a statement that the risks were similar for levofloxacin. Researchers conducted a retrospective cohort study among US veterans to test the hypothesis that taking azithromycin or levofloxacin would increase the risk of cardiovascular death and cardiac arrhythmia compared with persons taking amoxicillin.

Azithromycin and levofloxacin carry higher arrhythmia and mortality risks than amoxicillin, according to an observational study in the Annals of Family Medicine. The FDA issued a cardiac warning on azithromycin in March 2013.  Researchers studied nearly 1.8 million U.S. veterans (mean age, 57) who received outpatient prescriptions for one of the three antibiotics from 1999 to 2012.    On weighted analysis, the numbers of deaths by day 5 of treatment per million antibiotics dispensed were 154 for amoxicillin, 228 for azithromycin, and 384 for levofloxacin.  Patients receiving azithromycin had roughly a 50% increased risk for death and an 80% increased risk for serious arrhythmia, compared with those on amoxicillin. Risk increases were even greater for levofloxacin.

The researchers conclude: “There are usually multiple antibiotic choices available for older patients, especially those with cardiac comorbidities; physicians may consider prescribing medications other than azithromycin and levofloxacin.”

New (2014) AHA/ACC Guideline for Management of Valvular Heart Disease

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New, 2014 AHA/ACC, Guideline   for the Management of Patients With Valvular Heart Disease: has been   released.  This document is   a major revision of the 2006 and 2008 American College of Cardiology   (ACC)/American Heart Association (AHA) guidelines on the management of   patients with valvular heart disease. There are substantial changes in   multiple areas, and practitioners who are involved in the care of patients   with heart valve disease should read at least the executive summary, if not   the full guideline document.

The following are 10 areas with important changes to remember:

1. Stages of heart valve disease. The revised guidelines include a new classification of heart valve diseases with four progressive stages: A, at risk; B, progressive; C, asymptomatic severe; and D, symptomatic severe. For each valve lesion, stages are based on valve anatomy, valve hemodynamics, hemodynamic consequences, and symptoms.

2. The heart valve team. The guidelines recommend (Class I) that the management of patients with severe heart valve disease is best achieved by a heart valve team, composed minimally of a cardiologist and a cardiac surgeon; but potentially including cardiologists, structural valve interventionalists, cardiovascular imaging specialists, cardiovascular surgeons, anesthesiologists, and nurses, all of whom have expertise in the management and outcome of patients with severe heart valve disease.

3. Heart valve centers of excellence. The guidelines recommend (Class IIa) that consultation with or referral to a heart valve center of excellence is reasonable for asymptomatic patients with severe valve disease, patients with disease that could be best treated with valve repair rather than replacement, and patients with multiple comorbidities in whom valve intervention is considered. Specific criteria for a heart valve center of excellence include experienced providers from multiple disciplines, an ability to offer all available options for diagnosis and management, participation in regional or national outcome registries, demonstrated adherence to guidelines, ongoing quality improvement processes, and public reporting of intervention mortality and success rates.

4. Evaluation of surgical and interventional risk. The guidelines provide specific recommendations for the assessment of surgical and interventional risks that include the Society of Thoracic Surgeons (STS) predicted risk of mortality (PROM) calculator, patient frailty (e.g., Katz Activities of Daily Living and independence), the number of compromised major organ systems, and procedure-specific impediments.

5. Exercise testing. The guidelines place increased emphasis (Class IIa) on the use of exercise testing in the evaluation of asymptomatic patients with severe heart valve disease (notably including asymptomatic severe aortic stenosis [AS] and asymptomatic severe primary mitral regurgitation [MR]); aimed at confirmation of the absence of symptoms, assessment of the hemodynamic response to exercise, and assessment of prognosis.

6. Aortic stenosis. Changes were made in the characterization of and indications for intervention for AS:

  • Two important changes were made in the characterization of AS:

i)    ‘very severe’ AS is defined as aortic Vmax ≥5 m/s or mean gradient ≥60 mm Hg; and

ii)   symptomatic severe AS is subdivided into high gradient (Vmax ≥4 m/s or mean gradient ≥40 mm Hg), low-flow low-gradient (LFLG) with reduced left ventricular ejection fraction (LVEF) (severe leaflet calcification with severely reduced motion, effective orifice area [EOA] ≤1.0 cm2, and Vmax <4 m/s or gradient <40 mm Hg with LVEF <50%, and EOA remaining ≤1.0 cm2, but Vmax ≥4 m/s at any flow rate during dobutamine echocardiography), and LFLG with normal LVEF (or paradoxical LFLG severe AS; severe leaflet calcification with severely reduced motion, EOA ≤1.0 cm2 and Vmax <4 m/s or gradient <40 mm Hg with LVEF ≥50%).

  • Indications for intervention are expanded from previous to include patients with very severe AS (above) and low surgical risk (Class IIa); asymptomatic severe AS and decreased exercise tolerance or exercise-related decrease in blood pressure (Class IIa); and symptomatic  patients with LFLG severe AS and normal LVEF if clinical, hemodynamic, and  anatomic data support valve obstruction as the likely cause of symptoms      (Class IIa).

7. Transcatheter aortic valve replacement. Surgical aortic valve replacement (AVR) remains the intervention of choice for patients with an indication for AVR and low or intermediate operative risk (Class I). Transcatheter AVR (TAVR) is recommended for patients with an indication for AVR, but a prohibitive surgical risk (Class I). TAVR is a reasonable alternative to surgical AVR in patients with an indication for AVR and high surgical risk (Class IIa). Notably, members of a heart valve team should collaborate in order to optimize patient care for patients in whom TAVR or high-risk surgical AVR are being considered (Class I).

8. Management of primary MR. A clear distinction is drawn between chronic primary (degenerative) MR, with pathology of one or more components of the valve (leaflets, annulus, chordae, papillary muscles); and chronic secondary (functional) MR. Intervention for severe chronic primary MR remains indicated (all Class I) for symptoms, LV dysfunction (LVEF ≤60% and/or systolic diameter ≥40 mm), and at the time of other cardiac surgical intervention. Changes in the recommendations for mitral valve repair (MVr) include the following:

  • MVr is recommended over mitral valve replacement (MVR) when pathology  is limited to the posterior leaflet (Class I);
  • MVr is recommended over MVR when pathology involves the anterior or both leaflets and a successful and durable repair can be accomplished (Class I);
  • ‘Prophylactic’ MVr (repair in an asymptomatic patient with preserved LV function) is reasonable when performed at a heart valve center of excellence and the likelihood of successful and durable repair without      residual MR is >95% and operative mortality risk is <1% (Class IIa);
  • MVr is reasonable in an asymptomatic patient with severe nonrheumatic MR and preserved LV function in the setting of new-onset atrial fibrillation or resting pulmonary artery systolic pressure >50 mm Hg (Class IIa); and
  • MVr may be considered in the setting of rheumatic mitral valve disease when surgery is indicated and either successful repair is likely or when long-term anticoagulation management appears unreliable (Class IIb). There      is a Class III (harm) indication for MVR in the setting of isolated disease involving less than half of the posterior mitral leaflet unless repair was attempted and was unsuccessful.
  • Finally, transcatheter MVr may be considered in severely symptomatic patients who have favorable anatomy and a reasonable life expectancy and a prohibitive surgical risk due to comorbidities, and remain severely      symptomatic despite optimal medical therapy (Class IIb).

9. Management of secondary MR. Chronic secondary (functional) MR occurs as a result of abnormalities of the LV, and has more differences than similarities with chronic primary MR (above). The treatment of chronic secondary MR involves treatment of the underlying cardiomyopathy (Class I) and cardiac resynchronization therapy if indicated (Class I). Intervention for chronic secondary MR is reasonable at the time of coronary artery bypass grafting or other cardiac surgery if MR is severe (Class IIa) and not unreasonable if MR is moderate (Class IIb). Surgical intervention performed primarily for chronic secondary MR remains limited to severely (New York Heart Association class III-IV) symptomatic patients with persistent symptoms despite optimal medical therapy for heart failure (Class IIb); new in these guidelines is acceptance of equivalence among these patients between MVR and MVr.

10. Low molecular weight heparin (LMWH) ‘bridging’ of patients with a mechanical heart valve prosthesis. Low LMWH ‘bridging’ is now considered to be appropriate (Class I) among patients with a mechanical valve at high risk of thrombosis when warfarin needs to be interrupted in the context of an invasive or surgical procedure (previously Class IIb).

 

Source: D.S. Bach, MD (Cardiosource)

 

Vitamin D deficiency Linked to Inflammation

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An observational study published online on February 25, 2014 in the Journal of Clinical Endocrinology and Metabolism found that older, healthy individuals who were deficient in 25-hydroxy vitamin D (vitamin D) tended to have higher levels of biomarkers linked with CVD and inflammatory conditions such as multiple sclerosis and rheumatoid arthritis, in an observational study.

To investigate the link between vitamin-D status and markers of inflammation, the researchers analyzed data from 957 hypertensive participants in TUDA. The participants, with roughly equal numbers of men and women, had a mean age of 70.5 years.

Compared with individuals with sufficient serum levels of vitamin D (>75 nmol/L), those who were deficient (<25 nmol/L) had significantly higher levels of the inflammatory biomarkers IL-6 and CRP, and they were more likely to have CRP:IL-10 and IL-6:IL-10 ratios above 2, where IL-10 is an anti-inflammatory biomarker.

The results suggest that older adults with a deficiency in vitamin D may be at risk of having a more proinflammatory immune profile, which in itself may be a risk factor for development of acute or chronic cardiovascular disease, osteoporosis, and cognitive dysfunction.

This is the first study to demonstrate that vitamin-D status is linked with markers of inflammation in a population of independently living, older adults.

However, this is an observational study which may not provide much insight into the relationship between deficiency of vitamin D and chronic inflammation. The authors of this study expressed the urgent need for further studies to prove with certainty the serum level of vitamin-D that is optimal for immune function and the potential implications of increasing dietary recommendations for vitamin-D intake within the population.

The Vitamin D and Omega-3 Trial (VITAL), a randomized clinical trial of 20 000 men and women, which is looking at hard outcomes and expected to be completed in June 2016, should provide a clearer picture of the role for vitamin D and omega-3 supplements in reducing risk for development of cancer, heart disease and stroke.

 

Source: Laird E, McNulty H, Ward M. Vitamin D deficiency is associated with inflammation in older Irish adults. J Clin Endocrinol Metab 2014.

10 Key Points from the 2013 ESC Guidelines on the Management of Stable Coronary Artery Disease

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10 Key Points from the 2013 ESC   Guidelines on the Management of Stable Coronary Artery Disease

 

These guidelines should be applied to patients with stable known or suspected coronary artery disease (SCAD). This condition encompasses several groups of patients: (i) those having stable angina pectoris or other symptoms felt to be related to coronary artery disease (CAD) such as dyspnoea; (ii) those previously symptomatic with known obstructive or non-obstructive CAD, who have become asymptomatic with treatment and need regular follow-up; (iii) those who report symptoms for the first time and are judged to already be in a chronic stable condition (for instance because history-taking reveals that similar symptoms were already present for several months). Hence, SCAD defines the different evolutionary phases of CAD, excluding the situations in, which coronary artery thrombosis dominates clinical presentation (acute coronary syndromes).

The following are 10 key points from the 2013 European Society of Cardiology guidelines for the management of stable coronary artery disease (CAD), with emphasis since the last guidelines publication in 2006:
1. There are different underlying mechanisms of stable known or suspected CAD (SCAD). These include fixed or dynamic plaque-related obstruction of epicardial arteries, focal or diffuse spasm of normal or plaque-disease arteries, microvascular dysfunction, and left ventricular dysfunction caused by prior acute myocardial necrosis and/or hibernation. These mechanisms allow for consideration of ‘microvascular dysfunction and coronary vasospasm in diagnostic and prognostic algorithms.’
2. Coronary computed tomography angiography (CTA) may be considered an alternative to ischemia testing, especially in patients with chest pain symptoms with low to intermediate pretest probability. While CTA should not be overused, its very high negative predictive value can provide reassurance in select circumstances.
3. Although promising and valuable in offering information on both overall cardiac anatomy and function in the same examination, magnetic resonance coronary angiography is still regarded as a research tool and is not officially recommended in the diagnostic evaluation of SCAD.
4. Cardiac rehabilitation, commonly offered after myocardial infarction or recent coronary intervention, should be considered in all patients with SCAD.
5. The treatment of microvascular angina includes optimal coronary risk factor control and traditional anti-ischemic therapy. Beta-blockers are recommended as first-line therapy, given their role in relieving effort-related angina.
6. Patients with a high pretest probability for CAD and/or severe symptoms may benefit from early invasive coronary angiography without noninvasive risk stratification.
7. Fractional flow reserve (FFR), intravascular ultrasound, and optical coherence tomography are methods of intracoronary assessment of coronary artery stenosis severity. The measurement of FFR during adenosine infusion may identify functionally significant stenosis and should be used frequently. A patient with a stenosis and an FFR >0.80 should not be revascularized.
8. While it has been well established that there is genetic variation to the response to antiplatelet therapy (especially clopidogrel) in patients with acute coronary syndrome or myocardial infarction, there are no established recommendations to perform genetic testing to guide treatment with antiplatelet therapy in patients with SCAD.
9. Ranolazone, a selective inhibitor of late sodium current, has anti-ischemic and metabolic properties. It is useful as add-on treatment for the management of stable angina in patients inadequately controlled by first-line therapy, and does not impact heart rate or blood pressure.
10. In light of the results of the FREEDOM trial, coronary artery bypass grafting may be the preferred revascularization strategy in diabetic patients with multivessel disease.

 

Source:   Cardiosource

 

 

Cardiac Resynchronization may be harmful in narrow-QRS heart failure

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Cardiac-resynchronization therapy (CRT) reduces morbidity and mortality in chronic systolic heart failure with a wide QRS complex. Mechanical dyssynchrony also occurs in patients with a narrow QRS complex, which suggests the potential usefulness of CRT in such patients.

New data, from a randomized trial, presented at the European Society of Cardiology (ESC) 2013 Congress (also published in the New England Journal of medicine) concluded that cardiac resynchronization therapy (CRT) will not improve outcomes in patients with narrow QRS intervals (i.e.  <130 ms) and have evidence of ventricular dyssynchrony by echocardiographic criteria. In fact, it may actually increase the risk of cardiovascular death.

This  randomized trial involving 115 centers to evaluate the effect of CRT in patients with New York Heart Association class III or IV heart failure, a left ventricular ejection fraction of 35% or less, a QRS duration of less than 130 ms, and echocardiographic evidence of left ventricular dyssynchrony. All patients underwent device implantation and were randomly assigned to have CRT capability turned on or off. The primary efficacy outcome was the composite of death from any cause or first hospitalization for worsening heart failure.

At study closure, the 809 patients who had undergone randomization had been followed for a mean of 19.4 months. The primary outcome occurred in 116 of 404 patients in the CRT group, as compared with 102 of 405 in the control group (28.7% vs. 25.2%; hazard ratio, 1.20; 95% confidence interval [CI], 0.92 to 1.57; P=0.15). There were 45 deaths in the CRT group and 26 in the control group (11.1% vs. 6.4%; hazard ratio, 1.81; 95% CI, 1.11 to 2.93; P=0.02).

–       The primary end point had occurred in 218 patients with no significant difference between the two groups; however, there was a significant mortality increase in the CRT-on group (p=0.02).

–       There was no significant difference in changes in NYHA class from baseline to six months, nor were there differences in quality of life by the Minnesota Living with Heart Failure Questionnaire.

–       About 19% of CRT-on and 15.6% of CRT-off patients received ICD shocks, and significantly more CRT-on patients had inappropriate shocks, 5.0% vs 1.7% (p=0.01).

The authors concluded that in patients with systolic heart failure and QRS duration of less than 130 ms, CRT does not reduce the rate of death or hospitalization for heart failure and may increase mortality.

These findings shut down hopes that the usefulness of CRT might be extended to heart failure patients without significant QRS prolongation who have echo evidence of ventricular dyssynchrony.

The results of this study reinforce the notion that, at least until new methods of assessment are developed, QRS width (with or without mechanical dyssynchrony) remains the primary determinant of response to CRT. These data also suggest that CRT use in patients with QRS duration of less than 120 ms is unwarranted, could be harmful, and should not be considered. It also argues against the use of echocardiographic criteria for trying to identify patients with < 130 ms QRS duration who might respond to CRT.

Source:

–       Frank Ruschitzka, M.D., William T. Abraham, M.D., Jagmeet P. Singh, et al. Cardiac-Resynchronization Therapy in Heart Failure with a Narrow QRS Complex. NEJM; September 3, 2013DOI: 10.1056/NEJMoa1306687

Heavy coffee consumption linked with increased risk of all-cause death

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Previous studies had suggested an association between heavy coffee consumption and all-cause mortality and coronary heart disease, but many of these older studies are compromised, because heavy coffee drinkers were also smokers, two habits that went hand in hand. When adjusted for smoking, the coffee didn’t appear to be very toxic, and most of the later studies suggested that coffee consumption wasn’t harmful. In fact, there are some potential benefits of coffee;  there are studies suggesting coffee might protect against heart failure, diabetes, stroke, and other conditions.

In this latest study, which is published online August 15, 2013 in the Mayo Clinic Proceedings, lead investigator Dr Junxiu Liu (University of South Carolina, Columbia) and colleagues assessed the data from the Aerobics Center Longitudinal Study. The retrospective analysis included 43 727 participants followed for a median of 17 years, during which time 2512 deaths occurred. Of these deaths, 32% were the result of cardiovascular disease.

Drinking more than four cups of coffee per day is linked with increased risk of all cause of death, a new study suggests. Researchers report that heavy coffee consumption, defined as more than 28 cups of coffee per week, is associated with an increased risk of all-cause mortality among men.

For men and women 55 years of age and younger, the association between heavy coffee consumption and all-cause mortality is more pronounced.

The study authors explained that a massive acute dose of caffeine raises the pulse and blood pressure and that can be toxic.

Despite the limitations of the study, the authors suggested that people who report intakes of low amounts of coffee are not getting significant harm, and that’s up to about 28 cups a week (they pointed out that a cup of coffee as measured is an 8-oz cup, and not the supersized 20-ounce cups typical of Starbucks and other coffee chains).

In a multivariate analysis, men who drank more than 28 cups of coffee had a statistically significant 21% increased risk of all-cause mortality. In women, the risk was not statistically significant. In men younger than 55 years of age, drinking more than 28 cups per week was associated with a 56% increased risk of death compared with nondrinkers. In younger women, such heavy consumption increased the risk of death 113% compared with those who did not drink coffee.

Overall, there was no association between coffee consumption and cardiovascular mortality.

The authors could not explain the reason why noncardiovascular mortality is increased. The noncardiovascular mortality includes a lot of different things; it includes cancer and mortality from suicides, accidents and infections. Why would a high amount of coffee increase noncardiovascular mortality, particularly in young people? The mechanism is not clear. It might be only an association.

Dr. Lavie, one of the study authors, suggests that coffee is relatively safe if people limit themselves to less than four cups of coffee per day. For those who consume more, Lavie said the research is not intended to scare anyone, but it can’t hurt for people to think about the association.

 

SOURCE:

Liu J, Sui X, Lavie CJ, et al. Association of coffee consumption with all-cause and cardiovascular disease mortality. Mayo Clin Proc 2013; DOI:10.1016/j.mayocp.2013.06.020.

Are ICDs Useful in Preventing SCD in Children and Adolescents with HCM?

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Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in the young. The availability of  implantable cardioverter-defibrillators (ICDs) over the past decade for HCM has demonstrated the potential for sudden death prevention, predominantly in adult patients. In children and adolescents with hypertrophic cardiomyopathy , ICDs terminated life-threatening ventricular tachyarrhythmias, but frequently led to device-related complications.                                                                                                                                                                                                                                                                                                                                                                                                                         The multicenter, international registry study, published on April 1 in the Journal of the American College of Cardiology, looked at 224 patients with HCM under age 20, who were at high risk for sudden cardiac death (SCD), and who received ICDs for primary or secondary prevention. Results showed ICDs were activated appropriately to terminate ventricular tachycardia or ventricular fibrillation in 43 of 244 patients (19 percent) over a mean of 4.3 ± 3.3 years. Intervention rates were 4.5 percent per year overall, 14.0 percent per year for secondary prevention after cardiac arrest, and 3.1 percent per year for primary prevention on the basis of risk factors.

In addition, the primary prevention discharge rate terminating ventricular tachycardia or ventricular fibrillation was the same in patients who underwent implantation for 1, 2, or ≥3 risk factors (12 of 88 [14 percent], 10 of 71 [14 percent], and 4 of 29 [14 percent], respectively, p = 1.00). Extreme left ventricular hypertrophy was most frequently associated with appropriate interventions.  However, ICD-related complications, particularly inappropriate shocks and lead malfunction, occurred in 91 patients (41 percent) at 17 ± 5 years of age.

The authors support the current risk stratification strategy for identifying patients with HCM susceptible to life-threatening ventricular tachyarrhythmias, and underscore an important role for SCD prevention (with ICDs). However, since the rate of device complications adds a measure of complexity to ICD decisions in this age group, the authors conclude that it is important to balance considerations for the preservation of life using ICDs against the possibility of device-related complications that may be anticipated with implantation so early in life.

Source:

Maron BJ, et al. Prevention of Sudden Cardiac Death with Implantable Cardioverter-Defibrillators in Children and Adolescents with Hypertrophic Cardiomyopathy. J Am Coll Cardiol. 2013;61(14):1527-1535.

 

 

Does a closure of PFO prevent recurrent ischemic stroke?

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Whether closure of a patent foramen ovale is effective in the prevention of recurrent ischemic stroke in patients who have had a cryptogenic stroke is unknown. Two recently published multicenter studies have demonstrated no significant benefit of closure of a patent foramen ovale over medical therapy alone. Both studies were published in March 2013 issue of the New England Journal of Medicine.

The first study was reported by Dr. Bernhard Meier and colleagues (for the PC investigators) and conducted in 29 centers in Europe, Canada, Brazil, and Australia. Patients with a patent foramen ovale and ischemic stroke, transient ischemic attack (TIA), or a peripheral thromboembolic event were randomly assigned to undergo closure of the patent foramen ovale with the Amplatzer PFO Occluder or to receive medical therapy.

The primary end point was a composite of death, nonfatal stroke, TIA, or peripheral embolism. Analysis was performed on data for the intention-to-treat population.  The mean duration of follow-up was 4.1 years in the closure group and 4.0 years in the medical-therapy group. The primary end point occurred in 7 of the 204 patients (3.4%) in the closure group and in 11 of the 210 patients (5.2%) in the medical-therapy. Nonfatal stroke occurred in 1 patient (0.5%) in the closure group and 5 patients (2.4%) in the medical-therapy group, and TIA occurred in 5 patients (2.5%) and 7 patients (3.3%), respectively.

The second was reported by Dr. John D Carroll and colleagues (for the RESPECT investigators). In this prospective, multicenter, randomized, event-driven trial, they randomly assigned patients, in a 1:1 ratio, to medical therapy alone or closure of the patent foramen ovale. They enrolled 980 patients (18 to 60 years of age; mean age, 45.9 years) at 69 sites. 499 were randomly assigned to the closure group and 481 to the medical-therapy group. The medical-therapy group received one or more antiplatelet medications (74.8%) or warfarin (25.2%).

The authors of both studies concluded that closure of a patent foramen ovale for secondary prevention of cryptogenic embolism did not result in a significant reduction in the risk of recurrent embolic events or death as compared with medical therapy.

Source:

1) – Meier B, et al (for the PC Trial Investigators). N Engl J Med 2013; 368:1083-1091 March 21, 2013 DOI: 10.1056/NEJMoa1211716

2) – Carroll JD, et al (for the RESPECT Investigators).  N Engl J Med 2013; 368:1092-1100 March 21, 2013 DOI: 10.1056/NEJMoa1301440

 

Carvedilol superior to Metoprolol in treatment of heart failure

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In a study published on April 1, 2013 issue of the Journal of the American College of Cardiology, by Dr. Martin Ruwald (University of Rochester Medical Center, New York) and colleagues, comparing carvedilol to metoprolol in treatment of patients with heart failure reported that treatment with carvedilol was associated with a significant reduction in the risk of hospitalization for heart failure or death when compared with patients treated with metoprolol.  Treatment with carvedilol is associated with a significant 30% reduction in the risk of hospitalization for heart failure (HF) or death when compared with patients treated metoprolol, according to a new analysis of the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy  (MADIT-CRT).

In this analysis of MADIT-CRT, which included 1515 patients with left ventricular ejection fraction (LVEF) <30%, QRS duration >130 ms, and NYHA functional class 1 or 2, the primary end point of hospitalization for HF or death from any cause occurred in 132 patients (30%) taking carvedilol and 243 patients (23%) taking metoprolol. During the 3.4-year follow-up, 48 patients (10%) taking carvedilol and 104 patients (11%) taking metoprolol died.

The benefit of carvedilol over metoprolol was more pronounced in the subgroup of patients with a cardiac resynchronization therapy defibrillator (CRT-D), where carvedilol was associated with a significant 39% reduction in the risk of hospitalization for HF or death, and in those with left bundle branch block (LBBB). In the LBBB patients with a CRT-D, treatment with carvedilol was associated with a 49% reduction in risk compared with metoprolol.

There was also a pronounced dosage-dependent relationship between outcome and dose in carvedilol, which was not found in metoprolol-treated patients. The researchers note that mean Carvedilol and metoprolol doses in MADIT-CRT were 18 mg and 64 mg, respectively. These dosages are comparable to real-life dosages administered to patients in the clinical setting, although somewhat lower than in previous randomized controlled trials, according to the researchers.

In multivariate analysis, the reduction in the primary end point with carvedilol translated into a 30% reduction in risk compared with metoprolol, a benefit that was driven primarily by a reduction in HF hospitalizations. There was only a trend toward a reduction in the risk of ventricular tachycardia/ventricular fibrillation (VT/VF). The reduction in the risk of hospitalization for HF/death from any cause was more pronounced in patients receiving CRT-Ds.

Both metoprolol and carvedilol have a class IA indication in the management of patients with HF, with choice of the drug left to the discretion of the physician. In the Carvedilol or Metoprolol European Trial  (COMET), there was an absolute 5.7% survival benefit with carvedilol over metoprolol.

A number of small studies have shown differences between carvedilol and metoprolol in terms of the effect on ejection fraction and hemodynamics. A previous publication reported on 150 patients with heart failure who were randomly assigned to carvedilol or metoprolol. Carvedilol caused greater anti-adrenergic effects than metoprolol, larger increases in left ventricular ejection fraction, and greater decreases in mean pulmonary artery and pulmonary wedge pressure. Both drugs improved symptoms, submaximal exercise tolerance, and quality of life to a similar degree. Left ventricular ejection fraction may be a surrogate parameter for outcome in chronic heart failure patients, but the question ultimately remains whether these hemodynamic differences in favor of carvedilol will result in an advantageous effect on mortality or hospitalization in these patients.

Source:

  1. Ruwald MH, Ruwald AC, Jons C, et al. Effect of metoprolol versus carvedilol on outcomes in MADIT-CRT (Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy). J Am Coll Cardiol 2013; 61:1518-1526.
  2. Poole-Wilson PA et al. Comparison of Carvedilol and Metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003 Jul 5; 362(9377):7-13.
  3. Merta M. et al. Differential effects of beta-blockers in patients with heart failure: A prospective, randomized, double-blind comparison of the long-term effects of metoprolol vs. carvedilol. Circulation 2000;102:546-551.