another study that b-blockers post-MI are not needed longterm

 

A recent article found that continuing beta blocker therapy beyond one year after a myocardial infarction was not beneficial (see MI bblocker stopping NEJM2024 in dropbox, or DOI: 10.1056/NEJMoa2404204), from the ACTION Study Group in the ABYSS trial

 

 Details:

-- a multicenter open-label randomized noninferiority trial was conducted in 49 sites in France, with patients who had had a myocardial infarction with a left ventricular ejection fraction of least 40%, had no history of a cardiovascular event in the prior six months, and were receiving long-term beta blocker treatment. they were randomized to either continuing the beta blocker therapy or stopping it (the interruption group)

-- mean age 64, 83% male

-- median BMI 26, current smoker 21%, hypertension 43%, diabetes 20%, dyslipidemia 53%

-- ST-segment elevated MI 63%, non-ST segment elevated MI 37%

-- multi-vessel disease 52%, revascularization for index MI 95%, 23% were on prasugrel at time of randomization

-- left ventricular ejection fraction 60% (23% with a value of 40% to 50%)

-- residual angina 1%, median blood pressure 132/77, median heart rate 63

-- peripheral vascular disease 5%, stroke 3%, heart failure 2%

-- beta blockers: 72% bisoprolol, 11% acebutolol, 9% atenolol, 1% metoprolol, 1% carvedilol

-- median time from index MI 2.9 years

 

-- 3698 patients were randomized, 1846 to the interruption group and 1850 to the continuation group

-- primary endpoint: composite of death, nonfatal MI, nonfatal stroke, or hospitalization for cardiovascular reasons, at the longest follow-up time (minimum one year after an uncomplicated MI)

-- main secondary endpoint: changes in quality of life as measured by the European Quality of Life-5 Dimensions (EQ-5D) questionnaire

 

-- median follow-up 3.0 years

 

Results:

-- primary outcome: 

   -- interruption group: 432 of 1812 patients (23.8%)

    -- continuation group: 384 of 1821 patients (21.1%)

        -- hazard ratio 1.16 (1.01-1.33)

        -- risk difference of 2.8 percentage points, within the 3 percentage point difference that was their predetermined cutpoint of "noninferiority"

-- Individual outcomes, comparing the interruption group versus the continuation group:

    -- death: 4.1% in the interruption group and 4.0% in the continuation group

    -- MI: 2.5% versus 2.4%

    -- stroke :1% in each group

    -- hospitalization for cardiovascular causes: 18.9% versus 16.6%

        -- the above results were very similar in their per-protocol evaluation

 

-- Quality life, per the EQ-5D questionnaire:

    -- 0.033 in the interruption group versus 0.032 in the continuation group, nonsignificant

       -- ie, beta blocker interruption did not seem to improve the patient’s quality of life

 

Commentary:

-- as we know, MIs are very common: 2 million persons every year in the US and Europe have an acute MI and about 90% of patients are on beta blockers post-MI in most Western registries

-- much of the data showing longer-term (eg in the 2–3-year range) benefit of beta blockers for patients post-MIs are based on older studies that were prior to myocardial reperfusion and our current pharmacotherapy

-- this study addressed the issue of length of beta blocker therapy after an MI, to add to some of the newer studies (see below)

    -- this trial found no difference in either clinical outcomes or quality-of-life issues by stopping the beta blockers after one year in those patients who had an MI with an ejection fraction at least 40% and no cardiovascular events in the prior six months

    -- although not part of the primary analysis, there was a somewhat increased risk of “angina or ischemia” leading to hospitalization in those in the beta blocker interruption group, 3.6% versus 3.0%, with an attendant increase in angiography (7.9% versus 6.3%) and a small increase in percutaneous coronary interventions of 4.9% versus 4.5%

        -- this result is not unexpected: the acute MI tends to occur in the newer atherosclerotic lesions. 50% of acute coronary events are associated with lesions that have <50% stenosis and 78-97% have <75% stenosis. these newer atherosclerotic lesions have a fresh lipid core with inflammation, a more immature and fragile fibrous cap, and are more likely to rupture, leading to platelet aggregation and the acute MI. on the other hand, significantly decreased blood flow occurs in lesions >75% occlusion, which can lead to angina

        -- and we know that b-blockers do help with anginal symptoms from these more advanced, stenotic lesions

 

-- Another European study reported last year, this one done in Sweden, found that in 43,618 patients with an MI between 2005-2016 who were followed after one year of hospitalization:

    -- they also excluded patients with heart failure or left ventricle systolic dysfunction up to this one-year mark

    -- median age was 64 and 26% were female

    -- primary outcome was a composite of all-cause mortality, MI, unscheduled revascularization, and hospitalization for heart failure; follow-up was for 4.5 years: (MI bblockers not help after 1 year BMJ2023 in dropbox, or doi. org/10.1136/heartjnl-2022- 322115)

    -- the unadjusted rate of the primary outcome was lower among patients who received versus did not receive beta blockers (3.8 versus 4.9 events/100 person-years), HR 0.76 (0.73-1.04)

    -- however, using propensity score weighting and multivariable adjustment to balance the treatment group assignments, the risk of the primary outcome was not different according to beta blocker treatment, HR 0.99 (0.93-1.04). There was no difference on assessing any of the individual components of the composite outcome

 

-- the REDUCE-AMI study, a registry based trial in 45 centers in Sweden, Estonia, and New Zealand randomly assigned 5020 patients with an acute MI who had undergone coronary angiography and had LVEF of at least 50% to either long-term treatment with beta blockers (metoprolol or bisoprolol) or no beta blocker treatment:

    -- there was no difference in their primary endpoint of the composite of death from any cause or new myocardial infarction after median follow-up of 3.5 years

        -- ie, beta blockers that were initiated during the acute phase of an MI did not lead to a lower risk of death or new MI (see MI not need bblocker after MI and HFpEF NEJM2024 in dropbox ,or DOI: 10.1056/NEJMoa2401479), or see my evaluation of the study at https://gmodestmedblogs.blogspot.com/2024/06/mi-preserved-ef-beta-blockers-not-help.html

        -- and, on inspection of the graph above from the current study, it appears that there was no difference in outcomes if beta blockers were not given at all (ie, from time 0), though this was not a pre-specified outcome of the study

 

Limitations:

-- this current study was not a blinded study, which might have affected some of the conclusions, including both the clinical cardiovascular sequelae of both groups as well as their quality of life (ie, there well could be a placebo effect in those continuing vs stopping beta blockers)

-- it is not clear what dose of beta blockers the patients were on, and they may well have had decreasing doses over time, which could have affected the beta blocker effectiveness.

-- as a trial in a single country, despite the large number of sites, the results may be non-generalizable, given the cultural differences in other countries including differences in diet and exercise, imbibing red wine (this study was done in France…) , etc.

-- this trial was largely of men (83%), and we know that  there are pathophysiological differences in cardiac disease between men and women: eg men have a much higher rate of MI and at a younger age, and men with hypertension, high BMI, and diabetes have more MIs with similar risk factors to women (see MI men more than women with similar risk factors BMCcardiovasc2022 in dropbox, or https://doi.org/10.1186/s12872-022-02555-3). and this was despite women having more of other risk factors such as stress, serious life events, poorer sleep patterns, financial stress and depression in the year before the MI

    -- and there is  pretty different cardiac physiology and clinical presentations of heart disease between men and women: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980481/ 

    -- which all means that the results of this study may not be generalizable to women...

-- no mention of other meds that would affect the cardiovascular outcomes in these patients: statins (which all should be on....), the meds were used for their diabetes treatment (GLP-1's are particularly helpful, insulin/sulfonylureas are likely harmful), the antihypertensives that were used (those that give 24-hour protection and decrease blood pressure variability seem to be better in some studies), etc

 

So, another of several recent studies finding limited evidence for beta blockers for more than the short term, in particular after one year post-MI in those patients who had a preserved ejection fraction and no cardiovascular symptoms from the prior six months. This all translates to our strongly considering stopping beta blockers after one year, and perhaps even earlier per the REDUCE-AMI study (which did not even prescribe beta blockers at the time of the MI)

-- given the fairly large number patients we see in primary care who have been on continuing beta blockers post-MI for often many years, it does seem reasonable to titrate these patients off of the beta blockers after one year unless they are on them for another reason (such as heart failure with reduced ejection fraction or other indications). Though this study did not find any difference in patients quality-of-life by stopping the beta blockers, I strongly suspect there are many patients who might benefit from getting off the beta blockers in terms of improving their exercise tolerance for example, which is particularly important since exercise is so important to quality and quantity of life; but also because of  drug interactions, and the not-so-infrequent finding of significant bradycardia or hypotension associated with beta blockers

 

geoff

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