In our July 2014 What’s New in the Patient Safety World column “Issues on Timing of Beta Blockers in MI” we discussed a new analysis from the GRACE registry (Park 2014) that raised issues regarding the timing and route of administration of beta blockers in patients with ST-segment elevation MI (STEMI). But we also noted that studies had clearly demonstrated the long-term benefit of chronic beta blockers in patients with a history of MI and remained a mainstay in the treatment of patients who have had an MI.
Now even the latter practice has even come under scrutiny. A new meta-analysis was done on over 100,000 patients in randomized controlled trials of beta blockers after MI (Bangalore 2014). Importantly, the authors separated out the studies into the pre-reperfusion ear and the reperfusion era and found significant differences between the two timeframes. In the pre-reperfusion era beta-blockers were associated with a significant reduction in overall mortality as well as significant reductions in cardiovascular mortality, MI, and angina. In the reperfusion era there were still significant reductions in MI and angina with beta-blocker therapy but there was no overall mortality benefit. The reductions in MI and angina were balanced against increases in heart failure and cardiogenic shock. And even the benefit of reduced MI and angina appears to be limited to the period 30-days post-MI.
The authors recommend that clinical practice guidelines should reconsider the strength of recommendations for beta-blockers after myocardial infarction.
This may well result in yet another reversal of clinical practices which we had considered soundly “evidence-based” or practices that moved outside their originally researched clinical populations or settings. We’ve seen routine perioperative beta-blockers (for non-cardiac surgery) come and go. Prophylactic proton pump inhibitors gained widespread use outside ICU settings, only to have detrimental effects appear. Our push to mandate antibiotics within 4 hours for community-acquired pneumonia resulted in many patients without pneumonia being exposed unnecessarily to antibiotics. Intensive blood glucose control came and went for ICU patients. And these don’t even cover those things we mandated without a solid evidence base that continue to have unintended consequences pop up (eg. work hour restrictions, CPOE, etc.).
The Bangalore study is thus a good reminder that we need to have constant vigilance of even our most time-honored clinical practices to ensure that they are truly evidence-based, especially when other advances in medical care have occurred in the interim.
Even if the net benefit of beta-blockers after MI is neither positive nor negative, there are cost consequences to patients, hospitals, payors and society. Beta-blocker use in patients after MI is a core measure of most pay-for-performance and quality measurement programs and much time and effort is spent ensuring such patients get beta-blockers. The Bangalore group should be commended for questioning practices we’ve long felt did not need to be questioned. It will be very interesting to see whether practice guidelines are indeed reconsidered in view of the evidence they’ve presented.
One other area in which beta-blockers have often been used despite a weak evidence base is for patients with coronary heart disease without a history of prior MI. And another new analysis has further challenged that use as well (Andersson 2014). Those authors looked at over 26,000 consecutive patients discharged after a first coronary event (acute coronary syndrome or coronary revascularization) between 2000 and 2008 who had not previously been on beta-blockers. Beta-blockers were initiated within 7 days in over 19,000 of these patients. A lower risk of cardiac events with beta-blockers was seen only for patients with MI.
The accompanying editorial (Steg 2014), however, notes the Andersson study is limited by lack of data on clinical characteristics of the patients which may have influenced decisions about whether to use beta-blockers. Beta-blockers may, of course, be important in alleviation of angina in such patients so they likely will still have a role in some patients.
We suspect it is very unlikely that a randomized controlled trial of beta-blockers in either MI patients or those with other coronary syndromes will be done in the future. But the Bangalore and Andersson studies certainly raise awareness that the evidence base for such time-honored practices is far less hearty than most realize.
Park KL, Goldberg RJ, Anderson FA, et al. Beta-blocker Use in ST-segment Elevation Myocardial Infarction in the Reperfusion Era (GRACE). Am J Med 2014; 127(6): 503–511
Bangalore S, Makani H, Radford M, et al. Clinical outcomes with beta-blockers for myocardial infarction. Am J Med 2014; DOI: http://dx.doi.org/10.1016/j.amjmed.2014.05.032 Published Online: June 10, 2014
Andersson C, Shilane D, Go AS, et al. Beta-Blocker Therapy and Cardiac Events Among Patients With Newly Diagnosed Coronary Heart Disease. J Am Coll Cardiol 2014; 64(3): 247-252
Steg PG, De Silva R. Beta-Blockers in Asymptomatic Coronary Artery DiseaseNo Benefit or No Evidence? J Am Coll Cardiol 2014; 64(3): 253-255
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