Long-Term Beta Blockers Post-CABG Questioned, Even With Low LVEF

September 12, 2019

Patients taper off in their use of guideline-recommended cardiovascular meds over the years following coronary artery bypass (CABG) surgery, even though their risk of dying would continue to drop the longer they continued, an observational study suggests.

The analysis saw mortality go steadily down over about 8 years following CABG for patients who stayed on statins, antiplatelets, and renin-angiotensin system (RAS) inhibitors, but beta blockers conferred no such survival benefit.

The survival effects for all four medications were independent of age and applied to the cohort's 28,812 patients overall and to all evaluated subgroups.

Indeed, the study's "biggest surprise" was that beta blockers didn't help survival even in a subgroup that might seem more likely to benefit, those with poor left ventricular (LV) systolic function, Erik Björklund, MD, Sahlgrenska Academy, Gothenburg, Sweden, told theheart.org | Medscape Cardiology.

The analysis doesn't support long-term beta blockers after CABG, he noted, but it also highlights risks from going off other guideline-recommended medical therapy after CABG and should encourage its use even in the very elderly, in whom it's sometimes overlooked.

Björklund presented the SWEDEHEART registry analysis, covering all patients undergoing isolated first-time CABG surgery in Sweden from 2006 to 2015 who were alive 6 months after hospital discharge, here at the European Society of Cardiology Congress 2019.

How the study defined reduced LV ejection fraction (LVEF) might explain the lack of beta blocker survival benefit within that subgroup, Björklund said in an interview. That analysis categorized patients as having an LVEF < 50% or at least 50%.

"We had a very crude characterization of left ventricular function," he said. Perhaps beta blockers would show a survival effect in some patients in a more granular LVEF subgroup analysis, he added. "That's perhaps one reason. We plan on digging deeper."

On the other hand, the SWEDEHEART beta blocker findings are in line with the only published randomized trial to look at the drug class in patients who have undergone CABG, Björklund pointed out.

"Very few studies have actually shown that beta blockers reduce long-term mortality in patients with chronic coronary syndromes," agreed Sanjay Sharma, MD, St. George's University of London, England, using the term in new European guidelines for a patient category that includes those post-CABG.

Although he also was a bit "surprised" that beta blockers didn't improve survival in the current analysis, "I don't think that the SWEDEHEART investigation is suggesting that beta blockers should not be used in these individuals," Sharma, who was not associated with the study, told theheart.org | Medscape Cardiology.

In fact, no one should "draw any inference about the impact of any of those treatments on prognosis," given the potential for "hidden and unknown biases" in any registry analysis, said Martin J. Landray, MBChB, PhD, University of Oxford, England, who was comoderator after Björklund's presentation.

"I would be extraordinarily cautious, as in, I wouldn't do it," especially lacking randomized-trial support for the study's mortality findings, Landray said.

In the meantime, "we should stand by the guidelines," said Sharma. "The guidelines suggest that beta blockers should be used in patients with chronic coronary syndromes who have impaired left ventricular systolic dysfunction."

In current practice, he said, "we always leave people on beta blockers for at least a year, and some clinicians do it for 2 years. We should continue people permanently on beta blockers if there is evidence of LV systolic dysfunction." If LV dysfunction is resolved after 2 years, withdrawing beta blockers but continuing with antiplatelets, RAS inhibitors, and lipid-lowering agents "would be reasonable," he added.

Table 1. Proportions of Patients With Dispensed Prescriptions for Guideline-Recommended Post-CABG Therapy at Baseline and 8 Years Later

Medication

Baseline (%)

After 8 Years (%)

Statins

93.9

77.3

Beta Blockers

91.0

76.4

RAS Inhibitors

72.9

65.9

Antiplatelet Agents

93.0

79.8

The SWEDEHEART analysis followed patients for a median of 4.9 years from baseline, defined as the end of 6 months after CABG. Of the cohort, 19.6% were women, 30.3% had diabetes, 30% had an LVEF below 50%, and 21% were in heart failure.

Use of guideline-recommended meds was high early on but declined steadily and significantly in the ensuing years, Björklund reported.

Exposure to statins, RAS inhibitors, and antiplatelets — but not beta blockers — were each associated with significant drops in mortality over the follow-up and for each additional year of drug exposure, based on prescriptions dispensed and adjusted for age, sex, comorbidities, and use of other cardiovascular medications.

Table 2. Adjusted Hazard Ratio (HR) for Mortality Associated With Dispensed Drug Prescriptions Overall and Per Year of Exposure

Medication

Overall HR (95% CI) P value

HR (95% CI) P value, Per Year on Therapy

Statins

0.56 (0.52 - 0.60) < .001

0.90 (0.88 - 0.92) < .001

Beta Blockers

0.97 (0.90 - 1.06) .54

0.99 (0.96 - 1.01) .21

RAS Inhibitors

0.78 (0.73 - 0.84) < .001

0.98 (0.96 - 1.00) .016

Antiplatelet Agents

0.74 (0.69 - 0.81) < .001

0.93 (0.91 - 0.95) < .001

The findings may not entirely apply to populations outside Sweden, Björklund acknowledged, and the analysis had other limitations. For example, it didn't account for why some patients filled prescriptions for the drugs less often over time.

Björklund proposed that some patients simply may have chosen not to adhere to their prescriptions. "It's a year or more after CABG that people feel better on medications. So many of them stop using them because they feel better."

Alternatively, some could have had contraindications. Or their physicians may not have maintained the prescriptions over the long term. In Sweden, he said, patients tend to be under a cardiologist's routine care for a year or so after CABG, after which they would be seen by primary-care physicians, who may be less aware of the latest guidelines.

Björklund, Sharma, and Landray have disclosed no relevant financial relationships.

European Society of Cardiology (ESC) Congress 2019: Presentation 5059. Presented September 3, 2019.

Follow Steve Stiles on Twitter: @SteveStiles2. For more from theheart.org | Medscape Cardiology, follow us on Twitter and Facebook.

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