October 13, 2011 (Halifax, Nova Scotia) — More evidence that low-risk patients who have undergone elective coronary artery bypass (CABG) surgery do not benefit from treatment with an ACE inhibitor has come from a new cohort study [1].
The study, published online September 26, 2011 in the American Heart Journal, was conducted by a team led by Dr Dimitri Kalavrouziotis (Queen Elizabeth II Health Sciences Centre, Halifax, NS).
Kalavrouziotis explained to heartwire that it had been thought that ACE inhibitors may have some anti-ischemic properties that could benefit CABG patients, and animal studies have suggested that these drugs could stabilize the endothelium of the artery, making it less vulnerable to plaque formation, and might also stabilize vein grafts. "Such anti-ischemic effects of ACE inhibitors have been much debated, but our study suggests they are not of benefit in the CABG population."
He said the results were in line with several other trials. "All suggest that in optimally medically managed patients who are revascularized without a conventional indication for ACE inhibition, the addition of an ACE inhibitor provides no benefit."
For the study, Kalavrouziotis and colleagues analyzed pharmacy data on the use of ACE inhibitors, statins, and beta blockers in 3718 patients 65 years and older who underwent CABG at their institution between 1996 and 2005. Subsequent clinical events were determined from Canadian hospitalization databases and vital statistics for mortality.
The primary outcome was all-cause mortality or hospital readmission for cardiac events or procedures. After risk adjustment for potential confounding variables, there was a trend toward a higher rate of such events among patients treated with an ACE inhibitor after CABG, although this was not statistically significant. Statins were associated with a significant 35% reduction in the primary end point and beta blockers with a 17% reduction.
Risk of Mortality or Hospitalization for Cardiac Events or Procedures in CABG Patients With ACE Inhibitors, Statins, and Beta Blockers
Perioperative Treatment Not Addressed
He noted that the current study looked at outpatient treatment with ACE inhibitors in patients who had previously undergone CABG. It did not address the issue of perioperative treatment, which has been the subject of other studies, which have suggested a possible harmful effect of ACE inhibitors at the time of the surgery.
"My practice is to stop ACE inhibitors prior to cardiac surgery in most, if not all patients, mainly for two reasons: vasoplegia [decreased tensor response of blood vessels post–cardiopulmonary bypass] and renal impairment. Both can be complications of cardiopulmonary bypass, and both are more pronounced in patients treated pre- and perioperatively with ACE inhibitors," Kalavrouziotis said. He added: "We did not look at this in the current study. Rather, our goal was to address what medical therapies should be universally prescribed to CABG patients postop as secondary prevention of death and ischemic events, and we found that ACE inhibitors did not seem to reduce these events."
He noted that the IMAGINE trial [2] had also suggested no benefit of ACE inhibition in this population, but that in this trial, all patients were started on ACE inhibition within seven days after CABG surgery, which could have been one of the reasons for the negative result: "They [might have been] started too early following surgery, before the effects of cardiopulmonary bypass could be washed out of the body." The current study evaluated much later use of ACE inhibitors.
The current results are also consistent with the results of the PEACE trial, which found that in patients with stable coronary heart disease but without a history of heart failure or left ventricular dysfunction, the addition of an ACE inhibitor failed to provide any further benefit.
Kalavrouziotis added that many CABG patients would need to be on ACE inhibitors anyway for other indications, such as left ventricular dysfunction or diabetes, or those having had an ACS or MI. "We are talking about the low-risk elective patients who don't have a known indication for ACE inhibition. These patients are becoming fewer, as they would mostly be referred to PCI, but there are still some that go to CABG," he told heartwire .
Other findings in this cohort study showed that CABG patients did benefit from a statin, and it also suggested benefit of beta blockers. Kalavrouziotis commented: "All CABG patients should be on a statin. That has been shown conclusively in the past, and our study reinforces this. We also showed a modest benefit of beta blockers, but I would say this needs to be confirmed in randomized trials."
The study, published online September 26, 2011 in the American Heart Journal, was conducted by a team led by Dr Dimitri Kalavrouziotis (Queen Elizabeth II Health Sciences Centre, Halifax, NS).
Kalavrouziotis explained to heartwire that it had been thought that ACE inhibitors may have some anti-ischemic properties that could benefit CABG patients, and animal studies have suggested that these drugs could stabilize the endothelium of the artery, making it less vulnerable to plaque formation, and might also stabilize vein grafts. "Such anti-ischemic effects of ACE inhibitors have been much debated, but our study suggests they are not of benefit in the CABG population."
He said the results were in line with several other trials. "All suggest that in optimally medically managed patients who are revascularized without a conventional indication for ACE inhibition, the addition of an ACE inhibitor provides no benefit."
For the study, Kalavrouziotis and colleagues analyzed pharmacy data on the use of ACE inhibitors, statins, and beta blockers in 3718 patients 65 years and older who underwent CABG at their institution between 1996 and 2005. Subsequent clinical events were determined from Canadian hospitalization databases and vital statistics for mortality.
The primary outcome was all-cause mortality or hospital readmission for cardiac events or procedures. After risk adjustment for potential confounding variables, there was a trend toward a higher rate of such events among patients treated with an ACE inhibitor after CABG, although this was not statistically significant. Statins were associated with a significant 35% reduction in the primary end point and beta blockers with a 17% reduction.
Risk of Mortality or Hospitalization for Cardiac Events or Procedures in CABG Patients With ACE Inhibitors, Statins, and Beta Blockers
| Drug therapy | HR (95% CI) | p |
| ACE inhibitor | 1.12 (0.96–1.30) | 0.16 |
| Statin | 0.65 (0.57–0.74) | 0.0001 |
| Beta blocker | 0.83 (0.74–0.93) | 0.001 |
He noted that the current study looked at outpatient treatment with ACE inhibitors in patients who had previously undergone CABG. It did not address the issue of perioperative treatment, which has been the subject of other studies, which have suggested a possible harmful effect of ACE inhibitors at the time of the surgery.
"My practice is to stop ACE inhibitors prior to cardiac surgery in most, if not all patients, mainly for two reasons: vasoplegia [decreased tensor response of blood vessels post–cardiopulmonary bypass] and renal impairment. Both can be complications of cardiopulmonary bypass, and both are more pronounced in patients treated pre- and perioperatively with ACE inhibitors," Kalavrouziotis said. He added: "We did not look at this in the current study. Rather, our goal was to address what medical therapies should be universally prescribed to CABG patients postop as secondary prevention of death and ischemic events, and we found that ACE inhibitors did not seem to reduce these events."
He noted that the IMAGINE trial [2] had also suggested no benefit of ACE inhibition in this population, but that in this trial, all patients were started on ACE inhibition within seven days after CABG surgery, which could have been one of the reasons for the negative result: "They [might have been] started too early following surgery, before the effects of cardiopulmonary bypass could be washed out of the body." The current study evaluated much later use of ACE inhibitors.
The current results are also consistent with the results of the PEACE trial, which found that in patients with stable coronary heart disease but without a history of heart failure or left ventricular dysfunction, the addition of an ACE inhibitor failed to provide any further benefit.
Kalavrouziotis added that many CABG patients would need to be on ACE inhibitors anyway for other indications, such as left ventricular dysfunction or diabetes, or those having had an ACS or MI. "We are talking about the low-risk elective patients who don't have a known indication for ACE inhibition. These patients are becoming fewer, as they would mostly be referred to PCI, but there are still some that go to CABG," he told heartwire .
Other findings in this cohort study showed that CABG patients did benefit from a statin, and it also suggested benefit of beta blockers. Kalavrouziotis commented: "All CABG patients should be on a statin. That has been shown conclusively in the past, and our study reinforces this. We also showed a modest benefit of beta blockers, but I would say this needs to be confirmed in randomized trials."
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