High Doses of ACE Inhibitors, Beta Blockers, and Statins Lower Mortality in ACS Patients

June 21, 2010

June 21, 2010 (Beijing, China) - Acute coronary syndrome (ACS) patients should be discharged on the maximum tolerated doses of ACE inhibitors, beta blockers, and statins instead of starting low and titrating upward, data from a single European center suggest. Researchers showed that patients treated with the higher doses of the three agents had significantly lower mortality rates at one-year follow-up compared with those who were treated with low or intermediate doses.

"One of the key messages from this study is the clinician should be asking whether we can do a little bit more," said lead investigator Dr Rui Baptista (Coimbra University Hospital, Portugal). ”The dose at discharge should be as high as possible for the patients."

Presenting the results of the study at the World Congress of Cardiology 2010, Baptista said the most recent American College of Cardiology/American Heart Association guidelines emphasize the importance of titrating drugs to target doses or, for statins, to LDL-cholesterol levels after an ACS. Despite the guidelines, some studies examining the relationship between the optimal combination of medical therapy and long-term outcomes suggest the drugs are not uptitrated to target doses or LDL-cholesterol levels.

In particular, said Baptista, women, older patients, and individuals with heart or kidney failure have been reported to have a lower use of guideline-driven therapies. With that in mind, the group tested the prognostic effects of patients being discharged from the hospital following an ACS with high doses of ACE inhibitors, beta blockers, and statins.

Single-Center Observational Study

In this observational study, 597 patients with an ACS were prescribed the three drugs upon discharge. A scoring system, one where the individual dose of each drug was given a value based on the maximum recommended dose of each drug, was used to classify patients into the lower-dose group, intermediate-dose group, and high-dose group. The three most commonly prescribed drugs in each class were carvedilol, atorvastatin, and perindopril, and of those in the high-dose study arm, the mean dose of the drugs prescribed were 33 mg/dL for carvedilol, 27 mg/dL for atorvastatin, and 6.5 mg/dL for perindopril.

At one year, all-cause mortality was significantly lower among patients classified as receiving high doses of ACE inhibitors, beta blockers, and statins. The mortality curves diverged early and continued to separate over the 12 months.

One-Year All-Cause Mortality

End point Low dose, n=231 (%) Medium dose, n=193 (%) High dose, n=120 (%) p
Survival at 1 y 87.5 92.2 95.8 0.047

Commenting on the findings, Baptista noted that this was a single-center study with no control arm, and the doses of the drugs prescribed were left to the attending physician. The group is continuing to follow the patients and plans to present five-year data in the next couple of years. Baptista added that older patients, those aged 70 years and older, fared significantly better than younger ACS patients, suggesting that clinicians shouldn't let age interfere with maximizing the doses of drugs prescribed at discharge.

Commenting on the results of the study, session moderator Dr Gregory Lip (University of Birmingham, UK) noted that patients in the higher-dose treatment arm had significantly higher blood pressure at baseline--82.9% of patients in the high-dose arm had hypertension compared with just 63.0% in the low-dose arm--and questioned whether blood-pressure control during follow-up would have accounted for the reduction in mortality at one year.

"I think the magnitude of benefit at one year, with regard to all-cause mortality, is too large to be explained solely by blood-pressure control," countered Baptista. "We also measured stroke incidence, which would be more closely connected with high blood pressure, and there were no significant differences between the three treatment groups."

Speaking during the discussion, Baptista said that many patients are prescribed beta blockers in the hospital, but these drugs are not titrated to target levels by their clinician in the days and weeks after discharge. Lip agreed, saying that even getting patients to comply with their medications can be challenging. "In clinical practice, if they even get a little bit queasy, the usual response is just to stop the drugs," said Lip.

Baptista has no conflicts of interest.

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