Convincing data suggests that angiotensin-converting enzyme (ACE) inhibitors improve left ventricular remodeling in chronic heart failure, and in patients with left ventricular dysfunction after myocardial infarction.

Carvedilol also improves remodeling in heart failure patients. There is data showing that carvedilol improves remodeling in heart failure and after myocardial infarction. However, the post-myocardial infarction data comes from a study of carvedilol without ACE inhibitor. There was no data showing the effects of carvedilol plus ACE inhibitor on ventricular remodeling.

Investigators initiated a study to fill this data gap. This was a substudy of the CAPRICORN (Carvedilol Post-Infarct Survival Control in Left Ventricular Dysfunction) trial. The purpose of this study was to show the change in end-systolic volume in post-myocardial infarction patients who received carvedilol plus ACE inhibitor. The researchers used quantitative two dimensional echocardiography at baseline, 1, 3 and 6 months.

The substudy included 58 patients who received carvedilol and 67 who received placebo. In contrast to previous remodeling studies of post-myocardial infarction patients, a significant number of patients had prior history of myocardial infarction or heart failure (about 25% and 42%, respectively).

Carvedilol plus ACE inhibitor significantly reduced heart rate. At the end of 1 month, there was a marked reduction of about 8 beats per minute vs. placebo. At 3 months, the reduction was 12 beats per minute. This effect attenuated somewhat by month 6, for an overall reduction of 8 beats per minute.

There was a profound reduction in systolic and diastolic blood pressure at 1 month. There was also a reduction of blood pressure vs. placebo at 1 month (6.6 mmHg difference in systolic and 7.2 mmHg diastolic). By 3 months, the effect continued for systolic blood pressure, while diastolic blood pressure was similar for carvedilol and placebo.

Carvedilol plus ACE inhibitor also decreased left ventricular end-systolic volume at 1 month. There was an early increase in the placebo group, and an early decrease in the carvedilol group. These effects continued out to 6 months, with perhaps a slight further reduction with carvedilol. Overall, there was an 11% reduction in this measure at 6 months (p=0.037).

In addition, carvedilol plus ACE inhibitor somewhat attenuated increase in left ventricular end-diastolic volume. At 6 months, the difference was about 5%, or approximately 7 ml lower in the carvedilol group.

There was an early improvement in stroke volume at 1 month. This continued to 3 months. Because of a progressive increase in the placebo group, there was not a statistically significant difference in stroke volume at 6 months (p=0.053).

Likewise, left ventricular ejection fraction improved early and continued throughout the course of treatment. Overall, there was an absolute improvement in ejection fraction of 4 percentage points vs. placebo (p=0.0037). There was also early reduction in wall motion. This improvement attenuated over time and was not statistically different at 6 months.

This study suggests carvedilol provides different benefits to patients, depending on the length of treatment time.

The early and sometimes dramatic improvements in heart rate, blood pressure, stroke volume, left ventricular ejection fraction and left ventricular end-systolic volume are consistent with both the beta blocking and vasodilating effects of carvedilol.

The vasodilating effects appear to attenuate with time, as shown by the reduction in effect on heart rate, blood pressure and stroke volume. This is also when the improvement in left ventricular end-systolic volume is most obvious, showing the beta blocking benefit of carvedilol.