While both of these studies demonstrated a reduction in the combined end-point of death and hospitalizations, only the United States study found a significant mortality reduction. Differences in the study population (CHF secondary to ischemic heart disease versus IDCM, age, baseline EF), duration of follow-up, sample size and practice patterns between the two countries may account for these discrepant results. It is also interesting to note that, in both trials, significant increases in EF with carvedilol were observed. However, this hemodynamic benefit did not correspond to improvements in exercise tolerance and resulted in inconsistent improvements in NYHA functional class. ventolin inhalers
It is important to recognize the limitations of these trials when extrapolating the results of these data to clinical practice. One important feature of most beta-blocker trials was the open-label phase, during which eligible study patients received low dose beta-blocker therapy. During this period, patients were monitored closely for adverse effects and symptoms of worsening heart failure. Only patients who tolerated therapy during this open-label phase moved on to randomization and upward dose titration, thus selecting out patients whose heart failure would worsen upon institution of beta-blocker therapy. In the United States Carvedilol Heart Failure Study, 11% of patients who received carvedilol (during the dose titration and trial periods) were withdrawn from the study due to worsening heart failure. In clinical practice, if patients are started on high doses and are sent home unmonitored, there is a substantial risk of adverse events.