Other trials, however, have been unable to demonstrate beneficial effects of beta-blockers in heart failure . These trials, in contrast to the trials with favourable outcomes, are characterized by a small sample size (eight to 15 patients) and short term follow-up (ranging from a single dose to one month of therapy). It had become evident in the earlier trials that the benefits of beta-blocker therapy in CHF do not become apparent until three to six months of therapy. Furthermore, the dose of beta-blocker was rapidly escalated in these trials, even in patients with more advanced heart failure (NYHA classes III and IV). birth control pills
As with initiation of ACE inhibitors in patients with CHF, careful dose titration is required with beta-blockers to prevent the adverse hemodynamic consequences associated with abrupt withdrawal of the SNS. Many of the trials exhibiting beneficial effects included an open-label and dose titration phase, in which the beta-blocker was initiated in low doses. Only patients who were able to tolerate the open-label phase were subsequently randomized to placebo or beta-blocker therapy, thereby selecting out CHF patients who would decompensate on beta-blocker therapy.