Toprol XL: Excellent Marketing Works But Costs Your Patients Money
Harold J. DeMonaco, MS, Director of Drug Therapy Management
Volume XII, Issue 4

The publication of the results of the MERIT-HF trial1 has led to an increased interest in the use of beta-adrenergic blockers along with ACE inhibitors and diuretics in the management of patients with congestive heart failure (CHF). Toprol XL (metoprolol extended-release), generic metoprolol, bisoprolol, carvedilol and atenolol have all been studied in patients with CHF. All have been shown to be superior to placebo when added to standard therapy. But does Toprol XL deserve the widespread acceptance over other less expensive beta-blockers such as atenolol? If so, for what indications?

Serum Levels and Beta Blockade:

The makers of Toprol XL argue that their product provides a more even plasma concentration time profile than does atenolol. To that end, a 1988 manuscript by Blomqvist is cited.2 The unresolved question is whether these differences in plasma level continuity result in clinical differences.

Atenolol and Toprol XL in Hypertension:

Both atenolol and metoprolol have been shown to be both effective and well-tolerated in the management of hypertension when administered once a day. No comparative trials have been conducted with Toprol XL and atenolol. Previous studies comparing long-acting dosage forms of metoprolol with atenolol have failed to show an advantage in the duration of antihypertensive effect for metoprolol.

For reasons that remain obscure, many clinicians appear to dose atenolol twice a day. The duration of beta blockade and antihypertensive action of atenolol is 24 hours.3,4 It is important to note that the antihypertensive effect and duration of action of atenolol do not correlate with serum levels, so arguments about half-life are of little clinical significance.

Atenolol and Toprol XL in Angina:

Both atenolol and metoprolol have been shown to be effective and well-tolerated in the management of angina. Once again, there are no comparative trials comparing atenolol with Toprol XL. Many clinicians appear to prescribe atenolol for patients with angina on a twice-a-day dosing regimen. This practice appears unnecessary given the duration of beta-adrenergic blockade with once-a-day dosing. The duration of beta blockade is related to the drug half-life and the dose of drug administered.5

Atenolol and Toprol XL in Congestive Heart Failure:

The published results of the MERIT-HF study demonstrated the utility of Toprol XL in addition to conventional therapy in reducing all-cause mortality and hospitalizations, hospitalizations due to worsening heart failure, number of days of hospitalization and NYHA functional class improvement when compared to placebo.

Several studies, albeit not as large as the MERIT-HF, similarly demonstrated the value of atenolol in combination with standard therapy in patients with congestive heart failure. Sturm6 and colleagues studied the effects of atenolol and placebo in combination with enalapril in 100 patients with CHF. The patients treated with atenolol and enalapril had fewer hospitalizations for cardiac events, fewer hospitalizations for worsening failure and arrhythmias as compared to those receiving placebo and enalapril. The differences were statistically and clinically significant. Pacher and colleagues7 studied the effects of atenolol in combination with fosinopril as compared to fosinopril in NYHA class II and III failure, demonstrating an improvement in LV ejection fraction. Both groups received conventional therapy in addition to the study drugs.

 

Conclusion:

There is NO evidence to support the contention that Toprol XL is superior to atenolol in the treatment of patients with hypertension. There are no data to support a longer duration of action of Toprol XL as compared to atenolol. There are data to support the use of atenolol in the management of patients with congestive heart failure in addition to standard therapy. There are no comparative data for Toprol XL and atenolol, however.

The average retail price for a 30-day supply of atenolol 100mg is $5-10. The average retail price for Toprol XL is $28.00, a 3- to 6-fold difference in price. While the price difference in absolute dollars may not be viewed as substantial, the difference should be placed in the context of the other drug expenses borne by the CHF patient, many of whom are elderly and without prescription drug coverage.

 

  1. http://jama.ama-assn.org/issues/v283n10/rfull/joc92053.html

  2. Blomqvist I, Westergren G, Sandberg A, et al. Pharmacokinetics and pharmacodynamics of controlled-release metoprolol: a comparison with atenolol. Eur J Clin Pharmacol 1988; 33(Supp):S19-24.
  3. Kirch W, Gorg KG. Clinical pharmacokinetics of atenolol - a review. Eur J Drug Met Pharmacokinet 1982; 7:81-91.
  4. Harry JD, Shields AG. Relative activity of atenolol and metoprolol. Br Med J 1978; 2:128.
  5. Harron DW, Balnave K, Kinney CD et al. Effects on exercise tachycardia during forty-eight hours of a series of doses of atenolol, sotalol, and metoprolol. Clin Pharmacol Ther 1981; 29:295-302.
  6. Sturm B, Pacher R, Strametz-Juranek J et al. Effect of β1 blockade with atenolol on progression of heart failure in patients pretreated with high-dose enalapril. Eur J Heart Fail 2000; 2:407-412.
  7. Pacher R, Hulsmann M, Berger R et al. Effects of atenolol as add-on therapy to fosinopril in heart failure. Wien Klin Wochenschr 1997; 109:232-238.