Metoprolol Benefits Patients With Hypertrophic Obstructive Cardiomyopathy - TEMPO Trial

β-Blockers (BB) represent first-line therapy in symptomatic obstructive HCM (oHCM), and propranolol is the only medication with a U.S. Food and Drug Administration label for the treatment of oHCM. Recently, Dr Anne M. Dybro and her team conducted a study to investigate the effects of metoprolol on left ventricular outflow tract (LVOT) obstruction, symptoms, and exercise capacity in patients with obstructive HCM.

It was a double-blind, placebo-controlled, randomized crossover study of 29 patients with obstructive HCM and New York Heart Association (NYHA) functional class II or higher symptoms. Patients were administered with metoprolol or placebo for 2 consecutive 2-week periods in random order. The researchers evaluated the LVOT gradients, NYHA functional class, Canadian Cardiovascular Society (CCS) angina class, Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS), and cardiopulmonary exercise testing.

Key findings of the study:

♦ Upon analysis, the researchers found that the LVOT gradient:

• At rest was25 mm Hg with metoprolol succinate and 72 mm Hg with placebo.
• At peak, exercise was 28 mm Hg with metoprolol succinate and 62 mm Hg with placebo.
• Post-exercise, it was 45 mm Hg with metoprolol succinate and 115 mm Hg with placebo.
• During Valsalva, it was 94 mm Hg with metoprolol succinate and 119 mm Hg with placebo.

♦ They noted that during metoprolol treatment, 14% of patients were in NYHA functional class III or higher compared with 38% of patients receiving placebo.

♦ Similarly, they noted that no patients were in CCS class III or higher during metoprolol treatment compared with 10% during placebo treatment.

♦ The authors wrote, "These findings were confirmed by higher KCCQ-OSS during metoprolol treatment (76.2 ± 16.2 vs 73.8 ± 19.5; P = 0.039)".

♦ Measures of exercise capacity, peak oxygen consumption, and N-terminal pro–B-type natriuretic peptide did not differ between the study arms.

The authors conclude, "Compared with placebo, metoprolol reduced LVOT obstruction at rest and during exercise, provided symptom relief, and improved quality of life in patients with obstructive HCM. Maximum exercise capacity remained unchanged".

In an accompanying editorial, Dr Ahmad Masri wrote, "Dybro et al should be congratulated for conducting the first comprehensive RCT of BB in oHCM in over one-half century after their initial use for this disease. The trial provides important data to guide the use of metoprolol in the era of novel therapeutics in oHCM".

He further added, "Pharmacotherapy for HCM continues to evolve, with novel therapies directly targeting the molecular pathophysiology of the disease, leading to reappraisal of our current standard of care therapies".

For further information:

Dybro AM, Rasmussen TB, Nielsen RR, Andersen MJ, Jensen MK, Poulsen SH. Randomized Trial of Metoprolol in Patients With Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cariol. 2021 Dec, 78 (25) 2505–2517.