The efficacy and tolerability of a fixed combination of acetylsalicylic acid, paracetamol, and caffeine in patients with severe headache: a post-hoc subgroup analysis from a multicentre, randomized, double-blind, single-dose, placebo-controlled parallel group study.

BACKGROUND

We investigated efficacy and tolerability of two tablets of the fixed combination of 250 mg acetylsalicylic acid (ASA) + 200 mg paracetamol + 50 mg caffeine (Thomapyrin) in comparison to two tablets of placebo in a post-hoc analysis of a subgroup of patients with severe headache.

METHODS

Patients where included if they were used to treating their episodic tension-type headache or migraine attacks with non-prescription analgesics and reported a history of headache attacks characterized by at least severe pain and greatly impaired usual daily activities and treated headaches with pain intensity of at least 48 mm assessed on a 100-mm visual analogue scale and associated with greatly impaired usual daily activities.

RESULTS

For the primary endpoint 'time to 50% pain relief' in this intention-to-treat subset (n = 179 patients), the fixed combination of ASA, paracetamol, and caffeine was statistically significantly superior to placebo (p = 0.0008). The superior efficacy of the triple combination could also be shown for all secondary endpoints such as time until reduction of pain intensity to 10 mm, weighted sum of pain intensity difference (%SPIDweighted), extent of impairment of daily activities, and global assessment of efficacy. Both treatments were well tolerated. The incidence of adverse events observed was low. The results for this subgroup analysis are consistent with respect to all endpoints and to the patients with non-severe headache and the overall patient population. As with all post-hoc subgroup analyses, the findings are hypothesis generating only and must be interpreted with caution.

DISCUSSION: The results of this subgroup analysis confirm that the fixed combination of ASA (250 mg), paracetamol (200 mg), and caffeine (50 mg) is effective and well tolerated in a broad spectrum from mild to severe migraine and tension-type headache severity independently of the headache diagnosis.