Effect of effervescent paracetamol on blood pressure: a crossover randomized clinical trial

OBJECTIVE:To evaluate the effect of effervescent paracetamol on office and ambulatory blood pressure (BP) compared with noneffervescent paracetamol in hypertensive patients. DESIGN:This was a multicenter open crossover randomized clinical trial. SETTING:Primary care centers in Catalonia and the Basque Country. PARTICIPANTS:Inclusion criteria were office BP 150/95 mmHg or less and daytime ambulatory BP 140/90 mmHg or less, stable pharmacologic or nonpharmacologic antihypertensive treatment, and concomitant chronic osteoarticular pain. INTERVENTIONS:Baseline randomized assignment to 3-week periods of effervescent paracetamol (1 g three times a day) first and noneffervescent paracetamol later, or inversely, during a 7-week study period. At the start and end of each treatment period, 24-h ambulatory BP monitoring was performed. MAIN OUTCOME MEASURES:Differences in 24-h SBP between baseline and end of both treatment periods. The main analyses were performed according to the intention-to-treat principle. RESULTS:In intention-to-treat analysis, 46 patients were analyzed, 21 were treated with paracetamol effervescent and noneffervescent later, and 25 followed the opposite sequence. The difference in 24-h SBP between the two treatments was 3.99 mmHg (95% confidence interval 1.35–6.63; P = 0.004), higher in the effervescent paracetamol treatment period. Similarly, the per-protocol analysis showed a difference in 24-h SBP between the two groups of 5.04 mmHg (95% confidence interval 1.80–8.28; P = 0.004), higher in the effervescent paracetamol treatment period. Self-reported pain levels did not differ between groups and did not vary by treatment period. No serious adverse events were reported in either study arm. CONCLUSION:Effervescent paracetamol tablets are responsible for a significant daytime and overall increase in ambulatory 24-h SBP. TRIAL REGISTRATION:NCT02514538 EudraCT2010-023485-53.