Evaluation of the relationship between effervescent paracetamol and blood pressure: clinical trial.

BACKGROUND: Paracetamol's solubility is achieved by adding to the excipient sodium salts, either as bicarbonate, carbonate or citrate. As the relationship between salt and hypertension is well known, due to the sodium content it has raised a hypothesis that may interfere with the control of that risk factor. Therefore, the objective of this study is to evaluate the effect on blood pressure of effervescent paracetamol compared to non-effervescent, in hypertensive patients. METHODS/DESIGN: This is the protocol of a phase IV multicenter clinical trial, randomized, controlled, crossover, open, which will compare the effect of two different formulations of paracetamol (effervescent or non-effervescent) in the blood pressure of hypertensive patients, with a seven weeks follow up. 49 controlled hypertensive patients will be included (clinical BP lower than 150 and 95 mmHg, and lower than 135 mmHg and 85 mmHg in patients with diabetes or a history of cardiovascular event, and daytime ambulatory measurements lower than 140 and 90 mmHg) and mild to moderate pain (Visual Analog Scale between 1 and 4). The study was approved by the ethics committee of the Fundació Jordi Gol i Gurina and following standards of good clinical practice. The primary endpoint will be the variations in systolic BP in 24 h Ambulatory Blood Pressure Monitoring, considering significant differences 2 or more mmHg among those treated with non-effervescent and effervescent formulations. Intention-to-treat and per-protocol analysis will be held. DISCUSSION: Despite the broad recommendation not to use effervescent drugs in patients with hypertension, there are relatively little studies that show exactly this pressor effect due to sodium in salt that gives the effervescence of the product. This is the first clinical trial designed to study the effect of effervescence compared to the non-effervescent, in well-controlled hypertensive patients with mild to moderate pain, performed in routine clinical practice. TRIAL REGISTRATION: NCT 02514538.

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: NCT: 02514538 EudraCT: 2010-023485-53.

Frecuencia cardíaca y riesgo cardiovascular / Heart rate and cardiovascular risk

Una frecuencia cardíaca basal más elevada en la clínica se ha asociado a una mayor morbimortalidad cardiovascular. En gran parte de los estudios, la asociación entre frecuencia cardíaca y mortalidad se mantiene incluso tras ajustar el análisis para múltiples variables, como factores de riesgo cardiovascular, actividad física, función pulmonar, uso de betabloqueantes, tratamiento antihipertensivo, hemoglobina, hipertrofia ventricular izquierda, enfermedad coronaria o insuficiencia cardíaca. La taquicardia basal sería, por lo tanto, un marcador de enfermedad crónica subclínica o de la propia hiperactividad simpática. Tanto la frecuencia cardíaca clínica como la obtenida por monitorización ambulatoria de presión arterial—especialmente la frecuencia cardíaca nocturna- son útiles para estimar mejor el riesgo del hipertenso (AU)

A higher office basal heart rate has been associated with increased cardiovascular morbidity and mortality. The association between heart rate and mortality in most studies remains even after adjusting for multiple confounding variables such as cardiovascular risk factors, physical activity, lung function, use of beta blockers, antihypertensive treatment, hemoglobin, left ventricular hypertrophy, coronary disease or heart failure. Therefore, basal tachycardia seems to be a marker of subclinical chronic disease or a sign of the sympathetic hyperactivity. Both office heart rate and heart rate obtained by ambulatory blood pressure monitoring —especially nighttime heart rate- are useful to better estimate the cardiovascular risk of the hypertensive patient (AU)