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Arterial hypertension associated with PARPi: A meta-analysis of 41 placebo randomized controlled trials combined with a World Health Organization's pharmacovigilance study.
Blaize, Clémence; Surtouque, Ellina; Font, Jonaz; Dolladille, Charles; Postel-Vinay, Sophie; Da Silva, Angélique; Alexandre, Joachim; Morice, Pierre-Marie.
Afiliación
  • Blaize C; Department of Pharmacology, Caen-Normandy University Hospital, Caen, France.
  • Surtouque E; Department of Pharmacology, Caen-Normandy University Hospital, Caen, France.
  • Font J; Normandie Univ, UNICAEN, INSERM U1086 'Interdisciplinary Research Unit for Cancers Prevention and Treatment' (ANTICIPE), Caen, France.
  • Dolladille C; Department of Cardiology, Caen-Normandy University Hospital, Caen, France.
  • Postel-Vinay S; Normandie Univ, UNICAEN, INSERM U1086 'Interdisciplinary Research Unit for Cancers Prevention and Treatment' (ANTICIPE), Caen, France.
  • Da Silva A; PICARO Cardio-Oncology Program, Department of Pharmacology, Caen-Normandy University Hospital, Caen, France.
  • Alexandre J; European Research Council (ERC) StG Team, Inserm Unit U981, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France.
  • Morice PM; Drug Development Department (DITEP), Gustave Roussy Cancer Campus, Villejuif, France.
Fundam Clin Pharmacol ; 38(4): 610-629, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38268495
ABSTRACT

BACKGROUND:

Arterial hypertension has been recently reported from randomized controlled trials (RCTs) assessing poly (ADP-ribose) polymerase inhibitor (PARPi).

OBJECTIVE:

In a context of increasing use of PARPi, it is crucial to properly assess risk and incidence of this adverse event for clinical practice.

METHODS:

We performed a systematic review and meta-analysis in MEDLINE, Cochrane CENTRAL and ClinicalTrials.gov up to January 4, 2023 with an ongoing surveillance up to June 7, 2023. RCTs comparing PARPi to placebo in adult patients with solid tumors were included if hypertension was reported. The primary outcome was the summary risk ratio (RR, with 95% CIs) of any hypertension of PARPi class in placebo RCTs. Secondary outcomes were the summary risk and incidence of hypertension of each individual PARPi. To provide clinical features of PARPi-associated hypertension, we independently queried the WHO's pharmacovigilance database, up to September 1, 2022.

RESULTS:

In total, 41 placebo RCTs (n = 15 264 adult patients) were included. PARPi class was not associated with an increased risk of hypertension compared with placebo. In individual analyses, the risk of hypertension was lower with olaparib than placebo (RR 0.77 [95% CI 0.68-0.86], P < 0.01; I2 = 19%, χ2 P = 0.26). Niraparib monotherapy increased the risk of any (RR 2.84 [95% CI 1.76-4.57], P < 0.01; I2 = 66%, χ2 P = 0.01) hypertension with a summary incidence of 19.87% (95% CI 15.23-25.50). In real-life setting, niraparib-associated hypertension occurs within 20 days and was serious in 66%. Co-prescription of at least one antihypertensive or therapy-induced hypertension was reported in 20.5% or 14.4% of cases, respectively.

CONCLUSIONS:

In a context of extensive assessment of niraparib in combination, these data reinforce the need of a close monitoring of this adverse event to preserve its clinical benefit on patients' survival.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos Clínicos Controlados Aleatorios como Asunto / Farmacovigilancia / Inhibidores de Poli(ADP-Ribosa) Polimerasas / Hipertensión Tipo de estudio: Clinical_trials / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Fundam Clin Pharmacol Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ensayos Clínicos Controlados Aleatorios como Asunto / Farmacovigilancia / Inhibidores de Poli(ADP-Ribosa) Polimerasas / Hipertensión Tipo de estudio: Clinical_trials / Risk_factors_studies / Systematic_reviews Límite: Humans Idioma: En Revista: Fundam Clin Pharmacol Asunto de la revista: FARMACOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Reino Unido