Arterial hypertension associated with PARPi: A meta-analysis of 41 placebo randomized controlled trials combined with a World Health Organization's pharmacovigilance study

Clémence Blaize; Ellina Surtouque; Jonaz Font; Charles Dolladille; Sophie Postel-Vinay; Angélique Da Silva; Joachim Alexandre; Pierre-Marie Morice

doi:10.1111/fcp.12984

Arterial hypertension associated with PARPi: A meta-analysis of 41 placebo randomized controlled trials combined with a World Health Organization's pharmacovigilance study

Fundam Clin Pharmacol. 2024 Jan 25. doi: 10.1111/fcp.12984. Online ahead of print.

Authors

Clémence Blaize¹, Ellina Surtouque¹, Jonaz Font^{2

3}, Charles Dolladille^{2

4}, Sophie Postel-Vinay^{5

6

7}, Angélique Da Silva^{1

8}, Joachim Alexandre^{2

4}, Pierre-Marie Morice^{1

2}

Affiliations

¹ Department of Pharmacology, Caen-Normandy University Hospital, Caen, France.
² Normandie Univ, UNICAEN, INSERM U1086 'Interdisciplinary Research Unit for Cancers Prevention and Treatment' (ANTICIPE), Caen, France.
³ Department of Cardiology, Caen-Normandy University Hospital, Caen, France.
⁴ PICARO Cardio-Oncology Program, Department of Pharmacology, Caen-Normandy University Hospital, Caen, France.
⁵ European Research Council (ERC) StG Team, Inserm Unit U981, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France.
⁶ Drug Development Department (DITEP), Gustave Roussy Cancer Campus, Villejuif, France.
⁷ Faculté de Médicine, Université Paris-Sud, Université Paris-Saclay, Le Kremlin Bicêtre, France.
⁸ Department of medical oncology, Caen-Normandy University Hospital, Caen, France.

PMID: 38268495
DOI: 10.1111/fcp.12984

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.

Keywords: PARPi; arterial hypertension; meta-analysis; pharmacovigilance; placebo.

Publication types

Review