{
  "abstract": "Background Lipoprotein(a) [Lp(a)] is a genetically determined cardiovascular risk factor with limited therapeutic options. Emerging small interfering RNA (siRNA) therapies offer targeted Lp(a) reduction, but their comparative efficacy and safety remain unclear. We conducted a network meta-analysis (NMA) of randomized controlled trials (RCTs) to provide a comprehensive assessment of these emerging treatments.Methods We performed a systematic review and frequentist NMA of RCTs evaluating siRNA therapies in adults (≥18 years) with dyslipidemia, with a minimum ≥12 weeks follow-up. Databases (MEDLINE, Embase, Cochrane CENTRAL, and ClinicalTrials.gov) were searched from inception to May 2020. Outcomes included changes in Lp(a). Safety outcomes comprised overall adverse events, serious adverse events, and injection-site reactions.Results We included 15 RCTs (n=5966) evaluating six siRNA agents. Olpasiran exhibited the greatest effect (MD: -92.24). Zerlasiran (MD: 84.60) and Lepodisiran (MD: -81.03) showed slightly lower efficacy. Among non-targeted agents, only Inclisiran produced a modest yet significant Lp(a) reduction (−22.05%) figure 1. Inclisiran was most effective for LDL-C (MD: −42.74%) and apoB reduction (MD: −31.39%), whereas Lp(a)-targeted siRNAs showed limited effects on these parameters. Safety profiles were generally favorable. However, injection-site reactions were markedly elevated with Zerlasiran (OR: 33.61) and Inclisiran (OR: 5.31) figure 1.Conclusion Targeted siRNA therapies produce substantial reductions in Lp(a) levels, with Olpasiran demonstrating the greatest efficacy. Overall, these agents exhibit favorable safety profiles, although injection-site reactions are more frequent with Zerlasiran and Inclisiran. These findings support siRNA-based interventions as an effective and generally well-tolerated strategy for managing elevated Lp(a) in patients with residual cardiovascular risk.Abstract 186 Figure 1",
  "authors": [
    {
      "affiliations": [
        "Bahria University Health Sciences, Karachi, Pakistan"
      ],
      "name": "Muhammad Raza Sarfraz"
    },
    {
      "affiliations": [
        "Faisalabad Medical University, Faisalabad, Pakistan"
      ],
      "name": "Fatima Murtaza"
    },
    {
      "affiliations": [
        "Dow University of Health Sciences, Karachi, Pakistan"
      ],
      "name": "Ubaid Ahmed"
    },
    {
      "affiliations": [
        "Khawaja Muhammad Safdar Medical College, Sialkot, Pakistan"
      ],
      "name": "Ahmed Hassan Javed"
    },
    {
      "affiliations": [
        "Ziauddin University, Karachi, Pakistan"
      ],
      "name": "Muhammad Ahsan"
    },
    {
      "affiliations": [
        "Nishtar Medical University, Multan, Pakistan"
      ],
      "name": "Zain ul Abideen"
    },
    {
      "affiliations": [
        "Guys and St Thomas NHS Foundation Trust, London, UK"
      ],
      "name": "Iqra Mushtaq"
    },
    {
      "affiliations": [
        "Glan Clwyd Hospital, Betsi Cadwaladr University Health Board Prestatyn, Wales, UK"
      ],
      "name": "Malik Arjun"
    },
    {
      "affiliations": [
        "Multan Medical and Dental College, Multan, Pakistan"
      ],
      "name": "Saba Aliha"
    },
    {
      "affiliations": [
        "St Mary’s and St Clare’s Health, Denville, NJ, USA"
      ],
      "name": "Raam Mannam"
    },
    {
      "affiliations": [
        "Wrightington, Wigan and Leigh NHS Foundation Trust, Wigan, United Kingdom"
      ],
      "name": "Abdullah Hilal Zafar"
    },
    {
      "affiliations": [
        "Services Institute of Medical Sciences, Lahore, Pakistan"
      ],
      "name": "Ayesha Waseem"
    },
    {
      "affiliations": [
        "Dow University of Health Sciences, Karachi, Pakistan"
      ],
      "name": "Aqsa Hafeez"
    },
    {
      "affiliations": [
        "All India Institute of Medical Sciences, Jodhpur, India"
      ],
      "name": "Rahul Falodia"
    }
  ],
  "title": "186 Comparative efficacy of Lp(a)-targeted and non-targeted siRNA agents in lowering lipoprotein(a): a network meta-analysis of randomized trials",
  "uid": "dbeea2ae-b15f-5d8c-9dcc-4144cb5b989f"
}