Cardiology · Medical Literature
Losartan and prednisolone for post-COVID syndrome and cardiac inflammation: a randomized, double-blind, placebo-controlled trial.
Abstract
Persistent cardiac symptoms are common in post-COVID syndrome, even without structural heart disease. Evidence implicates immune dysregulation, endothelial dysfunction and low-grade cardiovascular inflammation. Yet no targeted treatment exists. Myoflame-19 is a multicenter, double-blind clinical trial of 279 participants with inflammatory cardiac involvement defined by cardiovascular magnetic resonance, randomized 1:1 to losartan plus prednisolone (n = 139) or matching placebos (n = 140) for 16 weeks. The modified intention-to-treat population comprised 124 and 122 participants. The primary endpoint, change in left ventricular (LV) ejection fraction, was neutral: between-group difference 0.74 percentage points (pp), 95%CI -0.14 to 1.62, p = 0.10, unpaired t-test; supportive baseline-adjusted ANCOVA 0.99, 95%CI 0.15-1.83, p = 0.021. Among prespecified secondary endpoints, several symptom and imaging measures showed numerical differences favoring intervention, including Average Symptom Score components (modified Canadian Chest Pain Scale -4.8 pp, 95%CI -17.3 to 7.6; NYHA class -8.1 pp, -20.6 to 4.3; Long COVID symptom burden -7.7 pp, -18.9 to 3.6), native T1 and T2 values (native T1 -2.46 ms, -8.35 to 3.42; native T2 -0.31 ms, -1.16 to 0.53), and LV end-diastolic volume ( + 1.45 ml/m², -0.09 to 3.00); however, confidence intervals included the null value and these findings should be regarded as hypothesis-generating.Treatment was safe and well-tolerated. These findings indicate a neutral treatment effect on the primary endpoint. They inform targeted immunomodulation and design of future trials in post-COVID syndrome and inflammatory cardiac involvement. Trial registration: EudraCT 2022-001682-12; NCT05619653.
Clinical relevance
Post-COVID syndrome with inflammatory cardiac involvement represents an unmet therapeutic need, as persistent cardiac symptoms — including chest pain, dyspnea, and reduced functional capacity — affect a significant proportion of COVID-19 survivors even in the absence of overt structural heart disease. The Myoflame-19 trial is the first multicenter, randomized, double-blind, placebo-controlled trial to prospectively evaluate targeted immunomodulation (combining renin-angiotensin system blockade with corticosteroid therapy) in this population, defined rigorously by cardiovascular magnetic resonance (CMR) criteria. Cardiologists and general physicians managing post-COVID patients need this evidence to contextualize the role — and current limitations — of anti-inflammatory and immunomodulatory strategies in this growing cohort.
Key findings
1. PRIMARY ENDPOINT — NEUTRAL: The primary outcome, change in left ventricular ejection fraction (LVEF), showed no statistically significant between-group difference: +0.74 percentage points (pp) favoring losartan plus prednisolone (95% CI −0.14 to 1.62; p = 0.10, unpaired t-test), though a pre-specified baseline-adjusted ANCOVA yielded a borderline significant result (0.99 pp, 95% CI 0.15–1.83; p = 0.021). 2. SYMPTOM SCORES — NUMERICALLY FAVORING INTERVENTION BUT NON-SIGNIFICANT: Modified Canadian Chest Pain Scale improved by −4.8 pp (95% CI −17.3 to 7.6); NYHA class improved by −8.1 pp (95% CI −20.6 to 4.3); Long COVID symptom burden improved by −7.7 pp (95% CI −18.9 to 3.6) — all confidence intervals crossed the null. 3. CMR TISSUE CHARACTERIZATION — NO SIGNIFICANT CHANGE: Native T1 mapping showed a numerical reduction of −2.46 ms (95% CI −8.35 to 3.42) and native T2 showed −0.31 ms (95% CI −1.16 to 0.53), both non-significant and regarded as hypothesis-generating. 4. LV VOLUMES — MARGINAL NUMERICAL SIGNAL: LV end-diastolic volume index showed a numerical increase of +1.45 ml/m² (95% CI −0.09 to 3.00) in the treatment arm, again with a confidence interval inclusive of zero. 5. TRIAL DESIGN AND POPULATION: 279 participants were randomized 1:1 (losartan + prednisolone n = 139 vs. matched placebo n = 140); the modified intention-to-treat population comprised 124 vs. 122 participants, treated for 16 weeks across multiple centers. 6. SAFETY: The combination of losartan and prednisolone was reported to be safe and well-tolerated, with no signal of significant adverse events reported in the abstract.
Practice implications
Based on the neutral primary endpoint, losartan combined with prednisolone cannot currently be recommended as standard therapy for post-COVID syndrome with CMR-defined inflammatory cardiac involvement, and routine immunomodulatory treatment of this phenotype remains without an evidence base. The numerical — but non-significant — trends across symptom and imaging secondary endpoints suggest that adequately powered future trials should consider these as candidate endpoints and may benefit from patient stratification by degree of myocardial inflammation on CMR (e.g., T1/T2 thresholds) to enrich for treatment-responsive subgroups. Clinicians should continue to manage post-COVID cardiac patients with guideline-directed supportive care, reserving immunomodulation for cases with confirmed active myocarditis meeting established criteria, while awaiting confirmatory trial data informed by the Myoflame-19 design.