The efficacy of behavioral interventions on cardiovascular risk factors in patients with type 2 diabetes: a systematic review and network meta-analysis of randomized trials.

Helping teens quit: A systematic review and network meta-analysis of smoking cessation interventions.

The completeness of revascularization in patients presenting with non-ST-elevation myocardial infarction (NSTEMI) and multivessel disease (MVD) remains understudied. The SLIM trial previously demonstrated a significant reduction in a composite endpoint of all-cause death, nonfatal myocardial infarction (MI), repeat revascularization, and stroke with complete revascularization under a frequentist framework. This post hoc Bayesian re-analysis offers a probabilistic interpretation beyond conventional significance testing. The primary composite endpoint was analyzed as in the original trial, while secondary endpoints of the composite were evaluated individually. Analyses under multiple priors assessed robustness. The minimal clinically important difference (MCID) was defined as 5% absolute risk difference (ARD) for the composite endpoint and 1% for individual endpoints. The primary model used a weakly informative prior on the log relative risk (RR) scale within a normal-normal Bayesian framework. Total 478 patients were randomized (complete: n = 240; culprit-only: n = 238). The posterior median RR for the composite endpoint was 0.41 (95% credible interval [CrI] 0.22-0.76), corresponding to an ARD of -7.9% (95% CrI -10.4% to -3.2%). The probability of any benefit was 99.8%, and the probability of meeting the MCID was 91.2%. For repeat revascularization, the ARD was -8.3% (95% CrI -10.0% to -4.5%), with a > 99.9% probability of clinically relevant benefit. For nonfatal MI, the ARD was -2.8% (95% CrI -4.2% to 0.9%), with a 94.8% probability of benefit. Results were consistent across all priors. Complete revascularization provides a high probability of clinically meaningful benefit in NSTEMI patients with MVD, primarily through reductions in nonfatal MI and repeat revascularization.

Etomidate, ketamine, and propofol are all used as induction agents for emergency tracheal intubation in critically ill adults but it remains uncertain which agent should be preferable. We searched MEDLINE and Embase (inception to December 2025) for randomized controlled trials comparing etomidate, ketamine, propofol, or ketamine-propofol combination (ketofol) for emergency or rapid sequence intubation in critically ill adults. We performed random-effects network meta-analysis using the frequentist framework. The primary outcome was short-term mortality (28-30day, or ICU/in-hospital mortality when unavailable). Secondary outcomes included cardiovascular collapse, post-induction hypotension, vasopressor use, first-pass intubation success, and peri-intubation cardiac arrest. Certainty of evidence was assessed using the CINeMA framework. Nine trials (4,672 patients, four treatments) were included. Ketamine and etomidate probably result in similar mortality (OR 0.96, 95% CI 0.80-1.16; [Formula: see text] = 30%; moderate certainty). Evidence for other mortality comparisons was very uncertain: ketamine vs propofol (OR 1.53, 0.80-2.93; 1 trial; low certainty) and etomidate vs propofol (OR 0.63, 0.32-1.24; indirect only; very low certainty). Compared with etomidate, ketamine probably increases cardiovascular collapse (OR 1.44, 1.20-1.71; moderate certainty) and may increase post-induction hypotension (OR 1.34, 1.07-1.68; low certainty) and peri-intubation vasopressor use (OR 1.45, 1.21-1.74; low certainty). There was probably little or no difference in first-pass intubation success or cardiac arrest. Etomidate and ketamine probably result in similar mortality, but confidence intervals are compatible with clinically important differences in either direction-ketamine probably causes more peri-intubation hemodynamic instability. Beyond one trial, no randomized evidence exists for propofol in emergency intubation of critically ill adults.

Bayesian Adaptive designs for time-to-event data are available under the restrictive assumption of proportional hazards. In the case of non-proportional hazards, literature is limited to designing non-adaptive fixed two-arm trials within a frequentist framework. A recently introduced frequentist approach proposes a sample size calculation for a fixed two-arm trial using the concept of Relative Time, thereby allowing non-proportional hazards by assuming survival times in the two arms come from two different Weibull distributions, providing researchers with the flexibility to model treatment effects that vary over time. We extend this frequentist approach to a Bayesian adaptive design that allows interim testing with complex features while simultaneously addressing a key limitation of the frequentist approach. We study the operational characteristics of our proposed method with extensive simulations and discuss the findings with two real-life applications.

Renin-angiotensin-aldosterone system (RAAS) inhibitors are widely used for lowering blood pressure, but the optimal choice of RAAS inhibitors in reducing cardiovascular events remains unclear. We aimed to compare the efficacy of RAAS inhibitors on cardiovascular outcomes in hypertensive population. A systematic literature search was performed in PubMed and the Central Cochrane Library. The primary efficacy outcome was major adverse cardiovascular events (MACE). Individual components of MACE including cardiovascular mortality, myocardial infarction, stroke, and heart failure were also analyzed. Network meta-analyses were conducted via a random-effects model within frequentist framework. We analyzed 43 randomized controlled trials. Mineralocorticoid receptor antagonists (MRAs) significantly reduced the risk of MACE compared with placebo [risk ratio (RR) 0.82; 95% confidence interval (CI) 0.75-0.90] and were superior to angiotensin receptor blockers (ARBs; RR 0.87; 95% CI 0.78-0.99) and direct renin inhibitors (DRIs; RR 0.83; 95% CI 0.70-0.99). MRAs showed a nonsignificant trend toward benefit compared with angiotensin-converting enzyme inhibitors (ACEIs; RR 0.91; 95% CI 0.78-1.05). After excluding trials that specifically enrolled patients with heart failure, protective effect of MRAs was not significant, but suggested a trend toward benefit (RR 0.89; 95% CI 0.78-1.01). Subgroup analyses for diabetes and chronic kidney disease consistently showed significant MACE reduction with MRAs, regardless of whether patients had these comorbidities at baseline or not, while other RAAS inhibitors showed inconsistent results in the subgroup analysis. For individual events, MRAs showed higher efficacy in reducing cardiovascular mortality (RR 0.80; 95% CI 0.72-0.88) and heart failure (RR 0.83; 95% CI 0.70-0.98) compared with placebo, while ACEIs were more effective in reducing myocardial infarction (RR 0.65; 95% CI 0.51-0.82) and ARBs showed higher efficacy in reducing stroke (RR 0.88; 95% CI 0.80-0.98) compared with placebo. MRAs outperformed ARBs and DRIs in reducing MACE in patients with hypertension, with a nonsignificant trend toward benefit compared with ACEIs. This benefit was most pronounced in populations with heart failure and MRAs provided consistent cardiovascular protection across subgroups with diabetes or renal comorbidities. Given the current positioning of the guidelines, MRAs may merit earlier consideration in hypertension management, pending confirmatory outcome-driven randomized trials. PROSPERO identifier number CRD42023473004, registered on 28 October 2023.

To systematically evaluate the relative efficacy and impact on cardiac function of sacubitril/valsartan (Sac/Val) vs. active antihypertensive comparators represented in the eligible evidence base for reversing left ventricular hypertrophy (LVH) in patients with hypertension using network meta-analysis. PubMed, Embase, The Cochrane Library, CNKI, Wanfang Data, and SinoMed databases were searched from inception to December 2025 for randomized controlled trials (RCTs) evaluating sacubitril/valsartan vs. active antihypertensive comparators in patients with essential hypertension and cardiovascular remodeling. The primary outcome was the change in left ventricular mass index (LVMI). Network meta-analysis was performed using STATA 18.0 software based on the frequentist framework. Given the clinical heterogeneity in imaging assessment modalities, a random-effects model was employed to calculate the weighted mean difference (MD) and 95% confidence intervals (CI). The surface under the cumulative ranking curve (SUCRA) was used as a supportive ranking metric, whereas comparative interpretation primarily relied on effect estimates and their confidence intervals. Eleven RCTs involving 851 patients were included. The network meta-analysis showed that Sac/Val achieved greater LVMI regression than Amlodipine (MD = -22.54 g/m2, 95% CI: -40.23, -4.86) and Valsartan (MD = -11.34 g/m2, 95% CI: -21.45, -1.23) in reversing LVMI. Compared with Enalapril and Olmesartan, Sac/Val also showed numerically greater LVMI regression, but these differences were not statistically significant. Sac/Val had the highest SUCRA value (96.4%); however, rankings were interpreted descriptively only, while comparative interpretation was primarily based on effect sizes and confidence intervals. Secondary outcome analysis indicated that while Sac/Val effectively reduced systolic and diastolic blood pressure, it had no significant impact on left ventricular ejection fraction (LVEF) (P > 0.05). In hypertensive patients with cardiovascular remodeling, sacubitril/valsartan was associated with greater LVMI regression than amlodipine and valsartan within the current network, whereas comparisons with enalapril and olmesartan remained inconclusive. Given the substantial heterogeneity, evidence of network incoherence, and low-to-very-low certainty of the main comparisons, these results should be regarded as tentative rather than definitive. PROSPERO CRD420261281426.

In comparative studies with time-to-event outcomes, stratified analyses are routinely used to adjust for imbalances in baseline characteristics between treatment groups, with the stratified Cox proportional hazards model being the most common choice. However, its validity depends on strong assumptions—proportional hazards within each stratum and a common hazard ratio across strata—that are rarely satisfied in practice. To address these limitations, model-free, nonparametric alternatives have been proposed within the frequentist framework. We briefly review these methods and then introduce a Bayesian counterpart that offers greater flexibility and a more intuitive interpretation of treatment effects. We illustrate both the frequentist and Bayesian approaches using data from the β-Blocker Evaluation of Survival Trial, evaluating treatment effects on an event-free survival endpoint. When only minimal prior information about treatment efficacy is available, Bayesian estimates typically resemble their frequentist counterparts. However, the Bayesian approach provides enhanced validity under weaker assumptions and more transparent interpretation. Moreover, it can directly quantify the probability that a treatment effect exceeds a prespecified, clinically meaningful threshold, a capability not readily available with standard frequentist methods. Open-source software for implementing the proposed Bayesian procedure is also provided.

The choice of surgical approach in total hip arthroplasty (THA) significantly influences early recovery and complication rates. However, comprehensive evidence comparing the efficacy and safety of multiple contemporary approaches remains limited. We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) from PubMed, Cochrane Library, Embase, and Web of Science (inception to July 2025). We included 85 RCTs (6,575 patients) comparing 13 surgical approaches. Frequentist framework NMA was performed, with effects reported as mean differences (MD), standardized mean differences (SMD), or risk ratios (RR) with 95% confidence intervals. Treatment rankings were assessed using surface under the cumulative ranking curve (SUCRA) values. The analysis of 85 RCTs (6,575 patients) demonstrated distinct performance profiles among the 13 surgical approaches. For functional recovery, the ranking probabilities suggested that minimally invasive anterolateral approach (MIS-ALA) was most likely to achieve the best early postoperative HHS (SUCRA = 88.7%), while modified direct anterior approach (DAA-Modified) ranked highest for medium-to-long-term HHS (SUCRA = 97.8%). regarding surgical efficiency, the minimally invasive posterolateral approach (MIS-PLA) was associated with the highest probability of having the shortest operative time (SUCRA = 98.4%), whereas MIS-ALA had the highest SUCRA value for blood loss control (SUCRA = 90.9%). For surgical trauma, MIS-PLA had the highest SUCRA value indicating the potential for the smallest postoperative CK increase (SUCRA = 82.4%), while anterior approaches (DAA-Modified, bikini direct anterior approach (DAA-Bikini), direct anterior approach (DAA)) ranked highest for suppressing CRP elevation (SUCRAs: 88.2%, 83.4%, and 80.8%). DAA had the highest SUCRA value for walking speed recovery (SUCRA = 91.8%), and supercapsular percutaneously-assisted total hip (SuperPath) had the highest SUCRA value for the physical component summary score (SUCRA = 95.4%). Safety analysis revealed direct lateral approach (DLA) had the highest SUCRA value for the lowest complication risk (SUCRA = 92.9%), while DAA-Bikini had the highest adverse event incidence. THA surgical approaches present distinct efficacy-safety profiles with varying probabilities of advantage. Clinical selection should be individualized based on patient characteristics and surgical expertise, as no single approach is universally superior across all outcomes.

Chronic low back pain (CLBP) is among the most disabling musculoskeletal disorders worldwide. Traditional in-person rehabilitation is often limited by time, geographic, and financial barriers. Telerehabilitation, which delivers personalized interventions through digital technologies (e.g., mobile apps, video coaching, wearable devices, virtual reality, and artificial intelligence feedback systems), is emerging as a complementary and alternative approach to conventional rehabilitation. However, there is currently no consensus on its efficacy and safety. Therefore, this study aims to evaluate the effectiveness of various forms of telerehabilitation in improving pain intensity, physical function, psychological symptoms, and quality of life in patients with CLBP. In addition, the study will assess intervention adherence, patient satisfaction, and safety (as measured by the incidence of adverse events) through systematic review and network meta-analysis. A systematic search will be conducted in the following databases: PubMed/MEDLINE, EMBASE, Cochrane Library, Scopus, and Web of Science, covering all records from database inception to 31 December 2025. Eligible studies will include randomized controlled trials (RCTs) involving adults (≥ 18years) with CLBP, comparing telerehabilitation interventions to any control intervention. The primary outcome will be pain intensity, while secondary outcomes will include physical function, psychological status, quality of life, and adverse events. The risk of bias for the included studies will be assessed using the revised Cochrane Risk of Bias 2.0 tool. The certainty of evidence will be evaluated using the CINeMA (Confidence in Network Meta-Analysis) web application. All network meta-analyses will be conducted within a frequentist framework using Stata 15 software and will apply random-effects models. Intervention rankings will be estimated using Surface Under the Cumulative Ranking (SUCRA) curves and illustrated with forest plots showing both individual and pooled effect sizes. Additional analyses will include assessments of statistical inconsistency, publication bias, heterogeneity, sensitivity, and subgroup differences. This study aimed to compare and rank the available evidence on various forms of telerehabilitation for the management of CLBP, as well as to assess its safety. The findings offer valuable insights for healthcare professionals and policymakers, supporting the advancement of patient-centered rehabilitation strategies. PROSPERO CRD420251015478.

Effects of non-pharmacological interventions on anxiety or depressive symptoms in patients with heart failure: A systematic review and network meta-analysis.

Several studies have demonstrated that beneficial gut microorganisms, such as probiotics, can treat functional constipation in children. We aim to evaluate the effectiveness of probiotics, prebiotics, and synbiotics in treating childhood functional constipation. We conducted a comprehensive search of eight electronic databases, dating from their inception up to July 11, 2024. The eligibility criteria were randomized controlled trials (RCTs) that reported on the use of probiotics, prebiotics, or synbiotics for treating childhood functional constipation. The RCTs were evaluated using the Cochrane Risk of Bias tool, and a random effects network meta-analysis was performed under a frequentist framework. Fifteen RCTs involving 1087 participants were identified. Seventeen types of interventions were investigated. With low or very low confidence in the evidence, no significant differences in bowel movements per week were detected between the intervention and placebo groups. Based on very low-certainty evidence, when Mixed was compared with S. boulardii, Mixed (SMD = 0.86, 95% CI [0.48, 1.23], P < 0.001) had positive effects on stool consistency, and synbiotics were supported by low-quality evidence. Compared with S. boulardii, Lactulose (SMD = 0.62, 95% CI [0.25, 0.99], P < 0.001, low certainty) was more efficacious in improving stool consistency. Synbiotics appeared to reduce abdominal pain. In particular, compared with Lcr35, Mixed (SMD = -1.44, 95% CI [-2.67, -0.22], P = 0.021) showed significant benefits in alleviating abdominal pain, although the certainty of evidence was very low. Prebiotics and synbiotics may have potential benefits in stool consistency and reducing abdominal pain. However, the certainty of the evidence is very low to low. Future research should conduct larger-scale, well-designed RCTs to verify these preliminary findings.

Patients with major trauma face high rates of coagulopathy, hemorrhage, and organ failure, with prehospital resuscitation strategies critical for stabilization. Comparative evidence on prehospital blood [red blood cells (RBCs) and plasma] and non-blood [intravenous crystalloids and dextran, intravenous crystalloids only, and tranexamic acid (TXA)] resuscitation strategies remains limited and inconclusive. To evaluate and compare the efficacy of prehospital blood and non-blood resuscitation strategies in patients with major trauma using network meta-analysis. Network meta-analysis of randomized controlled trials (RCTs). Databases: PubMed, CINAHL, Cochrane Library, and Web of Science and reference lists of relevant previous studies. Participants: patients with major trauma. Prehospital blood (RBC + plasma, RBC, and plasma) and non-blood (intravenous crystalloids + dextran, intravenous crystalloids only, and TXA) resuscitation strategies. Study outcomes were 24-h and 28-day mortality. Data analysis was performed using Frequentist and Bayesian frameworks on MetaInsight, an R-Language web-based analytical platform, presenting odds ratio (OR) and corresponding 95% confidence interval (95% CI). Ranking of prehospital resuscitation strategies was confirmed by the surface under cumulative ranking. A total of 15 RCTs involving 7504 participants were included. Compared with intravenous crystalloids only, RBC + plasma (OR: 0.68, 95% CI: 0.38-1.22), plasma (OR: 0.72, 95% CI: 0.46-1.16), TXA (OR: 0.73, 95% CI: 0.52-1.04), RBC (OR: 0.81, 95% CI: 0.22-3.08), and intravenous crystalloids + dextran (OR: 0.91, 95% CI: 0.65-1.28) demonstrated no significant difference in reducing 24-h mortality. Similarly, TXA (OR: 0.83, 95% CI: 0.35-1.92), intravenous crystalloids + dextran (OR: 0.84, 95% CI: 0.46-1.52), RBC + plasma (OR: 0.88, 95% CI: 0.21-3.73), RBC (OR: 0.94, 95% CI: 0.10-8.64), and plasma (OR: 0.97, 95% CI: 0.38-2.46) revealed no significant difference in reducing 28-day mortality compared with intravenous crystalloids only. Based on ranking probabilities, RBC + plasma (65.8%) for 24-h mortality and TXA (74.6%) for 28-day mortality were ranked highest. Prehospital blood (RBC + plasma, RBC, and plasma) and non-blood (intravenous crystalloids + dextran and TXA) resuscitation strategies were associated with comparable nonsignificant effects on early and late mortality. Current evidence is insufficient to support the superiority of a single prehospital intervention with future large-scale RCTs needed to clarify role of prehospital blood and non-blood resuscitation strategies.

A practitioner's guide to developing critical appraisal skills: How to understand and interpret frequentist and Bayesian approaches applied to serial and parallel diagnostic testing.

Loneliness and social isolation are prevalent and persistent in cancer patients, affecting their psychosocial adjustment. Non-pharmacological interventions have been shown to be effective in previous studies; however, the most effective types of non-pharmacological interventions for this population remain unclear. The aim of this systematic review and network meta-analysis (NMA) was to synthesize the existing evidence and compare the effectiveness of different types of non-pharmacological interventions in treating loneliness and social isolation among cancer patients. A systematic search was conducted in PubMed, Web of Science, Cochrane Library, Embase, CINAHL, PsycINFO, and MEDLINE databases from their inception to December 2024. Randomized controlled trials (RCTs) evaluating non-pharmacological interventions targeting loneliness and social isolation in cancer patients were included. NMA was performed using Stata 17.0 software under a frequentist framework. A total of 13 RCTs were included, including 9 non-pharmacological interventions and 1151 cancer patients. In order of probability, group logotherapy (SUCRA: 99.9%, SMD: -1.62, 95% CI: -2.23 to -1.01) was the most effective intervention for alleviating loneliness and social isolation, followed by psychoeducational therapy (SUCRA: 76.9%, SMD: -0.62, 95% CI: -1.16 to -0.07) and supportive expressive group therapy (SUCRA: 65.7%, SMD: -0.40, 95% CI: -0.75 to -0.05). The NMA suggests that, in terms of short-term efficacy, group logotherapy may be considered the optimal choice for reducing loneliness and social isolation levels in cancer patients. Healthcare professionals could regularly conduct group logotherapy among cancer patients to promote their psychosocial adaptation. PROSPERO Registration Number: CRD42024616937.

Positive and negative expectations crucially shape how we perceive our surroundings, including our emotional and cognitive abilities. Prior work shows that cognitive abilities in different domains can be modulated by placebo or nocebo effects, in clinical cohorts, but also in the absence of disease. However, these studies show inconclusive results and do not directly compare different expectation modulations with each other. This preregistered online study tested the effects of three types of expectations on cognitive performance in a visual attention task, using a mixed design. Participants (n=197) completed this task before and after a written suggestion, which was information that white noise played during the task would either improve (deceptive placebo), improve through the placebo effect (open-label placebo), worsen (nocebo), or not affect (no suggestion) their focus and thus cognitive performance. In a complementary frequentist and Bayesian analysis framework, we observed evidence for learning effects such as faster reaction times or lower error rates from before to during the treatment. However, we found direct evidence of absence regarding any group-related differences. Interestingly, the nocebo group had lower impact ratings than both placebo conditions and the influence of the noise was rated as stronger compared to its expected influence at baseline. This work underscores the importance of distinguishing between subjective and objective effects when evaluating the influence of treatment suggestions on cognitive performance.

Approaches for reporting and interpreting statistically nonsignificant findings in evidence syntheses: a systematic review.

India bears a heavy burden of iron deficiency anemia (IDA), affecting nearly 50% of the population and contributing to adverse pregnancy outcomes, accounting for 20% of maternal deaths. While IDA continues to be a major health issue in India, there is a lack of comparative data on the efficacy of Ayurvedic treatments. This review aims to fill this evidence gap by systematically evaluating and ranking the efficacy of different Ayurvedic treatments for IDA using network meta-analysis (NMA). A systematic search was undertaken on May 1, 2024 using MEDLINE (via PubMed), Scopus, ScienceDirect, AYUSH Research Portal, and Google Scholar to locate randomized controlled trial (RCTs) evaluating interventions and their impact on hemoglobin (Hb) and serum ferritin. We conducted a random-effects NMA using a frequentist framework to estimate the mean difference (MD) and 95% confidence intervals (CIs) for the effects of interventions on outcomes, accounting for heterogeneity (I2). Nineteen RCTs, comprising 2,121 individuals, assessed 26 different treatments for IDA and met the eligibility criteria. Results from the reference-based forest plots of the sensitivity analysis and corresponding P-scores revealed that both Sarva-Jvara-Hara-Lauha (SJHL) and Pippalyadi Yoga demonstrated statistically significant improvements in Hb levels, with MDs of 1.82 g/dL (95% CI: 0.66-2.98) and 1.45 g/dL (95% CI: 1.21-1.69), respectively. Among the interventions, Bibhitakadi Vatak demonstrated strong effectiveness in raising serum ferritin levels (MD: 3.87 ng/mL; 95% CI: -13.32-21.06). SJHL and Bibhitakadi Vatak were found to be the most effective strategies for treating IDA. Additional research is needed to substantiate these findings and assess their wider impact on public health. PROSPERO registration number CRD42024541803.

Climate change-induced extreme weather events increasingly threaten public health, with a particularly acute impact on the mental well-being of urban populations. This study evaluates regional disparities in mental health outcomes associated with climate-induced extreme weather in urban environments, where social and infrastructural vulnerabilities exacerbate environmental stressors. We synthesized data from cohort and cross-sectional studies using both traditional frequentist and Bayesian meta-analytic frameworks to assess the mental health sequelae of extreme weather events (e.g., heatwaves, floods, droughts, and storms). The traditional meta-analysis indicated a significant increase in the odds of adverse mental health outcomes (OR = 1.32, 95% CI: 1.07–1.57). However, this global estimate was characterized by extreme heterogeneity (I2 = 95.8%), indicating that the risk is not uniform but highly context-dependent. Subgroup analyses revealed that this risk is concentrated in specific regions; the strongest associations were observed in Africa (OR = 2.23) and Europe (OR = 2.26). Conversely, the Bayesian analysis yielded a conservative estimate, suggesting a slight reduction in odds (mean OR = 0.92, 95% CrI: 0.87–0.98). This divergence is driven by the Bayesian model’s shrinkage of high-magnitude outliers toward the high-precision data observed in resilient, high-income settings (e.g., USA). Given the extreme heterogeneity observed (I2 = 95.8%), we caution against interpreting either pooled estimate as a universal effect size. Instead, the regional subgroup findings—particularly the consistently elevated risks in Africa and Europe—offer more stable and policy-relevant conclusions. These findings emphasize urgent, context-specific interventions in urban areas facing compounded climate social risks.

Background: Myosin inhibitors have been shown to improve exercise capacity and symptoms, as well as reduce the left ventricular outflow tract (LVOT) gradient. This study explores the efficacy of mavacamten versus aficamten in hypertrophic cardiomyopathy (HCM) patients. Methods: From the inception to October 2024, the electronic databases [Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, and ClinicalTrials.gov] were searched. Using a random-effects model and a frequentist framework, specific effect sizes [mean difference (MD) and risk ratio (RR)] were pooled. Results: This network meta-analysis included six randomized controlled trials (RCTs). A total of 826 individuals with HCM were included; 443 of them received a cardiac myosin inhibitor, while 383 received placebo. Comparison of aficamten versus mavacamten through a common comparator, placebo, showed that aficamten caused a lesser decrease in resting LVOT gradient than that of mavacamten [MD = 14.74, 95% CI (3.02; 26.47)]. Therefore, mavacamten ranked higher (P-score = 0.9966) than aficamten (P-score = 0.5034) in decreasing resting LVOT gradient. Aficamten significantly reduced left ventricular ejection fraction (LVEF) in contrast to mavacamten [MD = –5.59, 95% CI (–10.43; –0.75)]. According to P-score ranking, mavacamten (0.5053) ranked higher than aficamten (0.0059). For New York Heart Association (NYHA) class improvement, there was no statistically significant difference between the two groups [MD = –0.37, 95% CI (–1.79; 1.06)]. But P-score ranked mavacamten (0.8466) higher than aficamten (0.6533). Discussion: Mavacamten ranked superior to aficamten in HCM management. However, this ranking is based not on the absolute clinical benefit but on the network point estimates. Additionally, due to a larger body of clinical evidence supporting mavacamten, it has a clear advantage in terms of reliability. Therefore, more direct trials comparing the two drugs would be required to confirm which one is better and provide conclusive evidence.