Muhammad Shariq Usman

Background: Frailty is common among patients with chronic coronary disease and is associated with worse outcomes. Methods: A pooled, post hoc analysis of the ISCHEMIA and ISCHEMIA‐CKD trials was conducted. Baseline frailty was assessed using a Frailty Index (FI), and participants were categorized into data‐derived tertiles. Multivariable Cox models with multiplicative interaction terms (frailty × treatment arm) were constructed to evaluate whether baseline frailty status modified the treatment effect of the initial invasive (vs conservative) strategy on a composite outcome of cardiovascular death, myocardial infarction, hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest and the secondary outcome of HRQoL (Seattle Angina Questionnaire [SAQ]). Results: Among 5322 participants (mean 64 years, 24% female), a high frailty burden (tertile 3 vs. tertile 1) was associated with lower baseline SAQ scores and increased risk of adverse clinical outcomes on follow‐up. Baseline frailty burden did not significantly modify the effect of the initial invasive strategy on the primary composite outcome ( P _interaction frailty × intervention arm = 0.30). However, frailty significantly modified the effect of the initial invasive strategy on HRQoL, with higher baseline frailty burden associated with greater improvement in SAQ scores at 1 year with initial invasive (vs. conservative) treatment ( P _interaction frailty × intervention arm < 0.001). The treatment effect of an initial invasive vs. conservative strategy on 12‐month SAQ score change was most pronounced in individuals with lower baseline SAQ scores in both higher and lower frailty burden groups. Conclusion: Patients with chronic coronary disease with a higher frailty burden are more likely to experience greater improvements in HRQoL with initial invasive management without a higher risk of adverse clinical events. Lower baseline SAQ scores predicted greater improvement in HRQoL with initial invasive management, independent of frailty burden.

Aim The efficacy and safety of bivalirudin when used concurrently with glycoprotein IIb/IIIa inhibitors (GPI) is uncertain. In this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of bivalirudin versus heparin in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) and to explore the impact of differential use (greater and balanced) of GPI. Methods Online databases were queried from inception to March 2023 to identify eight randomized controlled trials (n = 22,483) for inclusion. The primary outcomes included all-cause mortality, major bleeding, major adverse cardiovascular events (MACE), and net adverse clinical events (NACE). Secondary efficacy endpoints included cardiac death, reinfarction, stent thrombosis (ST), and stroke. Data were pooled using a random-effects model to derive risk ratios (RRs) and 95% confidence intervals (CIs). Results When compared to heparin, bivalirudin was associated with a significant reduction in all-cause mortality (RR 0.83; 95% CI 0.72–0.97; P = 0.02), major bleeding (RR 0.73; 95% CI 0.57–0.93; P = 0.01), cardiac death (RR 0.79; 95% CI 0.66–0.94; P = 0.01), and NACE (RR 0.80; 95% CI 0.72–0.89; P < 0.0001). However, while the bivalirudin arm showed an increased likelihood of ST in the greater GPI subgroup (RR 1.70; 95% CI 1.13–2.56; P = 0.01), it was associated with a decreased likelihood of ST in the balanced GPI subgroup (RR 0.40; 95% CI 0.24–0.65; P = 0.0003). Conclusion Overall, our findings suggest that bivalirudin may be a more efficacious intervention than heparin for reducing certain adverse events in patients with STEMI undergoing primary PCI.

Endpoint adjudication (EA) is a common feature of contemporary randomized controlled trials (RCTs) in cardiovascular medicine. Endpoint adjudication refers to a process wherein a group of expert reviewers, known as the clinical endpoint committee (CEC), verify potential endpoints identified by site investigators. Events that are determined by the CEC to meet pre-specified trial definitions are then utilized for analysis. The rationale behind the use of EA is that it may lessen the potential misclassification of clinical events, thereby reducing statistical noise and bias. However, it has been questioned whether this is universally true, especially given that EA significantly increases the time, effort, and resources required to conduct a trial. Herein, we compare the summary estimates obtained using adjudicated vs. non-adjudicated site designated endpoints in major cardiovascular RCTs in which both were reported. Based on these data, we lay out a framework to determine which trials may warrant EA and where it may be redundant. The value of EA is likely greater when cardiovascular trials have nuanced primary endpoints, endpoint definitions that align poorly with practice, sub-optimal data completeness, greater operator variability, and lack of blinding. EA may not be needed if the primary endpoint is all-cause death or all-cause hospitalization. In contrast, EA is likely merited for more nuanced endpoints such as myocardial infarction, bleeding, worsening heart failure as an outpatient, unstable angina, or transient ischaemic attack. A risk-based approach to adjudication can potentially allow compromise between costs and accuracy. This would involve adjudication of a small proportion of events, with further adjudication done if inconsistencies are detected.

BACKGROUND: It is not known whether the benefits of sodium-glucose cotransporter 2 inhibitors in heart failure persist after years of therapy. METHODS: In the EMPEROR-Reduced (Empagliflozin Outcome Trials in Chronic Heart Failure With Reduced Ejection Fraction) and EMPEROR-Preserved (Empagliflozin Outcome Trials in Chronic Heart Failure With Preserved Ejection Fraction) trials, patients with heart failure were randomly assigned (double-blind) to placebo or empagliflozin 10 mg/day for a median of 16 and 26 months, respectively. At the end of the trials, 6799 patients (placebo 3381, empagliflozin 3418) were prospectively withdrawn from treatment in a blinded manner, and, of these, 3981 patients (placebo 2020, empagliflozin 1961) underwent prespecified in-person assessments after ≈30 days off treatment. RESULTS: From 90 days from the start of closeout to the end of double-blind treatment, the annualized risk of cardiovascular death or hospitalization for heart failure was lower in empagliflozin-treated patients than in placebo-treated patients (10.7 [95% CI, 9.0–12.6] versus 13.5 [95% CI, 11.5–15.6] events per 100 patient-years, respectively; hazard ratio 0.76 [95% CI, 0.60–0.96]). When the study drugs were withdrawn for ≈30 days, the annualized risk of cardiovascular death or hospitalization for heart failure increased in patients withdrawn from empagliflozin but not in those withdrawn from placebo (17.0 [95% CI, 12.6–22.1] versus 14.1 [95% CI, 10.1–18.8] events per 100 patient-years for empagliflozin and placebo, respectively). The hazard ratio for the change in risk in the patients withdrawn from empagliflozin was 1.75 (95% CI, 1.20–2.54), P =0.0034, whereas the change in the risk in patients withdrawn from placebo was not significant (hazard ratio 1.12 [95% CI, 0.76–1.66]); time period-by-treatment interaction, P =0.068. After withdrawal, the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score declined by 1.6±0.4 in patients withdrawn from empagliflozin versus placebo ( P P <0.01). These physiological and laboratory changes were the inverse of the effects of the drug seen at the start of the trials during the initiation of treatment (≈1–3 years earlier) in the same cohort of patients. CONCLUSIONS: These observations demonstrate a persistent effect of empagliflozin in patients with heart failure even after years of treatment, which dissipated rapidly after withdrawal of the drug. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifiers: NCT03057977 and NCT03057951.

Objective: To compare the efficacy of fistulotomy and fistulotomy with marsupialization in the management of simple anal fistula. Study Design: Randomized Controlled study. Setting: Department of Surgery, District Head Quarter Hospital, Mardan, Pakistan. Period: 1^st September 2021 to 31^st August 2022. Material & Methods: A total of 60 Patients coming to hospital with simple anal fistula were randomized into two equal groups. In group A, 30 patients were treated with fistulotomy, while in group B, 30 patients were treated with fistulotomy with marsupialization. The primary outcome was set as time required for complete wound healing. Secondary outcomes were operation time, postoperative pain, anal incontinence, incidence of recurrence and patient satisfaction. Results: The mean wound healing time after 6 weeks was shorter in group B in comparison to group A (4.7± 0.74 versus 6.4± 0.85 weeks; p=0.0001). There was no significant difference in mean operation time between Group B and Group A. The difference in mean pain score was also not statistically significant. There was no significant difference in the incidence of anal incontinence, incidence of recurrence and patient’s satisfaction among two groups. Conclusion: Fistulotomy with marsupialization is more effective procedure than fistulectomy alone in shape of early wound healing without increase in operation time and therefore can be taken as surgical procedure of choice for the simple anal fistula.

Knowledge and awareness of patients’ rights are essential to reach the highest quality of care. In 2006, the Saudi Arabian government formulated “The Patients’ Bill of Rights” to ensure that healthcare delivery is at its highest standard. Despite their efforts, several studies revealed patients’ lack of awareness. In this study, we aim to investigate the patients’ awareness of their rights according to the policy of a teaching hospital in Saudi Arabia. A cross-sectional study was conducted where the participants (n= 384) were in-patients and out-patients of a tertiary care teaching hospital in the Eastern Province of Saudi Arabia. Informed consent was obtained, and confidentiality was maintained. The questionnaire consisted of 23 questions. Data were analyzed using Statistical Package Social Software version 26. Most of the participants were males (70.1%), in-patients (63.3%), and Saudi nationals (84.5%) with a mean age of 32 years. The mean awareness score was satisfactory (>7/14). However, more than half of the participants were unaware of their right to know the risks and benefits of treatment (55.1%), to know the identity of their healthcare providers (61.9%), to deny participation in research (58%), and appoint a healthcare proxy (64.8%). The present study revealed the lack of awareness of certain aspects of patients’ rights that require action in the means of hospital awareness campaigns and educational materials. Further research is required to generalize a consensus on the Saudi population’s level of awareness and consequent steps to optimize the delivery of healthcare in the country. (www.actabiomedica.it)

Stefan D Anker, MD PhD, Muhammad Shariq Usman, MBBS, Javed Butler, MD MPH MBA; ‘Normal Weight’ Is Really Not Normal in Chronic Disease, European Heart Journal,