Meta-Analysis Evaluating Risk of Hyperkalemia Stratified by Baseline MRA Usage in Patients with Heart Failure Receiving SGLT2 Inhibitors.

BACKGROUND: Both mineralocorticoid receptor antagonists (MRAs) and sodium-glucose co-transporter type 2 inhibitors (SGLT2is) have demonstrated beneficial reductions in cardiovascular outcomes. However, the risk of precipitating hyperkalemia with their concomitant usage remains unclear. METHODS: MEDLINE and Cochrane were searched from inception through March 2022. Randomized controlled trials on patients with heart failure (HF) evaluating the effect of SGLT2is on clinical outcomes between MRA users and non-users were considered for inclusion. Outcomes of interest were mild and moderate/severe hyperkalemia, for which hazard ratios (HR) were pooled using a random effects model. RESULTS: From the 972 articles retrieved from the initial search, three RCTs (n = 14,462 patients) were included in our meta-analysis. Pooled analysis demonstrated no significant difference in the incidence of mild hyperkalemia between MRA users (HR 0.82 [0.70-0.97]) and non-users (HR 0.95 [0.77-1.17]) (P-interaction = 0.28). The risk of severe hyperkalemia was significantly decreased in MRA users (HR 0.59 [0.44-0.78]; p = 0.0002; I2 = 0%) but not in non-users (HR 0.76 [0.56-1.02]; p = 0.07; I2 = 0%) (P-interaction = 0.22). Sensitivity analysis including patients with HF with reduced ejection fraction (HFrEF) revealed similar results across all subgroups, but no significant reduction in the incidence of mild hyperkalemia (HR 0.89 [0.76-1.04] was noted in MRA users with HFrEF. CONCLUSION: MRAs reduced the risk of mild or moderate/severe hyperkalemia, when added to SGLT2is. Future clinical trials should target scrupulous assessment of the risk of mild and moderate/severe hyperkalemia when used concomitantly with MRAs.

Novel oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation after transcatheter aortic valve replacement: A systematic review and meta-analysis.

BACKGROUND: The efficacy and safety of novel oral anticoagulants (NOACs) compared to the current guideline-recommended vitamin K antagonists (VKAs) in atrial fibrillation (AF) patients undergoing transcatheter aortic valve replacement (TAVR) has not been well established. We pooled evidence from all available studies to assess the risks and benefits of this drug class. METHODS: We queried electronic databases (MEDLINE, Scopus, and Cochrane central) up until January 28th, 2022 for studies comparing NOACs to VKAs in AF patients undergoing TAVR. Results from studies were presented as risk ratios (RR) and pooled using a random-effects model. Subgroup analysis by study design and meta-regression analysis were performed to explore heterogeneity. RESULTS: A total of 12 studies (3 RCTs and 9 observational) containing 12,203 patients (mean age 81.2 years; 50.5% men) were identified and included in the analysis. Pooled analysis revealed no significant difference between NOACs and VKAs in terms of stroke or systemic embolism (RR: 0.78; p = 0.18), major bleeding (RR: 0.84; p = 0.32), intracranial hemorrhage (RR 0.61; p = 0.06), all-cause mortality (RR: 0.69; p = 0.07), and myocardial infarction (RR: 1.60; p = 0.24) at a mean length of follow-up of 15.1 months. RCTs and observational studies did not significantly differ across outcomes on subgroup analysis. Meta-regression analysis found heterogeneity in all-cause mortality to be significantly explained by percentage of males (coefficient: 0.049, p = 0.007), mean age (coefficient: 0.221, p < 0.001), and CHA2DS2-VASc score (coefficient: -1.657, p < 0.001). CONCLUSIONS: This meta-analysis suggests that outcomes with NOACs do not significantly differ compared to VKAs following TAVR in patients with AF.

Left atrial function in heart failure with preserved ejection fraction: a systematic review and meta-analysis.

AIMS: Left atrial (LA) mechanical function may play a significant role in the development and progression of heart failure with preserved ejection fraction (HFpEF). We performed a systematic review and meta-analysis to evaluate association of impaired LA function with outcomes in HFpEF. METHODS AND RESULTS: Multiple databases were searched for original studies measuring different phases of LA function in HFpEF patients. Comparative LA function between HFpEF patients and healthy controls was assessed by pooling weighted mean differences (WMD). Adjusted hazard ratios (HRs) with 95% confidence intervals were pooled to evaluate the prognostic utility of LA function. Twenty-two studies (2 trials, 20 observational) comprising 1974 HFpEF patients and 751 healthy controls were included. HFpEF patients had decreased LA reservoir [WMD = -12.21% (-15.47, -8.95); P < 0.001], LA conduit [WMD = -5.68% (-8.56, -2.79); P < 0.001], and pump [WMD = -11.07% (-14.81, -7.34); P < 0.001] emptying fractions compared with controls. LA reservoir [WMD = -13.38% (-16.07, -10.68); P < 0.001], conduit [WMD = -4.09% (-6.77, -1.42); P = 0.003], and pump [WMD = -3.53% (-4.47, -2.59); P < 0.001] strains were also significantly lower in HFpEF patients. Decreased LA reservoir strain [HR 1.24 (1.02, 1.50); P = 0.03] was significantly associated with risk of composite all-cause mortality or heart failure hospitalization. CONCLUSIONS: Impaired LA function appears to have diagnostic and prognostic value in HFpEF, but whether indices of LA function truly refine discrimination for diagnosis or prognosis remains to be fully determined. Larger studies are needed to better evaluate associations between LA function and clinical outcomes and the role of LA function as a target for novel HFpEF therapies.

Outcomes Associated with Obesity in Patients Undergoing Left Ventricular Assist Device Implantation: A Systematic Review and Meta-Analysis.

Current data suggest that obesity does not impact survival, but may predispose patients to a higher rate of adverse events during left ventricular assist device (LVAD) support. We performed a systematic review and meta-analysis to assess the effects of obesity on clinical outcomes in LVAD recipients. We searched Medline, Scopus, Cochrane library, and clinicaltrials.gov from inception to February 2019 for studies comparing outcomes in obese (body mass index [BMI]> or ≥30 kg/m) and nonobese (BMI< or ≤30 kg/m) heart failure (HF) patients after LVAD implantation. Our primary endpoint was short-term (≤1 year) and long-term (>1 year) all-cause mortalities. The estimates are presented as random-effects risk ratios (RR) with 95% confidence intervals. In this meta-analysis of 15 observational studies (n = 26,842), obese patients receiving LVAD had significantly decreased 6 months (RR = 0.79 [0.73, 0.86]; p < 0.001, I = 0%) and 1 year all-cause mortality (RR = 0.87 [0.79, 0.97]; p = 0.008, I = 69%) compared with nonobese patients. However, both groups showed no significant difference in all-cause mortality at 2 years (RR = 0.95 [0.87, 1.04]; p = 0.12, I = 55%) or 3 years (RR = 0.84 [0.61, 1.15]; p = 0.28, I = 43%). Obese patients had significantly higher risk of device-related infections (RR = 1.48 [1.25, 1.75]; p < 0.001, I = 37%), right heart failure (RR = 1.41 [1.21, 1.65]; p < 0.001, I = 28%), and pump thrombosis (RR = 1.55 [1.37, 1.76]; p < 0.001, I = 0%) compared with nonobese patients. This meta-analysis suggests that obese patients with HF have short- but not long-term survival benefit after LVAD implantation when compared to nonobese patients, although bias may have impacted these findings.

Prevalence and Predictors of the Use of Sunscreen Amongst Medical Students: A Multi-center Cross-sectional Study.

Objective Sun exposure is a primary preventable risk factor for skin cancer. Sunscreen has been shown to reduce the risk of certain skin cancers such as squamous cell carcinoma and melanoma. We aimed to assess the prevalence and predictors of sunscreen use among medical students in Karachi. Methods A multi-center cross-sectional study was conducted among 578 students from multiple medical universities in Karachi, Pakistan. The levels of use of sunscreen were recorded using a comprehensive questionnaire consisting of 29 questions. Descriptive statistics were used and p-values less than 0.05 calculated using the chi-square test were considered significant. Results A majority (n=441, 73.9%) of the participants in this study were female students. Sunscreen use was prevalent in 415 (69.5%) participants. Female students were more aware of the risk of skin cancer from extended sun exposure (n=186, 72.4%). Sunscreen use was significantly associated with gender (p<0.001) and the propensity to get sunburned easily (p=0.001). Few (n=19, 5.0%) students reported being well-versed regarding skin cancer and its risk factors. Most participants were aware of the use of sunscreen for sunburn prevention (n=473, 79.2%), though knowledge of the additional benefits of sunscreen, such as the prevention of skin cancer (n=257, 43.0%) and aging (n=199, 33.3%), was lacking. Conclusion There is an evident lack of knowledge of the importance of sunscreen protection among medical students, particularly regarding the prevention of skin cancer and skin aging. However, an overall positive attitude was observed regarding the use of sunscreen among female students. Medical students are an imperative part of our future healthcare system and should be adequately informed on sunscreen benefits and skin cancer prevention.

Knowledge and Attitude Towards Cardiopulmonary Resuscitation Among Doctors of a Tertiary Care Hospital in Karachi.

Objective Cardiac arrest is an emergency, which can be managed effectively by sound knowledge and practice of basic life support (BLS) skills. However, it has been globally reported that the knowledge of doctors regarding cardiopulmonary resuscitation (CPR) and BLS is sub-standard. We conducted this study with the aim to assess the knowledge and attitude of doctors toward CPR in Dr. Ruth K.M. Pfau Civil Hospital, one of the largest tertiary care hospitals, in Pakistan. Methods We conducted a cross-sectional study, in Dr. Ruth K.M. Pfau Civil Hospital located in Karachi, Pakistan, using cluster sampling. A total of 285 doctors were interviewed. Results A majority of the doctors were unaware of the revised rate and depth of chest compressions (65.6% and 75.8% respectively). While many know the abbreviations of BLS and CPR (96.55% and 95.4%, respectively), 56.5% did not know what automated external defibrillator (AED) stood for. CPR was preferred over chest compression-only resuscitation (CCR) by 91.6% of the doctors. Half of the participants rated their knowledge as average. Most stated that they will not be reluctant to perform CPR in an emergency situation. The majority also agreed that BLS training should be an integral part of the medical curriculum. Conclusion There is an evident lack of knowledge of CPR among healthcare professionals, particularly regarding the updates made in the 2015 American Heart Association (AHA) guidelines. However, an overall positive attitude was observed.

Use of Balloon Atrial Septostomy in Patients With Advanced Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Despite the use and purported benefits of balloon atrial septostomy (BAS), its safety, efficacy, and therapeutic role in the setting of advanced pulmonary arterial hypertension (PAH) are not well defined. OBJECTIVE: The goal of this study was to conduct a systematic review and meta-analysis to better determine the evidence supporting the use of BAS in PAH. METHODS: MEDLINE, Scopus, Cochrane Library, and Clinicaltrials.gov were searched from inception through May 2018 for original studies reporting outcomes with PAH prior to and following BAS. Studies comparing BAS vs other septostomy procedures were excluded. Weighted mean differences and 95% CIs were pooled by using a random effects model. RESULTS: Sixteen studies comprising 204 patients (mean age, 35.8 years; 73.1% women) were included. Meta-analysis revealed significant reductions in right atrial pressure (-2.77 mm Hg [95% CI, -3.50, -2.04]; P < .001) and increases in cardiac index (0.62 L/min/m2 [95% CI, 0.48, 0.75]; P < .001) and left atrial pressure (1.86 mm Hg [95% CI, 1.24, 2.49]; P < .001) following BAS, along with a significant reduction in arterial oxygen saturation (-8.45% [95% CI, -9.93, -6.97]; P < .001). The pooled incidence of procedure-related (48 h), short-term (≤ 30 day), and long-term (> 30 days up to a mean follow-up of 46.5 months) mortality was 4.8% (95% CI, 1.7%, 9.0%), 14.6% (95% CI, 8.6%, 21.5%), and 37.7% (95% CI, 27.9%, 47.9%), respectively. CONCLUSIONS: The present analysis suggests that BAS is relatively safe in advanced PAH, with beneficial hemodynamic effects. The relatively high postprocedural and short-term survival with less impressive long-term survival suggest a bridging role for BAS; its contribution to this change needs to be verified by using a comparator group.

Prasugrel vs. Ticagrelor for Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.

BACKGROUND: The newer P2Y12 inhibitors have better efficacy than clopidogrel. However, whether ticagrelor or prasugrel have a better comparative safety and efficacy profile, especially in the long-term, remains inconclusive. OBJECTIVE: We compared prasugrel and ticagrelor in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). METHODS: MEDLINE and the Cochrane library were queried for randomized controlled trials (RCTs) or observational studies comparing prasugrel with ticagrelor in patients with ACS undergoing PCI. Random-effects pooling was used to calculate odds ratios (ORs) with 95% confidence intervals (CI). Analyses were stratified by duration of follow-up (short term [≤ 3 months] and long term [≥ 1 year]) and study design. RESULTS: In total, 14 studies (six RCTs, eight observational studies), including 40,188 patients, met eligibility criteria. Pooled analysis did not indicate that prasugrel significantly decreased all-cause mortality compared with ticagrelor in the short term (OR 0.49; 95% CI 0.20-1.20; p = 0.11) or long term (OR 0.74; 95% CI 0.48-1.15; p = 0.38). Pooled observational studies showed significantly lower long-term all-cause mortality (OR 0.63; 95% CI 0.43-0.92; p = 0.02) and short-term stent thrombosis (OR 0.46; 95% CI 0.28-0.75; p = 0.002) with prasugrel. No significant difference was observed in the risk of nonfatal myocardial infarction, ischemic stroke, bleeding, or repeat revascularization between the two groups. Results remained similar after stratification according to follow-up and study design. CONCLUSIONS: The present analysis suggests that prasugrel might have a better efficacy profile than ticagrelor in patients with ACS undergoing PCI. However, this advantage was only seen in pooled observational studies and is likely to be affected by selection bias.

Meta-analysis of use of balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension.

BACKGROUND: Current guidelines give balloon pulmonary angioplasty (BPA) a Class IIb recommendation for use in inoperable chronic thromboembolic pulmonary hypertension (CTEPH), as its safety and efficacy remain poorly defined. We conducted a systematic review and meta-analysis to evaluate BPA effectiveness. METHODS: Medline, Cochrane Library and Scopus were searched for original studies from database inception dates until 24th May 2018. Prospective studies reporting outcomes before and after BPA in inoperable CTEPH patients were included. Studies with <20 patients were excluded. Data were pooled using a random effects model represented as weighted mean differences with 95% confidence intervals (CIs). RESULTS: Seventeen noncomparative studies comprising 670 CTEPH patients (mean age 62 years; 68% women) were included. Meta-analysis showed significantly decreased mean pulmonary artery pressure (-14.2 mm Hg [95% CI -18.9, -9.5]), pulmonary vascular resistance (-303.5 dyn·s/cm5 [95% CI -377.6, -229.4]) and mean right atrial pressure (-2.7 mm Hg [95% CI -4.1, -1.3]) after BPA. Six-minute walk distance (67.3 m [95% CI 53.8, 80.8]) and cardiac output (0.2 l/min [95% CI 0.0, 0.3]) were significantly increased following BPA. From 12 studies reporting mortality with median follow-up of 9 months after BPA (range, 1-51 months), pooled incidence of short (≤1 month) and long-term mortality (>1 month) was 1.9% and 5.7%, respectively. CONCLUSION: This systematic review and meta-analysis suggests mildly improved hemodynamics and overall low mortality rates following BPA in inoperable CTEPH patients. This non-comparative evidence can be used to facilitate decision making until the results of larger, controlled studies become available.

Sodium-glucose co-transporter 2 inhibitors and cardiovascular outcomes: A systematic review and meta-analysis.

Background The risks and benefits of sodium-glucose co-transporter 2 (SGLT2) inhibitors on cardiovascular outcomes have not been well established. We pooled evidence from all available clinical trials to assess the cardiovascular effects of this drug. Design A systematic review and meta-analysis of randomised controlled trials. Methods We queried electronic databases (MEDLINE, Scopus, CENTRAL and clinicaltrials.gov) from their inception to July 2017 for published and unpublished placebo controlled trials of SGLT2 inhibitors. Only studies with a follow-up period of at least 24 weeks and reporting at least one cardiovascular outcome were included. Results from trials were presented as odds ratios (ORs) with 95% confidence intervals (CIs) and were pooled using a random-effects model. Results Thirty-five eligible studies (canagliflozin, nine; empagliflozin, eight; dapagliflozin, 18), consisting of 34,987 patients with type 2 diabetes mellitus were included. Pooled results show that SGLT2 inhibitors, when compared to placebo, significantly reduce all-cause mortality (OR 0.79, 95% CI 0.70-0.89; P < 0.001), major adverse cardiac events (OR 0.8, 95% CI 0.76-0.92; P < 0.001), non-fatal myocardial infarction (OR 0.85, 95% CI 0.73-0.98; P = 0.03) and heart failure/hospitalisation for heart failure (OR 0.67, 95% CI 0.59-0.76; P < 0.001) in patients with type 2 diabetes mellitus. No significant difference was noted in the occurrence of stroke (OR 1.02, 95% CI 0.85-1.21; P = 0.87), atrial fibrillation (OR 0.61, 95% CI 0.31-1.19; P = 0.15) or unstable angina (OR 0.95, 95% CI 0.73-1.25; P = 0.73). In addition, there was no heterogeneity between different drugs in the SGLT2 inhibitor class for all of the clinical outcomes studied ( I2 = 0). Conclusions SGLT2 inhibitors significantly reduce the incidence of mortality, major adverse cardiac events, non-fatal myocardial infarction and heart failure in patients with type 2 diabetes mellitus. Subtypes of SGLT2 inhibitors appear to have similar cardiovascular effects.