In-hospital initiation of a PCSK9 inhibitor in patients with acute coronary syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors have been shown to be effective and safe in patients with stable angina and previous myocardial infarction. However, evidence for initiating their use in patients hospitalized with acute coronary syndrome (ACS) is limited. This systematic review and meta-analysis was performed to provide more clinical evidence. METHODS: PubMed, Embase, OVID, Cochrane Library and ClinicalTrials.gov were systematically searched for eligible randomized controlled trials up to March 20, 2023. The risk ratios, standardized mean differences and 95% confidence intervals were calculated for primary and secondary outcomes. The bias risk of the included studies was assessed using the Cochrane RoB 2 criteria. RESULTS: About 8 randomized controlled trials involving 1255 inpatients with ACS were included. PCSK9 inhibitor treatment significantly reduced low-density lipoprotein cholesterol (LDL-C) (SMD -1.28, 95% CI -1.76 to -0.8, P = .001), triglycerides (TG) (SMD -0.93, 95% CI -1.82 to -0.05, P = .03), total cholesterol (SMD -1.36, 95% CI -2.01 to -0.71, P = .001), and apolipoprotein B (Apo B) (SMD -0.81, 95% CI -1.09 to -0.52, P = .001) within approximately 1 month. PCSK9 inhibitor treatment significantly reduced the total atheroma volume (TAV) (SMD -0.33, 95% CI -0.59 to -0.07, P = .012). It also significantly increased minimum fibrous cap thickness (FCT) (SMD 0.41, 95% CI 0.22-0.59, P = .001) in long-term follow-up (>6 months). PCSK9 inhibitor treatment significantly reduced the risk of readmission for unstable angina (RR 0.32, 95% CI 0.12-0.91, P = .032) in short-term follow-up (<6 months). There were no significant differences in all-cause mortality, cardiovascular death, myocardial infarction, ischemic stroke, coronary revascularization or heart failure. Only nasopharyngitis (RR 1.71, 95% CI 1.01-2.91, P = .047) adverse events were significantly observed in the PCSK9 inhibitor group. CONCLUSION: Application of a PCSK9 inhibitor in hospitalized patients with ACS reduced lipid profiles and plaque burdens and was well tolerated with few adverse events.

Percutaneous mechanical circulatory support devices in high-risk patients undergoing percutaneous coronary intervention: A meta-analysis of randomized trials.

BACKGROUND: Percutaneous mechanical circulatory support devices (pMCSDs) are increasingly used on the assumption (but without solid proof) that their use will improve prognosis. A meta-analysis was undertaken according to the PRISMA guidelines to evaluate the benefits of pMCSDs in patients undergoing high-risk percutaneous coronary intervention (hr-PCI). METHODS: We searched PubMed, EMbase, Cochrane Library, Clinical Trial.gov, and other databases to identify eligible studies. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated for 30-day and 6-month all-cause mortality rates, reinfarction, and other adverse events using a random effect model. RESULTS: Sixteen randomized controlled trials (RCTs) were included in this study. In the pooled analysis, intra-aortic balloon pump (IABP) was not associated with a decrease in 30-day and 6-month all-cause mortality (RR 1.01 95% CI 0.61-1.66; RR 0.88 95% CI 0.66-1.17), reinfarction (RR 0.89 95% CI 0.69-1.14), stroke/transient ischemic attack (TIA) (RR 1.75 95% CI 0.47-6.42), heart failure (HF) (RR 0.54 95% CI 0.11-2.66), repeat revascularization (RR 0.73 95% CI 0.25-2.10), embolization (RR 3.00 95% CI 0.13-71.61), or arrhythmia (RR 2.81 95% CI 0.30-26.11). Compared with IABP, left ventricular assist devices (LVADs) were not associated with a decrease in 30-day and 6-month all-cause mortality (RR 0.96 95% CI 0.71-1.29; RR 1.23 95% CI 0.88-1.72), reinfarction (RR 0.98 95% CI 0.68-1.42), stroke/TIA (RR 0.45 95% CI 0.1-1.95), acute kidney injury (AKI) (RR 0.83 95% CI 0.38-1.80), or arrhythmia (RR 1.52 95% CI 0.71-3.27), but LVADs were associated with a decrease in repeat revascularization (RR 0.26 95% CI 0.08-0.83). However, LVADs significantly increased the risk of bleeding compared with IABP (RR 2.85 95% CI 1.72-4.73). CONCLUSIONS: Neither LVADs nor IABP improves short or long-term survival in hr-PCI patients. LVADs are more likely to reduce repeat revascularization after PCI, but to increase the risk of bleeding events than IABP.

Percutaneous pulmonary valve implantation in patients with right ventricular outflow tract dysfunction: a systematic review and meta-analysis.

BACKGROUND: Pulmonary valve replacement is required for patients with right ventricular outflow tract (RVOT) dysfunction. Surgical and percutaneous pulmonary valve replacement are the treatment options. Percutaneous pulmonary valve implantation (PPVI) provides a less-invasive therapy for patients. The aim of this study was to evaluate the effectiveness and safety of PPVI and the optimal time for implantation. METHODS: We searched PubMed, EMBASE, Clinical Trial, and Google Scholar databases covering the period until May 2018. The primary effectiveness endpoint was the mean RVOT gradient; the secondary endpoints were the pulmonary regurgitation fraction, left and right ventricular end-diastolic and systolic volume indexes, and left ventricular ejection fraction. The safety endpoints were the complication rates. RESULTS: A total of 20 studies with 1246 participants enrolled were conducted. The RVOT gradient decreased significantly [weighted mean difference (WMD) = -19.63 mmHg; 95% confidence interval (CI): -21.15, -18.11; p < 0.001]. The right ventricular end-diastolic volume index (RVEDVi) was improved (WMD = -17.59 ml/m²; 95% CI: -20.93, -14.24; p < 0.001), but patients with a preoperative RVEDVi >140 ml/m² did not reach the normal size. Pulmonary regurgitation fraction (PRF) was notably decreased (WMD = -26.27%, 95% CI: -34.29, -18.25; p < 0.001). The procedure success rate was 99% (95% CI: 98-99), with a stent fracture rate of 5% (95% CI: 4-6), the pooled infective endocarditis rate was 2% (95% CI: 1-4), and the incidence of reintervention was 5% (95% CI: 4-6). CONCLUSIONS: In patients with RVOT dysfunction, PPVI can relieve right ventricular remodeling, improving hemodynamic and clinical outcomes.

Balloon pulmonary angioplasty vs riociguat in patients with inoperable chronic thromboembolic pulmonary hypertension: A systematic review and meta-analysis.

BACKGROUNDS: No previous meta-analyses have compared the efficacy and safety of BPA with riociguat therapy in inoperable CTEPH patients. METHODS: Relevant published studies were searched in the PubMed, Embase and ClinicalTrial.gov databases. RESULTS: Twenty-three clinical trials including 1454 patients (631 underwent BPA; 823 underwent riociguat therapy) were analyzed. BPA was associated with a greater improvement in RAP (mean difference (MD) = -3.53 mmHg, 95% CI: [-4.85, -2.21] vs MD = -1.05 mmHg, 95% CI: [-1.82, -0.29]); mPAP (MD = -15.02 mmHg, 95% CI: [-17.32, -12.71] vs MD = -4.19 mmHg, 95% CI: [-5.58, -2.80]); PVR (standard MD = -1.32 woods, 95% CI: [-1.57, -1.08] vs standard MD = -0.65 woods, 95% CI: [-0.79, -0.50]); NYHA functional class (RR = 6.78, 95% CI: [3.14, 14.64] vs RR = 1.49, 95% CI: [1.07, 2.07]); and 6MWD (MD = 71.66 m, 95% CI: [58.34, 84.99] vs MD = 45.25 m, 95% CI: [36.51, 53.99]) than riociguat treatment. However, the increase in CO was greater with riociguat (MD = 0.78 L/min, 95% CI: [0.61, 0.96]) than with BPA (MD = 0.33 L/min, 95% CI: [0.06, 0.59]). No significant difference in cardiac index (CI) was found between BPA (MD = 0.40 L/min/m2 , 95% CI: [0.21, 0.58]) and riociguat (MD = 0.40 L/min/m2 , 95% CI: [0.26, 0.54]). The most common complications of BPA were pulmonary injury (0.3%-5.6%) and pulmonary edema (0.8%-28.6%). The most common adverse events of riociguat were headache, dizziness, hypotension and nasopharyngitis. CONCLUSIONS: Our meta-analysis indicates that BPA might be associated with greater improvements in exercise tolerance and pulmonary hemodynamics except for cardiac output and cardiac index than riociguat therapy. However, both of them were well tolerated.

Efficacy and safety of spironolactone in the heart failure with mid-range ejection fraction and heart failure with preserved ejection fraction: A meta-analysis of randomized clinical trials.

BACKGROUND: Recent studies have shown the efficacy for using spironolactone to treat heart failure with reduced ejection fraction (HFrEF), but the efficacy of spironolactone for heart failure with mid-range ejection fraction (HFmrEF) and heart failure with preserved ejection fraction (HFpEF) is unclear. This meta-analysis investigated the efficacy and safety of spironolactone in patients with HFmrEF and HFpEF. METHODS AND RESULTS: We searched several databases including PubMed and the Cochrane Collaboration, for randomized controlled trials (RCTs) that assessed spironolactone treatment in HFmrEF and HFpEF. Eleven RCTs including 4539 patients were included. Spironolactone reduced hospitalizations (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.73-0.95; P = .006), improved New York Heart Association functional classifications (NYHA-FC) (OR, 0.35; 95% CI, 0.19-0.66; P = .001), decreased the levels of brain natriuretic peptide (BNP) (mean difference [MD], - 44.80 pg/mL; 95% CI, -73.44--16.17; P = .002), procollagen type I C-terminal propeptide (PICP) (MD, -27.04 ng/mL; 95% CI, -40.77--13.32, P < .001) in HFmrEF and HFpEF. Besides, it improved 6-minute walking distances (6-MWD) (standard weighted mean difference [SMD], 0.45 m; 95% CI, 0.27-0.64; P < .001), decreased amino-terminal peptide of procollagen type-III (PIIINP) (SMD, -0.37 µg/L; 95% CI, -0.59--0.15; P = .001) in HFpEF only. The risks of hyperkalemia (P<.001) and gynecomastia (P<.001) were increased. CONCLUSION: Patients with HFmrEF and HFpEF could benefit from spironolactone treatment, with reduced hospitalizations, BNP levels, improved NYHA-FC, alleviated myocardial fibrosis by decreasing serum PICP in HFmrEF and HFpEF, decreased PIIINP levels and increased 6-MWD only in HFpEF. The risks of hyperkalemia and gynecomastia were significantly increased with the spironolactone treatment.

Efficacy and safety of bivalirudin in coronary artery disease patients with mild to moderate chronic kidney disease: Meta-analysis.

BACKGROUND: Patients with chronic kidney disease (CKD) have elevated bleeding and ischemic outcomes. We aim to assess the short- and long-term efficacy and safety of bivalirudin compared to heparin plus glycoprotein IIb/IIIa inhibitors (GPIs) in coronary artery disease (CAD) patients with CKD. METHODS: Randomized trials were searched in PubMed, Cochrane, and Embase databases up to January 2017. Among the trials retrieved, efficacy endpoints were defined as mortality, myocardial infarction (MI), repeat revascularization, stent thrombosis, and major adverse cardiac events (MACEs). Safety endpoints were reported as non-coronary artery bypass grafting (CABG) related major bleeding and thrombolysis in myocardial infarction (TIMI) major bleeding. Risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome using a fixed effect model. RESULTS: Five studies with a total of 3796 patients were included. In short-term follow up (30 days), bivalirudin significantly reduced non-CABG related major bleeding (p=0.0004) and TIMI major bleeding (p=0.007) compared to heparin plus GPIs. No significant differences were observed in rates of mortality, MI, repeat revascularization, stent thrombosis, and MACEs between the two groups in short- and long-term follow up (6 months to 3 years). In patients with ST elevated myocardial infarction (STEMI) with concurrent CKD, the decreased non-CABG related major bleeding (p=0.04) without increasing ischemic events was also observed after short-term follow up. CONCLUSIONS: (1) Bivalirudin is safer than and as effective as heparin plus GPIs in CAD patients with CKD. (2) Impaired renal function does not affect the safety benefits of bivalirudin. (3) Similar efficacy profiles were identified between the two groups after both short- and long-term follow up in the CAD patients with CKD.