Browsing by Author "Khan, Safi U"

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    A Bayesian network meta-analysis of PCSK9 inhibitors, statins and ezetimibe with or without statins for cardiovascular outcomes
    (European Journal of Preventive Cardiology, 2018-05-01) Khan, Safi U; Talluri, Swapna; Riaz, Haris; Rahman, Hammad; Nasir, Fahad; Bin Riaz, Irbaz; Sattur, Sudhakar; Ahmed, Haitham; Kaluski, Edo; Krasuski, Richard
    © 2018, © The European Society of Cardiology 2018. Background: The comparative effects of statins, ezetimibe with or without statins and proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors remain unassessed. Design: Bayesian network meta-analysis was conducted to compare treatment groups. Methods: Thirty-nine randomized controlled trials were selected using MEDLINE, EMBASE, and CENTRAL (inception – September 2017). Results: In network meta-analysis of 189,116 patients, PCSK9 inhibitors were ranked as the best treatment for prevention of major adverse cardiovascular events (Surface Under Cumulative Ranking Curve (SUCRA), 85%), myocardial infarction (SUCRA, 84%) and stroke (SUCRA, 80%). PCSK9 inhibitors reduced the risk of major adverse cardiovascular events compared with ezetimibe + statin (odds ratio (OR): 0.72; 95% credible interval (CrI), 0.55–0.95; Grading of Recommendation Assessment, Development and Evaluation (GRADE) criteria: moderate), statin (OR: 0.78; 95% CrI: 0.62–0.97; GRADE: moderate) and placebo (OR: 0.63; 95% CrI: 0.49–0.79; GRADE: high). The PCSK9 inhibitors were consistently superior to groups for major adverse cardiovascular event reduction in secondary prevention trials (SUCRA, 95%). Statins had the highest probability of having lowest rates of all-cause mortality (SUCRA, 82%) and cardiovascular mortality (SUCRA, 84%). Compared with placebo, statins reduced the risk of all-cause mortality (OR: 0.88; 95% CrI: 0.83–0.94; GRADE: moderate) and cardiovascular mortality (OR: 0.84; 95% CrI: 0.77–0.90; GRADE: high). For cardiovascular mortality, PCSK9 inhibitors were ranked as the second best treatment (SUCRA, 78%) followed by ezetimibe + statin (SUCRA, 50%). Conclusion: PCSK9 inhibitors were ranked as the most effective treatment for reducing major adverse cardiovascular events, myocardial infarction and stroke, without having major safety concerns. Statins were ranked as the most effective therapy for reducing mortality.
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    Is Anticoagulation Beneficial in Pulmonary Arterial Hypertension?
    (Circulation. Cardiovascular quality and outcomes, 2018-09) Khan, Muhammad Shahzeb; Usman, Muhammad Shariq; Siddiqi, Tariq Jamal; Khan, Safi U; Murad, M Hassan; Mookadam, Farouk; Figueredo, Vincent M; Krasuski, Richard A; Benza, Raymond L; Rich, Jonathan D
    Background Data about anticoagulation in pulmonary arterial hypertension (PAH) patients are inconsistent. The objective of this study was to examine the impact of adjunctive oral anticoagulants in patients with PAH through meta-analysis, and to further assess whether response differs by PAH subtype. Methods and Results Cochrane CENTRAL, Medline, and Scopus databases were searched for randomized or nonrandomized studies that assessed the association between anticoagulation and outcomes in patients with PAH. Hazard ratios (HRs) for mortality were pooled using the random effects model. Subgroup analyses were performed for type of PAH and study design. Twelve nonrandomized studies, at moderate risk of bias, were included. These consisted of 2512 patients (1342 receiving anticoagulation and 1170 controls). Anticoagulation significantly reduced mortality in the overall PAH cohort (HR, 0.73 [0.57, 0.93]; P=0.001; I2=64%). On subgroup analysis, a significant mortality reduction was seen in idiopathic PAH patients (HR, 0.73 [0.56, 0.95]; P=0.02; I2=46%), whereas no significant difference was observed in connective tissue disease-related PAH (HR, 1.16 [0.58, 2.32]; P=0.67; I2=71%). Sensitivity analysis specific to scleroderma-associated PAH demonstrated a significant increase in mortality with anticoagulant use (HR, 1.58 [1.08, 2.31]; P=0.02; I2=9%). Conclusions This meta-analysis shows that use of anticoagulation may improve survival in idiopathic PAH patients, while increasing mortality when used in scleroderma-associated-PAH patients. Currently, no randomized clinical trials have been published, and until randomized data are available, anticoagulant use in PAH should be tailored to PAH subtype.