Browsing by Author "Ahmed, Haitham"

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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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    Association Between Obesity and Cardiovascular Outcomes: A Systematic Review and Meta-analysis of Mendelian Randomization Studies.
    (JAMA network open, 2018-11-02) Riaz, Haris; Khan, Muhammad Shahzeb; Siddiqi, Tariq Jamal; Usman, Muhammad Shariq; Shah, Nishant; Goyal, Amit; Khan, Sadiya S; Mookadam, Farouk; Krasuski, Richard A; Ahmed, Haitham
    Importance:Although dyslipidemia has been consistently shown to be associated with atherogenesis, an association between obesity and cardiovascular disease outcomes remains controversial. Mendelian randomization can minimize confounding if variables are randomly and equally distributed in the population of interest. Objective:To assess evidence from mendelian randomization studies to provide a less biased estimate of any association between obesity and cardiovascular outcomes. Data Sources:Systematic searches of MEDLINE and Scopus from database inception until January 2018, supplemented with manual searches of the included reference lists. Study Selection:Studies that used mendelian randomization methods to assess the association between any measure of obesity and the incidence of cardiovascular events and those that reported odds ratios (ORs) with 95% CIs estimated using an instrumental variable method were included. The 5 studies included in the final analysis were based on a consensus among 3 authors. Data Extraction and Synthesis:Two investigators independently extracted study characteristics using a standard form and pooled data using a random-effects model. The Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guideline was followed. Main Outcomes and Measures:Obesity associated with type 2 diabetes, coronary artery disease, or stroke. The hypothesis was formulated prior to data collection. Results:Of 4660 potentially relevant articles, 2511 titles were screened. Seven studies were included in the systematic review, and 5 studies with 881 692 participants were eligible to be included in the meta-analysis. Pooled estimates revealed that obesity was significantly associated with an increased risk of type 2 diabetes (OR, 1.67; 95% CI, 1.30-2.14; P < .001; I2 = 93%) and coronary artery disease (OR, 1.20; 95% CI, 1.02-1.41; P = .03; I2 = 87%). No association between obesity and stroke was found (OR, 1.02; 95% CI, 0.95-1.09; P = .65; I2 = 0%). Conclusions and Relevance:The present meta-analysis suggests that obesity is associated with type 2 diabetes and coronary artery disease. Although this analysis of mendelian randomization studies does not prove causality, it is supportive of a causal association. Hence, health care practitioners should continue to emphasize weight reduction to combat coronary artery disease.
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    Meta-analysis of Placebo-Controlled Randomized Controlled Trials on the Prevalence of Statin Intolerance.
    (Am J Cardiol, 2017-09-01) Riaz, Haris; Khan, Abdur Rahman; Khan, Muhammad Shahzeb; Rehman, Karim Abdur; Alansari, Shehab Ahmad Redha; Gheyath, Bashaer; Raza, Sajjad; Barakat, Amr; Luni, Faraz Khan; Ahmed, Haitham; Krasuski, Richard A
    The prevalence of intolerance varies widely. Stopping statin therapy is associated with worse outcomes in patients with cardiovascular disease. Despite extensive studies, the benefits and risks of statins continue to be debated by clinicians and the lay public. We searched the PubMed, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials of statins compared with placebo. Studies were included if they had ≥1,000 participants, had patients who were followed up for ≥1 year, and reported rates of drug discontinuation. Studies were pooled as per the random effects model. A total of 22 studies (statins = 66,024, placebo = 63,656) met the inclusion criteria. The pooled analysis showed that, over a mean follow-up of 4.1 years, the rates of discontinuation were 13.3% (8,872 patients) for statin-treated patients and 13.9% (8,898 patients) for placebo-treated patients. The random effects model showed no significant difference between the placebo and statin arms (odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.93 to 1.06). The results were similar for both primary prevention (OR = 0.98, 95% CI = 0.92 to 1.05, p = 0.39) and secondary prevention (OR = 0.92, 95% CI = 0.83 to 1.05, p = 0.43) studies. The pooled analysis suggested that the rates of myopathy were also similar between the statins and placebos (OR = 1.2, 95% CI = 0.88 to 1.62, p = 0.25). In conclusion, this meta-analysis of >125,000 patients suggests that the rate of drug discontinuation and myopathy does not significantly differ between statin- and placebo-treated patients in randomized controlled trials. These findings are limited by the heterogeneity of results, the variable duration of follow-up, and the lower doses of statins compared with contemporary clinical practice.