Browsing by Author "Riaz, Haris"

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Open Access
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.
Open Access
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.
Open Access
Best Practice Advisories Should Not Replace Good Clinical Acumen.
(Am J Med, 2016-09-15) Riaz, Haris; Krasuski, Richard A
Open Access
Conflicts of Interest and Outcomes of Cardiovascular Trials.
(Am J Cardiol, 2016-03-01) Riaz, Haris; Khan, Muhammad Shahzeb; Riaz, Irbaz Bin; Raza, Sajjad; Khan, Abdur Rahman; Krasuski, Richard A
Conflicts of interests have long been recognized as potential sources of influence in the conduct and reporting of clinical trials. This controversy was again rekindled after the publication of the latest statin guidelines and a series of studies regarding competing interests in leading medical journals. We investigate the association between declared author conflicts and the outcomes of large cardiovascular trials. We searched the Medline (PubMed) database to identify "phase 2" and "phase 3" clinical trials using the search term "cardiovascular" over the past decade using "10 years" as the filter. We perceived the competing interest as present regardless of the nature such as consulting fees, honoraria, travel imbursements, stock holding, and employment. Of the 699 titles retrieved, 114 studies met the inclusion criteria. Nearly 80% of studies had at least a single author with competing interests. The 114 studies had a total of 1,433 investigators, of which 725 had declared conflicts of interests (50.6%). A total of 66 studies (58%) had half or >50 percent of investigators who had some conflicts of interests. Of these studies, 54 studies had favorable outcomes and only 12 had unfavorable outcomes (p <0.001). Among the type of competing interests, consulting or personal fees was the most common present in 58 investigators (51%). This was followed by research grants present in 55 the researchers (48%). Among 25 (22%) studies, at least one investigator reported stakes in the industry, of which only 2 studies had unfavorable outcomes for the intervention being investigated. Just 1 of the 25 clinical trials with a sample size of >1,000 had no investigators with competing interests. In conclusion, authors conflicts are associated with favorable outcomes in cardiovascular outcome trials.
Open Access
Evaluation of Industrial Compensation to Cardiologists in 2015.
(Am J Cardiol, 2017-12-15) Khan, Muhammad Shahzeb; Siddiqi, Tariq Jamal; Fatima, Kaneez; Riaz, Haris; Khosa, Faisal; Manning, Warren J; Krasuski, Richard
The categorization and characterization of pharmaceutical and device manufacturers or group purchasing organization payments to clinicians is an important step toward assessing conflicts of interest and the potential impact of these payments on practice patterns. Payments have not previously been compared among the subspecialties of cardiology. This is a retrospective analysis of the Open Payments database, including all installments and payments made to doctors in the calendar year 2015 by pharmaceutical and device manufacturers or group purchasing organization. Total payments to individual physicians were then aggregated based on specialty, geographic region, and payment type. The Gini Index was further employed to calculate within each specialty to measure income disparity. In 2015, a total of $166,089,335 was paid in 943,744 payments (average $175.00 per payment) to cardiologists, including 23,372 general cardiologists, 7,530 interventional cardiologists, and 2,293 cardiac electro-physiologists. Payments were mal-distributed across the 3 subspecialties of cardiology (p <0.01), with general cardiology receiving the largest number (73.5%) and total payments (62.6%) and cardiac electrophysiologists receiving significantly higher median payments ($1,662 vs $361 for all cardiologists; p <0.01). The Medtronic Company was the largest single payer for all 3 subspecialties. In conclusion, pharmaceutical and device manufacturers or group purchasing organizations continue to make substantial payments to cardiac practitioners with a significant variation in payments made to different cardiology subspecialists. The largest number and total payments are to general cardiologists, whereas the highest median payments are made to cardiac electrophysiologists. The impact of these payments on practice patterns remains to be examined.
Open Access
Impact of Funding Source on Clinical Trial Results Including Cardiovascular Outcome Trials.
(Am J Cardiol, 2015-12-15) Riaz, Haris; Raza, Sajjad; Khan, Muhammad Shahzeb; Riaz, Irbaz Bin; Krasuski, Richard A
Previous authors have suggested a higher likelihood for industry-sponsored (IS) studies to have positive outcomes than non-IS studies, though the influence of publication bias was believed to be a likely confounder. We attempted to control for the latter using a prepublication database to compare the primary outcome of recent trials based on sponsorship. We used the "advanced search" feature in the clinicaltrials.gov website to identify recently completed phase III studies involving the implementation of a pharmaceutical agent or device for which primary data were available. Studies were categorized as either National Institutes of Health (NIH) sponsored or IS. Results were labeled "favorable" if the results favored the intervention under investigation or "unfavorable" if the intervention fared worse than standard medical treatment. We also performed an independent literature search to identify the cardiovascular trials as a case example and again categorized them into IS versus NIH sponsored. A total of 226 studies sponsored by NIH were found. When these were compared with the latest 226 IS studies, it was found that IS studies were almost 4 times more likely to report a positive outcome (odds ratio [OR] 3.90, 95% confidence interval [CI] 2.6087 to 5.9680, p <0.0001). As a case example of a specialty, we also identified 25 NIH-sponsored and 215 IS cardiovascular trials, with most focusing on hypertension therapy (31.6%) and anticoagulation (17.9%). IS studies were 7 times more likely to report favorable outcomes (OR 7.54, 95% CI 2.19 to 25.94, p = 0.0014). They were also considerably less likely to report unfavorable outcomes (OR 0.11, 95% CI 0.04 to 0.26, p <0.0001). In conclusion, the outcomes of large clinical studies especially cardiovascular differ considerably on the basis of their funding source, and publication bias appears to have limited influence on these findings.
Open Access
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.
Open Access
Safety and Use of Anticoagulation After Aortic Valve Replacement With Bioprostheses: A Meta-Analysis.
(Circ Cardiovasc Qual Outcomes, 2016-05) Riaz, Haris; Alansari, Shehab Ahmad Redha; Khan, Muhammad Shahzeb; Riaz, Talha; Raza, Sajjad; Luni, Faraz Khan; Khan, Abdur Rahman; Riaz, Irbaz Bin; Krasuski, Richard A
BACKGROUND: The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding. METHODS AND RESULTS: We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I(2) testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25-3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10-3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82-1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80-1.58; P=0.79). CONCLUSIONS: Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.
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Should Physicians be Encouraged to use Generic Names and to Prescribe Generic Drugs?
(Am J Cardiol, 2016-06-01) Riaz, Haris; Krasuski, Richard A
While using the brand names seems like a trivial issue at the outset, using these names is inherently problematic. Cardiovascular drugs remain the most commonly prescribed drugs by the physicians. The junior doctors are likely to introject practices of their seniors and consequently to reciprocate from the experiences learnt from their preceptors. Using the generic names may be one way to facilitate prescription of the generic drugs who have a better cost profile and similar efficacy than the more expensive branded drugs. In this editorial, we have outlined several arguments to suggest the importance of using the generic names in academic discussions and clinical documentation.
Unknown
Transcatheter closure of patent foramen ovale following cryptogenic stroke: An updated meta-analysis of randomized controlled trials.
(American heart journal, 2018-05) Riaz, Haris; Khan, Muhammad Shahzeb; Schenone, Aldo L; Waheed, Anam A; Khan, Arooj Razzak; Krasuski, Richard A
Transcatheter closure of patent foramen ovale (PFO) after cryptogenic stroke has long been a contentious issue. Herein, we pool aggregate data examining safety and efficacy of transcatheter closure of PFO compared with medical therapy following initial cryptogenic stroke.We searched for randomized clinical trials (RCT) that compared device closure with medical management and reported on subsequent stroke and adverse events. Stroke was considered as the primary efficacy endpoint, whereas bleeding and atrial fibrillation were considered primary safety endpoints. Data were pooled by the random effects model and I2 was used to assess heterogeneity.A total of 5 RCT investigating 3630 patients met inclusion criteria. Pooled analysis revealed that device closure compared to medical management was associated with a significant reduction in stroke (RR=0.3, 95% CI=0.02-0.57). There was, however, a significant increase in atrial arrhythmias with device therapy (RR=4.8, 95% CI=2.2-10.7). We found no increase in bleeding (RR=0.80, 95% CI=0.5-1.4), death (RR=0.76, 95% CI=0.3-1.99) or "any adverse events" (RR=1.02, 95% CI=0.85-1.23) with device therapy. Sub-group analysis revealed that device closure significantly reduced the incidence of the composite primary endpoint among patients who had moderate to large shunt sizes (RR=0.22, 95% CI=0.02-0.42).Transcatheter closure is associated with a significant reduction in the risk of stroke compared to medical management at the expense of an increased risk of atrial arrhythmias.

Browsing by Author "Riaz, Haris"

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