Amal Merhi

University of Oxford, Oxford, England, United Kingdom

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Publications (6)95.31 Total impact

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    ABSTRACT: Background The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. Methods We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124 513 participants, 68 342 person-years) and 474 trials of one NSAID versus another NSAID (229 296 participants, 165 456 person-years). The main outcomes were major vascular events (non-fatal myocardial in farction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, obstruction, or bleed). Findings Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1.37, 95% CI 1.14-1.66; p=0.0009) or diclofenac (1.41, 1.12-1.78; p=0.0036), chiefly due to an increase in major coronary events (coxibs 1.76, 1.31-2.37; p=0.0001; diclofenac 1.70, 1.19-2.41; p=0.0032). Ibuprofen also significantly increased major coronary events (2.22, 1.10-4.48; p=0.0253), but not major vascular events (1.44, 0.89-2.33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0.93, 0.69-1.27). Vascular death was increased significantly by coxibs (1.58, 99% CI 1.00-2.49; p=0.0103) and diclofenac (1.65, 0.95-2.85, p=0.0187), nonsignificantly by ibuprofen (1.90, 0.56-6.41; p=0.17), but not by naproxen (1.08, 0.48-2.47, p=0.80). The proportional effects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1.81, 1.17-2.81, p=0.0070; diclofenac 1.89, 1.16-3.09, p=0.0106; ibuprofen 3.97, 2.22-7.10, p<0.0001; and naproxen 4.22, 2.71-6.56, p<0.0001). Interpretation The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs. Although NSAIDs increase vascular and gastrointestinal risks, the size of these risks can be predicted, which could help guide clinical decision making.
    Full-text · Article · Aug 2013 · The Lancet
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    ABSTRACT: BACKGROUND: The vascular and gastrointestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs), including selective COX-2 inhibitors (coxibs) and traditional non-steroidal anti-inflammatory drugs (tNSAIDs), are not well characterised, particularly in patients at increased risk of vascular disease. We aimed to provide such information through meta-analyses of randomised trials. METHODS: We undertook meta-analyses of 280 trials of NSAIDs versus placebo (124,513 participants, 68,342 person-years) and 474 trials of one NSAID versus another NSAID (229,296 participants, 165,456 person-years). The main outcomes were major vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death); major coronary events (non-fatal myocardial infarction or coronary death); stroke; mortality; heart failure; and upper gastrointestinal complications (perforation, obstruction, or bleed). FINDINGS: Major vascular events were increased by about a third by a coxib (rate ratio [RR] 1.37, 95% CI 1.14-1.66; p=0.0009) or diclofenac (1.41, 1.12-1.78; p=0.0036), chiefly due to an increase in major coronary events (coxibs 1.76, 1.31-2.37; p=0.0001; diclofenac 1.70, 1.19-2.41; p=0.0032). Ibuprofen also significantly increased major coronary events (2.22, 1.10-4.48; p=0.0253), but not major vascular events (1.44, 0.89-2.33). Compared with placebo, of 1000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (0.93, 0.69-1.27). Vascular death was increased significantly by coxibs (1.58, 99% CI 1.00-2.49; p=0.0103) and diclofenac (1.65, 0.95-2.85, p=0.0187), non-significantly by ibuprofen (1.90, 0.56-6.41; p=0.17), but not by naproxen (1.08, 0.48-2.47, p=0.80). The proportional effects on major vascular events were independent of baseline characteristics, including vascular risk. Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper gastrointestinal complications (coxibs 1.81, 1.17-2.81, p=0.0070; diclofenac 1.89, 1.16-3.09, p=0.0106; ibuprofen 3.97, 2.22-7.10, p<0.0001; and naproxen 4.22, 2.71-6.56, p<0.0001). INTERPRETATION: The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs. Although NSAIDs increase vascular and gastrointestinal risks, the size of these risks can be predicted, which could help guide clinical decision making. FUNDING: UK Medical Research Council and British Heart Foundation.
    No preview · Article · Jan 2013
  • N. Bhala · J. Emberson · A. Merhi

    No preview · Article · Jan 2013
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    ABSTRACT: The effect of statin treatment on ventricular arrhythmic complications is uncertain. We sought to test whether statins reduce the risk of ventricular tachyarrhythmia, cardiac arrest, and sudden cardiac death. We searched MEDLINE, EMBASE, and CENTRAL up to October 2010. Randomized controlled trials comparing statin with no statin or comparing intensive vs. standard dose statin, with more than 100 participants and at least 6-month follow-up were considered for inclusion and relevant unpublished data obtained from the investigators. Twenty-nine trials of statin vs. control (113 568 participants) were included in the main analyses. In these trials, statin therapy did not significantly reduce the risk of ventricular tachyarrhythmia [212 vs. 209; odds ratio (OR) = 1.02, 95% confidence interval (CI) 0.84-1.25, P = 0.87] or of cardiac arrest (82 vs. 78; OR = 1.05, 95% CI 0.76-1.45, P = 0.84), but was associated with a significant 10% reduction in sudden cardiac death (1131 vs. 1252; OR = 0.90; 95% CI 0.82-0.97, P = 0.01). This compared with a 22% reduction in the risk of other 'non-sudden' (mostly atherosclerotic) cardiac deaths (1235 vs. 1553; OR = 0.78, 95% CI 0.71-0.87, P < 0.001). Results were not materially altered by inclusion of eight trials (involving 41 452 participants) of intensive vs. standard dose statin regimens. Statins have a modest beneficial effect on sudden cardiac death. However, previous suggestions of a substantial protective effect on ventricular arrhythmic events could not be supported.
    Full-text · Article · Feb 2012 · European Heart Journal
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    ABSTRACT: Objective To examine whether statins can reduce the risk of atrial fibrillation. Design Meta-analysis of published and unpublished results from larger scale statin trials, with comparison of the findings against the published results from smaller scale or shorter duration studies. Data sources Medline, Embase, and Cochrane's CENTRAL up to October 2010. Unpublished data from longer term trials were obtained through contact with investigators. Study selection Randomised controlled trials comparing statin with no statin or comparing high dose versus standard dose statin; all longer term trials had at least 100 participants and at least six months' follow-up. Results In published data from 13 short term trials (4414 randomised patients, 659 events), statin treatment seemed to reduce the odds of an episode of atrial fibrillation by 39% (odds ratio 0.61, 95% confidence interval 0.51 to 0.74; P<0.001), but there was significant heterogeneity (P<0.001) between the trials. In contrast, among 22 longer term and mostly larger trials of statin versus control (105 791 randomised patients, 2535 events), statin treatment was not associated with a significant reduction in atrial fibrillation (0.95, 0.88 to 1.03; P=0.24) (P<0.001 for test of difference between the two sets of trials). Seven longer term trials of more intensive versus standard statin regimens (28 964 randomised patients and 1419 events) also showed no evidence of a reduction in the risk of atrial fibrillation (1.00, 0.90 to 1.12; P=0.99). Conclusions The suggested beneficial effect of statins on atrial fibrillation from published shorter term studies is not supported by a comprehensive review of published and unpublished evidence from larger scale trials.
    Full-text · Article · Mar 2011 · BMJ British medical journal
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    ABSTRACT: To examine whether statins can reduce the risk of atrial fibrillation. Meta-analysis of published and unpublished results from larger scale statin trials, with comparison of the findings against the published results from smaller scale or shorter duration studies. Medline, Embase, and Cochrane's CENTRAL up to October 2010. Unpublished data from longer term trials were obtained through contact with investigators. Randomised controlled trials comparing statin with no statin or comparing high dose versus standard dose statin; all longer term trials had at least 100 participants and at least six months' follow-up. In published data from 13 short term trials (4414 randomised patients, 659 events), statin treatment seemed to reduce the odds of an episode of atrial fibrillation by 39% (odds ratio 0.61, 95% confidence interval 0.51 to 0.74; P < 0.001), but there was significant heterogeneity (P < 0.001) between the trials. In contrast, among 22 longer term and mostly larger trials of statin versus control (105,791 randomised patients, 2535 events), statin treatment was not associated with a significant reduction in atrial fibrillation (0.95, 0.88 to 1.03; P = 0.24) (P<0.001 for test of difference between the two sets of trials). Seven longer term trials of more intensive versus standard statin regimens (28,964 randomised patients and 1419 events) also showed no evidence of a reduction in the risk of atrial fibrillation (1.00, 0.90 to 1.12; P = 0.99). The suggested beneficial effect of statins on atrial fibrillation from published shorter term studies is not supported by a comprehensive review of published and unpublished evidence from larger scale trials.
    No preview · Article · Jan 2011 · BMJ (online)