Haris Riaz

Meta-analysis of revascularization versus medical therapy for atherosclerotic renal artery stenosis.

The aim of the study was to compare the efficacy of revascularization versus medical therapy in patients with atherosclerotic renal artery stenosis (ARAS). ARAS is the most common cause of secondary hypertension and is associated with several complications, such as renal failure, coronary artery disease, cardiac destabilization, and stroke. Medical therapy is the cornerstone for management of ARAS; however, numerous trials have compared medical therapy with revascularization in the form of percutaneous renal artery angioplasty (PTRA) or percutaneous renal artery angioplasty with stent placement (PTRAS). Medline (PubMed and Ovid SP), Embase, Cochrane Central Register of Controlled Clinical Trials (CENTRAL), and Cochrane Database of Systematic Review (CDSR) were searched till present (November 2013) to identify clinical trials where medical therapy was compared with revascularization (PTRA or PTRAS). We performed a meta-analysis using a random effects model. The heterogeneity was assessed using I2 values. The initial database search identified 540 studies and 7 randomized controlled trials, and 2,139 patients were included in the final analysis. Angioplasty with or without stenting was not superior to medical therapy with respect to any outcome. The incidence of nonfatal myocardial infarction was 6.74% in both the stenting and medical therapy group (odds ratio=0.998, 95% confidence interval 0.698 to 1.427, p=0.992), and incidence of renal events in stenting population was found to be 19.58% versus 20.53% in medical therapy (odds ratio=0.945, 95% confidence interval 0.755 to 1.182, p=0.620). In conclusion, PTRA or PTRAS does not improve outcomes compared with medical therapy in patients with ARAS. Future studies should investigate to identify patient subgroups that may benefit from such an intervention.

Increased Risk of Adverse Neurocognitive Outcomes With Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors.

Background— There is encouraging evidence of the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors; however, their long-term safety remains unclear. We performed a meta-analysis of studies to evaluate the long-term safety of PCSK9 inhibitors. Methods and Results— Our search strategy yielded 11 studies (9 smaller early-phase and 2 larger outcome trials). The outcomes assessed were cumulative serious adverse events, musculoskeletal adverse events, neurocognitive adverse events, and stroke. Odds ratio (OR) was calculated using the Mantel–Haenszel method. Subgroup analysis was done to assess the difference in safety between the smaller early-phase studies and the larger outcome studies. Our meta-analysis suggested no difference in the incidence of serious adverse events (OR, 1.00; 95% confidence interval [CI], 0.88−1.15), musculoskeletal adverse events (OR, 1.01; 95% CI, 0.87−1.13), neurocognitive adverse events (OR, 1.29; 95% CI, 0.64−2.59), or stroke (OR, 1.44; 95% CI, 0.57−3.65) with the use of PCSK9 inhibitors. Subgroup analysis of the 2 large outcome studies did suggest an increased incidence of neurocognitive adverse events (OR, 2.85; 95% CI, 1.34−6.06) with the use of PCSK9 inhibitors. However, the overall incidence of neurocognitive adverse events and stroke was <1%, whereas the cumulative incidence of serious adverse events and musculoskeletal events was >10% in both the groups. Conclusions— Our analysis suggests that PCSK9 inhibitors are not associated with an increased risk of cumulative severe adverse effects, musculoskeletal effects, or stroke. There is a signal toward adverse neurocognitive effects, seen in the outcome studies with a larger sample size and longer follow-up. There should be close monitoring, for the increased risk of neurocognitive events in the ongoing outcome studies and post-marketing surveillance.

The new oral anti-coagulants and the phase 3 clinical trials - a systematic review of the literature

BackgroundAnticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease. However, these agents have a slow onset of action which requires bridging therapy with heparin and its analogues, which are available only in parenteral route. To overcome these limitations, new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed. The aim of this article is to systematically review the phase 3 clinical trials of new oral anticoagulants in common medical conditions.MethodsWe searched PubMed (Medline) from January 2007 to February 2013 using “Oral anticoagulants”, “New oral anticoagulants”, “Randomized controlled trial”, “Novel anticoagulants”, “Apixaban”, “Rivaroxaban”, “Edoxaban”, “Dabigatran etexilate”, “Dabigatran” and a combination of the above terms. The available evidence from the phase 3 RCTs was summarized on the basis of individual drug and the medical conditions categorized into “atrial fibrillation”, “acute coronary syndrome”, “orthopedic surgery”, “venous thromboembolism” and “medically ill patients”.ResultsApixaban, rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk, superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding, non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed. Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism. However, compared to enoxaparin, apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients. Additional studies evaluating the specific reversal agents of these new drugs for the management of life-threatening bleeding or other adverse effects are necessary.ConclusionConsidering their pharmacological properties, their efficacy and bleeding complications, the new oral agents offer a net favourable clinical profile in orthopedic surgery, atrial fibrillation, acute coronary syndrome and increase the risk of bleeding in critically ill patients. Further studies are necessary to determine the long term safety and to identify the specific reversal agents of these new drugs.

Role of vitamin K2 in preventing the recurrence of hepatocellular carcinoma after curative treatment: A meta-analysis of randomized controlled trials

BackgroundHepatocellular cancer is notorious for recurrence even after curative therapy. High recurrence determines the long term prognosis of the patients. Vitamin K2 has been tested in trials for its effect on prevention of recurrence and improving survival. The results are inconclusive from individual trials and in our knowledge no systematic review which entirely focuses on Vitamin K2 as a chemo preventive agent is available to date. This review is an attempt to pool all the existing trials together and update the existing knowledge on the topic.MethodsMedline, Embase and Cochrane Register of Controlled trials were searched for randomized controlled trials where vitamin K2 or its analogues, in any dosage were compared to placebo or No vitamin K2, for participants of any age or sex. Reference lists and abstracts of conference proceedings were searched by hand. Additional papers were identified by a manual search of the references from the key articles. Attempt was made to contact the authors of primary studies for missing data and with the experts in the field.Trials were assessed for inclusion by two independent reviewers. Primary outcomes were recurrence rates and survival rates. There were no secondary outcomes. Data was synthesized using a random effects model and results presented as relative risk with 95% Confidence Intervals.ResultFor recurrence of hepatocellular cancer after hepatic resection or local ablative therapy, compared with controls, participants receiving Vitamin K2, pooled relative risks for hepatocellular cancer were 0.60; 95% CI: 0.28–1.28, p = 0.64) at 1 yr 0.66; 95% CI: 0.47–0.91), p = 0.01) at 2 yr; 0.71; 95% CI: 0.58–0.85, p = 0.004) at 3 yr respectively. The results were combined using the random analysis model.ConclusionFive RCTs evaluated the preventive efficacy of menatetrenone on HCC recurrence after hepatic resection or local ablative therapy. The meta-analysis of all five studies, failed to confirm significantly better tumor recurrence- free survival at 1 year. Improved tumor recurrence at 2nd and 3rd year may be just due to insufficient data. There was no beneficial effect on the overall survival. However, to confirm the beneficial effect or lack of it, large, higher quality randomized controlled trials are still required.

Efficacy and safety of transcatheter aortic valve replacement in intermediate surgical risk patients: A systematic review and meta-analysis.

The efficacy of transcatheter aortic valve replacement (TAVR) in aortic stenosis patients at high surgical risk has been established. The data on patients with intermediate risk is not conclusive. We performed a meta‐analysis of studies which compared TAVR with surgical aortic valve replacement (SAVR) in patients at intermediate surgical risk.

Polio vaccination workers gunned down in Pakistan.

On Dec 18 and 19, 2012, three women and one man were killed in Karachi, and one woman and two men were shot dead in Peshawar, Pakistan. The killings occurred as the polio vaccination volunteers were visiting homes on the second day of a 3 day national campaign. The incidents will probably have deleterious eff ects on the immunisation drive; Karachi is the largest city in Pakistan (with 18 million inhabitants) and Peshawar is the capital of the province with the most polio cases. 5·2 million children in Karachi alone are younger than 5 years. UNICEF and the health ministry temporarily suspended the immunisation campaign in Pakistan, which still has persistent active transmission of polio. Zulfi qar Bhutta (Aga Khan University, Pakistan) stated that the volunteers “were brutally murdered most reprehensibly” where most are in favour of vaccination programmes by people who were not from local areas. He denounced media reports suggesting that the killings were indicative of public sentiment against vaccinations after the US Central Intelligence Agency implemented a fake campaign to fi nd Osama Bin Laden. “I think one needs to be very careful in generalising, oversimplifying, and placing the blame of the current dysfunction...in the immunisation programme in the laps of the communities and families.” Bhutta says that, while much disinformation about the oral polio vaccine exists, the same is not true for

Safety and Use of Anticoagulation After Aortic Valve Replacement With Bioprostheses: A Meta-Analysis

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. I2 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.

Temporal Trends in Strut-Level Optical Coherence Tomography Evaluation of Coronary Stent Coverage: A Systematic Review and Meta-Analysis.

We sought to pool data from all studies with reported strut‐level data in human subjects evaluated by optical coherence tomography (OCT) surveillance and to compare the aggregate data of stent strut coverage on a longitudinal temporal timeline from initial implantation for different coronary stent subtypes.

Mortality Effect of ICD in Primary Prevention of Nonischemic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials

Implantation of an implantable cardioverter defibrillator (ICD) for primary prevention of sudden cardiac death (SCD) is controversial in view of the recent DANISH trial which suggested no benefit with ICD for primary prevention in patients with non‐ischemic cardiomyopathy (NICMP).

Impact of total occlusion of culprit artery in acute non-ST elevation myocardial infarction: a systematic review and meta-analysis

Aims Total occlusion (TO) of the culprit artery usually presents with ST-elevation myocardial infarction. A subset of patients with TO present as non-ST segment elevation myocardial infarction (NSTEMI) without classic ST-elevation on the electrocardiogram. This may lead to delay in identification of these patients and further management. We performed a meta-analysis to estimate the difference in outcomes between totally occluded and non-occluded culprit arteries in patients with NSTEMI. Methods and results Our literature search yielded seven studies with 40 777 patients. The outcomes assessed were clinical presentation (Killip class), left ventricular ejection fraction, time to angiography, major cardiac adverse events (MACE) and all-cause mortality. The generic inverse or Mantel-Haenszel method was used to pool relevant outcomes and the mean difference (MD) or relative risk (RR) was calculated. A total of 10 415 (25.5%) patients had an occluded culprit artery with a predominant infero-lateral distribution (40% right coronary and 33% left circumflex artery). There was an increased risk of both MACE (short-term RR: 1.41; CI: 1.17, 1.70; P = 0.0003; I2 = 26%; medium- to long-term RR: 1.32; CI: 1.11, 1.56; P = 0.001; I2 = 25%) and all-cause mortality (short-term RR: 1.67; CI: 1.31, 2.13; P < 0.0001; I2 = 41%; medium to long-term RR: 1.42; CI: 1.08, 1.86; P = 0.01; I2 = 32%) with TO of the culprit artery. Conclusion Our meta-analysis suggests that patients with NSTEMI who demonstrate a totally occluded culprit vessel on coronary angiography are at higher risk of mortality and major adverse cardiac events. Better risk stratification tools are needed to identify such high-risk acute coronary syndrome patients to facilitate earlier revascularization and potentially to improve outcomes.