A meta-analysis of adjusted hazard ratios from 20 observational studies of bilateral versus single internal thoracic artery coronary artery bypass grafting.

OBJECTIVE: In 2001, a landmark meta-analysis of bilateral internal thoracic artery (BITA) versus single internal thoracic artery (SITA) coronary artery bypass grafting for long-term survival included 7 observational studies (only 3 of which reported adjusted hazard ratios [HRs]) enrolling approximately 16,000 patients. Updating the previous meta-analysis to determine whether BITA grafting reduces long-term mortality relative to SITA grafting, we exclusively abstracte, then combined in a meta-analysis, adjusted (not unadjusted) HRs from observational studies. METHODS: MEDLINE and EMBASE were searched until September 2013. Eligible studies were observational studies of BITA versus SITA grafting and reporting an adjusted HR for long-term (≥4 years) mortality as an outcome. Meta-regression analyses were performed to determine whether the effects of BITA grafting were modulated by the prespecified factors. RESULTS: Twenty observational studies enrolling 70,897 patients were identified and included. A pooled analysis suggested a significant reduction in long-term mortality with BITA relative to SITA grafting (HR, 0.80; 95% confidence interval, 0.77 to 0.84). When data from 6 pedicled and 6 skeletonized internal thoracic artery studies were separately pooled, BITA grafting was associated with a statistically significant 26% and 16% reduction in mortality relative to SITA grafting, respectively (P for subgroup differences=.04). A meta-regression coefficient was significantly negative for the proportion of men (-0.00960; -0.01806 to -0.00114). CONCLUSIONS: Based on an updated meta-analysis of exclusive adjusted HRs from 20 observational studies enrolling more than 70,000 patients, BITA grafting seems to significantly reduce long-term mortality. As the proportion of men increases, BITA grafting is more beneficial in reducing mortality.

Effects of rosuvastatin versus atorvastatin on small dense low-density lipoprotein: a meta-analysis of randomized trials.

In addition to their high-intensity effects on the reduction in low-density lipoprotein (LDL) levels, rosuvastatin and atorvastatin would be expected to also reduce small dense LDL (sdLDL) levels. To determine which reduces sdLDL levels more, we performed the first meta-analysis and meta-regression of randomized head-to-head trials of rosuvastatin versus atorvastatin therapy. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through April 2012. Eligible studies were prospective, randomized controlled trials of rosuvastatin versus atorvastatin therapy reporting final sdLDL (directly measured or calculated) levels as an outcome. For each study, data regarding final sdLDL levels in both the rosuvastatin and atorvastatin groups were used to generate mean differences (MD) and 95 % confidence intervals (CI). Meta-regression analysis was performed to determine whether the effects of rosuvastatin therapy were modulated by the prespecified factors. Of 159 potentially relevant articles screened initially, 28 reports of randomized trials enrolling a total of 7802 patients were included. Pooled analysis suggested a significant reduction in final sdLDL levels among patients randomized to rosuvastatin versus atorvastatin therapy (MD, -1.56 mg/dl; 95 % CI, -2.30 to -0.83 mg/dl; P < 0.0001). The meta-regression coefficients were statistically significant for the baseline LDL/sdLDL level and the difference in LDL changes between the two groups. In conclusion, rosuvastatin rather than atorvastatin therapy is likely more effective in reduction of sdLDL levels. It should be further investigated whether the reduction in sdLDL levels implies overt clinical benefits of rosuvastatin over atorvastatin.

A meta-analysis of randomized controlled trials of azilsartan therapy for blood pressure reduction.

Although there have been a number of azilsartan trials, no meta-analysis of the findings has been conducted to date. We performed the first meta-analysis of randomized controlled trials of azilsartan therapy for the reduction of blood pressure (BP) in patients with hypertension. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched from the beginning of the records through March 2013 using web-based search engines (PubMed and OVID). Eligible studies were prospective randomized controlled trials of azilsartan (including azilsartan medoxomil) vs. any control therapy that reported clinic or 24-h mean BP as an outcome. For each study, data for the changes from baseline to final clinic systolic BP (SBP) and diastolic BP (DBP) in both the azilsartan group and the control group were used to generate mean differences and 95% confidence intervals (CIs). Of 27 potentially relevant articles screened initially, 7 reports of randomized trials of azilsartan or azilsartan medoxomil therapy enrolling a total of 6152 patients with hypertension were identified and included. Pooled analysis suggested a significant reduction in BP changes among patients randomized to 40 mg of azilsartan vs. control therapy (clinic SBP: -4.20 mm Hg; 95% CI: -6.05 to -2.35 mm Hg; P<0.00001; clinic DBP: -2.58 mm Hg; 95% CI: -3.69 to -1.48 mm Hg; P<0.00001; 24-h mean SBP: -3.33 mm Hg; 95% CI: -4.74 to -1.93 mm Hg; P<0.00001; 24-h mean DBP: -2.12 mm Hg; 95% CI: -2.74 to -1.49 mm Hg; P<0.00001). In conclusion, azilsartan therapy appears to provide a greater reduction in BP than control therapy in patients with hypertension.

A meta-analysis of randomized trials of telmisartan versus losartan for reduction of ambulatory blood pressure.

A previous meta-analysis of a few randomized controlled trials (RCTs) suggests a significant reduction in ambulatory blood pressure (BP) with telmisartan as compared with losartan monotherapy. We performed an updated meta-analysis of RCTs of telmisartan versus losartan therapy for reduction of ambulatory BP in patients with hypertension. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through July 2012 using PubMed and OVID. Eligible studies were RCTs of telmisartan versus valsartan therapy enrolling individuals with hypertension and reporting ambulatory BP as an outcome. For each study, data regarding changes from baseline in ambulatory (24 h, last 6 h, morning, daytime and nighttime) BP in both the telmisartan and losartan groups were used to generate mean differences (MDs) and 95% confidence intervals (CIs). Of 34 potentially relevant articles screened initially, 9 reports of RCTs enrolling a total of 2409 patients with hypertension were identified and included. Pooled analysis suggested significant reductions in all of 24-h (MD of systolic/diastolic BP, -2.09/-1.57 mm Hg; 95% CI, -3.39/-2.32 to -0.79/-0.82 mm Hg), last 6-h (-2.96/-2.15 mm Hg; -3.80/-2.72 to -2.13/-1.59 mm Hg), morning (-2.71/-2.37 mm Hg; -3.73/-3.33 to -1.69/-1.41 mm Hg), daytime (-1.74/-1.73 mm Hg; -3.27/-2.84 to -0.20/-0.62 mm Hg) and nighttime BP (-2.70/-2.08 mm Hg; -4.07/-3.24 to -1.33/-0.92 mm Hg) among patients randomized to telmisartan versus losartan therapy. In conclusion, telmisartan therapy appears to reduce ambulatory BP more than losartan therapy in patients with hypertension.

A meta-analysis of transcatheter aortic valve implantation versus surgical aortic valve replacement.

BACKGROUND: Our preliminary meta-analysis suggests that transcatheter aortic valve implantation (TAVI) may not reduce the 30-day mortality rate over surgical aortic valve replacement (AVR) in high-risk patients with severe aortic stenosis (AS). We performed an updated formal meta-analysis of TAVI vs AVR for reduction not only of early but also of late all-cause mortality in AS. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through October 2012. Eligible studies were randomized controlled trials or adjusted observational comparative studies of TAVI vs AVR enrolling individuals with AS and reporting early (30-day or in-hospital) or late all-cause mortality, or both, as an outcome. Odds ratios or hazard ratios with 95% confidence intervals (adjusted odds ratios or hazard ratios in case of observational studies) were abstracted from each study. RESULTS: We identified two randomized trials and 15 adjusted observational studies enrolling 4,873 patients with severe AS. Pooled analysis suggested no significant difference in early (odds ratio, 0.92; 95% confidence interval, 0.70 to 1.19) and midterm (3-month to 3-year) total mortality (hazard ratio, 0.99; 95% confidence interval, 0.83 to 1.17) among patients assigned to TAVI vs AVR. Exclusion of any single study from the analysis did not substantively alter the overall result of our analysis. No evidence of significant publication bias was found. CONCLUSIONS: Our meta-analysis of data of approximately 5,000 patients from 17 studies showed that TAVI is likely ineffective in reducing early and midterm all-cause mortality vs AVR in high-risk patients with AS.

A meta-analysis of randomized trials for repeat revascularization following off-pump versus on-pump coronary artery bypass grafting.

To determine whether repeat revascularization rates are increased following off-pump coronary artery bypass grafting (CABG), we performed a meta-analysis of randomized controlled trials of off-pump vs on-pump CABG. Databases including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through March 2013 using web-based search engines (PubMed, OVID). Studies considered for inclusion met the following criteria: the design was a prospective randomized controlled clinical trial; the study population was patients undergoing CABG; patients were randomly assigned to off-pump vs on-pump CABG and outcomes included repeat revascularization rates at ≥1 year. Our exhaustive search identified 12 prospective randomized controlled trials of off-pump vs on-pump CABG. Pooled analysis demonstrated a statistically significant 38% increase in repeat revascularization rates with off-pump relative to on-pump CABG in the fixed-effects model (odds ratio, 1.38; 95% confidence interval, 1.09-1.76; P = 0.008). In general, exclusion of any single trial from the analysis did not substantively alter the overall result of our analysis. There was no evidence of significant publication bias. The results of our analysis suggest that off-pump CABG may increase repeat revascularization rates by 38% over on-pump CABG.

Telmisartan as a metabolic sartan: the first meta-analysis of randomized controlled trials in metabolic syndrome.

Telmisartan has been proposed to be a promising cardiometabolic sartan due to its unique peroxisome proliferator-activated receptor-gamma-inducing property. To determine whether telmisartan improves metabolic parameters in metabolic syndrome, we perform the first meta-analysis of randomized controlled trials (RCTs). MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through September 2012 using PubMed and OVID. Eligible studies were RCTs of telmisartan therapy enrolling individuals with metabolic syndrome and reporting metabolic parameters as outcomes. Of 31 potentially relevant articles screened initially, 10 reports of RCTs, enrolling a total of 546 patients with metabolic syndrome, were identified and included. Pooled analysis suggested significant reductions in % changes of fasting glucose (standardized mean difference, -0.51; 95% confidence interval [CI], -0.96 to -0.06; P = .03), insulin (-0.23; 95% CI, -0.40 to -0.06; P = .008), glycosylated hemoglobin (-0.26; 95% CI, -0.44 to -0.08; P = .005), and homeostasis model assessment index (-0.22; 95% CI -0.39 to -0.05; P = .01); and a significant increase in % changes of adiponectin (0.75; 95% CI, 0.40 to 1.09; P < .0001) among patients with metabolic syndrome randomized to telmisartan versus control therapy. Telmisartan therapy appears to significantly improve metabolic parameters in patients with metabolic syndrome.

A meta-analysis of randomized trials of telmisartan vs. valsartan therapy for blood pressure reduction.

A previous meta-analysis of six randomized head-to-head trials suggests that the blood pressure (BP)-lowering capabilities of telmisartan may be comparable to those of valsartan. We performed an updated meta-analysis of telmisartan vs. valsartan therapy for the reduction of BP in hypertensive patients. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through August 2012 using web-based search engines (PubMed, OVID). Eligible studies were prospective randomized controlled trials examining telmisartan vs. valsartan therapy and reporting clinic BP as an outcome. For each study, the data regarding changes from baseline to final clinic systolic BP (SBP) and diastolic BP (DBP) in both the telmisartan and valsartan groups were used to generate mean differences (MDs) and 95% confidence intervals (CIs). Of the 62 potentially relevant articles initially screened, 17 reports about prospective randomized controlled clinical trials of telmisartan vs. valsartan therapy, including a total of 5422 patients with hypertension, were identified and included. Pooled analysis suggested significant differences in BP reductions among the patients randomized to telmisartan vs. valsartan therapy (MD for SBP, -2.04 mm Hg; 95% CI, -2.80 to -1.28 mm Hg; P<0.00001; MD for DBP, -1.08 mm Hg; 95% CI, -1.55 to -0.62 mm Hg; P<0.00001). When data from the monotherapy and combination therapy (with hydrochlorothiazide) trials were pooled separately, telmisartan therapy was associated with a statistically significant difference in BP reductions relative to valsartan therapy in both the monotherapy and combination therapy groups. In conclusion, telmisartan therapy appears to reduce BP more than valsartan therapy in patients with hypertension.

Effects of telmisartan on proteinuria or albuminuria: a meta-analysis of randomized trials.

BACKGROUND: Although telmisartan is suggested to improve proteinuria/albuminuria (or prevents progression of proteinuria/albuminuria), conclusive evidence is still lacking. We perform the first meta-analysis of randomized controlled trials of telmisartan therapy on proteinuria/albuminuria. METHODS: MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched through February 2012. Eligible studies were prospective randomized controlled trials of telmisartan therapy versus other angiotensin receptor blocker (ARB), angiotensin converting enzyme inhibitor (ACEI), other anti-hypertensive drug therapy, placebo, or no medication and reporting urinary protein/albumin excretion (UPE/UAE) or urinary protein/albumin to creatinine ratio (UPCR/UACR) levels as an outcome. For each study, data regarding percent changes from baseline to final UPE/UAE/UPCR/UACR levels in both the telmisartan and control groups were used to generate mean differences (MDs) and 95% confidence intervals (CIs). RESULTS: Of 49 potentially relevant articles screened initially, 20 reports of randomized trials enrolling a total of 25,425 patients were included. Pooled analysis suggested a significant reduction in percent changes of UPE/UAE/UPCR/UACR in the 7 ARB-control (MD, -19.99%; 95% CI, -28.68% to -11.30%; p<0.00001), 7 ACEI-control (MD, -14.08%; 95% CI, -25.36% to -2.80%; p=0.01), 6 non-ARB/ACEI-control (MD, -39.82%; 95% CI, -55.96% to -23.69%; p<0.00001), and all the 20 trials (MD, -24.36%; 95% CI, -32.85% to -15.87%; p<0.00001). CONCLUSION: We found that, based on a meta-analysis of 20 randomized controlled trials including >25,000 patients, telmisartan therapy is likely effective in the improvement of proteinuria/albuminuria or in the prevention of progression in proteinuria/albuminuria.

Effects of telmisartan therapy on interleukin-6 and tumor necrosis factor-alpha levels: a meta-analysis of randomized controlled trials.

A recent meta-analysis of randomized head-to-head trials suggests that therapy with telmisartan, an angiotensin II receptor blocker (ARB) and partial agonist of peroxisome proliferator-activated receptor-gamma, may increase adiponectin levels more strongly than other ARB therapies. Therefore, telmisartan would be expected to reduce interleukin-6 (IL-6) or tumor necrosis factor-alpha (TNF-α). To determine whether telmisartan reduces IL-6 or TNF-α, we performed the first meta-analysis of randomized controlled trials of telmisartan therapy. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched through November 2011. Eligible studies were prospective randomized controlled trials of telmisartan vs. unrestricted control therapy reporting IL-6 or TNF-α levels as an outcome. For each study, data regarding percent changes from baseline to final IL-6 or TNF-α levels in both the telmisartan and control groups were used to generate standardized mean differences (SMDs) and 95% confidence intervals (CIs). Nine reports of randomized trials enrolling a total of 645 patients were identified. Pooled analysis of seven and five trials demonstrated a statistically significant reduction in percent changes of IL-6 (fixed-effects SMD, -0.385; 95% CI, -0.581 to -0.189; P<0.001; P for heterogeneity=0.073) and TNF-α levels (random-effects SMD, -0.627; 95% CI, -0.945 to -0.308; P<0.001; P for heterogeneity=0.029) with telmisartan relative to control therapy, respectively. In conclusion, based on a meta-analysis of nine randomized controlled trials, telmisartan therapy is likely effective in reducing IL-6 and TNF-α levels.