Background:
Garlic has been suggested to lower blood pressure; however, studios evaluating this parameter have provided conflicting results.
Objective:
To examine the effect of garlic on blood ...pressure in patients with and without elevated systolic blood pressure (SPB) through meta-analyses of randomized controlled trials.
Methods:
A systematic search of MEDLINE, CINAHL, and the Cochrane Central Register of Controlled Trials was conducted to identify randomized controlled trials in humans evaluating garlic's effect on blood pressure. All databases were searched from their inception through June 26, 2008, using the key words garlic, Allium sativum, and allicin. A manual search of published literature was used to identify additional relevant studies. To be included in the analysis, studies must have been written in English or German and reported endpoints of SBP or diastolic blood pressure (DBP). Studies whose population had a mean baseline SBP greater than 140 mm Hg were evaluated separately from those whose population had lower baseline blood pressures. Garlic's effect on SBP and DBP was treated as a continuous variable and weighted mean differences were calculated using a random-effects model.
Results:
Ten trials were included in the analysis; 3 of these had patients with elevated SBP. Garlic reduced SBP by 16.3 mm Hg (95% CI 6.2 to 26.5) and DBP by 9.3 mmHg (95% CI 5.3 to 13.3) compared with placebo in patients with elevated SBP. However, the use of garlic did not reduce SBP or DBP in patients without elevated SBP. There was only a minor degree of heterogeneity in the analyses and publication bias did not appear to influence the results.
Conclusions:
This meta-analysis suggests that garlic is associated with blood pressure reductions in patients with an elevated SBP although not in those without elevated SBP. Future research should focus on the impact of garlic on clinical events and the assessment of the long-term risk of harm.
In order to determine the impact of garlic on total cholesterol (TC), TAG levels, as well as LDL and HDL, and establish if any variables have an impact on the magnitude of this effect, a ...meta-analysis was conducted. A systematic literature search of MEDLINE, CINAHL and the Cochrane Database from the earliest possible date through to November 2007 was conducted to identify randomised, placebo-controlled trials of garlic that reported effects on TC, TAG concentrations, LDL or HDL. The weighted mean difference of the change from baseline (with 95 % CI) was calculated as the difference between the means in the garlic groups and the control groups using a random-effects model. Subgroup and sensitivity analyses were performed to determine the effects on type, brand and duration of garlic therapy as well as baseline TC and TAG levels, the use of dietary modification, and study quality on the meta-analysis's conclusions. Twenty-nine trials were included in the analysis. Upon meta-analysis garlic was found to significantly reduce TC ( - 0.19; 95 % CI - 0.33, - 0.06 mmol/l) and TAG ( - 0.11; 95 % CI - 0.19, - 0.06 mmol/l) but exhibited no significant effect on LDL or HDL. There was a moderate degree of statistical heterogeneity for the TC and TAG analyses. Garlic reduces TC to a modest extent, an effect driven mostly by the modest reductions in TAG, without appreciable LDL lowering or HDL elevation. Higher baseline line TC levels and the use of dietary modification may alter the effect of garlic on these parameters. Future studies should be conducted evaluating the impact of adjunctive garlic therapy with fibrates or statins on TAG concentrations.
The published evidence on strategies for avoiding the discontinuation of statin therapy due to muscular adverse effects is reviewed.
Statin medications are a cornerstone of the prevention and ...treatment of coronary heart disease, but about 20% of treated patients develop myalgia or other muscle-related adverse effects that can lead to the discontinuation of statin use. As there are no consensus guidelines or firm practice recommendations on continuing or reinitiating statin therapy in patients who experience statin-related muscular adverse effects, a literature search was conducted to evaluate a variety of strategies that have been studied. The search results indicated that the most widely used strategies are (1) alternative statin dosing, (2) co-enzyme Q10 supplementation, (3) vitamin D supplementation, (4) conversion to red yeast rice (RYR) therapy, and (5) conversion to a different statin. While positive results in some patients have been reported with all of the strategies reviewed, the available evidence is insufficient to support the routine use of any of the strategies in clinical practice. In particular, the use of RYR, which contains a naturally occurring statin, is not recommended due to limited and inconsistent study results and uncertainty about the contents of commercially available RYR products.
In patients intolerant to statin therapy due to myalgia or other muscular adverse effects, strategies such as alternative statin dosing schedules, coenzyme Q10 or vitamin D supplementation, and conversion to RYR or an alternative statin may allow some patients to continue to receive the benefits of lipid-lowering therapy.
Patients with ischemic heart disease and preserved ventricular function experience considerable morbidity and mortality despite standard medical therapy.
To compare benefits and harms of using ...angiotensin-converting enzyme (ACE) inhibitors, angiotensin II-receptor blockers (ARBs), or combination therapy in adults with stable ischemic heart disease and preserved ventricular function.
MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews (earliest date, July 2009) were searched without language restrictions.
Two independent investigators screened citations for trials of at least 6 months' duration that compared ACE inhibitors, ARBs, or combination therapy with placebo or active control and reported any of several clinical outcomes.
Using standardized protocols, 2 independent investigators extracted information about study characteristics and rated the quality and strength of evidence. Disagreement was resolved by consensus.
41 studies met eligibility criteria. Moderate- to high-strength evidence (7 trials; 32 559 participants) showed that ACE inhibitors reduce the relative risk (RR) for total mortality (RR, 0.87 95% CI, 0.81 to 0.94) and nonfatal myocardial infarction (RR, 0.83 CI, 0.73 to 0.94) but increase the RR for syncope (RR, 1.24 CI, 1.02 to 1.52) and cough (RR, 1.67 CI, 1.22 to 2.29) compared with placebo. Low-strength evidence (1 trial; 5926 participants) suggested that ARBs reduce the RR for the composite end point of cardiovascular mortality, nonfatal myocardial infarction, or stroke (RR, 0.88 CI, 0.77 to 1.00) but not for the individual components. Moderate-strength evidence (1 trial; 25 620 participants) showed similar effects on total mortality (RR, 1.07 CI, 0.98 to 1.16) and myocardial infarction (RR, 1.08 CI, 0.94 to 1.23) but an increased risk for discontinuations because of hypotension (P < 0.001) and syncope (P = 0.035) with combination therapy compared with ACE inhibitors alone.
Many studies either did not assess or did not report harms in a systematic manner. Many studies did not adequately report benefits or harms by various patient subgroups.
Adding an ACE inhibitor to standard medical therapy improves outcomes, including reduced risk for mortality and myocardial infarctions, in some patients with stable ischemic heart disease and preserved ventricular function. Less evidence supports a benefit of ARB therapy, and combination therapy seems no better than ACE inhibitor therapy alone and increases harms.
Agency for Healthcare Research and Quality.
Evidence regarding combination therapy for the management of hypertension is reviewed.
Numerous clinical trials have demonstrated the importance of early aggressive lowering of blood pressure, ...especially in patients at high cardiovascular risk. However, one of the difficulties with achieving these blood pressure goals quickly is that monotherapy is often insufficient. Many large randomized trials have shown that two or more antihypertensive agents are required for patients to reach their treatment goals. Recent data have suggested that the use of combination therapy in patients with hypertension may be beneficial in terms of improving blood-pressure-lowering efficacy, obtaining blood pressure goals earlier, and reducing major adverse cardiovascular events. Studies have found that therapy with a calcium channel blocker (CCB) combined with an angiotensin-converting-enzyme (ACE) inhibitor significantly reduces both blood pressure and major clinical events compared with an ACE inhibitor-diuretic combination. Combination ACE inhibitor-CCB therapy has also demonstrated superior blood-pressure-lowering efficacy and safety compared with either group used as monotherapy, including lower rates of peripheral edema compared with those achieved with increased doses of CCBs. The combination of an ACE inhibitor and an angiotensin II-receptor blocker has not been found to be superior to either group as monotherapy in patients with hypertension and should not be recommended at this time.
Combination drug therapy for the treatment of hypertension is supported by numerous randomized trials and clinical management guidelines. The addition of a diuretic or CCB to renin-angiotensin-aldosterone-system blocker therapy may provide an effective combination for reducing blood pressure and cardiovascular events.
Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery, occurring in 20% to 60% of patients. Advanced age, history of atrial fibrillation (AF), heart failure, ...peripheral arterial disease and chronic obstructive pulmonary disease are predictors of POAF. The pathogenesis of AF seems to be multifactorial, and includes electrical and structural remodeling as well as inflammation (a systemic response caused by cardiopulmonary bypass and cardiotomy). Numerous pharmacologic agents can decrease the incidence of POAF. It is also necessary to evaluate an agent's ability to decrease stroke, mortality, length of stay and hospital costs. Currently, the use of beta-blockers with adjunctive amiodarone has been shown to reduce POAF and several of its complications. Two therapeutic choices exist in patients with POAF: rate control and rhythm control. The decision which is more important to target should be based on the symptoms of the individual patient. Unlike in patients with chronic AF, POAF is generally transient, and the risks of anticoagulation may outweigh the benefits. Surgical ablation techniques and ablation devices have progressed considerably. This made the procedures quicker and simpler, and therefore feasible in virtually all clinical contexts. In turn, this has raised the issue of post-ablation arrhythmias. Although relapsing AF is generally addressed conservatively, it may require ablation, frequently transseptal. Further research is needed to identify the predictors of POAF and the most effective pharmacological and invasive methods for the prevention and treatment of POAF.
Thienopyridine antiplatelet drugs have been used for 15 years for the prevention of coronary stent thrombosis in patients undergoing percutaneous coronary intervention with stent placement. ...Ticlopidine, the first approved thienopyridine, has in large part been replaced by clopidogrel, a more potent and better tolerated thienopyridine. Now, prasugrel, the newest agent, is currently available for use in the United States. Although prasugrel is similar to clopidogrel, it is about 10 times more potent and has a quicker onset of action. Data from the largest trial comparing clopidogrel and prasugrel indicate that this increased potency and quicker onset of prasugrel equate to a reduction in major adverse cardiovascular events, although higher rates of major bleeding were reported. Prasugrel also differs from clopidogrel in that it may be less prone to drug‐drug interactions and patient nonresponsiveness, although further research is needed in both of these areas. Given the totality of data available, prasugrel appears to be a promising treatment option for patients with acute coronary syndromes who are undergoing percutaneous coronary interventions.
Background:
Several studies have evaluated the impact on myocardial infarction (MI), stroke, and overall mortality of perioperative β-blocker use in patients undergoing noncardiac surgery (NCS). ...However, most studies did not have adequate sample size and statistical power and were therefore underpowered to adequately evaluate these end points.
Objective:
To conduct a meta-analysis to determine the balance of benefits and harms associated with perioperative β-blocker use in NCS.
Methods:
A systematic literature search of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted from January 1960 through February 2009. Manual reference search was performed to identify additional relevant trials. Randomized, double-blinded, placebo-controlled trials comparing the use of β-blockars with placebo; using β-blockers perioperatively in β-blocker–naïve patients undergoing NCS; and evaluating endpoints of Ml, stroke, or all-cause mortality were included.
Results:
Six trials (N = 10,183) met our inclusion criteria. Perioperative β-blocker use was associated with a significant reduction in patients' odds of developing Ml (OR 0.74, 95% CI 0.61 to 0.89) but a significant increase in odds of developing stroke (OR 1.98, 95% CI 1.23 to 3.20) and also a nonsignificant increase in mortality (OR 1.21, 95% CI 0.98 to 1.49) versus placebo. Control-rate meta-regression determined that patients with highest baseline odds of stroke had decreased relative odds of having a stroke with a β-blocker versus placebo (β coefficient –0.97; 95% credible interval –1.04 to –0.90).
Conclusions:
When perioperative β-blockers are used in NCS patients, there is a trade-off between reduction in MI and increase in stroke, with a troubling trend toward an increase in mortality. Patients with lower baseline odds of developing stroke appear to be at greater risk of β-blockgr–induced stroke.
Introduction
The objective of this review was to conduct a systematic review with meta-analysis and Bayesian mixed treatment comparisons (MTC) evaluating the impact of biologics on non-Psoriasis Area ...and Severity Index (PASI) health outcomes in patients with moderate-to-severe plaque psoriasis.
Methods
MEDLINE and Cochrane Central Register of Controlled Trials were searched from 1966 to May 2009. Citations were screened for randomized, controlled trials of biologics versus either placebo or each other in adults with moderate-to-severe plaque psoriasis and reported any of several outcomes. Traditional and Bayesian MTC meta-analyses were conducted for each endpoint using either a random- or fixed-effect model where appropriate.
Results
Thirty-eight studies met eligibility criteria. All biologics showed significant improvement in achieving a good response on the static physician’s global assessment (PGA) versus placebo while, in the MTC, differences were noted between individual drugs. In achieving a good response on the dynamic PGA, all biologics showed significant improvements over placebo, while the MTC showed significant improvements with the anti-interleukins versus anti-T cells. Relative to placebo, antitumor necrosis factor (TNF) agents and anti-interleukins showed significant improvements in the Dermatology Life Quality Index (DLQI). Compared with placebo, the anti-TNF agents showed significant improvements in both 36-item Medical Outcomes Study Short-Form General Health Survey (SF-36) mental and physical component scores, while anti-T cell agents showed no improvements. The MTC showed no differences between any biologics for either the DLQI or SF-36.
Conclusion
Individual biologics and classes showed consistent benefits across non-PASI health outcomes in patients with moderate-to-severe plaque psoriasis while MTC meta-analyses suggested that some differences exist.
Two beta-blockers are approved for the treatment of heart failure (HF): carvedilol and metoprolol XL. Bucindolol, an investigational agent under FDA review for the treatment of HF, is a nonspecific ...beta-blocker with weak alpha-blocking properties that may or may not possess intrinsic sympathomimetic activity. The largest and most comprehensive clinical trial evaluating the effect of bucindolol on HF outcomes was the Beta-Blocker Evaluation of Survival Trial (BEST). This randomized, placebo-controlled trial was terminated early because of an inability to demonstrate a survival benefit with bucindolol versus placebo. However, subsequent analyses from BEST have demonstrated benefits in discrete subgroups, including a genetically identified subgroup. If approved, bucindolol may become the first genetically targeted medication for the treatment of HF. PUBLICATION ABSTRACT
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