How renin inhibitors (RIs) compare with angiotensin converti | Figure 1
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How renin inhibitors (RIs) compare with angiotensin converting enzyme (ACE) inhibitors for treating
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Review question
We determined how renin inhibitors (RIs) compared with angiotensin converting enzyme (ACE) inhibitors for treating hypertension.
Background
Hypertension is a worldwide public‐health challenge associated with high levels of occurrence and risks of circulatory and kidney disease. RIs were introduced into clinical use for hypertension in 2007. ACE inhibitors are widely prescribed for hypertension. However, the comparative effectiveness and safety of RIs and ACE inhibitors is not known.
Search date
We searched for evidence up to August 2020.
Study characteristics
We included randomized, active‐controlled, double‐blinded studies (RCTs) for this review. We include 11 RCTs involving 13,627 participants, with an average age from 51 to 74 years. Length of follow‐up ranged from four weeks to 36 months.
Key results and certainty of evidence
Low‐certainty evidence showed no difference between RIs and ACE inhibitors for deaths from any cause, for heart attacks, for serious side effects or for leaving the study because of side effects. Low‐certainty evidence suggested that RIs reduce blood pressure more than ACE inhibitors do, but this could have been due to bias in the design and conduct of the studies. More independent RCTs are needed to assess illnesses and deaths, and to see if the difference in blood pressure‐lowering is real.
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\ \ Review question\ What is the evidence for cholinesterase inhibitors (medicines designed to improve memory and thinking in people with dementia), when used with people who have vascular dementia?\ Background\ Vascular dementia (or vascular cognitive impairment) is a term used when a person has problems with memory and thinking that are caused by a disruption of blood supply. There are few drug treatments for vascular dementia.\ In this review, we evaluated three drugs from the cholinesterase inhibitor family, donepezil, rivastigmine, and galantamine. These medications are widely used in Alzheimer's dementia but may also be useful in people with vascular dementia. Previous reviews of these cholinesterase inhibitor drugs could not draw definitive conclusions for people with vascular dementia.\ Purpose of this review\ We wanted to learn whether cholinesterase inhibitors benefit people with vascular dementia. We were interested in their effects on memory, thinking, and daily functioning. We wanted to learn of any harms associated with these drugs.\ As some time has passed since the previous reviews, we wanted to update them by searching for new studies. We combined the three previous reviews on donepezil, rivastigmine and galantamine into one review.\ What we did\ We searched for studies that described the effects of donepezil, rivastigmine, and galantamine for people with vascular dementia. We searched databases of scientific studies and contacted drug manufacturers and experts in vascular dementia. Our search is current to 19 August 2020.\ To be included in our review, studies had to randomly assign people with vascular dementia to treatment with a cholinesterase inhibitor, or a dummy pill (placebo) and then compare the two groups. Studies comparing one cholinesterase inhibitor against another were also included. We combined the results of the included studies for each medicine to estimate how effective they were and how likely they were to cause side effects. We assessed how well the studies were conducted and how credible the results were.\ We did not find studies which compared different cholinesterase inhibitors with each other. To see whether the different cholinesterase inhibitor drugs differed in their effects, we used a technique called network meta‐analysis, which can provide an idea of how the medicines might perform if they were compared head‐to‐head.\ What we found\ We found 8 studies including a total of 4373 people with vascular dementia (or vascular cognitive impairment). The studies tested the drug donepezil at two different doses (5mg and 10mg daily), against each other and against placebo. Rivastigmine and galantamine were tested against placebo only. Rivastigmine is available as a skin patch, but the studies only tested the pill version. All eight studies evaluated participants when they first started taking the medicine or placebo and again six months later. Different tests were used to measure the effects. All studies included tests of memory, thinking and reported side effects.\ People taking donepezil or galantamine had better scores on memory and thinking tests than people taking placebo, but the benefits were modest and may not be large enough to be evident in daily life. There was no evidence of a difference for rivastigmine, but the evidence was less certain, and the doses taken by some participants may have been too low to show an effect. We found evidence that when compared to placebo, side effects such as nausea and diarrhoea, were more common in people taking donepezil 10mg and galantamine, but probably not donepezil 5mg. We were unable to draw conclusions about side effects of rivastigmine from the studies.\ No vascular dementia trials comparing the different cholinesterase against each other have been conducted. Using the information from the individual studies, we made indirect assessments of how the drugs would perform if tested head‐to‐head. The results suggested that donepezil 10 mg had the greatest effect on memory and thinking, but caused more side effects than donepezil 5 mg or galantamine.\ There were only a small number of studies for each drug. Certainty in the results varied between drugs and between outcomes, from high to very low certainty. The studies showed only a small benefit at most; however, in the absence of any other treatments, people living with dementia may still wish to consider use of these drugs.](https://app.figure1.com/case-detail/10edca9a-0f4d-4601-beed-79b6281cbf49)
\ \ Introduction and aims\ Sprains, strains, and bruises are common injuries, and people with these injuries often require pain relief, given as a tablet or capsule that is swallowed (oral). Many types of oral painkillers are available to treat such injuries. We wanted to know whether there were any differences in people's pain, swelling, function, or unwanted side effects when sprains, strains, and bruises were treated with oral non‐steroidal anti‐inflammatory drugs (NSAIDs, e.g. ibuprofen) compared with paracetamol, opioids (e.g. codeine), complementary or alternative medicines, or combinations of these.\ This is an update of a Cochrane review published in 2015.\ What did we do?\ We searched medical databases up to January 2020 for studies that compared NSAIDs with other painkillers in people with sprains, strains, and bruises. Study participants could be any age. We assessed the included studies to judge the reliability (certainty) of the evidence. We categorised the evidence as being of high, moderate, low, or very low certainty. High certainty means we are confident in the evidence, moderate certainty means we are fairly confident, low or very low certainty means that we are unsure or very unsure of the reliability of the evidence.\ Results of our search and description of studies\ We included 20 studies, with 3305 participants. Seven studies included people with ankle sprain only. Three studies included children only. Most of the participants of the other studies were young adults, and there were slightly more men than women. Few participants were aged over 65 years. Eleven studies compared NSAIDs with paracetamol, six studies compared NSAIDs with opioids, and four studies compared NSAIDs with paracetamol combined with an opioid. Studies reported outcomes at times varying from one hour after taking the medication, up to 10 to 14 days.\ Main results\ There is no difference between NSAIDs and paracetamol in pain after one to two hours, or after two to three days (high‐certainty evidence), and there may be no difference after a week or more (low‐certainty evidence). There is low‐certainty evidence that NSAIDs may make little difference to swelling after a week or more. We are uncertain whether NSAIDs make a difference to return to function after a week or more (very low‐certainty evidence). There is low‐certainly evidence that NSAIDs may slightly increase unwanted side effects related to the gut.\ There is probably no difference between NSAIDs and opioids in pain at one hour (moderate‐certainly evidence), and there may be no difference four or seven days after taking medication (low‐certainty evidence). We are uncertain whether NSAIDs make a difference to swelling after 10 days (very low‐certainty evidence). There is low‐certainty evidence that NSAIDs may increase return to function in 7 to 10 days. There is moderate‐certainty evidence that NSAIDs probably result in fewer unwanted side effects, such as nausea and dizziness, compared with opioids.\ The evidence suggests that there is little or no difference between NSAIDs and paracetamol combined with opioids in pain, swelling, return to function, or unwanted side effects. However, the evidence was very low certainty, so we are uncertain of these results.\ No studies reported the risk of re‐injury after treatment.\ We found no studies comparing NSAIDs with complementary or alternative medicines.\ Conclusions\ The body of evidence to date has found no difference between NSAIDs and other pain killers for pain relief for strains, sprains, and bruises in younger people. However, we need more, and better evidence on return to function and unwanted side effects in all age groups, particularly in older people.](https://app.figure1.com/case-detail/1b22ae79-f8d2-4864-a092-abfc66c02fca)
\ \ Perioperative beta‐blockers for preventing surgery‐related mortality and morbidity in adults undergoing non‐cardiac surgery\ This review assessed evidence from randomized controlled trials (RCTs) on whether beta‐blockers reduce deaths or other serious events when given to people undergoing surgery other than heart surgery. The findings for heart surgery are covered in another review.\ Background\ Surgery increases stress in the body, which responds by releasing the hormones adrenaline and noradrenaline. Stress from surgery can lead to death or other serious events such as heart attacks, stroke, or an irregular heartbeat. For surgery that does not involve the heart, an estimated 8% of people may have injury to their heart around the time of surgery. Beta‐blockers are drugs that block the action of adrenaline and noradrenaline on the heart. Beta‐blockers can slow down the heart, and reduce blood pressure, and this may reduce the risk of serious events. However, beta‐blockers may lead to a very low heart rate or very low blood pressure which could increase the risk of death or a stroke. Prevention of early complications after surgery is important, but using beta‐blockers to prevent these complications is controversial.\ Study characteristics\ The evidence is current to 28 June 2019. We included 83 RCTs with 14,967 adults who were undergoing different types of surgery other than heart surgery. Eighteen studies are awaiting classification (because we did not have enough details to assess them), and three studies are ongoing. The types of beta‐blockers used in the studies were: propranolol, metoprolol, esmolol, landiolol, nadolol, atenolol, labetalol, oxprenolol, and pindolol. Studies compared these beta‐blockers with either a placebo (disguised to look like a beta‐blocker but containing no medicine) or with standard care.\ Key results\ Beta‐blockers may make little or no difference to the number of people who die within 30 days of surgery (16 studies, 11,446 participants; low‐certainty evidence), have a stroke (6 studies, 9460 participants; low‐certainty evidence), or experience ventricular arrhythmias (irregular heartbeat rhythms, starting in the main chambers of the heart, that are potentially life‐threatening and may need immediate medical treatment; 5 studies, 476 participants; very low‐certainty evidence). We found that beta‐blockers may reduce atrial fibrillation (an irregular heartbeat, starting in the atrial chambers of the heart, that increases the risk of stroke if untreated; 9 studies, 9080 participants; low certainty‐evidence), and the number of people who have a heart attack (12 studies, 10,520 participants; low‐certainty evidence). However, taking beta‐blockers may increase the number of people who experience a very low heart rate (49 studies, 12,239 participants; low‐certainty evidence), or very low blood pressure (49 studies, 12,304 participants; moderate‐certainty evidence), around the time of surgery.\ In a few studies, we also found little or no difference in the number of people who died after 30 days, who died because of a heart problem, or had heart failure. We found no evidence of whether beta‐blockers alter the length of time in hospital.\ No studies assessed whether people who were given beta‐blockers had a better quality of life after heart surgery.\ Certainty of the evidence\ The certainty of the evidence in this review was limited by including some studies that were at high risk of bias, and we noticed that some of our findings were different if we only included placebo‐controlled studies or studies that reported how participants were randomized. We also found one large, well‐conducted, international study that had different findings to the smaller studies. It showed a reduction in heart attacks and an increase in stroke and all‐cause mortality when beta‐blockers were used, whilst the other studies did not show a clear effect. We were also less certain of the findings for outcomes with few studies, such as for ventricular arrhythmias.\ Conclusion\ Although beta‐blockers may make little or no difference to the number of people who die within 30 days, have a stroke, or have ventricular arrhythmias, they may reduce atrial fibrillation and heart attacks. Taking beta‐blockers may increase the number of people with a very low heart rate or very low blood pressure around the time of surgery. Further evidence from large, placebo‐controlled trials is likely to increase the certainty of these findings, and we recommend the assessment of impact on quality of life.](https://app.figure1.com/case-detail/28d23f1e-5e1f-4ccf-bacf-ddde5b44d221)
\ \ Cochrane Review; 5 trials (451 patients with bacterial meningitis) that compared glycerol with placebo. In the studies steroids were often given as well, but this did not appear to modify any of the effects seen with glycerol.\ Background:\ Osmotic therapies increase the concentration of the blood by exerting an osmotic pressure across a semi-permeable membrane (such as a cell wall or blood vessel lining in the brain). This draws water from the brain into the blood, thereby reducing pressure in the brain. Potentially osmotic therapies could increase the rate of survival, or they could do harm.\ Key findings\ Giving glycerol, an osmotic diuretic, probably has little or no effect on death (moderate-certainty evidence), but may reduce subsequent deafness (moderate-certainty evidence) or neurological disability (low-certainty evidence).\ What are the main results of the review?\ This review detected no benefit from glycerol relating to death. There appeared to be marginal protection against deafness and against neurological disability. No effect on epileptic seizures at follow-up was noted. Glycerol was not associated with any severe adverse effects. The number of trials included was small and only two tested a large number of participants.](https://app.figure1.com/case-detail/35b40836-b6c2-4d2e-9dcb-e4ff56ec107a)
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