Table 2 Authors’ conclusions

Horjus, et al.

This review found inconclusive evidence to decide on the use of creatine analogues in clinical practice.

The effect on death and the size of myocardial infarction and the heart function were unclear.

Given the small sample size of the discussed trials and the heterogeneity of the population included in these reports, larger clinical studies are needed to confirm these observations.

Zhao P, et al.

In terms of BP lowering efficacy, for 24-hour SBP and DBP, the data suggests that better blood pressure control was achieved with bedtime dosing than morning administration of antihypertensive medication, the clinical significance of which is not known.

Siebenhofer, et al.

The magnitude of the effects are uncertain as a result of the small number of patients and studies that could be included in the analyses.

It is not known whether weight loss reduces mortality and morbidity.

No useful information on adverse effects was reported in the relevant trials.

In conclusion, there is no evidence for effects of weight loss diets on death or long-term complications and adverse events.

In addition, results on blood pressure and body weight could be considered uncertain, because not all studies were included in the analyses.

Chen, et al.

The different effect on diastolic BP means that beta-blockers have little or no effect on pulse pressure whereas thiazides cause a significant dose-related decrease in pulse pressure.

Batterink, et al.

From the limited available evidence, spironolactone appears to lower blood pressure compared to placebo to a similar degree in patients with primary (essential) hypertension when doses of 100-500 mg/day are given.

A dose of 25 mg/day did not statistically significantly reduce systolic or diastolic blood pressure, compared to placebo.

Given the lack of a dose-response, coupled with a possible increased risk in adverse events with higher doses, doses of 25 to 100 mg/day are reasonable.There is no evidence of the effect of spironolactone on clinical outcomes in hypertensive patients.

Heran, et al.

ENaC blockers do not have a statistically or clinically significant BP lowering effect at low doses but trials at higher doses are not available.

The review did not provide a good estimate of the incidence of harms associated with ENaC blockers

Wiysonge, et al.

Thirteen RCTs were found and these trials suggested that first-line beta-blockers for elevated blood pressure were not as good at decreasing mortality and morbidity as other classes of drugs: thiazides, calcium channel blockers, and renin angiotensin system inhibitors.

Heran, et al.

The BP lowering effect of alpha blockers is modest; the estimate of the magnitude of trough BP lowering of -8/-5 mmHg is likely an overestimate.

There are no clinically meaningful BP lowering differences between different alpha blockers.

The review did not provide a good estimate of the incidence of harms associated with alpha blockers because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.

Heran, et al.

There are no clinically meaningful BP lowering differences between different ACE inhibitors.

The BP lowering effect of ACE inhibitors is modest.

The review did not provide a good estimate of the incidence of harms associated with ACE inhibitors because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials

Heran, et al.

The evidence from this review suggests that there are no clinically meaningful BP lowering differences between available ARBs.

The BP lowering effect of ARBs is modest and similar to ACE inhibitors as a class.

The review did not provide a good estimate of the incidence of harms associated with ARBs because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials

Ho, et al.

Due to the possible unreliability of some of the included studies, it is uncertain whether or not coenzyme Q10 reduces blood pressure in the long-term management of primary hypertension

Chen, et al.

Thiazides when given as a second-line drug have a dose related effect to lower blood pressure that is similar to when they are added as a first-line drug. This means that the BP lowering effect of thiazides is additive.

Because of the short duration of the trials and lack of reporting of adverse events, this review does not provide a good estimate of the incidence of adverse effects of diuretics given as a second-line drug

Musini, et al.

Based on the limited number of published RCTs, the SBP/DBP lowering effect of loop diuretics is modest … and is likely an overestimate due to the high risk of bias in the included studies.

There is no clinically meaningful BP lowering differences between different drugs within the loop diuretic class.

The dose ranging effects of loop diuretics could not be evaluated.

The review did not provide a good estimate of the incidence of harms associated because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.

Shamon & Perez

Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs.

However, we could not make definite conclusions regarding the dose-response pattern because of the small number of included trials.

More RCTs are needed to assess the effects of reserpine on blood pressure and to determine the dose-related safety profile before the role of this drug in the treatment of primary hypertension can be established

McGuinness, et al.

There is no convincing evidence from the trials identified that blood pressure lowering in late-life prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease.

There were significant problems identified with analysing the data, however, due to the number of patients lost to follow-up and the number of placebo patients who received active treatment. This introduced bias.

More robust results may be obtained by conducting a meta-analysis using individual patient data.

Mah, et al.

Methyldopa lowers blood pressure to varying degrees compared to placebo for patients with primary hypertension.

Its effect on clinical outcomes, however, remains uncertain.

Overall reporting of adverse effects was poor so no conclusions can be drawn about the adverse effect profile.

This meta-analysis shows that methyldopa reduces systolic/diastolic blood pressure by approximately 13/8 mmHg compared to placebo.

Musini, et al.

Aliskiren has a dose-related blood pressure lowering effect better than placebo.

This effect is similar to that determined for ACE inhibitors and ARBs

Wright & Musini

First-line low-dose thiazides reduce all morbidity and mortality outcomes.

First-line ACE inhibitors and calcium channel blockers may be similarly effective but the evidence is less robust.

Dickinson, et al.

In view of the poor quality of included trials and unexplained variation between trials, the evidence in favour of causal association between relaxation and blood pressure reduction is weak.

It was difficult to disentangle their effects, especially as many trials used a combination of methods

some of the reduction in blood pressure was almost certainly due to aspects of treatment that were not related to relaxation, such as frequent contact with professionals who were trying to help.

Dickinson, et al.

Due to small number of participants in the two high quality trials, the short duration of follow-up, and the unexplained heterogeneity between trials, the evidence about the effect of potassium supplementation on blood pressure is not conclusive.

Further high quality RCTs of longer duration are required to clarify whether potassium supplementation can reduce blood pressure and improve health outcomes.

Most included trials were of poor quality, so their results may not be reliable.

The trials were not long enough or large enough to measure whether potassium supplements reduce the risk of death, heart attack or stroke, which may be caused by high blood pressure.

This review does not confirm whether potassium supplements can lower high blood pressure and therefore does not recommend them for treating hypertension.

More trials enrolling a large number of participants with long periods of follow-up are necessary to know whether or not potassium supplements can lower high blood pressure.

Dickinson, et al.

In view of the poor quality of included trials and the heterogeneity between trials, the evidence in favour of a causal association between magnesium supplementation and blood pressure reduction is weak and is probably due to bias.

This is because poor quality studies generally tend to over-estimate the effects of treatment.

Larger, longer duration and better quality double-blind placebo controlled trials are needed to assess the effect of magnesium supplementation on blood pressure and cardiovascular outcomes.

Dickinson, et al.

Due to poor quality of included trials and heterogeneity between trials, the evidence in favour of causal association between calcium supplementation and blood pressure reduction is weak and is probably due to bias.

This is because poor quality studies generally tend to over-estimate the effects of treatment.

Larger, longer duration and better quality double-blind placebo controlled trials are needed to assess the effect of calcium supplementation on blood pressure and cardiovascular outcomes.

Musini, et al.

Treating healthy persons (60 years or older) with moderate to severe systolic and/or diastolic hypertension reduces all cause mortality and cardiovascular morbidity and mortality. The decrease in all cause mortality was limited to persons 60 to 80 years of age.

Beyer, et al.

None of the trials were of high quality, so their results may not be reliable.

We found no robust evidence that supplements of any combination of potassium, magnesium or calcium reduce mortality, morbidity or BP in adults.

More trials are needed to investigate whether the combination of potassium & magnesium is effective.

He & MacGregor

Our meta-analysis demonstrates that a modest reduction in salt intake for a duration of 4 or more weeks has a significant and, from a population viewpoint, important effect on blood pressure.

These results support other evidence suggesting that a modest and long-term reduction in population salt intake could reduce strokes, heart attacks, and heart failure.