Hypertension

Half a million studies


Pak J Pharm Sci. 2018 Jan;31(1):237-244.

Review: Beyond conventional therapies: Complementary and alternative medicine in the management of hypertension: An evidence-based review.

Wong AP1, Kassab YW2, Mohamed AL2, Abdul Qader AM1.

Author information

Abstract

Hypertension is one of the major causes of morbidity and mortality. Worldwide, Hypertension is estimated to cause 7.5 million deaths, about 12.8% of the total of all deaths. This accounts for 57 million disability adjusted life years (DALYS) or 3.7% of total DALYS. This led WHO to set a target of 25% reduction in prevalence by 2025. To reach that, WHO has adopted non-conventional methods for the management of hypertension? Despite worldwide popularity of such non-conventional therapies, only small volume of evidence exists that supports its effectiveness. This review attempted to make a critical appraisal of the evidence, with the aim to (1) describe the therapeutic modalities frequently used, and (2) review the current level of evidence attributable to each modality. Databases from Cochrane Library, MEDLINE, PUBMED, and EMBASE were searched from 2005-2015. A total of 23 publications have been identified and selected. Out of these, 15 systematic reviews and/or meta-analysis of RCTs, 5 RCTs, 1 non-RCT, and 2 observational studies without control. Among those 23 publications, therapeutic modalities identified are: fish oil, qigong, yoga, coenzyme Q10, melatonin, meditation, vitamin D, vitamin C, monounsaturated fatty acids, dietary amino-acids, chiropractic, osteopathy, folate, inorganic nitrate, beetroot juice, beetroot bread, magnesium, and L-arginine. The followings were found to have weak or no evidence: fish oil, yoga, vitamin D, monounsaturated fatty acid, dietary amino-acids, and osteopathy. Those found to have significant reduction in blood pressure are: magnesium, qigong, melatonin, meditation, vitamin C, chiropractic, folate, inorganic nitrate, beetroot juice and L-arginine. Coenzyme Q10on the other hand, showed contradicting results were some studies found weak or no effect on blood pressure while others showed significant blood pressure reduction effect. By virtue of the research designs and methodologies, the evidence contributed from these studies is at level 1. Results from this review suggest that certain non-conventional therapies may be effective in treating hypertension and improving cardiac function and therefore considered as part of an evidence-based approach.

PMID:

29348109

Am J Hypertens. 2018 Feb 9. doi: 10.1093/ajh/hpy027. [Epub ahead of print]

Comparative efficacy of antihypertensive agents in salt-sensitive hypertensive patients: a network meta-analysis.

Qi H1, Liu Z1, Cao H1, Sun WP1,2, Peng WJ1, Liu B1, Dong SJ3, Xiang YT4, Zhang L1.

Author information

Abstract

BACKGROUND:

Salt-sensitive hypertension (SSH) is an intermediate inherited phenotype of essential hypertension as well as being an independent risk factor for cardiovascular disease. However, effective medications for the treatment of SSH have not been clarified. This study was to compare the efficacious of different classes of antihypertensive agents combined with salt intake on the reduction of blood pressure in patients with salt-sensitive hypertension (SSH).

METHODS:

We used sources as PubMed, EMBASE, Cochrane Library, CENTRAL, ClinicalTrials.gov, ICTRP, CNKI and WANFANG database from inception to November 2016. Studies that compared the efficacy of two or more antihypertensive agents or placebos in adult salt-sensitive hypertensive patients were included. The outcomes included variations in mean arterial blood pressure, systolic and diastolic blood pressure.

RESULTS:

Twenty-five studies were involved in this meta-analysis. A CCB with hydrochlorothiazide and moderate salt intake was significantly the most efficacious in comparison with placebo [standardized mean differences (SMD), 95% credibility intervals (CI): 26.66, 12.60-40.16], ARBs [SMD, 95% CI: 22.94, 5.26-40.51] and the other interventions for patients with SSH and no concomitant diseases. For SSH patients who were obese, the effect size of CCB with metformin and moderate salt intake was [SMD, 95% CI: 17.90, 6.26 -29.33].

CONCLUSIONS:

For SSH patients with no concomitant diseases, CCB combined with hydrochlorothiazide and moderate salt intake were optimal in reducing blood pressure, while CCB combined with metformin and moderate salt intake were the most efficacious at reducing blood pressure in SSH patients with coexisting obesity.

KEYWORDS:

Salt-sensitive hypertension; antihypertensive agents; network meta-analysis

PMID:

29438454

DOI:

10.1093/ajh/hpy027


Cochrane Database Syst Rev. 2017 Jan 20;1:CD002003. doi: 10.1002/14651858.CD002003.pub5.

Beta-blockers for hypertension.

Wiysonge CS1,2, Bradley HA3, Volmink J1,2, Mayosi BM4, Opie LH5.

Author information

Abstract

BACKGROUND:

Beta-blockers refer to a mixed group of drugs with diverse pharmacodynamic and pharmacokinetic properties. They have shown long-term beneficial effects on mortality and cardiovascular disease (CVD) when used in people with heart failure or acute myocardial infarction. Beta-blockers were thought to have similar beneficial effects when used as first-line therapy for hypertension. However, the benefit of beta-blockers as first-line therapy for hypertension without compelling indications is controversial. This review is an update of a CochraneReview initially published in 2007 and updated in 2012.

OBJECTIVES:

To assess the effects of beta-blockers on morbidity and mortality endpoints in adults with hypertension.

SEARCH METHODS:

The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to June 2016: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (2016, Issue 6), MEDLINE (from 1946), Embase (from 1974), and ClinicalTrials.gov. We checked reference lists of relevant reviews, and reference lists of studies potentially eligible for inclusion in this review, and also searched the the World Health Organization International Clinical Trials Registry Platform on 06 July 2015.

SELECTION CRITERIA:

Randomised controlled trials (RCTs) of at least one year of duration, which assessed the effects of beta-blockers compared to placebo or other drugs, as first-line therapy for hypertension, on mortality and morbidity in adults.

DATA COLLECTION AND ANALYSIS:

We selected studies and extracted data in duplicate, resolving discrepancies by consensus. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI) and conducted fixed-effect or random-effects meta-analyses, as appropriate. We also used GRADE to assess the certainty of the evidence. GRADE classifies the certainty of evidence as high (if we are confident that the true effect lies close to that of the estimate of effect), moderate (if the true effect is likely to be close to the estimate of effect), low (if the true effect may be substantially different from the estimate of effect), and very low (if we are very uncertain about the estimate of effect).

MAIN RESULTS:

Thirteen RCTs met inclusion criteria. They compared beta-blockers to placebo (4 RCTs, 23,613 participants), diuretics (5 RCTs, 18,241 participants), calcium-channel blockers (CCBs: 4 RCTs, 44,825 participants), and renin-angiotensin system (RAS) inhibitors (3 RCTs, 10,828 participants). These RCTs were conducted between the 1970s and 2000s and most of them had a high risk of bias resulting from limitations in study design, conduct, and data analysis. There were 40,245 participants taking beta-blockers, three-quarters of them taking atenolol. We found no outcome trials involving the newer vasodilating beta-blockers (e.g. nebivolol).There was no difference in all-cause mortality between beta-blockers and placebo (RR 0.99, 95% CI 0.88 to 1.11), diuretics or RAS inhibitors, but it was higher for beta-blockers compared to CCBs (RR 1.07, 95% CI 1.00 to 1.14). The evidence on mortality was of moderate-certainty for all comparisons.Total CVD was lower for beta-blockers compared to placebo (RR 0.88, 95% CI 0.79 to 0.97; low-certainty evidence), a reflection of the decrease in stroke (RR 0.80, 95% CI 0.66 to 0.96; low-certainty evidence) since there was no difference in coronary heart disease (CHD: RR 0.93, 95% CI 0.81 to 1.07; moderate-certainty evidence). The effect of beta-blockers on CVD was worse than that of CCBs (RR 1.18, 95% CI 1.08 to 1.29; moderate-certainty evidence), but was not different from that of diuretics (moderate-certainty) or RAS inhibitors (low-certainty). In addition, there was an increase in stroke in beta-blockers compared to CCBs (RR 1.24, 95% CI 1.11 to 1.40; moderate-certainty evidence) and RAS inhibitors (RR 1.30, 95% CI 1.11 to 1.53; moderate-certainty evidence). However, there was little or no difference in CHD between beta-blockers and diuretics (low-certainty evidence), CCBs (moderate-certainty evidence) or RAS inhibitors (low-certainty evidence). In the single trial involving participants aged 65 years and older, atenolol was associated with an increased CHD incidence compared to diuretics (RR 1.63, 95% CI 1.15 to 2.32). Participants taking beta-blockers were more likely to discontinue treatment due to adverse events than participants taking RAS inhibitors (RR 1.41, 95% CI 1.29 to 1.54; moderate-certainty evidence), but there was little or no difference with placebo, diuretics or CCBs (low-certainty evidence).

AUTHORS' CONCLUSIONS:

Most outcome RCTs on beta-blockers as initial therapy for hypertension have high risk of bias. Atenolol was the beta-blocker most used. Current evidence suggests that initiating treatment of hypertension with beta-blockers leads to modest CVD reductions and little or no effects on mortality. These beta-blocker effects are inferior to those of other antihypertensive drugs. Further research should be of high quality and should explore whether there are differences between different subtypes of beta-blockers or whether beta-blockers have differential effects on younger and older people.

Update of

PMID:

28107561

PMCID:

PMC5369873

DOI:

10.1002/14651858.CD002003.pub5

Cochrane Database Syst Rev. 2017 Aug 16;8:CD008276. doi: 10.1002/14651858.CD008276.pub2.

Pharmacotherapy for hypertension in adults aged 18 to 59 years.

Musini VM1, Gueyffier F, Puil L, Salzwedel DM, Wright JM.

Author information

Abstract

BACKGROUND:

Hypertension is an important risk factor for adverse cardiovascular events including stroke, myocardial infarction, heart failure and renal failure. The main goal of treatment is to reduce these events. Systematic reviews have shown proven benefit of antihypertensive drug therapy in reducing cardiovascular morbidity and mortality but most of the evidence is in people 60 years of age and older. We wanted to know what the effects of therapy are in people 18 to 59 years of age.

OBJECTIVES:

To quantify antihypertensive drug effects on all-cause mortality in adults aged 18 to 59 years with mild to moderate primary hypertension. To quantify effects on cardiovascular mortality plus morbidity (including cerebrovascular and coronary heart disease mortality plus morbidity), withdrawal due adverse events and estimate magnitude of systolic blood pressure (SBP) and diastolic blood pressure (DBP) lowering at one year.

SEARCH METHODS:

The Cochrane Hypertension Information Specialist searched the following databases for randomized controlled trials up to January 2017: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (from 1946), Embase (from 1974), the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We contacted authors of relevant papers regarding further published and unpublished work.

SELECTION CRITERIA:

Randomized trials of at least one year' duration comparing antihypertensive pharmacotherapy with a placebo or no treatment in adults aged 18 to 59 years with mild to moderate primary hypertension defined as SBP 140 mmHg or greater or DBP 90 mmHg or greater at baseline, or both.

DATA COLLECTION AND ANALYSIS:

The outcomes assessed were all-cause mortality, total cardiovascular (CVS) mortality plus morbidity, withdrawals due to adverse events, and decrease in SBP and DBP. For dichotomous outcomes, we used risk ratio (RR) with 95% confidence interval (CI) and a fixed-effect model to combine outcomes across trials. For continuous outcomes, we used mean difference (MD) with 95% CI and a random-effects model as there was significant heterogeneity.

MAIN RESULTS:

The population in the seven included studies (17,327 participants) were predominantly healthy adults with mild to moderate primary hypertension. The Medical Research Council Trial of Mild Hypertension contributed 14,541 (84%) of total randomized participants, with mean age of 50 years and mean baseline blood pressure of 160/98 mmHg and a mean duration of follow-up of five years. Treatments used in this study were bendrofluazide 10 mg daily or propranolol 80 mg to 240 mg daily with addition of methyldopa if required. The risk of bias in the studies was high or unclear for a number of domains and led us to downgrade the quality of evidence for all outcomes.Based on five studies, antihypertensive drug therapy as compared to placebo or untreated control may have little or no effect on all-cause mortality (2.4% with control vs 2.3% with treatment; low quality evidence; RR 0.94, 95% CI 0.77 to 1.13). Based on 4 studies, the effects on coronary heart disease were uncertain due to low quality evidence (RR 0.99, 95% CI 0.82 to 1.19). Low quality evidence from six studies showed that drug therapy may reduce total cardiovascular mortality and morbidity from 4.1% to 3.2% over five years (RR 0.78, 95% CI 0.67 to 0.91) due to reduction in cerebrovascular mortality and morbidity (1.3% with control vs 0.6% with treatment; RR 0.46, 95% CI 0.34 to 0.64). Very low quality evidence from three studies showed that withdrawals due to adverse events were higher with drug therapy from 0.7% to 3.0% (RR 4.82, 95% CI 1.67 to 13.92). The effects on blood pressure varied between the studies and we are uncertain as to how much of a difference treatment makes on average.

AUTHORS' CONCLUSIONS:

Antihypertensive drugs used to treat predominantly healthy adults aged 18 to 59 years with mild to moderate primary hypertension have a small absolute effect to reduce cardiovascular mortality and morbidity primarily due to reduction in cerebrovascular mortality and morbidity. All-cause mortality and coronary heart disease were not reduced. There is lack of good evidence on withdrawal due to adverse events. Future trials in this age group should be at least 10 years in duration and should compare different first-line drug classes and strategies.

PMID:

28813123

DOI:

10.1002/14651858.CD008276.pub2

[Indexed for MEDLINE]Cochrane Database Syst Rev. 2017 Aug 8;8:CD011575. doi: 10.1002/14651858.CD011575.pub2.

Blood pressure targets for hypertension in older adults.

Garrison SR1, Kolber MR, Korownyk CS, McCracken RK, Heran BS, Allan GM.

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Abstract

BACKGROUND:

Eight out of 10 major antihypertensive trials in older adults attempted to achieve a target systolic blood pressure (BP) less than 160 mmHg. Collectively these trials demonstrated benefit for treatment, as compared to no treatment, for an older adult with BP greater than 160 mmHg. However an even lower BP target of less than 140 mmHg is commonly applied to all age groups. At the present time it is not known whether a lower or higher BP target is associated with better cardiovascular outcomes in older adults.

OBJECTIVES:

To assess the effects of a higher (less than 150 to 160/95 to 105 mmHg) BP target compared to the lower BP target of less than 140/90 mmHg in hypertensive adults 65 years of age or older.

SEARCH METHODS:

The Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials up to February 2017: the Cochrane Hypertension Specialised Register, MEDLINE, Embase, ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform. We also contacted authors of relevant papers regarding further published and unpublished work.

SELECTION CRITERIA:

Randomised trials, of at least one year's duration, conducted on hypertensive adults aged 65 years or older, which report the effect on mortality and morbidity of a higher systolic or diastolic BP treatment target (whether ambulatory, home, or office measurements) in the range of systolic BP less than 150 to 160 mmHg or diastolic BP less than 95 to 105 mmHg as compared to a lower BP treatment target of less than 140/90 mmHg or lower.

DATA COLLECTION AND ANALYSIS:

Two authors independently screened and selected trials for inclusion, assessed risk of bias, and extracted data. We combined data for dichotomous outcomes using the risk ratio (RR) with 95% confidence interval (CI) and for continuous outcomes we used mean difference (MD). Primary outcomes were all-cause mortality, stroke, institutionalisation, and cardiovascular serious adverse events. Secondary outcomes included cardiovascular mortality, non-cardiovascular mortality, unplanned hospitalisation, each component of cardiovascular serious adverse events separately (including cerebrovascular disease, cardiac disease, vascular disease, and renal failure), total serious adverse events, total minor adverse events, withdrawals due to adverse effects, systolic BP achieved, and diastolic BP achieved.

MAIN RESULTS:

We found and included three unblinded randomised trials in 8221 older adults (mean age 74.8 years), in which higher BP targets of less than 150/90 mmHg (two trials) and less than 160/90 mmHg (one trial) were compared to a lower target of less than 140/90 mmHg. Treatment to the two different BP targets over two to four years failed to produce a difference in any of our primary outcomes, including all-cause mortality (RR 1.24 95% CI 0.99 to 1.54), stroke (RR 1.25 95% CI 0.94 to 1.67) and total cardiovascular serious adverse events (RR 1.19 95% CI 0.98 to 1.45). However, the 95% confidence intervals of these outcomes suggest the lower BP target is probably not worse, and might offer a clinically important benefit. We judged all comparisons to be based on low-quality evidence. Data on adverse effects were not available from all trials and not different, including total serious adverse events, total minor adverse events, and withdrawals due to adverse effects.

AUTHORS' CONCLUSIONS:

At the present time there is insufficient evidence to know whether a higher BP target (less than 150 to 160/95 to 105 mmHg) or a lower BP target (less than 140/90 mmHg) is better for older adults with high BP. Additional good-quality trials assessing BP targets in this population are needed.

PMID:

28787537

DOI:

10.1002/14651858.CD011575.pub2

Nutr J. 2017 May 5;16(1):26. doi: 10.1186/s12937-017-0247-4.

Dose-response relationship between dietary magnesium intake, serum magnesium concentration and risk of hypertension: a systematic review and meta-analysis of prospective cohort studies.

Han H1, Fang X2, Wei X3, Liu Y3, Jin Z1, Chen Q1, Fan Z4, Aaseth J5,6, Hiyoshi A7, He J8, Cao Y9,7.

Author information

Abstract

BACKGROUND:

The findings of prospective cohort studies are inconsistent regarding the association between dietary magnesium intake and serum magnesium concentration and the risk of hypertension. We aimed to review the evidence from prospective cohort studies and perform a dose-response meta-analysis to investigate the relationship between dietary magnesium intake and serum magnesium concentrations and the risk of hypertension.

METHODS:

We searched systematically PubMed, EMBASE and the Cochrane Library databases from October 1951 through June 2016. Prospective cohort studies reporting effect estimates with 95% confidence intervals (CIs) for hypertension in more than two categories of dietary magnesium intake and/or serum magnesium concentrations were included. Random-effects models were used to combine the estimated effects.

RESULTS:

Nine articles (six on dietary magnesium intake, two on serum magnesium concentration and one on both) of ten cohort studies, including 20,119 cases of hypertension and 180,566 participates, were eligible for inclusion in the meta-analysis. We found an inverse association between dietary magnesium intake and the risk of hypertension [relative risk (RR) = 0.92; 95% CI: 0.86, 0.98] comparing the highest intake group with the lowest. A 100 mg/day increment in magnesium intake was associated with a 5% reduction in the risk of hypertension (RR = 0.95; 95% CI: 0.90, 1.00). The association of serum magnesium concentration with the risk of hypertension was marginally significant (RR = 0.91; 95% CI: 0.80, 1.02).

CONCLUSIONS:

Current evidence supports the inverse dose-response relationship between dietary magnesium intake and the risk of hypertension. However, the evidence about the relationship between serum magnesium concentration and hypertension is limited.

KEYWORDS:

Dietary intake; Dose-response relationship; Hypertension; Magnesium; Prospective cohort study; Serum concentration

PMID:

28476161

PMCID:

PMC5420140

DOI:

10.1186/s12937-017-0247-4

PLoS One. 2017 Apr 18;12(4):e0174967. doi: 10.1371/journal.pone.0174967. eCollection 2017.

Oral potassium supplementation for management of essential hypertension: A meta-analysis of randomized controlled trials.

Poorolajal J1,2,3, Zeraati F4, Soltanian AR3,5, Sheikh V6, Hooshmand E7, Maleki A1.

Author information

Abstract

IMPORTANCE:

Increased dietary potassium intake is thought to be associated with low blood pressure (BP). Whether potassiumsupplementation may be used as an antihypertensive agent is a question that should be answered.

OBJECTIVE:

To assess the effect of oral potassium supplementation on blood pressure in patients with primary hypertension.

SEARCH METHODS:

We searched Medline, Web of Science, Scopus, Cochrane Central Register of Controlled Trials until October 2016. We also screened reference lists of articles and previous reviews. We applied no language restrictions.

SELECTION CRITERIA:

We included randomized placebo-controlled clinical trials addressing the effect of potassium supplementation on primary hypertension for a minimum of 4 weeks.

DATA COLLECTION AND ANALYSIS:

We extracted data on systolic and diastolic BP (SBP and DBP) at the final follow-up. We explored the heterogeneity across studies using Cochran's test and I2 statistic and assessed the probability of publication bias using Begg's and Egger's tests. We reported the mean difference (MD) of SBP and DBP in a random-effects model.

RESULTS:

We found a total of 9059 articles and included 23 trials with 1213 participants. Compared to placebo, potassium supplementation resulted in modest but significant reductions in both SBP (MD -4.25 mmHg; 95% CI: -5.96 to -2.53; I2 = 41%) and DBP (MD -2.53 mmHg; 95% CI: -4.05 to -1.02; I2 = 65%). According to the change-score analysis, based on 8 out of 23 trials, compared to baseline, the mean changes in SBP (MD -8.89 mmHg; 95% CI: -13.67 to -4.11) and DBP (MD -6.42 mmHg; 95% CI: -10.99 to -1.84) was significantly higher in the intervention group than the control group.

CONCLUSIONS:

Our findings indicated that potassium supplementation is a safe medication with no important adverse effects that has a modest but significant impact BP and may be recommended as an adjuvant antihypertensive agent for patients with essential hypertension.

PMID:

28419159

PMCID:

PMC5395164

DOI:

10.1371/journal.pone.0174967

[Indexed for MEDLINE]

Free PMC Article

Medicine (Baltimore). 2016 Jul;95(30):e4071. doi: 10.1097/MD.0000000000004071.

Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement.

Paz MA1, de-La-Sierra A, Sáez M, Barceló MA, Rodríguez JJ, Castro S, Lagarón C, Garrido JM, Vera P, Coll-de-Tuero G.

Author information

Abstract

BACKGROUND:

The relative efficacy of antihypertensive drugs/combinations is not well known. Identifying the most effective ones and the patients' characteristics associated with best performance of the drugs will improve management of hypertensive patients.

OBJECTIVE:

To assess the blood pressure (BP) reduction attributed to antihypertensive drugs and identify characteristics associated with BP decrease.

DATA SOURCES:

MEDLINE, Cochrane Central Register of Controlled Trials from inception through July 2012 and selected papers.

STUDY ELIGIBILITY CRITERIA:

Double-blind, randomized clinical trials whose main result was the reduction in BP by antihypertensive treatment, with study population ≥50 or ≥25 if the study was a crossover, follow-up of at least 8 weeks, and available required data.

STUDY APPRAISAL AND SYNTHESIS METHODS:

Study data were independently extracted by multiple observers and introduced in an electronic database. Inconsistencies were resolved by discussion and referral back to the original articles. Meta-analysis was performed according to PRISMA statement and using a Bayesian framework.

MAIN OUTCOME(S) AND MEASURE(S):

Mean decrease in systolic (SBP) and diastolic blood pressure (DBP) achieved by each drug or combination.

RESULTS:

Two hundred eight trials including 94,305 patients were identified. In monotherapy, most drugs achieved 10 to 15 mm Hg SBP and 8 to 10 mm Hg DBP decreases.Olmesartan/amlodipine, olmesartan/hydrochlorothiazide, felodipine/metoprolol, and valsartan/hydrochlorothiazide were the combinations leading to the greatest mean SBP reductions (>20 mm Hg). Female sex and body mass index >25 kg/m were associated with more pronounced SBP and DBP reductions, whereas Afro-American ethnicity was associated with BP reductions smaller than the median. Results were adjusted by study duration, cardiovascular disease, and diabetes mellitus. Still, the estimation was performed using the mean administered doses, which do not exactly match those of the available drug formats.

LIMITATIONS:

Data corresponded to those obtained in each of the included trials; the analysis of the combinations was limited to the most recent ones; estimations were performed using the mean administered doses.

CONCLUSIONS AND IMPLICATIONS:

Certain drug combinations achieve BP reductions ranging from 20 to 25/10 to 15 mm Hg. Sex, ethnicity, and obesity are associated with antihypertensive response. This information can contribute to better selection of the antihypertensive drug, depending on the magnitude of pretreatment BP elevation. Guidelines should be revised.

PMID:

27472680

PMCID:

PMC5265817

DOI:

10.1097/MD.0000000000004071

Ugeskr Laeger. 2015 May 11;177(20):949-51.

[Thiazide diuretics in the treatment of hypertensive patients].

[Article in Danish]

Rasmussen K1.

Author information

Abstract

This Cochrane review had the objectives to determine the dose-related decrease in blood pressure due to thiazide diuretics compared with placebo control in the treatment of hypertensive patients. Hydrochlorothiazide has a dose-related blood pressure-lowering effect over the dose range 6.25, 12.5, 25 and 50 mg/day of 4/2, 6/3, 8/3 and 11/5 mmHg, respectively. This exceeds the mean 3 mmHg reduction achieved by angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers as shown in other Cochrane reviews, which have compared these antihypertensive drugs with placebo having used similar inclusion/exclusion criteria.

PMID:

25967243

[Indexed for MEDLINE]

Hypertens Res. 2012 Jan;35(1):77-81. doi: 10.1038/hr.2011.143. Epub 2011 Sep 1.

Cilnidipine, but not amlodipine, ameliorates osteoporosis in ovariectomized hypertensive rats through inhibition of the N-type calcium channel.

Shimizu H1, Nakagami H, Yasumasa N, Mariana OK, Kyutoku M, Koriyama H, Nakagami F, Shimamura M, Rakugi H, Morishita R.

Author information

Abstract

Both osteoporosis and high blood pressure are major diseases in aging populations. Recent studies demonstrated that some antihypertensive drugs reduced the risk of bone fracture in elderly patients. Although calcium channel blockers (CCB) are widely used as first-line antihypertensive agents, there is no evidence that they prevent osteoporosis. In this study, we investigated the effects of two types of CCB on bone metabolism: cilnidipine (L-/N-type CCB), which suppresses norepinephrine release from the sympathetic nerve, and amlodipine(L-type CCB). In ovariectomized female spontaneous hypertensive rats, administration of cilnidipine, but not amlodipine, resulted in a significant increase in the ratio of alkaline phosphatase to tartrate-resistant acid phosphatase (TRAP) and a decrease in the number of osteoclasts, as assessed by TRAP staining in the proximal tibia. Bone mineral density, moreover, was significantly higher in the cilnidipine group as compared with the amlodipine group and was associated with a significant decrease in a urinary collagen degradation product (deoxypyridinoline). The degree of prevention of osteoporosis by cilnidipine was similar to that of carvedilol (a β-blocker) because β-blockers reduce fracture risks though the inhibition of osteoclast activation. Interestingly, these effects cannot be attributed to the reduction of blood pressure because all three drugs significantly decreased blood pressure. In contrast, both cilnidipine and carvedilol, but not amlodipine, significantly decreased heart rate, indicating that both cilnidipine and carvedilol suppressed sympathetic nervous activity. Overall, our present data showed that cilnidipine (L-/N-type CCB) ameliorated osteoporosis in ovariectomized hypertensive rats. These pleiotropic effects of antihypertensive drugs such as cilnidipine and carvedilol might provide additional benefits in the treatment of hypertensive postmenopausal women.

PMID:

21881574

DOI:

10.1038/hr.2011.143

Ophthalmology. 2018 Feb 9. pii: S0161-6420(17)30944-2. doi: 10.1016/j.ophtha.2018.01.007. [Epub ahead of print]

Systemic Medication Associations with Presumed Advanced or Uncontrolled Primary Open-Angle Glaucoma.

Zheng W1, Dryja TP1, Wei Z2, Song D2, Tian H3, Kahler KH3, Khawaja AP4.

Author information

Abstract

PURPOSE:

To identify associations between systemic medications and primary open-angle glaucoma (POAG) requiring a procedure using United States insurance claims data in a hypothesis-generating study.

DESIGN:

Database study.

PARTICIPANTS:

In total, 6130 POAG cases (defined as patients with POAG undergoing a glaucoma procedure) were matched to 30 650 controls (defined as patients undergoing cataract surgery but without a coded glaucoma diagnosis, procedure, or medication) by age, gender, and region of residence.

METHODS:

Participant prescription drug use was calculated for the 5-year period before the glaucoma procedure or cataract surgery. Separately for individual generic drugs and drug classes, logistic regression was used to assess the association with POAG status. This was done across all generic drugs and drug classes that were prescribed in at least 1% of cases and controls. Analyses were adjusted for age, sex, region of residence, employment status, insurance plan type, and the total number of drugs prescribed.

MAIN OUTCOME MEASURES:

Odds ratio (OR) and 95% confidence intervals (CIs) for the association between each drug or drug class and POAG.

RESULTS:

The median age of participants was 72 years, and 52% were women. We tested for associations of POAG with 423 drug classes and 1763 generic drugs, resulting in a total of 2186 statistical tests and a Bonferroni-adjusted significance threshold of P < 2.3 × 10-5. Selective serotonin reuptake inhibitors (SSRIs) were strongly associated with a reduced risk of POAG (OR, 0.70; 95% CI, 0.64-0.76; P = 1.0 × 10-15); the most significant drug in this class was citalopram (OR, 0.66; 95% CI, 0.57-0.77; P = 1.2 × 10-7). Calcium channel blockers were strongly associated with an increased risk of POAG (OR, 1.26; 95% CI, 1.18-1.35; P = 1.8 × 10-11); the most significant drug in this class was amlodipine (OR, 1.27; 95% CI, 1.18-1.37; P = 5.9 × 10-10).

CONCLUSIONS:

We present data documenting potential associations of SSRIs and calcium channel blockers with POAG requiring a procedure. Further research may be indicated to better evaluate any associates of serotonin metabolism or calcium channels in glaucoma, or establish whether the associations are due to variations in the patterns for prescribing these drugs.

Copyright © 2018 American Academy of Ophthalmology. All rights reserved.

PMID:

29433851

DOI:

10.1016/j.ophtha.2018.01.007

Cancer Epidemiol. 2017 Oct;50(Pt A):113-124. doi: 10.1016/j.canep.2017.08.012. Epub 2017 Sep 1.

Calcium channel blockers and breast cancer incidence: An updated systematic review and meta-analysis of the evidence.

Wright CM1, Moorin RE2, Chowdhury EK3, Stricker BH4, Reid CM5, Saunders CM6, Hughes JD7.

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Abstract

Controversy exists regarding the potential association between taking calcium channel blockers (CCBs) and the development of breast cancer. As a positive association would have important public health implications due to the widespread use of CCBs, this study aimed to incorporate new evidence to determine whether an association is likely to exist. We searched MEDLINE, EMBASE and the Cochrane Library to 28 June 2016 for relevant literature. References and citing articles were checked and authors contacted as necessary. Two authors independently selected articles and extracted data. Twenty-nine studies were reviewed; 26 were non-randomised studies (NRS). Meta-analysis of study data where adjustment for 'confounding by indication' was judged to be present suggests that an association, if any, is likely to be modest in magnitude (pooled odds/risk ratio 1.09 (95% confidence interval (CI) 1.03-1.15, I2=0%, 8 sub-studies; pooled hazard ratio 0.99 (95% CI 0.94-1.03, I2=35%, 9 sub-studies)). There are credible study data showing an increased relative risk with long-term use of CCBs, but the results of our meta-analysis and of meta-regression of log relative risk against minimum follow-up time are mixed. The current summative evidence does not support a clear association between taking CCBs and developing breast cancer. However, uncertainty remains, especially for long-term use and any association might not be uniform between different populations and/or breast cancer sub-types. We thus recommend further NRS in settings where CCB use is highly prevalent and population-based cancer, prescription and health-registries exist, to resolve this continuing uncertainty. PROSPERO, CRD42015026712.

KEYWORDS:

Amlodipine; Breast neoplasms; Calcium channel blockers; Dihydropyridines; Nifedipine; Verapamil

J Hypertens. 2015 Jun;33 Suppl 1:e124. doi: 10.1097/01.hjh.0000467686.77672.9e.

9C.05: META-ANALYSIS OF AMLODIPINE VERSUS ANGIOTENSIN RECEPTOR BLOCKERS ON BLOOD PRESSURE, SOME ECHOCARDIOGRAPHIC INDICATORS OF LEFT VENTRICULAR DAMAGE AND ADVERSE EVENTS IN PATIENTS WITH HYPERTENSION.

Xu H1, Wang Q, Yang M, Yu J.

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Abstract

OBJECTIVE:

The aim of this meta-analysis is to evaluate two echocardiographic indicators of left ventricular damage, amlodipine and angiotensin receptor blockers, and associated adverse events in patients with hypertension.

DESIGN AND METHOD:

A meta-analysis was conducted using PubMed, Cochrane Library and EMBASE to investigate and analyze the effects of amlodipine versus angiotensin receptor blockers for blood pressure, associated adverse events, and cardiac structure and function. Data was collected from database inception through October 2014.

RESULTS:

Nineteen randomized-control clinical trials were included in the meta-analysis. 4,248 subjects from the collected trials were given either amlodipine or angiotensin receptor blockers (ARBs) for management of hypertension. The results showed no significant differences between amlodipine and ARBs in ability to lower blood pressure. However, when measuring the decrease of left ventricular mass index (LVMI), amlodipine was shown to be inferior to both irbesartan (weighted mean difference= -15.1, 95% confidence intervals: -22.97 to -7.23, P < 0.001) and valsartan (weighted mean difference = -17.77, 95% confidence intervals:-31.28 to -4.27, P = 0.01). Amlodipine showed decreased performance compared to losartan in early diastolic mitral annular velocity (E[Combining Acute Accent]), the ratio of left ventricular early diastolic filling velocity to early diastolic mitral annular velocity (E/E[Combining Acute Accent]) and an increased number of adverse events[(E[Combining Acute Accent]:weighted mean difference= -0.09, 95%CI -1.76 to -0.04, P = 0.04), (E/E[Combining Acute Accent]:weighted mean difference = 3.00,95%CI 1.22 to 4.78, P = 0.001), (adverse events: OR = 3.78, 95%CI 1.29 to 11.06, P = 0.02)]. Additionally, amlodipine led to more adverse events when compared with valsartan (OR = 1.80, 95% confidence intervals:1.17 to 2.78, P = 0.008).

CONCLUSIONS:

Amlodipine is comparable to several ARBs in its potential to lower blood pressure. However, it is less effective in prevention of left ventricular hypertrophy and exhibits a higher incidence of clinically adverse events, such as dizziness, fatigue, headache, peripheral edema, and erectile dysfunction.

PMID:

26102722

DOI:

10.1097/01.hjh.0000467686.77672.9e