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Diuretics Versus Beta Blockers As The First Step In Drug Therapy

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Question:

Discuss about the Diuretics Versus Beta Blockers as the First Step in Drug Therapy.
 
 

Answer:

Introduction

Arterial hypertension affects millions of people worldwide. The condition is associated with high incidence of cardiovascular outcomes. Therefore choosing the right kind of medication warrants health and economic favour. The two most widely prescribed drugs which are used as first line drugs are diuretics and beta-blockers which functions.

Beta blockers are drugs that targets beta-adrenergic receptors and acts by blocking the action of adrenaline. Such drugs are used commonly as a first line drug to treat hypertension, arrhythmia, angina, migraine as well as anxiety. By blocking the action of adrenaline the heart beat is reduced thereby reducing the pressure exerted on the arterial walls and improving blood flow. The activity of beta-blockers depends upon the chemistry of the drug. Some of the beta blockers are Acebutolol, Bisoprolol, Nevivolol, Propanolol, Metaprolol etc. The prescription of beta-blockers, however, is not considered till other medications such as diuretics, are considered ineffective.

Although there are advantages of using beta blockers, there are associated side effects of the drugs that need to be accounted. Some of the side-effects are tiredness, weight gain, insomnia, depression and to some extent shortness of breath . The drug is not prescribed for patients with asthma as it might trigger adverse reaction. Moreover, this class of drug is known to promote imbalance in lipid profile temporarily.

 


Diuretics, unlike beta-blockers, do not block androgen but rather helps in expelling excess salts and water from the body. Release of sodium into the urine leads to increased dispense of water thereby reducing the fluid volume in the blood vessel and finally leading to decreased pressure on the arterial walls. Three types of diuretics are usually prescribed by physicians which are thiazide, loop diuretics and potassium-sparing diuretics .

The present article presents the advantages and disadvantages of using these two classes of drugs for management of hypertension based on research articles available in the public domain.

Sources and selection criteria

In order to select suitable scientific studies on the use of beta-blockers and diuretics as first line drugs a thorough literature search was conducted on NCBI PubMed, Google Scholar and pharmaceutical-journal.com. Search terms “beta-blockers and diuretics”, “hypertension first line drugs”, “beta-blockers first line drugs” and “diuretics first line drugs” were used to arrive at lists of articles before choosing few important and relevant ones. The search was limited to publications between 2000 and 2017. Major decisive factors for selecting research studies were involvement of a large population, randomized control trials, meta-analysis and clinical trials. Weightage were given if follow up was considered in the study subjects. Impact factors and reputation of the journal in scientific community was also considered for the selection of research articles. However, research publications which are conducted by pharma companies or sponsored by pharma companies were not selected as there are high possibility of getting a biased report.

Methodology and results

The search for clinical trials, meta analysis and RCTs resulted in many relevant research reports. However, 3  reports on meta analysis were selected for the study. The three selected literatures were based on comparison of diuretics and beta blockers, meta analysis on beta blockers alone or meta analysis on diuretics alone.

According to Cochrane review of beta-blocker a clear indication of insignificance of the class of drugs on its ability to manage hypertension and a higher efficacy of calcium channel blocker is indicated (5). This is seen with a similar observation by Lindholm et al.,which accounted for 105951 subjects it was observed that beta blockers increases the risk of stroke by 16% as compared to other drugs. It also increases the mortality rate by 3%. Out of the beta blockers, medication with atenolol has the highest risk of stroke(6).

 


Many clinical trials endorses the use of diuretics, thiazide in particular, for management of hypertension. In MRC trial with a large population it was observed that diuretics with or without beta blockers has the potential to reduce incidence of stroke as compared to the placebo control group. In a landmark clinical trial consisting of 33357 subjects above 55 years of age it was observed that there is no significant difference in the non-fatal myocardial infarction in groups with different medications but showed a reduced risk in long term use (7). The most important clinical trial on diuretics is perhaps the ALLHAT trial in which the choice of diuretics is kept as primary compared to other classes of drugs (8). This may be due to the efficacy and cost factor that plays an important role.

Thiazides are used as monotherapy (9) however, it is seen to be much more effective in combination with other drugs (10). The efficacy also depends upon various factors such as age, race as well as renal health. It is recommended that instead of increasing the dose of thiazide for control of blood sugar a second drug should be coupled to obtain most efficient control (11). This is because thiazide is also seen to be linked to renal abnormalities in the long term. 

Diuretics on the other hand has significantly reduced the number of stroke and heart attacks when used a first line drug for management of hypertension(12). However, loop diuretics are not seen to reduce blood pressure significantly (13). Therefore, efficacy of managing hypertension largely depends upon the type of diuretic

Advantages and disadvantages

In a meta-analysis by Lindholm et al., it was observed that beta-blockers used as primary drug to manage hypertension is associated with higher risk of stroke when compared with other antihypertensive drugs (6). The study analysed data obtained from randomized control trials of a collection of beta-blockers. The study further adds that the efficacy of beta blockers as antihypertensive drugs is suboptimum and does not reduce risk of mortality or myocardial infarction.(14, 15)

Both the type of drugs are not tolerated and both functions worse than other antihypertensive drugs. It was observed that patients on beta blocker tends to withdraw from the course in twice the numbers compared to diuretic patients (16). On the other hand, thiazide medication is seen to cause nephrotoxicity in the long run and even leading to renal carcinoma. Therefore, the question remains as to which drug should be preferred as first line drugs for hypertension management.

 

Discussion

It is estimated that more than ¼ of the adult population of the world are hypertensive and finding an effective drug with minimum unwanted side-effect will be of utmost importance. Beta-blockers and Diuretics that are prescribed as first line drugs to control hypertension have shown efficacy in management of the condition. Many of the patients with high blood pressure depends upon either diuretics, beta blockers (17), ACE inhibitors, calcium antagonists or angiotensin receptor blockers. The unwanted outcome of beta blockers is evident from the LIFE trial which states that approximately 1,25,000 strokes are preventable in a period of 5.5 years in the European Union just by replacing the drug with angiotensin receptor blockers. In a similar study of ASCOT-BPLA replacement of beta blockers with calcium antagonists resulted in reduction of stroke by 23% (18). A comparison between placebo and beta blocker treated patients showed that there is no statistical reduction in blood pressure.

With increase in the prevalence of hypertension in both developing and developed nations it is mandatory to set a specific guideline for management of the condition. As for instance despite the fact that beta blockers are less effective and promotes higher risk of strokes and cardiovascular abnormalities the use of the drug has remained high for the past 10 years in Germany with a 54% of the patients taking the drug. Comparatively, diuretics is the second most common drug with 48% of the patients using it (19).

Although there has been an increase in number of hypertensive patients, the average mean of systolic and diastolic blood pressure has dropped by approximately 5 mmHg. This indicates efficacy in managing the disease by medications.

The present research is further limited because of the availability of meta-analysis data that combines studies from latter part of the 20th century. A significant literature source is available from this period which is easy to be missed unless curated properly.

 

Conclusion

With reference to the analysed research studies on beta blockers and diuretics it is observed that diuretics remains a first preference for management of hypertension. This is because the use of the class of drug is seen to be far more efficient than the beta blockers as it reduces chances of stroke and heart attacks much efficiently than beta blocker (20). However, the choice of the type of diuretics also matters as it was observed that thiazide diuretics are far more efficient than loop diuretics.

A significant number of studies were conducted around the 1970s and 1980s and did not qualify our study criteria and had to be excluded from our analysis. However, the studies had significant information as a large population was analysed and is representative.

It would have been more conclusive had there been meta-analysis based exclusively on more recent publications. The result of the study is also justified by the number of supportive evidence resulting in similar conclusions  as those studies in the 1980s with more recent observations. It would have been more interesting had there been few more publications that studies the efficacy of different types of diuretics although we know that diuretics are a better choice over beta blockers.

In conclusion it should be noted that Diuretics should be considered as first line drugs as it is the most economical and most effective and beta-blockers should not be considered as first line medication. It should also be a task to identify uncomplicated hypertension where no such medications are required.

 

References

 Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: 4. Effects of various classes of antihypertensive drugs–overview and meta-analyses. Journal of hypertension. 2015;33(2):195-211.

Bangalore S, Messerli FH, Kostis JB, Pepine CJ. Cardiovascular protection using beta-blockers: a critical review of the evidence. Journal of the American College of Cardiology. 2007;50(7):563-72.

Ko DT, Hebert PR, Coffey CS, Sedrakyan A, Curtis JP, Krumholz HM. β-blocker therapy and symptoms of depression, fatigue, and sexual dysfunction. Jama. 2002;288(3):351-7.

Ernst ME, Moser M. Use of diuretics in patients with hypertension. New England Journal of Medicine. 2009;361(22):2153-64.

Wiysonge CSU, Bradley HA, Mayosi BM, Maroney RT, Mbewu A, Opie L, et al. Beta?blockers for hypertension. The Cochrane Library. 2007.

Lindholm LH, Carlberg B, Samuelsson O. Should β blockers remain first choice in the treatment of primary hypertension? A meta-analysis. The Lancet. 2005;366(9496):1545-53.

Shah S, Anjum S, Littler W. Use of diuretics in cardiovascular disease:(2) hypertension. Postgraduate medical journal. 2004;80(943):271-6.

Appel LJ. The verdict from ALLHAT—thiazide diuretics are the preferred initial therapy for hypertension. Jama. 2002;288(23):3039-42.

Rovin B, Hebert L. Thiazide diuretic monotherapy for hypertension: diuretic's dark side just got darker. Kidney international. 2007;72(12):1423-6.

Harman J, Walker ER, Charbonneau V, Akylbekova EL, Nelson C, Wyatt SB. Treatment of hypertension among african americans: The jackson heart study. The Journal of Clinical Hypertension. 2013;15(6):367-74.

Wing LM, Reid CM, Ryan P, Beilin LJ, Brown MA, Jennings GL, et al. A comparison of outcomes with angiotensin-converting–enzyme inhibitors and diuretics for hypertension in the elderly. New England Journal of Medicine. 2003;348(7):583-92.

Lawes CM, Bennett DA, Feigin VL, Rodgers A. Blood pressure and stroke. Stroke. 2004;35(3):776-85.

Brater D. Clinical pharmacology of loop diuretics. Drugs. 1991;41(3):14-22.

Samuelsson O, Hedner T, Berglund G, Persson B, Andersson O, Wilhelmsen L. Diabetes mellitus in treated hypertension: incidence, predictive factors and the impact of non-selective beta-blockers and thiazide diuretics during 15 years treatment of middle-aged hypertensive men in the Primary Prevention Trial Goteborg, Sweden. Journal of human hypertension. 1994;8(4):257-63.

Chen J, Radford MJ, Wang Y, Marciniak TA, Krumholz HM. Effectiveness of beta-blocker therapy after acute myocardial infarction in elderly patients with chronic obstructive pulmonary disease or asthma. Journal of the American College of Cardiology. 2001;37(7):1950-6.

Choudhury D, Ahmed Z. Drug-induced nephrotoxicity. Medical Clinics of North America. 1997;81(3):705-17.

Wilhelmsen L, Berglund G, Elmfeldt D, Fitzsimons T, Holzgreve H, Hosie J, et al. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. Journal of hypertension. 1987;5(5):561-72.

Greenberg G. MRC TRIAL OF TREATMENT OF MILD HYPERTENSION-PRINCIPAL RESULTS. British Medical Journal. 1985;291(6488):97-104.

Sarganas G, Knopf H, Grams D, Neuhauser HK. Trends in antihypertensive medication use and blood pressure control among adults with hypertension in Germany. American journal of hypertension. 2015:hpv067.

Lievre M, Gueyffier F, Ekbom T, Fagard R. Efficacy of diuretics and beta-blockers in diabetic hypertensive patients: Result from a meta-analysis. Diabetes Care. 2000;23:B65.

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