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Choosing Antihypertensive Drugs for Essential Hypertension

Essential hypertension requires appropriate treatment options to prevent complications such as acute myocardial infarction, cerebrovascular disease, kidney failure, and death.

Choosing Antihypertensive Drugs for Essential Hypertension
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Choosing first-line drugs in treating essential hypertension is an issue that is often discussed. In initiating treatment in the general population, JNC-8 recommends a diuretic group (thiazide-type), CCB, ACEI, or ARB. These four classes have a good effect on reducing mortality and complications such as cardiovascular, cerebrovascular, and kidney disorders, except heart failure. In the case of complications of heart failure, the recommended initial treatment options are diuretics, ACEI, and CCB.


The British National Institute of Clinical Excellence (NICE) guidelines recommend:
  • In hypertensive patients aged 55 and over, or black patients of any age, initial therapy should be either a calcium channel blocker or a thiazide-type diuretic.
  • In hypertensive patients younger than 55, the first choice initial therapy should be an ACEI(or an ARB if an ACEI is not tolerated).
  • If initial therapy was with a CCB or thiazide-type diuretic and a second drug is required, add an ACE inhibitor (or ARB if the ACEI is not tolerated). 
  • If initial therapy was with an ACEI, then add a CCB or a thiazide-type diuretic.
  • If the treatment with three drugs combination is required, the combination of ACEI (or an ARB), CCB, and thiazide-type diuretic should be used. 

The guidelines recommend that drug therapy is offered to patients with: 
  • Persistent high blood pressure of 160/100mmHg or more
  • Persistent BP above 140/90mmHg and raised cardiovascular risk (10-year risk of cardiovascular disease of at least 20%, existing CVD or target organ damage) 
  • Aim to reduce BP to < 140/90mmHg, adding more drugs as needed until further treatment is inappropriate or declined. 
  • Patients over 80 years should be offered the same treatment as those over 55 but taking account of comorbidity and other drugs they may be taking. Patients with isolated systolic hypertension (systolic BP > 160mmHg) should be given the same treatment as patients with both raised systolic and diastolic blood pressure. 

Evidence-based studies do not lead to one drug in cases of stage1 hypertension given monotherapy or combination therapy. Drug selection depends on effectiveness, side effects, and cost. Comorbid and other risk factors must also be considered to avoid complications.

In stage 2 hypertension, hypertensive drugs combination may be needed. Avoid the combination of non-dihydropyridine CCB with beta-blockers because it will increase the risk of becoming an AV block.

Thiazide-type diuretics reduce systolic pressure more than diastolic, thereby reducing pulse pressure by 4-6 mmHg. When compared with other classes of drugs (ACEI, ARB, CCB, and beta-blockers), the decrease in pulse pressure (the difference between systole and diastolic blood pressure) is lower. Thiazides are superior in reducing mortality and the incidence of cerebrovascular disease compared with CCB, ACEI, and beta-blockers.

ACEI and ARB have statistically insignificant differences in effects on cardiovascular disease (RR 1.07, 95% CI 0.96 - 1.19) and total mortality (RR: 0.98, 95% CI 0.88 - 1.10).
Side effects are more common in patients with ACE inhibitors so that more dropouts occur due to side effects. Compared with ARB, the most common side effect complained of in the ACE inhibitor group is the dry cough.

A meta-analysis study comparing CCB with ARB did not have different mortality effects due to all significant causes (8.5% CCB vs. 8.6% ARB; RR, 0.99; 95% CI 0.91 - 1.07).

CCB is better in reducing cerebrovascular and cardiovascular disease (acute myocardial infarction) than ARB. In terms of complications of heart failure, there was no significant difference even though more inclined ARB gave better results than CCB (5% CCB vs. 3.9% ARB; RR 1.4, 95% CI 0.99 - 1.98). 

Anti-Hypertension Medication for Essential Hypertension with Comorbid

Beta-blockers are the first choice in recommendation if there are comorbidities coronary heart disease (CHD) such as stable angina pectoris, post-acute myocardial infarction, congestive heart failure, postoperative CHD, and obstructive hypertrophic cardiomyopathy.

Beta-blockers are not recommended for essential hypertension without CHD. They do not reduce the risk of CHD and can even increase cardiovascular events in essential hypertension cases without CHD.

ACE inhibitors have also been shown to reduce cardiovascular events, but it is not beneficial in CHD cases with normal left ventricular function.

The combination of Beta-blockers with ACEI or ARB (with or without aldosterone antagonists) is recommended for essential hypertension with comorbid congestive heart failure.

ACEI and ARB have equivalent effectiveness. Aldosterone antagonists should be given if hypertension drugs are still needed in the ejection fraction of less than 35%, have received ACEI or ARB and beta-blockers.

The American Diabetic Association (ADA) recommends ACEI or ARB classes for essential hypertension with comorbid diabetic nephropathy. Furthermore, ADA recommends using ACEI in type 1 diabetes mellitus and ARB in type 2 diabetes mellitus.

Recommendations from JNC-8 (2014), European Society of Hypertension / European Society of Cardiology 2013, and Kidney Disease: Improving Global Outcome recommend the use of ACEI or ARB in patients with comorbid chronic kidney failure.

The first choice of antihypertensive medication with atrial fibrillation comorbid is beta-blockers. The second option is the non-dihydropyridine CCB. ACEI and ARB do not prevent the occurrence or recurrence of Atrial Fibrillation.

Conclusion
Antihypertensive drug choices that are recommended for essential hypertension are thiazide-types diuretic, ACEI, ARB, CCB. Combination therapy can be considered to achieve blood pressure targets. Thiazides are superior to other groups in hypertension without comorbidities. Considerations for the choice of antihypertensive drugs are based on effectiveness, side effects, and costs.

In comorbid hypertension, in addition to reducing blood pressure, it is also necessary to consider the effect of the drug on comorbid diseases. Comorbid-based treatment recommendations according to evidence-based studies:

  • CHD: beta-blocker
  • Congestive heart failure: ACEI or ARB with or without aldosterone antagonists
  • Diabetes mellitus: ACEI or ARB
  • Chronic kidney failure: ACEI or ARB
  • Atrial fibrillation: beta-blocker or non-dihydropyridine CCB

References

1. James PA, Oparil S, Carter B, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 2014 Evidence-based guideline for the management of high blood pressure in adults. Report from the panel members appointed to the eighth joint national committee (JNC 8). JAMA, Dec 2013
2. Gupta R, Guptha S. Strategies for initial management of hypertension. Indian J Med Res, 2010; 132(5):531-542
3. NICE Guideline. Hypertension in adults: diagnosis and management. Updated: Nov 2016. Cited: 27-Oct 2017. Available from: https://www.nice.org.uk/guidance/cg127
4. BMJ Best Practice. Essential Hypertension. Cited: 27-Oct 2017. Available from: http://bestpractice.bmj.com/best-practice/monograph/26/treatment/step-by-step.html
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7. Li EC, Heran BS, Wright JM. Angiotensin-converting enzyme (ACE) inhibitors versus angiotensin receptor blockers for primary hypertension. Cochrane Database Syst Rev. 2014;(8): CD009096
8. Wu L, Deng SB, She QS. Calcium channel blocker compared with angiotensin receptor blocker for patients with hypertension: a meta-analysis of randomized controlled trials. J Clin Hypertens, 2014;16:838-845
9. American Diabetes Association.Standards of medical care in diabetes 2013. DiabetesCare, 2013;36(suppl1):S11-S66
10. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J, 2013;34(28):21592219
11. Kidney Disease; Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int Suppl. 2012;2(5):337-414

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