Angiotensin converting enzyme inhibitors and angiotensin receptor blockers in hypertension
BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d1673 (Published 07 April 2011) Cite this as: BMJ 2011;342:d1673
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We agree with Ritter(1) that there is no convincing evidence for
routine use of dual renin-angiotensin-aldosterone system (RAAS) blockade
in hypertension, but there may be a case for its cautious use in selected
patients with diabetic nephropathy. Hard endpoints such as mortality, are
the Holy Grail of intervention studies, but are not always available; in
diabetic kidney disease, proteinuria is a strong predictor of disease
progression(2) and we would advocate dual RAAS blockade in selected
patients with progressive proteinuria despite optimal blood pressure
control to slow progression. The ONTARGET(3) trial had no primary renal
end-points, only 38% of the participants had diabetes and much fewer had
proteinuria. In VALIANT(4), only 25% of participants had diabetes and no
data on proteinuria were available. Thus, neither of these trials
adequately assessed the impact of dual RAAS blockade in diabetic
proteinuria. By contrast, small studies in patients with diabetic
nephropathy(5)(6)(7) have shown reduced proteinuria progression - when
endpoint data are unavailable do we withhold treatment or make judgements
based on established surrogates?
References:
1.Ritter JM. Angiotensin converting enzyme inhibitors and angiotensin
receptor blockers in hypertension. BMJ. 2011 April 7, 2011;342.
2.de Zeeuw D, Remuzzi G, Parving H-H, Keane WF, Zhang Z, Shahinfar S,
et al. Proteinuria, a target for renoprotection in patients with type 2
diabetic nephropathy: Lessons from RENAAL. Kidney Int. 2004;65(6):2309-20.
3.Ontarget. Telmisartan, Ramipril, or Both in Patients at High Risk
for Vascular Events. New England Journal of Medicine. 2008;358(15):1547-
59.
4.Pfeffer MA, McMurray JJV, Velazquez EJ, Rouleau J-L, K?ber L,
Maggioni AP, et al. Valsartan, Captopril, or Both in Myocardial Infarction
Complicated by Heart Failure, Left Ventricular Dysfunction, or Both. New
England Journal of Medicine. 2003;349(20):1893-906.
5.Rossing K, Jacobsen P, Pietraszek L, Parving H-H. Renoprotective
Effects of Adding Angiotensin II Receptor Blocker to Maximal Recommended
Doses of ACE Inhibitor in Diabetic Nephropathy. Diabetes Care. 2003 August
1, 2003;26(8):2268-74.
6.Jacobsen P, Andersen S, Rossing K, Jensen BR, Parving H-H. Dual
blockade of the renin-angiotensin system versus maximal recommended dose
of ACE inhibition in diabetic nephropathy. Kidney Int. 2003;63(5):1874-80.
7.Parving H-H, Persson F, Lewis JB, Lewis EJ, Hollenberg NK.
Aliskiren Combined with Losartan in Type 2 Diabetes and Nephropathy. New
England Journal of Medicine. 2008;358(23):2433-46.
Competing interests: No competing interests
The management of hypertension remains a core public health function
of primary care and as such has to be systematised so that the bulk of it
can be managed by nurses. It is a common problem, and the QOF requirement
to achieve the target blood pressure is a challenge.
This involves the production of rational protocols for titrating
management against target blood poressure, taking into account individual
patient characteristics.
This article cites a rare patient, as he is a young white man. I have
tried to modify his risk factors on Qrisk 2 and the joint societies
programmes and cannot get up to the stated 26%.
What would be more helpful to GPs and practice teams is the typical
example of a 78 year old woman with a confirmed eGFR of 58, already on a
proton pump inhibitor (watch for hyponatraemia), a past history of wrist
fracture (watch for falls secondary to postural hyoptension), who had a
DVT after delivering one of her children (and so a tendency to get ankle
swelling on that side), who relies on the unreliable bus service for
attendance at the surgery. Putting her on an ACE inhibitor can be complex,
expensive, time consuming and potentially risky. Citing falling drug cost
is only one part of the story.
http://qrisk.org/index.php
http://www.bhsoc.org/cardiovascular_risk_charts_and_calculators.stm
Competing interests: No competing interests
When initiating an ACE inhibitor or ARB, Ritter encourages physicians
to ask "Does the patient's current treatment include a regular NSAID,
potassium sparing diuretics, or potassium supplements?"(1) Lithium should
undoubtedly be added to this list.
Lithium is recommended by NICE as a first line treatment for
prophylaxis in bipolar affective disorder,(2) but has a narrow therapeutic
index, and toxicity can be fatal. Lithium is excreted primarily by the
kidney, and any salt depletion or reduction in GFR will cause serum
lithium concentrations to rise. The problem can become self-perpetuating:
as the vomiting and diarrhoea of toxicity cause further dehydration, the
lithium level is pushed yet higher.
A large nested case-control study in 2004 asked whether lithium
toxicity in older adults is associated with ACE inhibitors.(3) The results
were striking, with a new prescription of ACE inhibitors causing a
substantial increase in the risk of admission to hospital with lithium
toxicity (Relative Risk =7.6, 95% CI=2.6-22.0). It seems reasonable to
assume that ARBs carry the same risk.
Initiation of ACE inhibitors or ARBs in people already on lithium
should therefore be accompanied by scrupulous monitoring of lithium
levels, preferably in consultation with secondary care services. Patients
should also be alerted to the risks.
(1) Ritter, J.M., Angiotensin converting enzyme inhibitors and
angiotensin receptor blockers in hypertension. BMJ, 2011. 342: p. 868-73.
(2) National Institute for Health and Clinical Excellence, The
management of bipolar disorder in adults, children and adolescents, in
primary and secondary care. (Clinical Guideline 38.) 2006.
http://guidance.nice.org.uk/CG38
(3) Juurlink, D.N., et al., Drug-induced lithium toxicity in the
elderly: a population-based study. J Am Geriatr Soc, 2004. 52(5): p. 794-
8.
Competing interests: No competing interests
The risk to renal function of ACEIs/ARBs (which also apply to the
direct renin inhibitors such as aliskiren) during concurrent illness with
salt and water depletion, is emphasised in Ritter's article (1). Acute
physicians and nephrologists are frequently involved in cases of acute
kidney injury where renin-angiotensin inhibition is a contributory factor.
The preferential efferent over afferent arteriolar vasodilatation in the
glomerulus is one reason why these drugs cause a predictable reduction in
GFR in normal individuals. The added insults of salt and water depletion,
often with the vasodilatation of sepsis, causes a reduction in renal blood
flow that can result in acute kidney injury, particularly as the normal
physiological response to these insults requires secretion of renin and,
eventually, the action of angiotensin II.
In addition to avoiding starting these drugs during such illnesses
(as stated in the article) I think it is also important to instruct
patients, verbally and in writing, that the drugs must be stopped
temporarily if such an illness is acquired once they are established on
the drug. Of course the same advice should be given for diuretics and
NSAIDs. I suggest that the practice of informing patients in this way is
adopted by all prescribers of these classes of drugs.
(1) Angiotensin converting enzyme inhibitors and angiotensin receptor
blockers in hypertension. J M Ritter. BMJ 2011
342:d1673doi:10.1136/bmj.d1673
Competing interests: No competing interests
Treatment of secondary hypertension
We read with interest the informative and comprehensive article
Angiotensin converting enzyme inhibitors and angiotensin receptor blockers
in hypertension.1 We are aware that the authors main focus was "on
starting antihypertensive treatment with an Angiotensin converting enzyme
inhibitor (ACE inhibitor) or an angiotensin receptor blocker (ARB)" 1
however we feel that the treatment of secondary hypertension should also
be addressed.
In patients developing hypertension secondary to coarctation of the
aorta, ACE inhibitors, ARBs and diuretics were not usually effective in my
experience. In this situation, before surgically correcting the defect,
Beta blockers are helpful in controlling central aortic blood pressure and
"preventing aneurysm formation."2
The other omission is that the treatment of hypertension in pregnancy
has not been fully discussed. 5-10% of pregnant women develop pregnancy-
induced hypertension.3 Pregnancy-induced hypertension comprises of
gestational hypertension and pre-eclampsia. Both gestational hypertension
and pre-eclampsia develop after 20 weeks but the difference between the
two is that pre-eclampsia is associated with significant proteinuria,
whereas gestational hypertension is not.4 The author rightfully mentions
that ACE inhibitors and ARBs are contraindicated in pregnancy,1 but there
is no mention of the other drugs that can be given in this situation.
Women who develop gestational hypertension or pre eclampsia with a blood
pressure of 150/100 - 159/109 mmHg or gestational hypertension with a BP
greater than or equal to 160/110 mmHg should start antenatal treatment
with labetalol.4 However for non-responders or if side effects are
unacceptable, the alternatives are nifedipine and methyldopa.4 In regards
to the use of diuretics to prevent the onset of pre-eclampsia, there is
insufficient evidence to justify this approach and diuretics may do more
harm than good.5
Singh37@hotmail.com
References
1. Ritter JM. Angiotensin converting enzyme inhibitors and angiotensin
receptor blockers in hypertension. BMJ 2011;342: 868-873.
2. De Giovanni JV, Lip GYH, Osman K, Mohan M, Islim IF, Gupta J,
Watson RDS, Singh SP. Percutaneous balloon dilatation of aortic
coarctation in adults. Am. J. Cardiol.1996;77(5):435-439
3. Magee LA, Ornstein MP, von Dadelszen P. Management of hypertension
in pregnancy. BMJ 1999;318(7194): 1332-1336
4. National Institute for Health and Clinical Excellence.
Hypertension in pregnancy. The management of hypertensive disorders during
pregnancy- August 2010. Available from:
http://www.nice.org.uk/nicemedia/live/13098/50416/50416.pdf (Accessed 18
May 2011)
5. Churchill D, Beevers GDG, Meher S, Rhodes C. Diuretics for
preventing pre-eclampsia. Cochrane Database of Systematic Reviews 2007,
Issue 1. Art. No.: CD004451. DOI: 10.1002/14651858.CD004451.pub2 (Accessed
19 May 2011)
Competing interests: No competing interests