Matchar DB, McCrory DC, Orlando LA, et al. Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Antagonists (ARBs) for Treating Essential Hypertension. Comparative Effectiveness Review No. 10. (Prepared by Duke Evidence-based Practice Center under Contract No. 290-02-0025.) Rockville, MD: Agency for Healthcare Research and Quality. November 2007. Accessed from http://effectivehealthcare.ahrq.gov/repFiles/ACEI_ARBFullReport.pdf on 12/11/2007
Why is this of concern?
Angiotensin-converting enzyme inhibitors (ACEIs) are a preferred alternative to Angiotensin II receptor antagonists (ARBs) for treatment of hypertension, unless they are not tolerated. However, in the first quarter of 2007/2008 the ratio of ARBs represented about 30% of the total number of ACEIs and ARBs prescribed. ARBs are considerably more expensive and than generic ACEs – indeed the costs of ARB prescribing was £63 million, compared to £47 million for ACEis. It is well known that ARBs produce less cough in a small proportion of patients, but this does not seem to explain the apparent high use of ARBs.
Is there something we have missed? The four boxes of safety, effectiveness, cost and patient factors are often used to compare therapeutic choices (see NPC podcast on ‘Barbers boxes’). Could it be that ARBs really are more effective than ACEIs, even for specific subgroups of patients. Or perhaps, other than producing less cough, are they better tolerated or any safer than ACEIs?
What does the new study tell us?
These questions were asked in a publicly funded review carried out for the Agency for Healthcare Research and Quality in the USA. It was wide ranging and comprehensive, considering the results from 69 comparative clinical trials for the treatment of hypertension. It came to the conclusion that the answer to each of these questions was NO.
The review confirmed a decreased risk of cough with ARBs compared with ACEIs. However, evidence from randomised controlled trials (RCTS) was that the absolute difference in rates between ACEIs and ARBS was only 6.7%, giving a number needed to treat (NNT) of 15 – for every 15 people treated with an ARB rather than an ACEI, one fewer would have cough. For cohort studies, the difference was even lower (1.1%) — an NNT of 87. This latter figure was felt by the investigators to be more clinically relevant, presumably as patients in cohort studies are more likely to resemble those seen in clinical practice.
Despite significant issues with the heterogeneity of the studies, the absolute difference in the rates of people who withdrew from studies due to adverse effects was estimated to be 3.7% less in those taking ARBs rather than ACEIs (NNT = 27).
ACEIs and ARBs were found to have similar long-term effects on blood pressure, and there were insufficient numbers of deaths or major cardiovascular events in the included studies, to discern any differential effect of ACEIs vs. ARBs for these critical outcomes. Only 9 of the studies compared these drugs for longer than a year. No differences were found in measures of general quality of life. There was also no evidence for differences in comparative effectiveness, adverse events, or tolerability for any particular patient subgroup.
With the exception of rates of cough, the hypothesis that ACEIs and ARBs have clinically meaningful differences in long-term outcomes in individuals with essential hypertension is not strongly supported by the available evidence.
Until there is good quality evidence to the contrary, where an ACEI or ARB is indicated for hypertension, prescribe ACEIs ahead of ARBs, as per NICE guidance. A switch to an ARB can always be made, should an intolerable cough develop. However, this is only likely to occur in a very small proportion of cases.
- National Institute for Health and Clinical Excellence. NICE Clinical guideline 34. Hypertension: management of hypertension in adults in primary care (partial update of NICE clinical guideline 18). June 2006. Accessed from www.nice.org.uk/CG034 on 12/11/2007
- Matchar DB, McCrory DC, Orlando LA, et al. Comparative Effectiveness of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin II Receptor Antagonists (ARBs) for Treating Essential Hypertension. Comparative Effectiveness Review No. 10. (Prepared by Duke Evidence-based Practice Center under Contract No. 290-02-0025.) Rockville, MD: Agency for Healthcare Research and Quality. November 2007. Accessed from http://effectivehealthcare.ahrq.gov/repFiles/ACEI_ARBFullReport.pdf on 12/11/2007