Re: Antihypertensives in octogenarians
A recent summary of the extension to active treatment in the HYVET population has been published (Beckett 2012) and was heralded as further evidence of the benefits of treating hypertension in the elderly (Mancia 2012). We are looking at the benefit of starting treatment in the group previously left untreated (the placebo group). We do this by looking at the excess events in the untreated group, and measuring how this excess is reduced by starting treatment - or at least this is the reasonable expectation.
The results are surprising because, rather than a reduction of excess events, there is an increase. For all cause mortality, the excess events in the placebo group was 12.4, but on starting this group on treatment, the excess events climbed to 20.2; for noncardiovascular deaths, it climbed from 5.5 (placebo) to 7.6 (on starting treatment); for cardiovascular deaths it went from 6.8 to 9.4. The conclusion is that starting treatment caused an increase in all cause mortality of 7.8 per 1,000 (NNH 128 over 1 year, the harm being death). This is certainly not to be taken as further evidence of benefit. For comparison, we have an increased mortality with a NNH1y 128 and a possible benefit on mortality with a NNT1y of 81. While it is true that the harm is a one-off event (hence comparing figures at 1 year), it is nonetheless the case that we are accepting the death of 10 patients for each 16 to 26 patients we save in the first year, as a sort of ‘collateral damage’. As the life expectancy may not exceed the 2 years in this population (Szucs 2010), the ability to offset this initial harm may be very limited.
It is quite reasonable to expect a number of iatrogenic adverse events to occur rather early on starting new medication (some being possibly fatal). It is likely that we are looking at this effect, probably related to hypotensive episodes as well as side effects and toxicity of the drugs used. For the ongoing treatment group, those early adverse events will have occurred at the start of HYVET and were offset by benefits. When we compare a group where medication related adverse events have been excluded (as the fatalities and dropping out will have occurred beforehand) with a group starting treatment afresh, we can appreciate the significance of those adverse events. There are no treatments without risk, and a degree of such ‘collateral damage’ has to be accepted if we are to treat anyone at all. What is at stake is the clarification of the significance of this effect and the acceptability of the harm/benefit ratio. While at population level this can be glossed out by offsetting harm with larger benefits, we should not forget that those who die have no personal benefit from the survival of others.
Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A, Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt C. Treatment of Hypertension in Patients 80 Yearsof Age or Older. New England Journal of Medicine 2008;358(18):1887–1898.
Beckett NS, Peters R, Tuomilehto J, Swift C, Sever P, Potter J, McCormack T, Forette F, Gil-Extremera B, Dumitrascu D, Staessen J A, Thijs L, Fletcher L, Bulpitt C. Immediate and late benefits of treating very elderly people with hypertension: results from active treatment extension to Hypertension in the Very Elderly randomised controlled trial. BMJ 2012;344:d7541 (Published 04 January 2012)
Bejan-Angoulvant T, Saadatian-Elahi M, Wright JM, Schron EB, Lindholm LH, Fagard R, Staessen JA, Gueyffier F. Treatment of hypertension in patients 80 years and older: The lower the better? A meta-analysis of randomized controlled trials. Journal of Hypertension. 2010; 28(7):1366-1372
Mancia G. Treatment in Octogenerians: treatment has lasting benefits. BMJ 2011;343:d7293
Musini VM, Tejani AM, Bassett K, Wright JM. Pharmacotherapy for hypertension in the elderly. Cochrane Database of Systematic Reviews. 2009; Issue 4:CD000028.
Szucs TD, B Waeber B, Tomonaga Y. Cost-effectiveness of antihypertensive treatment in patients 80 years of age or older in Switzerland: an analysis of the HYVET study from a Swiss perspective. Journal of Human Hypertension (2010) 24, 117–123