By Dr. Geoffrey Modest
BMJ printed a new population-based cohort study looking at guideline-recommended drugs and deaths in older adults with multiple chronic conditions (see BMJ 2015;351:h498). These guidelines were typically based on randomized control studies with younger people and a single chronic condition.
Details:
- 8578 older adults (mean age 77 with 36% >80yo, 59% women, 87% white), having multiple chronic conditions: hypertension (HTN) 92%, hyperlipidemia (HL) 77% , diabetes (DM) 40% , coronary artery disease (CAD) 39%, depression (DEP) 26%, heart failure (HF) 20%, atrial fibrillation (AF) 19%, chronic kidney disease (CKD) 12%, and thromboembolic disease 6%.
- Data were from Medicare Current Beneficiary Survey cohort, a nationally representative sample of Americans >65yo, followed through 2011
- The 9 study drugs: RAS blockers (ACE-I or ARBs) were used in 54%, statins in 53%, thiazides 47%, b-blockers 47%, calcium channel blockers (not differentiated by class) in 33%, SSRIs/SNRIs 21%, warfarin 14% , metformin 14%, clopidogrel 13%. 54% took at least 3 of the 9 study drugs. Mean total number of drugs (including nonstudy drugs) was 10. They also tracked changes in meds over the study period
- Median follow-up of 24 months. 15% (1287) people died during follow-up.
Results:
- Mortality over the 24 months: 27% in those with AF, 19% with CAD, 17% with DM, 33% with HF, 11% with HL, 15% with HTN
- For the specific drugs (all of below were statistically significant), the HR for mortality was:
- b-blockers: adjusted HR of 0.59 for AF, 0.70 for CAD, 0.68 for HF, and 0.48 for combo of AF/CAD/HL/HTN, 0.59 for HF/CAD/HL/HTN [note: an HR of 0.59 means a 41% decrease in mortality]
- Statins: HR 0.75 for CAD, 0.75 for DM, 0.68 for HL, and 0.65 for combo DM/CAD/HL/HTN, 0.68 for HF/CAD/HL/HTN, 0.70 for DEP/CAD/HL/HTN
- Calc channel blockers: HR 0.78 for AF, 0.85 for HTN, and 0.69 for DM/CAD/HL/HTN, 0.71 for AF/CAD/HL/HTN and 0.72 for HF/CAD/HL/HTN
- Thiazides: no significant benefits for HTN or any of the combo comorbidities
- RAS blockers: 0.72 for HF, 0.80 for HTN, 0.82 for CAD, and 0.73 for AF/CAD/HL/HTN, 0.77 for HF/CAD/HL/HTN
- Clopidogrel: no significant benefit for AF or CAD, or any of the combos (aspirin use could not be tracked in this database)
- SSRI/SNRI: no significant benefit for DEP or any of the combos
- Metformin: no significant benefit for DM or any of the combos
- Warfarin: 0.69 for AF, 0.44 for thromboembolic dz, but no benefit for any of the combos
So, this study, I think, is important for several reasons:
- It largely reinforces what we are already doing, treating older patients with comorbidities based on the usual randomized controlled trials which typically limited the age range to younger patients and those usually limited to a single disease (e.g., excluding those with renal failure, etc.). And, of course, as people get older, they regularly and routinely develop multiple comorbid conditions
- The study shows that in patients with multiple common comorbidities, the usual medications do improve mortality, even in a pretty short-term 2-year study. And the association between drug use and mortality was pretty similar across patterns of coexisting comorbidities, suggesting that similar benefits were evident despite the presence of comorbidities. This last finding supports the utility of randomized control trials limited to a single disease and then being applied more generally, at least in the above diseases/medications.
- Although there is empirical evidence that observational studies usually have similar results to controlled intervention studies (see Cochrane Database Syst Rev 2014;4:MR000034), one has to remain somewhat skeptical that there could be unexpected biases. This study was quite good in that it incorporated certain social comorbidities (e.g. functional level, amount of time in the hospital, and living in a nursing facility), but still is open to the potential for other potential biases
- For example, it is pretty clear that many of the cardiac meds do well. The hardest one for me to accept is that metformin does not have clear benefit, though on each analysis, there was a clear non-significant trend to benefit. My guess is that there is a strong selection bias here: those who are sicker do not get metformin. My bet is that they have a little (or lot) of renal dysfunction, or heart failure, etc., which scare the providers away from using metformin, leaving only the healthier elderly on it (and with a lower likelihood of showing mortality benefit in the healthier subgroup over a short 2-year study). [Though, there are strong arguments that metformin is still a safe drug in many of these cases, esp. at a lower dose: See https://stg-blogs.bmj.com/bmjebmspotlight/2015/01/23/primary-care-corner-with-geoffrey-modest-md-metformin-in-renal-failure/]
- There have been increasing studies showing that, for example, anticoagulation for the very common condition of atrial fibrillation seems to be safer in the elderly than we thought in the old days, and I do have several patients into their late 80’s/early 90’s doing very well on them. And we know that the benefits of statins are typically evident within 6 months of starting them (based on studies of mostly younger people but some elderly) – i.e., these drugs seem to work well and are pretty well tolerated in the elderly.
- So, bottom line, this study provides some pretty strong scientific rationale for continuing to treat elderly patients with their common multiple medical conditions with the same meds we have been using based on studies of younger people with single diseases. But, it is also important to bear in mind that this study only looked at mortality, which is not the only important end-point….
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