The Effects of Comorbidity on the Benefits and Harms of Treatment for Chronic Disease: A Systematic Review

BACKGROUND: There are concerns about the potential for unintentional harms when clinical practice guidelines are applied to patients with multimorbidity. The objective was to summarize the evidence regarding the effect(s) of comorbidity on the outcomes of medication for an index chronic condition. METHODS: A systematic review was conducted of studies published in MEDLINE and Cochrane Trials before May 2012. The search strategy was constructed to identify articles indexed with “comorbidity” or a related term or by a given condition and one or more additional specified comorbid conditions. The search yielded 3252 articles, of which 37 passed the title/abstract screening process, and 22 were included after full-text review. An additional 23 articles were identified by screening the reference lists for included articles. Information was extracted on study design; population; therapy; comparison groups; outcome(s); main findings. FINDINGS: Indexing of articles was inconsistent, with no term for “multimorbidity,” and rare use of “comorbidity”. Only one article examined the effects of comorbidity per se, finding no benefit of tight control of DM among persons with high comorbidity, defined using a comorbidity index. The remainder examined pairs of conditions, the majority of which were post-hoc analyses of randomized controlled trials and which found no difference in outcomes according to whether a comorbid condition was present. Several demonstrated no difference or an increased risk of adverse outcome among persons with DM and tight control of HTN as compared to usual control. Several demonstrated lack of benefit of statins among persons with end-stage renal disease. CONCLUSIONS: There is limited evidence regarding the effects of multiple comorbidities on treatment outcomes. The majority of studies demonstrated no effect of a single comorbid condition on outcomes. Additional studies examining a broad range of comorbidity are required, along with clear and consistent indexing to allow for improved synthesis of the evidence.