Exploring the Intersection of Chronic Disease, Adherence, and Life Expectancy

October 14, 2014

Multiple studies in recent years have discussed what happens when patients with chronic conditions do not take medications as prescribed. The impact of poor adherence on both health and healthcare costs is so well documented that CMS now asks accountable care organizations (ACOs) to take steps to ensure better adherence when patients leave the hospital, to help hold down readmission rates.

Multiple studies in recent years have discussed what happens when patients with chronic conditions do not take medications as prescribed. The impact of poor adherence on both health and healthcare costs is so well documented that CMS now asks accountable care organizations (ACOs) to take steps to ensure better adherence when patients leave the hospital, to help hold down readmission rates.1

Yet despite the attention to the problem of adherence, alongside data that show increases in life expectancy are hitting plateaus among older Americans, 2 it appears less attention has been paid to knitting together evidence on a related question. In this era of healthcare reform, is anyone asking whether challenges with adherence are contributing not only to poor health, but also to lower life expectancy?

The question arises in the wake of a new study led by Johns Hopkins researcher Eva DuGoff, PhD, who in August published results that examined how having multiple chronic conditions at once affected life expectancy. DuGoff’s analysis, based on records from 1.4 million Medicare enrollees and evaluating 21 conditions, found that on average, each chronic condition takes 1.8 years off a person’s life after the age of 67 years.2

As DuGoff described in a statement released by Johns Hopkins, that average is based on its cumulative effect on older persons; the first disease takes off only a fraction from the life span, with the effect growing with each additional disease. The results showed that different diseases have different effects on the life span, too. But in her conclusions, DuGoff said the key finding—that there are limits to what can be done for patients who suffer from multiple conditions—was important for Medicare and Social Security administrators, who have a keen interest in knowing how long beneficiaries will live.3

“Living with multiple chronic diseases such as diabetes, kidney disease, and heart failure is now the norm and not the exception in the United States,” DuGoff said. “The medical advances that have allowed sick people to live longer may not be able to keep up with the growing burden of chronic disease.”

While DuBoff joined those calling for increased efforts to prevent chronic disease, left unanswered in her study is how patient adherence to multiple medications—needed to manage all those chronic conditions—factored into the life expectancy equation. Elsewhere, it has been demonstrated that taking medication consistently is linked to better health.

A review by Boswell and colleagues in The American Journal of Pharmacy Benefits found that the connection between adherence and positive clinical outcome varies depending on the chronic condition, but overall the pattern is consistent: there was a positive relationship between taking medication and good outcomes in 81% of the 79 outcomes evaluated.4

Simply put, while it may seem obvious, there’s evidence that if you take your medication, it’s better for your health. Boswell’s review found taking medication was most important for patients who had suffered heart attacks and for those with hypertension, diabetes, high cholesterol, and schizophrenia.4 Perhaps it’s not a surprise that 8 of the 33 early measures of whether ACOs are delivering quality care—which Medicare will examine to determine reimbursement under its Shared Savings Program—are tied to diabetes and cardiovascular conditions.1

While adherence has received plenty of attention in the literature, much of the focus has been on the economic impact—in other words, the question asked is, “How does the failure of patients to take medication contribute to rising healthcare costs?” For example, Health Affairs cited a $290 billion price tag for nonadherence.5 A study from Excellus BlueCross and BlueShield found that in upstate New York alone, the cost of nonadherence was $2.87 billion just for depression, diabetes, hypercholesterolemia, and hypertension.6

Mona Chitre, PharmD, vice president and chief pharmacy officer at Excellus Blue Cross and Blue Shield, said, “The number of people who don’t take their medications as directed is nothing short of astounding. This signifies a huge health improvement and cost savings opportunity for our upstate New York regions ($2.87 billion in this 1 part of New York alone). But as you know, the problem of nonadherence is a national issue, and not unique to upstate New York.”

A 5% or 10% increase in adherence can yield hundreds of millions in savings for patients suffering from multiple conditions. For the majority of studies reviewed by Boswell and colleagues, the connection between adherence and death was not specifically measured or reported.4 The connection between infarction or the need for revascularization may imply risk of death, but the direct relationship between nonadherence and risk of death has not been well explored.

A study published in the Journal of the American Medical Association did support such a link. In 2007, researchers studied the outcomes of more than 31,000 older Canadian patients who had experienced a heart attack and who subsequently filled a prescription for a statin, beta-blocker, and/or a calcium channel blocker, which was considered a control medication for this study.7

The authors, who categorized the patients by their level of adherence, found that “Among statin users, compared with their high-adherence counterparts, the risk of mortality was greatest for low adherers” (adjusted hazard ratio [HR], 1.25; P =.001). The risk of mortality was also elevated among those with intermediate levels of adherence versus the low adherence group (adjusted HR, 1.12; 95% CI, 1.01-1.25; P =.03). The authors found a similar relationship for patients who took beta-blockers. No such correlation was found with mortality in those taking calcium blockers.7

In 2014, Canadian researchers published a meta-analysis of studies involving populations taking statin medications. They found that nonadherence with statin medications resulted in up to a 2.54-fold increased mortality.8

How Many Have Multiple Chronic Diseases?

Research from the National Center for Health Statistics and CDC estimated that approximately 117 million American adults have at least 1 of 10 common chronic illnesses.9 This estimate, based on self-reports from the 2012 National Health Interview Survey, does not consider chronic disease in children, in addition to several other important chronic disorders, including mental health diseases, autoimmune diseases such as inflammatory bowel disease, and multiple sclerosis. This same review estimated that 1 in 4 adults have more than 1 chronic disease,9 and that the likelihood of having multiple chronic diseases increases with age (Table 1).

By the age of 65 years, it is more likely that Americans will have 3 or more chronic diseases than 1 or 2.9 The magnitude of this phenomenon in the United States was identified by the Johns Hopkins study, which found that nearly 80% of Medicare beneficiaries (aged 67 years or more) have at least 2 chronic conditions, more than 60% have 3 or more chronic conditions, and more than 33% have at least 5 chronic illnesses.2 A rise in multiple chronic disease overall, coupled with its increased prevalence among older Americans, appears to already be making an impact on the flattening of life expectancy in the United States relative to other developed countries, based on what the Johns Hopkins researchers found.2

Reasons Behind Multiple Conditions, Poor Adherence

If adherence is a recognized problem, is the problem worse when a patient has multiple chronic conditions? Does being older further complicate things? And if so, how?

Preventing nonadherence in the elderly is a difficult challenge, according to Thuy-Tien Dam, MD, assistant professor of medicine at Columbia University Medical Center, New York. “Barriers to nonadherence in the elderly include cognitive impairment, which can impact ‘executive function’ such as paying bills and deciding which mail should be kept and which should be thrown away,” she said, “Adhering to medications also becomes an issue with early or mild cognitive decline, which is very common with aging. Most people over age 65 years who are living in the community are taking at least 3 medications, and these regimens can be confusing for older individuals.”

Nonadherence can also be related to other critical factors, Dam said. “For example, physicians may not have the time to explain to patients why they need to take the medication and how it will help them. Second is the possibility that side effects or drug interactions are causing patients to discontinue the regimen,” she said.

Questions about the ability to pay for medications often arise in studies on adherence. But prescription co-payments are not always be the only issue, or the main issue. In an important 2011 multicenter study of patients who had suffered a heart attack, adherence with pharmacologic therapy ranged between 36% and 49%.8 They also found that even if the patients had full coverage for their medications in this study (without any co-payments), adherence rates rose only a maximum of 6 percentage points. However, even with this small increase, the rate of vascular events was still significantly less than in the group with lower adherence (who had usual coverage).

Consider this effect in the older patient with multiple drug regimens for several comorbidities. Said Dam, “I think that nonadherence for several diseases is synergistic, although there’s not much evidence to support this specifically. If you have high cholesterol and hypertension, and you’re nonadherent with 3 of your medications (for any reason), then the risk of having negative cardiovascular outcomes is greater.

“With polypharmacy, the instructions to the patient may be more complex, and it is to be expected that patients will have more difficulty in adhering to their medications. They will also experience more side effects, which can influence patients to stop taking their medication, also resulting in negative health outcomes,” she said. Examples of complex instructions include “Don’t take this medication without a meal,” or “Don’t take these 2 together.”

A study by HealthPartners in Minneapolis10 reported similar findings when it asked patients with diabetes or asthma to self-report barriers to adherence. Other barriers included failure to get timely refills and simply that there are too many pills to accurately track.

Polypharmacy is one of the greatest challenges in caring for the elderly, according to Renae Smith-Ray, PhD, research scientist at the Center for Research on Health and Aging, University of Illinois at Chicago. She told Evidence-Based Diabetes Management, “One of the main causes of falls among older adults is polypharmacy, and this results in a great deal of disability. It is very unusual to meet an older adult who doesn’t take any medications. Most are taking 3 or more.”

This issue of “nonadherence” affects health promotion as well. In her research on behavioral change, Smith-Ray found that “Adherence to behavior change programs is notoriously difficult. Some reasons may be intuitive—we’re creatures of habit, and making abrupt change is difficult. Although most people know that physical activity is necessary for maintaining good health, physical activity takes considerable exertion relative to other health behaviors. “We know that the initial phase of behavior change is most challenging; that is, when one first begins the new behavior.

Consider an adult with arthritic knee pain: the most tempting thing to do is to keep your feet up on a sofa and remain immobile to prevent pain. It is much easier not to begin an exercise program, and there may be a mistaken perception that exercising will cause more arthritis-related pain. However, we have found exactly the opposite to be true, that improving endurance and lower-extremity strength removes pressure from weight-bearing arthritic joints, which decreases pain.”

Smith-Ray believes that cognitive training programs can also be a useful tool for improving many aspects of health. “Through our research, we found that many participants report a noticeable difference in attentiveness to daily tasks following a 10-week intervention for cognitive training done in a classroom setting.” Perhaps one of these tasks can be taking medication and following other medical recommendations.

“Nonadherence Affects Length of Life”

“Medication adherence is strongly related to both disease progression and control,” stated Vittorio Maio, PharmD, MS, MSPH, associate professor, Thomas Jefferson University School of Population Health. “As former surgeon general C. Everett Koop said, ‘Drugs don’t work in patients who don’t take them.’ There is no doubt, therefore, that poor adherence is consistently associated with poor clinical, economic, and utilization outcomes. Nonadherence affects length of life.”

Maio affirmed, “Clearly, adherence to treatments would become even more important in patients with multiple conditions, a quite common situation in the elderly, because these patients are already at much greater risk of poor outcomes. In these subjects, poor adherence to prescribed treatments would lead to suboptimal clinical responses to medications, which could in turn largely increase the onset of medical (and often lethal) complications as a consequence of poor therapeutic control.”


1. ACO shared savings program quality measures. CMS website. http://www.cms.gov/Medicare/Medicare-Fee-for-Service-Payment/sharedsavingsprogram/Downloads/ACO-Shared-Savings-Program-Quality-Measures.pdf. Accessed August 22, 2014.

2. DuGoff EH, Canudas-Romo V, Buttorff C, Leff B, Anderson GF. Multiple chronic conditions and life expectancy: a life table analysis. Med Care. 2014;52(8):668-694.

3. Life expectancy gains threatened as more older Americans suffer from multiple chronic conditions [press release]. http://www.jhsph.edu/news/news-releases/2014/life-expectancy-gains-threatened-as-more-older-americans-suffer-from-multiple-medical-conditions.html. Baltimore, MD: Bloomberg School of Public Health; July 23, 2014.

4. Boswell KA, Cook CL, Burch SP, Eaddy MT, Cantrell CR. Associating medication adherence with improved outcomes: a systematic literature review. Am J Pharm Benefits. 2012;4(4):e97-e108.

5. McKethan A, Benner J, Brookhart A. Seizing the opportunity to improve medication adherence. Health Affairs blog. www.healthaffairs.org/blog/2012/08/28/seizing-the-opportunity-to-improve-medication-adherence/. Published August 28, 2012. Accessed August 2, 2014.

6. Medication adherence among upstate New York adults: a multi-billion dollar health improvement opportunity. Excellus BlueCross BlueShield website. (https://www.excellusbcbs.com/wps/wcm/connect/e3a05c81-35d2-466f-a71a-f8bba660f978/Rx+Adherence+FS-EX+FINAL.pdf?MOD=AJPERES&CACHEID=e3a05c81-35d2-466f-a71a-f8bba660f978). Published August 12, 2014. Accessed August 18, 2014.

7. Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality rate after acute myocardial infarction. JAMA. 2007;297:177-186.

8. Choudhry NK, Avorn J, Glynn Rj, et al. Full coverage for preventing medications after myocardial infarction. N Engl J Med. 2011;365:2088-2097.

9. Ward BW, Scholler JS, Goodman RA. Multiple chronic conditions among US adults: a 2012 update. Prev Chron Dis. 2014;11:130389.

10. Rolnick SJ, Asche S, Pawloski PA, Bruzek RJ, Hedblom B. Barriers to and facilitators of medication adherence. Am J Pharm Benefits. 2013;5(5):209-215.