Drugs with ‘silent’ but significant health effects

Benjamin Franklin wrote under a nom de plume that “an ounce of prevention is worth a pound of cure.” Although Franklin was referencing fire prevention, this pithy observation’s bearing on health is particularly salient today. 

Many preventive interventions, including the use of medications, have “silent” health effects. They don’t always relieve suffering immediately, but many can prevent it later in life.

Drugs with silent health benefits are often discontinued by patients because their positive effects go unnoticed, especially in light of adverse side effects, like gastrointestinal upset. However, these drugs can be incredibly important to health and, when given due consideration, should be resumed.

Here are five drugs with silent but important health effects:

Statins

No question about it: Statins are effective medications. In one meta-analysis of all major statin clinical trials, statin therapy yielded a 21% decrease in the relative risk of major vascular events for every 1.0 mmol/L decrease in LDL cholesterol levels. Similarly, statins led to a 24% reduction in major coronary events for every 1.0 mmol/L decrease in LDL cholesterol levels.

In patients at risk of heart attack or stroke, however, the benefits of statin therapy appear silent—or the absence of pathology. People may not realize the benefit of statins because their cardiovascular health is sustained while on the drugs. Indeed, this perceived lack of effect may be one reason why more than half of people taking statins stop treatment within 1 year of starting, and more quit the drug over longer periods.

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“Patient-related factors leading to non-adherence include low health literacy, lack of understanding of the disease being treated, attitudes concerning the effectiveness of the treatment, negative previous experience with pharmacological therapies, presence of psychological problems, and/or cognitive impairment,” wrote the authors of one review article.

According to researchers, promising strategies to boost statin adherence include reinforcement and reminders, as well as better patient education.

Antidepressants

Some researchers have shown mid-level evidence that antidepressants can help treat symptoms of moderate to severe depression. Over time, people taking antidepressants may feel more “normal,” and wish to discontinue the medications due to adverse effects, including sexual dysfunction, insomnia, headache, and drowsiness. However, people tend to forget the depths of depression when their symptoms are muted by antidepressants. By discontinuing antidepressant medications, they lose the preventive effects of the drugs, putting themselves at risk for another bout of depression. Moreover, discontinuance can lead to antidepressant withdrawal, which takes on flu-like symptoms, mood swings, insomnia, and more.

In one survey-based Canadian study involving 137 elderly adults with depression, researchers found that 69.3% of participants adhered to their antidepressant medications, whereas the remainder didn’t. Furthermore, participants were more likely to quit their meds due to sleep disturbances, gastrointestinal problems, and nervous system effects. However, participants with palpitations due to the drugs were more likely to continue treatment.

“Healthcare professionals need to address the presence of side effects, especially those related to sleep disturbance, gastrointestinal and nervous systems, when treating older adults. Calling for better follow-up of patients treated with antidepressants and implementing shared decision-making may help improve adherence to medications,” the authors concluded.

Blood pressure-lowering medications

According to results from several observational studies and clinical trials, antihypertensive medications decrease the risk of cardiovascular disease (CVD). In one study published in Lancet, researchers found that every 10-mmHg reduction in systolic blood pressure from antihypertensive agents significantly decreased the risk of major CVD events by 20%, and reduced all-cause mortality by 13%.   

Other researchers have shown that patients who reported good adherence to antihypertensive medications experienced a 56% drop in CVD risk during a period of 6 years vs those who were poorly adherent.

According to the results from one high-powered Australian study, between 40% and 70% of Australians quit taking their blood pressure medications, often within 6-12 months of treatment initiation. Adherence was best with fixed-dose combinations, followed by angiotensin II receptor blockers (ARBs), beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, and diuretics. Between 30% and 50% of those who discontinued treatment eventually restarted within a year.

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The authors of the study hypothesize that the silent benefits of blood pressure agents may underlie nonadherence:

“Consistent with the literature, we found low short? and long?term persistence and poor adherence to all [blood-pressure lowering] agents. This is possibly due to the lack of symptoms of hypertension and the preventive nature of [blood-pressure lowering agent] use among people with no indications of other cardiovascular comorbidities or risk factors. Reflective of this hypothesis, we found improved persistence to [blood-pressure lowering] agents among those with dyslipidemia or who were on anti?platelet or anti?coagulant therapy, which indicated existing or high risks of CVD.”

Metformin

Guidelines from various organizations, including the American Diabetes Association and the European Association for the Study of Diabetes, recommend metformin as first-line treatment for type 2 diabetes. These recommendations are based on results from both prospective and retrospective studies in which researchers have shown that the drug decreases the risk of death from heart disease, does not result in hypoglycemia, and causes either weight loss or has no effect on weight. This enviable profile of silent benefits along with its low cost makes metformin the most prescribed antidiabetic medication in the world. The downside of metformin is that up to 20% of those who take it experience diarrhea, nausea, abdominal pain, and bloating. Consequently, 5% of people taking the drug quit.

The reason why metformin causes gastrointestinal upset is unclear, although various conjectures have been voiced. One hypothesis: Metformin may not only act on the liver to decrease gluconeogenesis but also combat diabetes through gastrointestinal means that also lead to gastrointestinal disturbance.

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Authors of a pharmacokinetic study published in Diabetes, Obesity and Metabolism discounted various hypotheses on the mechanism of metformin intolerance:

“We showed that the differences between tolerant and intolerant cohorts in the absorption, distribution or elimination of metformin, or in systemic lactate, serotonin or bile acid concentrations, were too small to be the mechanism of intolerance. It would be interesting to investigate further the link between transporter genotype, pharmacokinetics, and tolerance of metformin, as genotype was not considered in the present study."

Aspirin

For decades the use of low-dose aspirin for the primary prevention of atherosclerotic CVD was routine. To its credit, aspirin does reduce the risk of atherothrombosis, a silent but important benefit. However, aspirin increases bleeding risk, and this concern has called into question its net benefit for most people.

In joint guidelines from the American College of Cardiology and the American Heart Association, low-dose aspirin as primary prevention is recommended in select patients without blood dyscrasias aged 40-70 years who are at higher risk of atherosclerotic CVD. But even if prescribed aspirin, roughly a quarter of patients are nonadherent. For instance, in one study out of Duke, researchers found that consistent aspirin use was only 71% among patients with coronary artery disease.