Why was the medication (likely an antihypertensive or statin) discontinued for an adult patient with a chronic condition, such as hypertension or hyperlipidemia?

Why Medications Are Discontinued in Adult Patients

Most Common Reasons for Discontinuation of 20mg Daily Medications

The most common reasons for discontinuing a 20mg daily medication (typically a statin like atorvastatin or rosuvastatin) are adverse effects—particularly muscle symptoms, elevated liver enzymes, or drug intolerance—followed by clinical reassessment in patients with poor health status, limited life expectancy, or multimorbidity where the medication burden outweighs potential benefits. 1

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Discontinuation Due to Adverse Effects

Muscle-Related Symptoms

• Severe muscle symptoms or fatigue warrant immediate discontinuation, with evaluation for rhabdomyolysis by checking creatine kinase levels, kidney function, and urine myoglobin 1
• Mild to moderate muscle symptoms require temporary discontinuation until symptoms can be evaluated for alternative causes including hypothyroidism, reduced kidney or liver function, rheumatologic disorders, or vitamin D deficiency 1
• After symptom resolution, rechallenge with the original or lower dose establishes causality between symptoms and therapy 1
• In clinical trials, only 5.3% of patients discontinued atorvastatin due to laboratory abnormalities or side effects, while the remainder stopped due to patient or physician preference 2

Hepatic Toxicity

• Persistent elevation of ALT or AST >3 times the upper limit of normal on two consecutive tests mandates discontinuation 2
• Intensive statin therapy (such as atorvastatin 80mg or rosuvastatin 20-40mg) increases risk of elevated transaminases to <1.5% over 5 years, though no cases of hepatic failure were reported in major trials 2
• The dose can be halved for abnormal liver function tests before complete discontinuation is considered 2

Other Intolerance Issues

• Creatine kinase elevation >10 times upper limit of normal with muscle aches or weakness requires immediate discontinuation 2
• All 18 international cardiovascular prevention guidelines recommend discontinuation for statin intolerance, including muscle symptoms and transaminase elevation 2, 1

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Discontinuation Based on Patient Health Status

Age and Life Expectancy Considerations

• For adults ≥75 years with functional decline, multimorbidity, or frailty, discontinuation should be considered as potential benefits may no longer outweigh risks 1
• Patients with life expectancy <3 years should have statins discontinued, as cardiovascular benefits require years to accrue while risks remain immediate 1
• Evidence for primary prevention benefit becomes sparse and uncertain in adults >75-85 years, with only 8% of trial participants being >75 years in major statin trials 2, 1
• For adults >85 years in primary prevention settings, discontinuation is reasonable as evidence for benefit is extremely limited 1

Multimorbidity and Polypharmacy

• Discontinuation is appropriate when medication burden contributes to adverse effects, drug interactions, or poor adherence in patients with multiple chronic conditions 2, 1
• Polypharmacy (≥5 medications) has increased from 24% in 2000 to 39% in 2012 in older adults, and is the strongest predictor of prescribing problems 2
• Three international guidelines suggest considering discontinuation in patients with poor health status, including those with short life expectancy, multimorbidity, or functional decline 2, 1

End-of-Life and Palliative Care

• In patients enrolled in palliative care programs, statin discontinuation has demonstrated feasibility and acceptance by participants and caregivers 2
• Medications are often continued inappropriately until death, and regular reassessment is necessary to ensure cardiovascular prevention remains aligned with patient goals and prognosis 1
• One randomized trial showed statin discontinuation in palliative care improved quality of life without adverse cardiovascular consequences 2

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Nonadherence and Patient/Physician Preference

Rates of Discontinuation

• In clinical trials, 42% of subjects prematurely discontinued statin therapy, with 55% due to physician or patient preference rather than adverse events 2
• In real-world registries of patients with coronary heart disease, adherence to statin therapy reaches only 50% at 1 year 2
• Only 50-60% of patients remain adherent within 1 year of initiation, declining to 30-40% at 2 years 2

Contributing Factors

• Nonadherence is multifactorial and influenced by demographic and socioeconomic factors, lifestyle habits, time since last provider visit, adverse effects, and complex medication regimens 2
• Approximately 30-75% of older adults do not take medications as prescribed, and 33-69% of drug-related hospital admissions are attributed to nonadherence 2
• Primary nonadherence is as high as 30% in primary care settings, increasing to 60% by 3 years for chronic cardiac conditions 2

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Clinical Reassessment and Deprescribing

Shifting Treatment Goals

• Deprescribing is the process of withdrawing drugs to reduce polypharmacy and adverse drug reactions while improving outcomes, taking into account multimorbidity, care goals, and patient values 2
• When patients require extensive assistance with activities of daily living, complex medication regimens demand external support to be maintained 2
• Treatment priorities shift as health status declines, and life expectancy shortens, while risks of adverse effects increase due to pharmacokinetic and pharmacodynamic changes 2

Lack of Evidence in Specific Populations

• High-quality evidence is not available for statin-based prevention in people ≥85 years or those with complex health problems, as they are excluded from trials 2
• The ACC/AHA guidelines make no recommendations regarding statin discontinuation in patients with NYHA class II-IV ischemic systolic heart failure or maintenance hemodialysis, reflecting lack of evidence for benefit 1

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Important Clinical Nuances

Secondary Prevention Considerations

• Caution should be exercised when discontinuing statins in high-risk secondary prevention patients, particularly those with recent acute coronary syndrome or stroke 1
• Continual use of statins after a coronary event significantly reduces recurrences, and stopping results in increased risks of recurrence 2
• One study of 17,204 adults >75 years who discontinued statins found an increased risk of 1.33 (95% CI, 1.18-1.50) for any cardiovascular event 2

Withdrawal Effects

• Discontinuation of cardiovascular drugs including statins could be associated with adverse withdrawal effects, requiring careful planning 2
• Statins provide persistent cardiovascular protection after discontinuation without rebound adverse effects, making discontinuation safer than previously thought 1

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Common Pitfalls to Avoid

Failure to Establish Baseline

• Obtain baseline history of muscle symptoms before starting statin therapy to avoid attributing pre-existing symptoms to statins 1
• Providers are not adept at recognizing nonadherence, failing to inquire about adherence in one-third of patients with poor blood pressure control 2

Inappropriate Continuation

• Avoid continuing statins reflexively until death, as medications are often continued inappropriately in end-of-life care 1
• Failing to reassess indication is a common pitfall—regular review is necessary to ensure cardiovascular prevention remains aligned with patient goals 1

Inadequate Rechallenge Protocol

• After evaluating for alternative causes of symptoms, rechallenge patients with mild-moderate symptoms to determine if symptoms are truly statin-related 1
• In the A to Z trial, 28% of premature discontinuations were due to adverse experiences, while 55% were due to patient or physician preference without documented adverse effects 2

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Shared Decision-Making Framework

Shared decision-making is crucial, involving discussion of goals of care, treatment priorities, and patient preferences 1

• Many patients who prefer fewer medicines do not share their beliefs with providers and recall few instances of provider-initiated medication discontinuation 3
• Strengthening patient-provider relationships and eliciting patient attitudes about taking fewer medications enables appropriate discontinuation of unnecessary medications 3
• Discontinuation may improve quality of life by reducing pill burden, medication costs, and side effects, particularly in frail older adults 1