Can patients with well-controlled hypertension, diabetes, dyslipidemia, or gout discontinue their chronic medications, such as lisinopril (angiotensin-converting enzyme inhibitor), metformin (biguanide), atorvastatin (HMG-CoA reductase inhibitor), or allopurinol (xanthine oxidase inhibitor), and what are the rationales for discontinuation in each condition?

Discontinuation of Chronic Medications for Hypertension, Diabetes, Dyslipidemia, and Gout

Discontinuation of chronic medications for these conditions is generally not recommended and carries significant risks, but specific clinical scenarios exist where temporary or permanent cessation may be appropriate, with hypertension medications having the most evidence-based discontinuation protocols while diabetes, dyslipidemia, and gout medications should rarely if ever be stopped in well-controlled patients.

Hypertension Medications (Lisinopril/ACE Inhibitors)

When Discontinuation May Be Considered

Discontinuation can be attempted when home blood pressure monitoring consistently shows diastolic BP <80 mm Hg, but this requires structured monitoring protocols. 1

• Patients with mild hypertension, no target organ damage, and favorable characteristics may be candidates for discontinuation trials 1
• Temporary discontinuation for diagnostic evaluation of secondary hypertension is safe when performed in specialized settings with appropriate monitoring protocols 2
• In acute ischemic stroke, pre-existing antihypertensives should be temporarily discontinued during the first 24 hours 1

Critical Contraindications to Discontinuation

Never discontinue antihypertensive therapy in patients with severe baseline hypertension (SBP ≥180 mm Hg or DBP ≥110 mm Hg) or pre-existing cardiovascular disease. 1

• Discontinuation in patients with type 2 diabetes is associated with dramatically increased risks: macrovascular events (HR 3.23), microvascular events (HR 1.38), and all-cause mortality (HR 7.99) 3
• The highest risk occurs in the first year after discontinuation 3
• At 2 years, 41.3% of patients who stopped antihypertensive treatment had not restarted therapy, representing substantial unmet need 4

Discontinuation Protocol

Taper medications one at a time rather than stopping all simultaneously, with specific attention to drug class. 1

• Beta-blockers must never be stopped abruptly due to risk of rebound tachycardia, severe hypertension, and precipitation of angina or myocardial infarction; taper over minimum 7-10 days 1
• Clonidine and central alpha-agonists cause dangerous rebound hypertension within 24-72 hours if stopped abruptly 1
• ACE inhibitors/ARBs have fewer acute withdrawal symptoms but cause gradual blood pressure elevation 1
• Calcium channel blockers can cause reflex tachycardia if discontinued rapidly 1

Monitoring Requirements

Reassess blood pressure within 2-4 weeks of stopping medication using home BP monitoring to detect white coat effect versus true hypertension. 1

• Continue annual monitoring indefinitely even after successful discontinuation 1
• Restart medication immediately if systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg on home monitoring 1
• Monitor for symptoms including headache, chest pain, or visual changes 1

Special Populations

In patients with CKD and eGFR <30 ml/min/1.73 m², follow a specific hierarchy: reduce or stop RAS inhibitors first if symptomatic hypotension occurs. 5, 1

• Continue ACE inhibitors/ARBs unless serum creatinine rises >30% within 4 weeks of initiation 5
• In heart failure with reduced ejection fraction, use structured down-titration rather than complete cessation 1
• Perioperatively, consider holding ACE inhibitors/ARBs 24 hours before surgery to reduce intraoperative hypotension risk 1

Diabetes Medications (Metformin)

Rationale Against Discontinuation

Metformin should not be discontinued in well-controlled diabetes as it provides ongoing glycemic control and cardiovascular protection without the discontinuation evidence base that exists for antihypertensives.

• No clinical trial evidence supports safe discontinuation criteria for metformin in controlled diabetes 5
• The medication's benefits extend beyond glucose lowering to include cardiovascular and metabolic advantages 5

Mandatory Temporary Discontinuation Scenarios

Metformin must be temporarily discontinued before procedures using iodinated contrast, during hospitalizations, and when acute illness compromises renal or liver function. 5

• Contraindicated in advanced renal insufficiency (eGFR <30 mL/min/1.73 m²) 5
• Use lower doses with eGFR 30-45 mL/min/1.73 m² and monitor eGFR every 3-6 months 5
• Discontinue in hypoperfusion, hypoxemia, impaired hepatic function, or heart failure due to lactic acidosis risk 5

Dose Reduction Rather Than Discontinuation

For persistent gastrointestinal side effects or reduced appetite in older adults, reduce or eliminate metformin rather than continuing at intolerable doses. 5

• Slowly increase daily dose to minimize gastrointestinal effects 5
• Monitor for vitamin B12 deficiency in long-term users 5

Simplification in Older Adults

In older adults on complex insulin regimens, prandial insulin can be reduced by 50% and replaced with noninsulin agents, but basal therapy should continue. 5

• If prandial insulin >10 units/dose, decrease by 50% and add noninsulin agent 5
• Titrate prandial insulin down as noninsulin agent doses increase with aim to discontinue prandial insulin 5

Dyslipidemia Medications (Atorvastatin/Statins)

Rationale Against Discontinuation

Statins should not be discontinued in patients with established cardiovascular disease or high ASCVD risk, as they provide ongoing cardiovascular protection independent of current cholesterol levels.

• For secondary prevention (evidence of cardiovascular disease), statin therapy is indicated up to age 75 when total cholesterol >5.0 mmol/L 5
• For primary prevention, statin therapy is indicated up to age 70 when total cholesterol >5.0 mmol/L and 10-year CHD risk >30% 5
• At 2 years, 29.2% of patients discontinued lipid-lowering therapy, with only 49.9% reaching treatment targets 4

No Evidence-Based Discontinuation Criteria

Unlike antihypertensives, no guideline provides criteria for safe statin discontinuation in well-controlled patients, reflecting the ongoing nature of cardiovascular risk.

• Patients prescribed both antihypertensive and lipid-lowering therapy remain on treatment longer and achieve better outcomes than those treated for single risk factors 4
• Diabetic patients are more likely to reach cholesterol targets compared to blood pressure targets 4

Combination Therapy Considerations

In patients with diabetes and CKD, add ezetimibe, PCSK9 inhibitors, or icosapent ethyl based on ASCVD risk and lipid levels rather than discontinuing statin therapy. 5

Gout Medications (Allopurinol/Xanthine Oxidase Inhibitors)

Limited Evidence for Discontinuation

The strength of evidence for identifying patients who can safely discontinue urate-lowering therapy is insufficient, though some patients remain asymptomatic for 2-3 years after stopping treatment. 5

• Three prospective observational studies found serum urate levels in presence or absence of treatment strongly predict which patients remain asymptomatic 5
• No clinical trial has tested a discontinuation strategy 5

Treatment Philosophy

Treating to a serum urate target necessarily means increasing medication doses in asymptomatic patients, a strategy with strong biologic appeal but unproven value. 5

• No trial has based treatment decisions on different specific targets (e.g., 416 vs. 357 µmol/L) 5
• Examples from other conditions show treating intermediary biomarkers to target can result in more adverse effects than benefits 5

Symptomatic Management Approach

For acute gout, colchicine, NSAIDs, and corticosteroids effectively reduce symptoms, but chronic urate-lowering therapy discontinuation should be approached with extreme caution. 5

• Elevated serum uric acid should be treated with diet, urate-influencing drugs (losartan, fibrates, atorvastatin), or urate-lowering drugs in symptomatic patients with gout and s-UA >6 mg/dL 5
• The only monitoring method to assess urate-lowering therapy effectiveness is serum urate measurement, but no direct evidence supports or refutes monitoring value 5

Special Population: Nephrogenic Diabetes Insipidus

In the unique context of nephrogenic diabetes insipidus treated with thiazides, discontinuation is recommended at age ≥18 years due to concerns including gout, hypercholesterolemia, and non-melanoma skin cancer. 5

• This represents a specific exception where thiazide-induced gout risk outweighs benefits in a particular disease context 5

Common Pitfalls Across All Medication Classes

Simultaneous Discontinuation

Never stop multiple medications simultaneously; taper one at a time to identify which medication was providing benefit and to prevent rebound effects. 1

Office-Only Blood Pressure Monitoring

Do not discontinue therapy based solely on office BP readings; confirm with home monitoring to rule out white coat hypertension. 1

Inadequate Follow-Up

Discontinuation without structured follow-up leads to loss of cardiovascular protection and accelerated target organ damage. 1

• Event rates are highest in the first year after discontinuation 3
• Clinicians must identify high-risk patients early after discontinuation for urgent investigation and management 3

Polypharmacy Concerns

While polypharmacy is a legitimate concern, continuation of medications without proven effect may cause harm through drug-drug interactions, but discontinuation of proven therapies causes greater harm. 6