How to manage a 57-year-old patient with hypertension, hyperlipidemia, and obstructive sleep apnea who is experiencing side effects from Crestor (Rosuvastatin) and has not achieved the blood pressure goal of <130/80 mmHg despite current medication and lifestyle advice?

Management of Resistant Hypertension with Statin Intolerance and Untreated Sleep Apnea

Blood Pressure Management

Add chlorthalidone 12.5-25mg daily as a fourth antihypertensive agent to address the uncontrolled home blood pressure readings of 130s/85s. 1, 2

Rationale for Adding a Diuretic

• This patient has resistant hypertension (BP above goal on three medications including a diuretic that was discontinued), and the most critical step is reintroducing diuretic therapy, as occult volume expansion is the primary mechanism underlying treatment resistance. 3, 4
• Chlorthalidone is preferred over hydrochlorothiazide due to its longer half-life (24-72 hours) and superior cardiovascular outcomes data, though the patient previously experienced dizziness on this medication. 2, 5
• Start at the lowest dose (12.5mg) and titrate slowly to minimize orthostatic symptoms that caused discontinuation previously. 2
• If chlorthalidone remains intolerable, hydrochlorothiazide 25mg daily is an acceptable alternative, though less effective. 2

Alternative Fourth-Line Agent if Diuretic Cannot Be Tolerated

• Add spironolactone 25mg daily if chlorthalidone/hydrochlorothiazide cannot be tolerated, as it is the most effective fourth-line agent for resistant hypertension and addresses aldosterone-mediated volume retention. 1, 2, 3
• Monitor serum potassium and creatinine within 1 week of initiating spironolactone due to hyperkalemia risk when combined with lisinopril. 3
• Alternative fourth-line agents if spironolactone is contraindicated include amiloride, doxazosin, eplerenone, or clonidine. 1, 2

Critical Underlying Issue: Obstructive Sleep Apnea

The untreated moderate obstructive sleep apnea is likely the primary driver of resistant hypertension and must be addressed immediately. 3, 4, 6

• OSA is one of the three most common causes of truly resistant hypertension (along with chronic kidney disease and hyperaldosteronism), and CPAP therapy can reduce BP by 5-10 mmHg systolic. 3, 4, 6
• The patient's neck circumference >40cm, snoring, and daytime sleepiness despite adequate sleep duration are classic indicators of significant OSA. 6
• Strongly counsel the patient to resume CPAP therapy immediately and repeat the sleep study to optimize settings, as medication adjustments alone will likely fail without addressing this fundamental cause. 3
• Consider referral to a sleep medicine specialist for CPAP adherence counseling and alternative therapies if CPAP remains intolerable. 3

Blood Pressure Monitoring and Targets

• The home BP readings of 130s/85s confirm true hypertension (home BP ≥135/85 mmHg threshold), ruling out white-coat hypertension. 1
• Target BP is <130/80 mmHg given the patient's high cardiovascular risk profile (hyperlipidemia, likely metabolic syndrome given OSA). 1
• Continue daily home BP monitoring and reassess within 2-4 weeks after medication adjustment. 1, 2

Lifestyle Modifications

• Sodium restriction to <2g/day can provide 5-10 mmHg systolic reduction and is particularly important in resistant hypertension. 1, 2, 4
• Weight loss is critical—every 10kg reduction produces approximately 6 mmHg systolic and 4.6 mmHg diastolic reduction. 2
• Limit alcohol to <100g/week, as heavy alcohol intake directly contributes to resistant hypertension. 1, 4, 7
• Verify the patient is not taking NSAIDs or other interfering substances that elevate BP. 4, 5, 7

Statin Management for Familial Hypercholesterolemia

Switch from rosuvastatin (Crestor) 5mg to pravastatin 40mg or fluvastatin 80mg, as these are the most hydrophilic statins with the lowest rates of muscle-related side effects. 8

Rationale for Statin Switch

• The patient's complaint of feeling "off" on rosuvastatin 5mg suggests statin intolerance, which occurs in 10-15% of patients and includes myalgias, fatigue, and cognitive symptoms. 8
• Rosuvastatin carries FDA warnings for myopathy and rhabdomyolysis, with risk factors including age >65 years (this patient is 57 but approaching this threshold). 8
• Pravastatin and fluvastatin have the lowest lipophilicity and lowest rates of muscle symptoms among statins. 8

Alternative Strategies if Statin Intolerance Persists

• If muscle symptoms recur on pravastatin/fluvastatin, implement alternate-day dosing or twice-weekly dosing to maintain some LDL reduction while minimizing side effects. 8
• Consider adding bempedoic acid 180mg daily, a non-statin LDL-lowering agent that does not cause myopathy, as it can be combined with ezetimibe 10mg (already taking). 8
• PCSK9 inhibitors (evolocumab or alirocumab) are highly effective for familial hypercholesterolemia and have no muscle-related side effects, though cost and insurance coverage may be barriers. 8

Monitoring for Statin-Related Adverse Effects

• Check baseline CK, liver enzymes, and lipid panel before switching statins. 8
• Instruct the patient to report unexplained muscle pain, tenderness, or weakness immediately, particularly if accompanied by fever or unusual fatigue. 8
• Recheck lipid panel in 6-8 weeks after statin switch to assess efficacy. 8

Non-Pharmacologic Lipid Management

• Increase soluble fiber intake to 10-25g/day (oats, psyllium, beans) to reduce LDL by 5-10%. 8
• Add plant sterols/stanols 2g/day to reduce LDL by an additional 6-15%. 8
• Omega-3 fatty acids (EPA/DHA) 2-4g/day can reduce triglycerides by 20-50% but have minimal effect on LDL. 8
• The 1500 calorie diet with strict macro tracking should emphasize Mediterranean dietary patterns with emphasis on monounsaturated fats. 3

Medication Adherence and Follow-Up

• Verify medication adherence before making further changes, as non-adherence is the most common cause of apparent treatment resistance. 2, 3, 4, 5
• Consider single-pill combination therapy to simplify the regimen and improve adherence. 1, 3
• Schedule follow-up within 2-4 weeks after adding the diuretic to assess BP response and check electrolytes. 1, 2
• Refer to a hypertension specialist if BP remains uncontrolled (≥160/100 mmHg) despite four-drug therapy at optimal doses. 1, 3