In patients who do not respond to or do not tolerate treat- ment with 2 to 3 medications or medication combinations, additional trials of treatment tend to be ineffective or poorly tolerated. Some patients may become disillusioned and lost to follow-up, whereas others will identify an alternative health- care provider, including nontraditional healers, or will try popular home remedies. Working with this more demanding subset requires provider expertise, patience, and a mecha- nism to respond efficiently and sensitively to concerns as they arise. In this setting, team-based care (see Section 12) may be effective, encouraging coupling of nonpharmacological and pharmacological treatments, while improving access to and communication with care providers. In the setting of medication intolerance, consider allowing a defined period of time to evaluate the effects of lifestyle mod- ification in patients with a relatively low CVD risk (10-year risk of ASCVD <10%, based on the ASCVD Risk Estimator [http://tools.acc.org/ASCVD-Risk-Estimator]), with sched- uled follow-up visits for assessment of BP levels, including a review of HBPM data, and an appraisal of lifestyle change goal achievements. For patients with a higher level of CVD risk or with significant elevations in BP (SBP or DBP >20 or >10 mm Hg above target, respectively), medication is usually started even while the patient is pursuing lifestyle change (see Section 8.1.2). Consideration of patient comorbidities, lifestyle, and pref- erences may suggest better tolerance or greater effect from one class of medication versus other classes. For example, if hyponatremia is present, it would be important to avoid or stop thiazide diuretic therapy. In this case, a loop diuretic should be used if a diuretic is required. If hypokalemia is present, primary or secondary aldosteronism should be excluded, after which one should consider a potassium-sparing agent, such as spironolactone, eplerenone, triamterene, or amiloride. 