Therapeutic Strategies to Prevent Recurrent Stroke

Antihypertensive treatment reduces the risk of stroke recurrence and is beneficial in patients with hypertension and even in subjects who were normotensive before suffering the first stroke. The optimal blood pressure (BP) target after stroke is not the same for all patients and depends on age, frailty, and comorbidities, among other conditions. In addition to lifestyle changes (smoking cessation, Mediterranean or DASH diet, alcohol cessation, low-salt consumption, weight loss, physical activity), antihypertensive trials suggest that benefits largely depend on BP lowering per se, and then all available drugs and rational combinations can be used. However, the choice of specific drugs and targets should be individualized based on patient characteristics for which specific agents are indicated. Antihypertensive treatment with angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), in association with thiazide or thiazide-like diuretics and dihydropyridine calcium channel blockers (CCB) has demonstrated the greatest benefits for stroke patients. Combination therapy is more effective than monotherapy and should be initiated once post-stroke patients are stabilized, usually several days or weeks after the event. The preferred strategy for secondary prevention of stroke in patients with type 2 diabetes mellitus (T2DM) should include a combination of metformin and glucagon-like peptide-1 receptor antagonist (GLP-1RA). Meta-analyses in T2DM patients suggest greater benefits for pioglitazone and some GLP-1RA compared to other classes of antidiabetic medications. Despite the significant cardiovascular benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i), they have not demonstrated to reduce the risk of recurrent stroke. In addition to lifestyle-behavioural changes, aggressive management of dyslipidaemia is recommended by major guidelines for secondary prevention of stroke. For high-risk patients, low density lipoprotein-C (LDL-C) target is <70 mg/dL. For very high-risk patients, LDL-C goal <55 mg/dL is recommended. High-intensity statin therapy is the first line treatment. If LDL-C targets are not achieved, ezetimibe and/or proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) should be added. If the patient has baseline triglyceride levels between 150 and 500 mg/dL, treatment with IPE may be considered to lower risk of recurrent events.