Is it appropriate for a patient with a history of stroke, hypertension, type 2 diabetes mellitus (DMII), and heart disease to be on Trulicity (dulaglutide), Januvia (sitagliptin), and Actos (pioglitazone)?

Medication Appropriateness in High-Risk Cardiovascular Patient

This patient should continue Trulicity (dulaglutide) given his established cardiovascular disease and stroke history, but Actos (pioglitazone) should be discontinued due to heart failure risk, and Januvia (sitagliptin) can be continued as it is cardiovascular-neutral.

Trulicity (Dulaglutide) - RECOMMENDED

Dulaglutide is specifically indicated for patients with type 2 diabetes and established cardiovascular disease to reduce major adverse cardiovascular events including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke 1. This patient's history of stroke qualifies as established cardiovascular disease, making dulaglutide an evidence-based choice.

Supporting Evidence for Dulaglutide:

• The REWIND trial demonstrated that dulaglutide reduced the composite primary outcome of non-fatal MI, non-fatal stroke, or cardiovascular death by 12% (HR 0.88,95% CI 0.79-0.99; p=0.026) over 5.4 years of follow-up 2
• GLP-1 receptor agonists including dulaglutide are recommended by the 2019 ESC guidelines for patients with type 2 diabetes and established cardiovascular disease to reduce cardiovascular events 3
• The American Diabetes Association recommends GLP-1 receptor agonists like dulaglutide for patients with established cardiovascular disease 4
• Dulaglutide has no contraindication for use in patients with hypertension 4

Important Caveat:

• Gastrointestinal adverse events are common (47.4% vs 34.1% with placebo), so monitor for nausea, vomiting, and diarrhea 2

Januvia (Sitagliptin) - ACCEPTABLE TO CONTINUE

Sitagliptin is cardiovascular-neutral and can be safely continued in this patient, though it provides no additional cardiovascular protection beyond glycemic control 5.

Supporting Evidence for Sitagliptin:

• The TECOS trial demonstrated that sitagliptin was noninferior to placebo for major adverse cardiac events in patients with type 2 diabetes and established cardiovascular disease 5
• DPP-4 inhibitors including sitagliptin have a neutral effect on heart failure risk and may be considered 3
• Sitagliptin does not increase risk of hypoglycemia or weight gain 5
• No evidence suggests sitagliptin affects stroke incidence 6

Important Consideration:

• While sitagliptin is safe, it does not provide the cardiovascular risk reduction that dulaglutide offers, making it a less optimal choice as monotherapy in this high-risk patient 5

Actos (Pioglitazone) - NOT RECOMMENDED

Thiazolidinediones including pioglitazone are contraindicated in patients with heart failure and should be avoided in this patient with established heart disease 3.

Evidence Against Pioglitazone in This Patient:

• The 2019 ESC guidelines explicitly state that thiazolidinediones (pioglitazone and rosiglitazone) are not recommended in heart failure 3
• While pioglitazone reduced recurrent stroke risk in the PROactive trial subgroup analysis (HR 0.53,95% CI 0.34-0.85; p=0.0085), this benefit is outweighed by heart failure risk in patients with established heart disease 7
• Pioglitazone increases fluid retention and weight gain, which can precipitate or worsen heart failure 8

Exception to Consider:

• The only scenario where pioglitazone might be considered is if this patient has documented absence of heart failure on echocardiography and recurrent stroke despite optimal therapy, but even then, alternative agents are preferred 7, 6

Blood Pressure Management

This patient requires aggressive blood pressure control with target <130/80 mm Hg using ACE inhibitors or ARBs combined with thiazide diuretics 3.

• Angiotensin-converting enzyme inhibitors combined with thiazide diuretics reduce stroke recurrence risk in patients with prior stroke 3
• The 2021 AHA/ASA stroke prevention guidelines recommend office BP goal <130/80 mm Hg for most patients with prior stroke or TIA 3
• ACE inhibitors or ARBs should not be combined together as this increases adverse events without additional benefit 4

Lipid Management

High-intensity statin therapy (atorvastatin 80 mg) with ezetimibe if needed to achieve LDL-C <70 mg/dL is essential for this patient 3.

• Patients with ischemic stroke and atherosclerotic disease require LDL-C goal <70 mg/dL 3
• Statin therapy reduces cardiovascular events and stroke recurrence in diabetic patients with established cardiovascular disease 3

Clinical Algorithm Summary

1. Continue Trulicity (dulaglutide) - provides cardiovascular and stroke risk reduction 1, 2
2. Continue Januvia (sitagliptin) - cardiovascular-neutral, safe option 5
3. Discontinue Actos (pioglitazone) - contraindicated in heart disease due to heart failure risk 3
4. Optimize blood pressure control with ACE inhibitor/ARB + thiazide diuretic to target <130/80 mm Hg 3
5. Ensure high-intensity statin therapy with LDL-C goal <70 mg/dL 3
6. Consider adding SGLT2 inhibitor for additional cardiovascular and renal protection 3, 4