AusDoc 31st Oct | Page 23

ausdoc. com. au 31 OCTOBER 2025

HOW TO TREAT 23 risk [ RR ] 0.75; 95 % CI 0.67-0.85); fatal / non-fatal stroke( RR 0.69; 95 % CI 0.51-0.92); and fatal / non-fatal MI( RR 0.70; 95 % CI 0.54-0.90). 37 For this reason, rosuvastatin and atorvastatin are the most prescribed drugs on the PBS, with more than 80 per 1000 Australians taking them every day. 38

It is standard practice to start at the lowest dose and reassess LDL-C lowering and adherence 4-6 weeks later. The goal is to reduce the patient’ s LDL-C by more than 50 % of their baseline level. If this goal is not met, the statin dose is then increased, re-evaluated and increased further as required. Highrisk patients will usually need to take 40-80mg of atorvastatin or 20-40mg of rosuvastatin daily( see table 1).

The PBS subsidises the use of statins and ezetimibe for lipid-lowering therapy in patients with T2DM without CVD based on longstanding criteria that predate the widespread use of CVD risk calculators( see box 3). Nonetheless, these criteria effectively capture most patients with T2DM at increased CVD risk.

In patients with a moderate risk of CVD( 5-10 % on the cardiovascular risk calculator), moderate-intensity statin therapy, in addition to lifestyle modifications, can be used to reduce the risk of MI or stroke( by about 30 %). But with lower baseline CVD risk, the absolute benefit from treatment is also lower in these patients. The decision to prescribe statins in primary care in this setting should therefore be a shared decision, informed by the potential for limited but significant benefits, as well as costs and the risk of side effects. Most patients with moderate CVD risk, but not all, are captured through the PBS subsidy program, with the remainder being able to access statins through relatively low-cost private scripts for statins.

In general, patients with T2DM at low CVD risk do not need to be treated with a statin, but their CVD risk should be monitored closely, and the need for therapy re-evaluated, as required.

In patients with T2DM on maximum tolerated statin doses, additional lipid-lowering therapy may be considered where there remains substantial residual risk( eg, patients with chronic kidney disease, persistent dyslipidaemia, high CAC score, strong family history). Inhibiting cholesterol absorption with ezetimibe, used in a fixed-dose combination with their statin of choice, can provide a simple add-on and is PBS subsidised. PCSK9 inhibitors( eg, evolocumab, alirocumab and inclisiran) can also achieve substantial lipid lowering but are not currently subsidised for patients with T2DM without established CVD, and the high cost of a private prescription is prohibitive for most patients.

Optimal blood pressure control

Most people with T2DM will not have adequate control of their blood pressure or achieve recommended blood pressure targets without medication. A key component of diabetes management is to improve blood pressure control, without unduly increasing the treatment burden, side effects

Assess and manage residual risks

First line

Foundation

or cost and their knock-on impact on adherence. Measure the blood pressure of all patients with T2DM, in a standardised way, at every clinic visit, with additional home or ambulatory monitoring applied where office blood pressure measurements are equivocal. All patients with T2DM at increased CVD risk should aim to achieve and maintain an office systolic blood pressure of

less than 130mmHg to lower their risk of cardiovascular events and improve survival. A lower systolic blood pressure target, of less than 120mmHg, may be appropriate for some individuals at increased CVD risk, particularly to reduce the risk of stroke and / or albuminuric kidney disease.

If a patient has a high CVD risk, just targeting a systolic blood pressure of less than 140mmHg may not optimally reduce their risks. For example, the recent BPROAD( Blood Pressure Control Target in Diabetes) study compared systolic blood-pressure targets of less than 120mmHg and less than 140mmHg in 12,821 patients with T2DM at increased CVD risk across 145 sites in China, using treatment protocols similar to the SPRINT( Systolic Blood Pressure Intervention Trial) study in non-diabetic individuals. 39, 40 Over

GLP-1 RAs

↓HbA1c

SGLT2i

a median of 4.2 years, the composite outcome of MACE and heart failure hospitalisation was reduced by 21 %( hazard ratio [ HR ] 0.79; 95 % CI 0.69-0.90) by intensive blood-pressure control. This benefit was most driven by the strong effect on stroke, which constituted more than 70 % of all primary cardiovascular outcome events in the standard of care group. 39 A similar benefit on fatal and non-fatal stroke was also observed in the ACCORD( Action to Control Cardiovascular Risk in Diabetes) trial( HR 0.59; 95 % CI 0.39-0.89) and the ADVANCE( Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation) study( HR 0.82; 95 % CI 0.68- 0.98). 41, 42 Although a blood pressure target of less than 130mmHg remains the same, noting that East Asian patients, and particularly those with T2DM and high CVD risk, have an elevated stroke risk compared with Caucasian individuals, lower blood pressure targets may be considered of particular value in such patients. 43 Equally, as women have a higher risk of stroke than men, this may warrant a lower blood pressure target in selected female patients with T2DM at high CVD risk. 44

Referral

CCB ± diuretic

↓SBP with RAASi

Almost all individuals with T2DM at high CVD risk will likely need treatment with a combination of antihypertensive agents to rapidly achieve and maintain adequate blood pressure control. 45 This means that consideration of which agent may be best is largely moot, superseded by what will be the best combination for any individual. The most important feature of effective treatment is longterm adherence using easy regimens with few or no side effects. It is generally recommended that blood pressure lowering in patients with T2DM is achieved with an ACEI or ARB, with or without a long-acting dihydropyridine calcium-channel blocker( CCB) or a thiazide-like diuretic( eg, chlorthalidone). This is ideally delivered as a fixed-dose combination with renin-angiotensin-aldosterone system( RAAS) inhibition to enhance treatment adherence, which is rapidly up-titrated to target. If the blood pressure target has not been achieved, triple therapy with a RAAS inhibitor, CCB and a thiazide-like diuretic is recommended. As those with T2DM often experience a non-dipping pattern of high blood pressure, it has been suggested that evening dosing with antihypertensive agents could be beneficial. This is known

46, 47 as‘ chronotherapy’.

SGLT2 inhibition

Treatment with SGLT2 inhibitors lowers the risk of MACE,

Highintensity statin

Ezetimibe

Cardiovascular risk assessment and communication Diet and lifestyle optimisation Adherence + education + monitoring + screening

Figure 5. Multifactorial management of patients with T2DM and high CVD risk. RA = receptor agonist, CCB = calcium-channel blocker, i = inhibitor, SBP = systolic blood pressure, RAAS = renin-angiotensin-aldosterone system.

Table 1. Statin doses High-intensity statin Moderate-intensity statin Low-intensity statin Atorvastatin 40-80mg Atorvastatin 10-20mg Simvastatin 10mg Rosuvastatin 20-40mg Rosuvastatin 5-10mg Pravastatin 10-20mg Simvastatin 20-40mg Lovastatin 20mg Pravastatin 40-80mg Fluvastatin 20-40mg Lovastatin 40mg Pitavastatin 1mg Fluvastatin XL Fluvastatin Pitavastatin

80mg 40mg bd

2-4mg

A key component of diabetes management is to improve blood pressure control.

Box 3. The PBS criteria for subsidised use of lipid-lowering therapy in patients with T2DM without established CVD( ie, primary prevention).

• Aged 60 or older, or

• Total cholesterol greater than 5.5mmol / L, or

• Family history of CVD, or

• Elevated urinary albumin-tocreatinine ratio( greater than 2.5 for males, greater than 3.5 for females), or

• Indigenous patients.

Lowdose aspirin

cardiovascular mortality and heart failure in people with T2DM at high CVD risk. 48 Most of these data have been demonstrated in patients with established CVD, and heterogeneity analyses suggest that the relative benefit of SGLT2 inhibition may be similar in patients without CVD. 49 Real-world data also support a substantial reduction in cardiovascular events in patients with T2DM without CVD( ie, primary prevention), including a reduction in new-onset heart failure( that is increasingly the first presentation of CVD in patients with T2DM; see earlier). 50

Noting the additional benefits of SGLT2 inhibition in chronic kidney disease( all patients with T2DM and high risk for CVD may be considered high risk for chronic kidney disease), current guidelines recommend the use of SGLT2 inhibitors in all adults with T2DM at high CVD risk, regardless of baseline HbA1c; this is to reduce the risk of MACE, kidney failure and / or hospitalisation due to heart failure. 5, 6, 48 In July 2024, the PBAC recommended that SGLT2 inhibitors be PBS-subsidised for the treatment of T2DM in combination with metformin( unless contraindicated / intolerant), for patients at high risk of a cardiovascular event.

GLP-1 receptor agonists

Most people with T2DM and elevated CVD risk have overweight or obesity, reflecting the key role of excess ectopic fat in the development and progression of T2DM and CVD. Significant weight loss( greater than 10 %) is associated with improved cardiovascular risk

51, 52 factors in patients with T2DM. The induction of significant weight loss with GLP-1 RAs, alongside powerful effects on glucose control, has markedly increased the use of incretin-based therapies in T2DM. In addition, recent trials in people with T2DM at high CVD risk have reported that treatment with GLP-1 RAs is independently associated with a reduction in cardiovascular events, including benefits in individuals without CVD. 53 These eight cardiovascular outcome trials collectively showed that