Step 1 is relevant for all patients with PAD regardless of severity or comorbidity. All patients should be counseled on diet and exercise, be taught about home-based exercise and/or referred to supervised exercise where available, should stop smoking, and should have optimized blood pressure and cholesterol levels. Data from the HOPE trial demonstrated a reduction in MACE with ramipril, an angiotensin-converting enzyme inhibitor (ACEi) with consistent benefit in patients with PAD. Therefore, there is preference to use ACEi therapy, particularly in patients with diabetes. Patients with PAD and hypertension may need more than one agent. Beta blockers are safe to use in PAD if there is an indication (e.g. concomitant coronary disease). Selection of antihypertensive agents should be similar to that for blood pressure control in patients with atherosclerosis.
Cholesterol lowering has shown benefit in patients with atherosclerosis and specifically in patients with PAD. The Heart Protection Study demonstrated that simvastatin (vs. placebo) reduced major adverse cardiovascular events in a broad population with consistent benefit in those with PAD. A subsequent analysis in the PAD population showed a reduction in peripheral revascularizations. In addition, smaller studies have shown functional improvements with statins. Non-randomized data from the REACH registry suggest that statin therapy reduces amputation in patients with PAD. The FOURIER trial demonstrated that adding a PCSK9 inhibitor to statin therapy resulted in significant reductions in MACE and MALE in patients with PAD. These benefits were evident regardless of whether there was concomitant symptomatic coronary or cerebrovascular disease. Importantly, the benefits of reducing LDL-C for MACE and MALE extended to very low levels of LDL-C (<10 mg/dL) with no imbalance of adverse events or safety issues. The broad benefits in PAD for this therapy translated to a number needed to treat for MACE or MALE for 2.5 years of 16. Adherence can be an issue with all therapies and it is important to provide education, reinforce the benefits of therapy at each visit, answer questions, and monitor targets.