Cardiovascular Risk Reduction in Patients with Type 2 Diabetes
Journal of Clinical Outcomes Management. 2017 February;24(2)
References
) [44,45].
When should initiating pharmacotherapy to reduce risk in primary prevention be considered?
In the population with diabetes, statins and renin-angiotensin-aldosterone inhibition are the mainstays of pharmacotherapy for cardiovascular risk reduction. In the presence of clinical macrovascular disease, the standard of care includes both of these therapies. However, there is also a great deal of data that supports the use of these therapies for primary prevention.
Statins
Major studies on the benefits of statin therapy in people with diabetes have consistently shown decreased cardiovascular disease and mortality. The Heart Protection Study included a subgroup of patients with diabetes in which patients over the age of 40 were randomly assigned to simvastatin or placebo. Consistently across all subgroups, there was a relative risk reduction of 22% to 33% for the primary outcome of first cardiovascular event over 5 years. This effect was maintained even in those who did not have elevated LDL-C at randomization [46]. Similarly, the Collaborative Atorvastatin Diabetes Study (CARDS) randomized patients with T2DM, over age 40, with at least 1 other vascular risk factor to atorvastatin 10 mg or placebo. They found a 37% risk reduction in time to first event over 4 years with atorvastatin, with consistent results across all subgroups [47].
Based on these studies, it is recommended that all patients with diabetes be placed on statin therapy to reduce vascular risk at age 40 years (CDA, ADA, American College of Cardiology/American Heart Association [ACC/AHA]) [20,45,48]. If under age 40 years, statin therapy should be considered in the presence of other risk factors (ADA, ACC/AHA) [45,48], or if diabetes duration is more than 15 years and age is greater than 30 years, or there are micro- or macrovascular complications (CDA) [20].
Renin-Angiotensin-Aldosterone Inhibition
Similar to research into statin therapy, a considerable amount of research has been dedicated to renin-angiotensin-aldosterone system (RAAS) blockade for the primary purpose of vascular risk reduction, even in the absence of hypertension, in those with diabetes. In a prespecified substudy of the Heart Outcomes Prevention Evaluation (HOPE) trial, known as MICRO HOPE, patients with diabetes who were older than 55 years of age, with at least 1 other cardiovascular risk factor, were randomized to receive ramipril 10 mg daily or placebo. In this study, ramipril reduced the risk for myocardial infarction (22%), stroke (33%), cardiovascular death (37%), and all-cause mortality (24%) over 4.5 years [49]. In the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET), patients at high risk for cardiovascular disease were randomized to telmisartan 80 mg or ramipril 10 mg. In the diabetes subgroup, there were similar risk reductions and no statistical difference between the groups [50]. A 2012 meta-analysis assessed the benefits of RAAS blockade compared with placebo for primary prevention in high-risk individuals, or secondary prevention in those with established vascular disease. A reduction in cardiovascular death, all-cause mortality, fatal or nonfatal myocardial infarction, and stroke was seen across all subgroups, including those with and without diabetes or hypertension [51].
The CDA currently recommends that an ACE inhibitor or ARB be given to all patients with diabetes who are 55 years of age or older, or have macro- or microvascular disease, for the primary purpose of decreasing risk for vascular disease, even in the absence of hypertension. An agent and dose with proven vascular protective benefit should be chosen when selecting an ACE inhibitor or ARB [20].
