MACROVASCULAR COMPLICATIONS, DYSLIPIDEMIA and HYPERTENSION 2003 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada

VASCULAR PROTECTION  Some of the available treatments, such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor II antagonists (ARBs) have potential uses in controlling blood pressure and reducing the risks for cardiovascular disease (CVD) and renal disease.  The priorities for vascular and renal protection should be: 1. Vascular protection 2. Blood pressure control 3. Renal protection

PRIORITIES FOR VASCULAR & RENAL PROTECTION Clinical IssueTarget PopulationInterventions 1. Vascular protectionAll people w/DMACE inhibitor, ASA, BP control, glycemic control, lifestyle modification, lipid control, smoking cessation 2. Elevated BPAll people w/DM with hypertension (regardless of whether nephropathy is present) Rx according to hypertension guidelines 3. Renal protectionAll people w/DM with nephropathy (even in the absence of hypertension) Rx according to nephropathy guidelines

STRATEGIES FOR VASCULAR PROTECTION In alphabetical order: ACE inhibitor Antiplatelet therapy (e.g. ASA) Blood pressure control Glycemic control Lifestyle modification Lipid control Smoking cessation

DYSLIPIDEMIA  Diabetes is associated with high risk for vascular disease and aggressive lipid management is generally necessary. Attention to the full lipid profile is required because hypertriglyceridemia and low HDL-cholesterol are particularly common.  Patients should be assessed for their risk of a vascular event. Most patients with diabetes are at high risk. Younger patients with a shorter duration of diabetes and without other risk factors and without diabetic complications would be considered at moderate risk.

LIPID TARGETS BASED ON RISK OF A VASCULAR EVENT Risk LDL-C (mmol/L) TC : HDL-C High (most DM) < 2.5and< 4.0 Moderate< 3.5and< 5.0  Moderate risk = younger age with short duration of DM, no complications and no other CVD risks.  TG are not indicated as a target because almost all individuals with hyper- triglyceridemia can be identified as having an elevated TC:HDL-C.  Optimal TG is < 1.5 mmol/L. Optimal apo B: < 0.9 g/L for high-risk individuals, and 1.05 g/L for moderate-risk individuals

TREATMENT OF DYSLIPIDEMIA Lipid statusTherapy LDL-C above targetLifestyle + statin High risk patients with: TG 1.5 – 4.5 mmol/L and HDL-C < 1.0 and LDL-C at target Lifestyle + statin or fibrate TG > 4.5 mmol/LLifestyle + fibrate When monotherapy plus lifestyle fails to achieve lipid targets, the addition of a second drug from another class should be considered.

DRUGS FOR DYSLIPIDEMIA

HYPERTENSION  Recommended blood pressure (BP) targets are: < 130/80 mm Hg  Values above systolic 130 mm Hg or diastolic 80 mm Hg are the BP thresholds recommended to initiate treatment.  These values apply regardless of whether nephropathy is present.

HYPERTENSION  Results of the Hypertension Optimal Treatment (HOT) and UKPDS 38 trials provide strong evidence for the diastolic target of 80 mm Hg. Both trials demonstrated clinically important reductions in micro- and macrovascular complications and CV death.  The evidence for a systolic target of 130 mm Hg is less strong, and includes 2 prospective cohort studies and the ABCD trial.

HYPERTENSION TREATMENT  For people with diabetes without nephropathy, any one of these is recommended as initial choice (in the following order) if BP cannot be controlled by lifestyle interventions:  ACE inhibitor  ARB  Cardioselective beta-blocker  Thiazide-like diuretic  Long-acting CCB  Clinical trial evidence exists for each of these classes of drugs reducing clinically important vascular outcomes in people with diabetes.

HYPERTENSION TREATMENT  Multiple drugs will often be needed to approach, if not meet, the recommended BP targets.  For example, in the UKPDS, 29% of subjects randomized to tight control required at least 3 antihypertensive drugs by trial’s end.

ANTIPLATELET THERAPY  Platelet dysfunction in diabetes may contribute, in part, to the increased risk of CVD morbidity and mortality. Patients with diabetes have a variety of alterations in platelet function that can predispose to increased platelet activation and thrombosis.  ASA appears to be as effective as other antiplatelet agents and is the best choice given that it is the most widely studied and the most economical. The lowest effective dose ( mg/day) should be used to limit both gastrointestinal toxicity and potential adverse effects of prostaglandin inhibition on renal function or BP control.  ASA therapy does not increase the risk of vitreous hemorrhage in patients with diabetic retinopathy.

MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS  The first priority in the prevention of diabetes complications should be reduction of cardiovascular (CV) risk by vascular protection through a comprehensive multifaceted approach (in alphabetical order):  ACE inhibitor and antiplatelet therapy (e.g. acetylsalicylic acid [ASA]) as recommended  optimize BP and glycemic control  lifestyle modifications  optimize lipid control and  smoking cessation [Grade D, Consensus].

 People with type 1 or type 2 diabetes should be encouraged to adopt a healthy lifestyle to lower their risk of CVD. This entails adopting healthy eating habits, achieving and maintaining a healthy weight, engaging in regular physical activity, and stopping smoking [Grade D, Consensus]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 A fasting lipid profile (TC, HDL-C, TG and calculated LDL-C) should be conducted at the time of diagnosis of diabetes and then every 1 to 3 years as clinically indicated. Apo B can also be measured to accurately estimate atherogenic particle number. More frequent testing should be done if treatment for dyslipidemia is initiated [Grade D, Consensus]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 Most people with type 1 and type 2 diabetes should be considered at high risk for vascular disease [Grade A, Level 1]. However, some people with type 1 or type 2 diabetes may be considered at moderate risk, such as younger patients with shorter duration of disease and without complications of diabetes and without other risk factors [Grade A, Level 1]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 Patients with diabetes should be treated to achieve the following target lipid goals:  for patients at high risk of a vascular event: LDL-C < 2.5 mmol/L and TC:HDL-C < 4.0;  for patients at moderate risk of a vascular event: LDL-C < 3.5 mmol/L and TC:HDL-C < 5.0 [Grade D, Consensus]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 Although current evidence does not support specific targets for apo B or TG, the optimal TG level is < 1.5 mmol/L, and the optimal levels for apo B are < 0.9 g/L for high-risk patients and < 1.05 g/L for moderate-risk patients [Grade D, Consensus]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 The following should be considered when choosing treatments for patients with dyslipidemia:  In cases where LDL-C is above target, a statin should be prescribed [Grade A, Level 1A].  In high-risk patients with TG levels of 1.5 to 4.5 mmol/L, HDL-C < 1.0 and LDL-C at target, either a statin [Grade A, Level 1A] or fibrate [Grade B, Level 2] can be prescribed.  In patients with marked hypertriglyceridemia (TG levels > 4.5 mmol/L), a fibrate should be prescribed [Grade D, Consensus].  When monotherapy fails to achieve lipid targets, the addition of a second drug from another class should be considered [Grade D, Consensus]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 Lifestyle interventions to reduce BP, including achieving and maintaining a healthy weight, and limiting sodium and alcohol intake, should be considered [Grade D, Consensus]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 BP should be measured at every diabetes visit. Patients with systolic BP > 130 mm Hg or diastolic BP > 80 mm Hg should have their BP remeasured on a separate visit [Grade D, Consensus].  Persons with diabetes should be treated to target a systolic BP 130 mm Hg and diastolic BP > 80 mm Hg are the thresholds recommended to initiate treatment [Grade D, Consensus]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 For people with diabetes, no diabetic nephropathy, and BP levels > 130 mm Hg and/or > 80 mm Hg despite lifestyle modification, any 1 of the following drugs is recommended as the initial choice of therapy, in the following order [Grade D, Consensus for the order]  ACE inhibitor [Grade A, Level 1A];  ARB [Grade A, Level 1A for co-existent left ventricular hypertrophy (LVH); Grade B, Level 2 if LVH is not present];  cardioselective beta blocker [Grade B, Level 2];  thiazide-like diuretic [Grade A, Level 1A]; or  long-acting CCB [Grade B, Level 2]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 If BP targets cannot be reached despite the use of 1 of the above drug choices as monotherapy, use of 1 or more of these or other antihypertensive drugs in combination should be considered [Grade D, Consensus].  Alpha-adrenergic blocker are not recommended as first-line agents for the treatment of hypertension in persons with diabetes [Grade A, Level 1A]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS

 Unless contraindicated, low-dose ASA therapy (80 to 325 mg/day) is recommended in all patients with diabetes with evidence of CVD, as well as for those individuals with atherosclerotic risk factors that increase their likelihood of CV events [Grade A, Level 1A]. MACROVASCULAR COMPLICATIONS - RECOMMENDATIONS