MACROVASCULAR COMPLICATIONS, DYSLIPIDEMIA and HYPERTENSION 2003 Clinical Practice Guidelines for the…

MACROVASCULAR COMPLICATIONS, DYSLIPIDEMIA and HYPERTENSION

2003 Clinical Practice Guidelinesfor 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 protection2. Blood pressure control3. Renal protection

PRIORITIES FOR VASCULAR & RENAL PROTECTION

Clinical Issue Target Population Interventions1. Vascular protection

All people w/DM ACE inhibitor, ASA, BP control, glycemic control, lifestyle modification, lipid control, smoking cessation

2. Elevated BP All people w/DM with hypertension (regardless of whether nephropathy is present)

Rx according to hypertension guidelines

3. Renal protection All people w/DM with nephropathy (even in the absence of hypertension)

Rx according to nephropathy guidelines

STRATEGIES FORVASCULAR PROTECTION

In alphabetical order:ACE inhibitorAntiplatelet therapy (e.g. ASA)Blood pressure controlGlycemic controlLifestyle modificationLipid controlSmoking 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) < 2.5 and < 4.0

Moderate < 3.5 and < 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 DYSLIPIDEMIALipid status Therapy

LDL-C above target Lifestyle + 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/L Lifestyle + fibrate

When monotherapy plus lifestyle fails to achieve lipid targets, the addition of a second drug from another class should be considered.

Drug class Effect(s) Otherconsiderations

Bile acid sequestrants Lower LDL-C Tend to raise TG

Cholesterol absorptioninhibitor

Lower LDL-C Use as monotherapy orwith a statin

Fibrates Lower TGRaise HDL-CLower TC:HDL-CShift LDL-C from smallerto larger particles

May paradoxically raiseLDL-C in 10-15% ofpatients

Nicotinic acid Lowers TG, LDL-C, apo BRaises HDL-C

May cause insulinresistance and worsenglycemic control

Statins (HMG-CoAreductase inhibitors)

Lower LDL-C and apo BImprove TC:HDL-C

Modest TG lowering andHDL-C raising at highdoses

DRUGS FOR DYSLIPIDEMIA

Drug class Generic Name Trade name

Bile acid sequestrants cholestyraminecolestipol

Questran, Questran light,Colestid

Cholesterol absorptioninhibitor

ezetimibe Ezetrol

Fibrates bezafibratefenofibrategemfibrozil

BezalipLipidil Micro, Lipidil SupraLopid

Niacin derivatives nicotinic acid

Statins (HMG-CoAreductase inhibitors)

atorvastatinfluvastatinlovastatinpravastatinrosuvastatinsimvastatin

LipitorLescolMevacorPravacholCrestorZocor

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 (80-325 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].


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].


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].


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].


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].


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].


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


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 [Grade C, Level 3] and a diastolic BP 80 mm Hg [Grade A, Level 1A]. Systolic BP > 130 mm Hg and diastolic BP > 80 mm Hg are the thresholds recommended to initiate treatment [Grade D, Consensus].


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].


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].


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].


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