Canadian Lipid Guidelines Update

1 FacultyCanadian LipidGuidelines Update Expert Opinions is published by Pharmacomm Ltd. J. Robin Conway, MD, PhDCanadian Centre for Researchon DiabetesSmiths Falls, ONJacques Genest,MDMcGill UniversityMontr al, QCRafik Habib, MDCentre cardiovasculaire de LavalLaval, QCLawrence Leiter,MDSt. Michael s HospitalUniversity of TorontoToronto, ONPublications Mail Agreement Number 40816046 Canada Post: Please return undeliverable mail blocks to:PTM Health, 20 Torbay Road, Markham, ON L3R 1G6 Volume 1, number 10 For more information please 1/25/07 8:14 AM Page 1 Update on Lipid management in CanadaSince the last publication of recommendations for the management andtreatment of dyslipidemia,1,2important new clinical data has emerged tosupport more intensive Lipid lowering in certain patient groups.

2 Recentstudies in subjects with both stable coronary artery disease (CAD) as wellas in those with an acute coronary syndrome (ACS), such as theTreatment to New Targets (TNT),3 Incremental Decrease in Endpointsthrough Aggressive Lipid Lowering (IDEAL)4and PRavastatin OratorVastatin Evaluation and Infection Therapy (PROVE-IT)5studies haveshown that lowering LDL-cholesterol more intensively, to a value of at least< mmol/L is associated with additional cardiovascular risk reduction inthese high-risk individuals. This has been further supported by two surro-gate endpoint studies, REVERSal of Atherosclerosis with Lipitor (REVER-SAL)6and A Study To Evaluate the effect of Rosuvastatin On Intravascularultrasound-Derived coronary atheroma burden (ASTEROID),7which bothdemonstrated slowing or regression of atherosclerosis using intravascularultrasound (IVUS).

3 Treatment benefit in intermediate- and high-risk (5-10% of the study population) groups was also shown in the Anglo-Scandinavian Cardiac Outcome Trial (ASCOT),8even in those patientswithout overt dyslipidemia. As a result of some of this data, the NationalCholesterol Education Program Adult Treatment Panel III updated theirtreatment recommendations in 2004 to reflect an optional lower LDL-C target in very high risk to Canadian Recommendations for Lipid ManagementIn light of these recent data, Canadian Guidelines for the management ofdyslipidemia have been updated and recently published, by both theCanadian Cardiovascular Society (CCS)10and the Canadian DiabetesAssociation (CDA).

4 11 The CCS position statement was developed basedon reviews of meta-analyses of studies of the efficacy and safety of Lipid -lowering therapies, and of the predictive value of established and emerg-ing risk factors. Emerging risk factors may play a role in moving patientsat intermediate risk to a higher or lower risk category. These risk factorsinclude: laboratory measurements such as apo B, hsCRP, Lp(a), andHbA1C (in patients with elevated plasma glucose); assessment of exer-cise capacity by graded exercise stress testing; non-invasive assessmentof atherosclerosis, such as determination of ankle-brachial index (ABI)and carotid imaging.

5 In high-risk patients, pharmacological treatment isrecommended immediately with diet and exercise. The primary treat-ment goal for most high-risk patients is to achieve an LDL-C of < Once the LDL-C target has been achieved, attempts should bemade to achieve a TC/HDL-C ratio of < by further lifestyle modifica-tion, or through the addition of further Lipid -modifying therapy. Weightloss (if required) and increased physical activity can increase HDL-C levels by approximately 7-10%. If HDL-C is not sufficiently increasedusing these lifestyle modifications, niacin can increase HDL-C levels by15-20%, or fibrates can induce an increase of 6-10%.

6 It is noted thatpeople considered to be at low or moderate risk may actually have highlifetime risk because of other comorbidities such as obesity. It is knownthat the reduction in CAD and stroke events and overall cost-effectivenessof therapy is proportional to the decrease in is therefore recommended that one consider pharmacologic therapy for an LDL-C> mmol/L in patients at moderate risk, and > mmol/L for those atlow risk, and aiming for an LDL-C reduction of at least 40% is con-sidered to be generally appropriate. A 40% LDL reduction can generallybe achieved with atorvastatin 20 mg, rosuvastatin 10 mg, simvastatin 40 mg, or lovastatin 80 recently published national chart audit study of 2473 Canadianpatients with type 2 diabetes revealed that 55% of patients with a diag-nosis of diabetes of 2 years had dyslipidemia.

7 This proportion rose to66% in those who had had diabetes for 15 this, lessthan 50% of diabetic patients in Canada are treated with any Lipid -lower-ing agent. This high burden of dyslipidemia in patients with diabetes, aswell as the increasing compelling trial evidence on the benefits of inten-sive management of dyslipidemia in diabetes, led to a review of the lipidrecommendations published in the Canadian Diabetes Association 2003 Clinical Practice Guidelines for the Prevention and Management ofDiabetes in Canada. The 2006 Lipid Expert Committee used the sameevidence-based methodological principles of the 2003 Guidelines todevelop revised recommendations for adults with diabetes.

8 Once again,it is recommended that the vast majority of people with established dia-betes be considered at high risk of a vascular event, and should betreated accordingly. The targets for people with diabetes previously con-sidered at moderate risk of a vascular event have been eliminated inthese new recommendations. Instead, the LDL-C target has been low-ered from < mmol/L to mmol/L and is now recommended as theprimary goal in the management of dyslipidemia. First-line treatmentshould consist of optimally dosed statin therapy. This means giving anappropriate statin at an appropriate dose.

9 If this does not lower LDL to 2 mmol/L, then the addition of a cholesterol absorption inhibitor suchas ezetimibe should be associated with a further 20% LDL-C the LDL-C target has been achieved, physicians can consider addi-tional therapies to achieve the secondary target of a TC/HDL-C ratio of< to Achieving Lower LDL-C TargetsThere is a major challenge in Lipid management today in achieving therecommended LDL-C treatment goal. An analysis from 8182 patients intwo prospective Canadian registries (Vascular Protection [VP] and theGuideline Orientated Approach to Lipid Lowering [GOALL])14showed that78% of high-risk patients (with either established cardiovascular diseaseor diabetes) were receiving a Lipid -lowering agent.

10 However, only ofthese patients had achieved the then recommended LDL-cholesterol targetof < mmol/L. For patients with diabetes without cardiovascular disease,the target was achieved in only of patients. Persons with both vas-cular disease and diabetes are at the highest CV risk, yet only 59% ofthese individuals had an LDL-C mmol/L. Similarly, the Canadian LipidStudy-Observational (CALIPSO)15studied 3721 patients on statin therapy,and showed that 68% of these subjects were at high risk for coronaryartery disease. Of these high-risk patients, 36% had not achieved the thentarget LDL-C of < mmol/L.