A plea for statin use in

primary prevention

Nicolas DANCHIN,

HEGP, Paris nicolasdanchin@yahoo.fr

Research grants: Astra-Zeneca, Eli-Lilly, GSK, Merck, Novartis, Pfizer, sanofi-aventis, Servier, The MedCo

Fees for lectures and/or consulting: Astra-Zeneca, Bayer, BMS, Boehringer-Ingelheim, GSK, Daiichi-Sankyo, Eli-Lilly, MSD, Novo-Nordisk, Pfizer, Pierre Fabre, Roche, sanofi-aventis, Servier, The MedCo

Primary prevention: A medical issue

• The most severe CHD events are often the first:

62 46

0

20

40

60

80

100

Men Women

Framingham

83 85

0

20

40

60

80

100

Men Women

FAST-MI 2010

Murabito et al. Circulation 1993; 88: 2548; Hanssen et al. Heart 2012

% of patients with AMI or CV death as first coronary event

% of STEMI patients without previous CHD history

Technical specifications for optimal primary prevention

• Primary prevention is aimed at people who have no complaints

• Ideal primary prevention measures:

– Should not generate any anxiety about the possible occurrence of the disease they are aimed at

– Should not alter quality of life ("joie de vivre")

– Should decrease "target" risk without increasing risk of developing other medical conditions

WHO clofibrate trial in primary prevention

5.9

1.6

4.9

7.4

1.8

3.8

0

1

2

3

4

5

6

7

8

IHDcomplications

IHD death All-causedeath

Clofibrate

Placebo*

Br Heart J 1978; 40: 1069

*

WHO trial Men in Budapest, Prague, Edinburgh - 5331 clofibrate - 5296 placebo 5-year F/U

Mean decrease in cholesterol level on clofibrate: 9%

Meta-analysis of statins Efficacy on CV events according to CV risk

CTT collaborators Lancet 2012; 380: 581

- 0.18 / year

- 0.87/ year

Statins in primary prevention: trials based upon lipid parameters

OR: 0.78 (0.65-0.94) (fixed effects)

OR: 0.87 (0.77-0.97) (fixed effects)

Personal data

Meta-analysis of statins Efficacy on mortality according to CV risk

CTT collaborators Lancet 2012; 380: 581

Short- and long-term tolerance

Statins and cancer: No increased incidence or mortality

CTT collaborators Lancet 2012

Statins and survival in cancer patients: Danish registry

Nielsen et al. NEJM 2012

Statins and new onset diabetes

Lancet 2010

OR

1.14 1.11

1.18

1.03

0.98

Statin dose and new onset diabetes

Preiss et al. JAMA 2011

Statins and new onset diabetes JUPITER

Ridker et al. Lancet 2012

If any risk factor for diabetes present: 134 events or deaths avoided vs 54 cases of diabetes induced If no risk factor for diabetes: 86 events or deaths avoided, no case of diabetes induced

The regulatory point of view

• EMA: The PhVWP concluded that HMGCoA reductase inhibitors may increase the risk of NOD in patients already at risk of developing this disease, but that overall the risk-benefit balance remains clearly positive, given the benefit of HMGCoA reductase inhibitors in reducing major cardiovascular events. A warning should therefore be included in the product information of all HMG CoA reductase inhibitors authorised inthe EU aiming at monitoring of patients at risk.

• FDA: … reports of increased blood sugar and glycosylated hemoglobin (HbA1c) levels has been added to the statin labels. FDA continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.

Myalgia after statin treatment introduction

Adjusted HR = 1.29 (1.15-1.45) HR = 2.12 (1.92-2.35)

Nichols GA et al. Clin Ther 2007

32,225 HMO members 1997-2004 Matched on age and year

Adherence to treatment

Naderi et al. Am J Med 2012

In summary

• Statins reduce CV events and mortality in primary prevention, whatever the risk level

• Tolerance is satisfactory, although there is a definite risk of myalgia

• No increased risk of cancer

• Increased risk of DM at high doses in patients with DM risk factors

Population impact of statin

therapy on CV risk

BEH février 2006

Hommes et femmes 35-74 ans

Br J Clin Pharm 2005

Prescription de statines

= France

Statin use in Europe

Change in standardised incidence of hospitalised AMI: France, 2002-2008

-10.2

-22.7

6.7

-23.7

-30

-25

-20

-15

-10

-5

0

5

10

Men

Women

< 65 years ≥ 65 years

De Peretti et al. BEH 2012; 41: 459-65

Incidence decrease: 2.5 % per year

Statin use and risk of first AMI in France PGRX case-controlled study

• 2238 patients with a recent first MI (≤ 1 month) matched on age, sex, Hx of non CV disease, and date with 2238 patients seen in GP practices.

• OR for developing AMI associated with statin use:

– Current use of statins: 0.67 [0.56 – 0.79]

– Any statin use ≤24 months: 0.73 [0.62 – 0.86]

Grimaldi-Bensouda et al. AHA 2012

Conclusion

• Statins are highly efficacious and have relatively few side-effects.

• From a public health standpoint, statin prescription is justified when CV risk is moderate to high.

• When CV risk is low, whether one would accept the bother of a daily consumption of a pill to further reduce this low risk should be a matter of individual preference.

Back-up

Même les mesures d'hygiène de vie peuvent être dangereuses …

http://www.theheart.org/article/1024841.do