Statins for Prevention of CV Events and Mortality in Older Men

Abstract and Introduction

Abstract

Background/Objectives We sought to determine whether statin use for primary prevention is associated with a lower risk of cardiovascular events or mortality in older men.

Design Prospective cohort study.

Setting Physicians' Health Study participants.

Participants 7,213 male physicians ≥70 years without a history of cardiovascular disease (CVD).

Measurements Multivariable propensity score for statin use with greedy matching (1:1) to minimize confounding by indication.

Results Median baseline age was 77 (70–102), median follow-up was 7 years. Non-users were matched to 1,130 statin users. Statin use was associated with an 18% lower risk of all-cause mortality, HR 0.82 (95% CI 0.69–0.98) and non-significant lower risk of CVD events, HR 0.86 (95% CI 0.70–1.06) and stroke, HR 0.70 (95% CI 0.45–1.09). In subgroup analyses, results did not change according to age group at baseline (70–76 or >76 years) or functional status. There was a suggestion that those >76 at baseline did not benefit from statins for mortality, HR 1.14 (95% CI 0.89–1.47), compared to those 70–76 at baseline, HR 0.83 (95% CI 0.61–1.11); however the CIs overlap between the two groups, suggesting no difference. Statin users with elevated total cholesterol had fewer major CVD events than non-users, HR 0.68 (95% CI 0.50–0.94) and HR 1.43 (95% CI 0.99–2.07)), respectively.

Conclusions Statin use was associated with a significant lower risk of mortality in older male physicians ≥70 and a nonsignificant lower risk of CVD events. Results did not change in those who were >76 years at baseline or according to functional status. There was a suggestion that those with elevated total cholesterol may benefit. Further work is needed to determine which older individuals will benefit from statins as primary prevention.

Introduction

Guidelines suggest there is limited evidence to recommend statins for primary prevention of cardiovascular disease (CVD) in adults >75 years.^[1,2] This may be a direct result of excluding older individuals, particularly those with multimorbidity, from randomized trials.^[3] However, prescriptions for statins for individuals >70 has increased significantly in the last two decades.^[4] In 2008, 40% of the Medicare population was prescribed a statin.^[5] In 2011, 12.5 million Medicare beneficiaries were >80,^[6] amounting to a significant investment of resources for a drug for which there is as yet no clear evidence of benefit in the oldest and fastest growing segment of the population.^[7]

Multiple primary and secondary prevention trials^[8–13] demonstrated that statins reduce mortality and cardiovascular (CV) events in those <75 years. A meta-analysis of primary prevention statin trials in older adults (mean age 73) revealed a reduction in CV events, but not mortality.^[14] Limited, conflicting evidence has generated significant debate,^[15–17] and calls for additional trials.^[18]

One challenge involves identifying older adults at increased CVD risk who might benefit from statins for primary prevention. Using the Pooled Cohort Risk Assessment Equation,^[1] as recommended by cholesterol guidelines, white men >70 with optimal risk factors have a predicted 10-year risk of CVD of 15.7%. The guidelines suggest that those with an estimated risk >7.5% should be offered a statin. No specific recommendations are made for patients >75. Existing risk assessments, such as the Framingham risk score and the European SCORE were not developed in older cohorts and do not account for multimorbidity, function, frailty, or life limiting illnesses.^[19]

Additionally, the older adult population has long had inconsistent prescription patterns for many medications, including under-prescription of statins.^[20] This may reflect clinicians' hesitancy to use a drug with side effects and drug-drug interactions that has not been studied in the very old.^[21] Thus, we sought to examine the relationship between statin use for primary prevention of major CV events and mortality in men >70, with particular attention to those >75 years in subgroup analysis.

Table 1. Baseline Characteristics of 2,260 US Male Physicians According to Statin Use and Propensity Score Matching
Variable*	Propensity Score Matched (%)
Statin (n = 1,130)	No Statin (n = 1,130)	P-value
Age, mean (SD)	76.0 ± 4.5	76.0 ± 4.6	.88
BMI, mean (SD)^a	25.6 ± 3.1	25.6 ± 3.2	.68
White race^a	94.3	94.0	.79
Smoking Status^a
Current	2.9	3.3
Past	48.9	50.5	.61
Never	48.2	46.2
Hyperlipidemia	98.1	97.9	.65
Hypertension^a	73.8	75.3	.42
Diabetes^a	13.0	13.1	.94
Heart failure^a	2.9	3.0	.80
Renal disease^a	10.8	10.6	.88
Liver disease^a	15.2	16.1	.58
Cancer	20.0	20.9	.60
Depression^a	12.7	13.1	.79
Dementia	2.7	2.7	.90
Aspirin use	72.5	71.3	.53
Hypertension medication^a	52.2	48.4	.07
Diabetes medication^a	9.1	8.9	.89
Alcohol Use^a
Daily	45.3	45.1
Weekly	36.0	37.2	.90
Monthly	3.8	3.6
Rarely/never	14.9	14.1
Weekly exercise^a	60.2	59.3	.67
Health Significantly limits:
Moderate activity^a	12.2	12.2	.99
Walking >1mile^a	17.6	17.6	.97
Walking 1 block^a	2.9	2.2	.26
Climbing one flight of stairs^a	5.0	4.5	.60
Bending, kneeling^a	24.8	24.4	.82
Lifting/carrying groceries^a	6.2	6.5	.80
Bathing or dressing^a	2.4	2.1	.65
Self-rated general health as excellent or very good^a	82.4	83.1	.68

Table 1. Baseline Characteristics of 2,260 US Male Physicians According to Statin Use and Propensity Score Matching

Variable*

Propensity Score Matched (%)

Statin (n = 1,130)

No Statin (n = 1,130)

P-value

Age, mean (SD)

76.0 ± 4.5

76.0 ± 4.6

.88

BMI, mean (SD)^a

25.6 ± 3.1

25.6 ± 3.2

.68

White race^a

94.3

94.0

.79

Smoking Status^a

Current

2.9

3.3

Past

48.9

50.5

.61

Never

48.2

46.2

Hyperlipidemia

98.1

97.9

.65

Hypertension^a

73.8

75.3

.42

Diabetes^a

13.0

13.1

.94

Heart failure^a

2.9

3.0

.80

Renal disease^a

10.8

10.6

.88

Liver disease^a

15.2

16.1

.58

Cancer

20.0

20.9

.60

Depression^a

12.7

13.1

.79

Dementia

2.7

.90

Aspirin use

72.5

71.3

.53

Hypertension medication^a

52.2

48.4

.07

Diabetes medication^a

9.1

8.9

.89

Alcohol Use^a

Daily

45.3

45.1

Weekly

36.0

37.2

.90

Monthly

3.8

3.6

Rarely/never

14.9

14.1

Weekly exercise^a

60.2

59.3

.67

Health Significantly limits:

Moderate activity^a

12.2

.99

Walking >1mile^a

17.6

.97

Walking 1 block^a

2.9

2.2

.26

Climbing one flight of stairs^a

5.0

4.5

.60

Bending, kneeling^a

24.8

24.4

.82

Lifting/carrying groceries^a

6.2

6.5

.80

Bathing or dressing^a

2.4

2.1

.65

Self-rated general health as excellent or very good^a

82.4

83.1

.68

Table 2. Hazard Ratios and 95% Confidence Intervals for Major Cardiovascular Events and Mortality According to Statin Use in 2,260 Propensity Score Matched US Male Physicians
Outcome	Statin N = 1,130	No Statin N = 1,130	HR (95% CI)	P-value
N with event	N with event
Major CV Events^a	169	193	0.86 (0.70–1.06)	.17
All-cause mortality	227	276	0.82 (0.69–0.98)	.03
CHD only^b	125	137	0.95 (0.74–1.21)	.66
Stroke only^c	33	47	0.70 (0.45–1.09)	.12

Table 3. Hazard Ratios (95% Confidence Intervals) for Major Cardiovascular Events and Mortality Stratified by Age, Functional Status, and Total Cholesterol
Outcome	Sub-group	Statin	No Statin	HR (95% CI)	P-value	P-interaction
Total number	Number with event (%)	Total number	Number with event (%)
Major CVD Events	Age Category
	<76	587	79 (13.5)	587	93 (15.8)	0.83 (0.61–1.11)	.21	.27
	≥76	398	77 (19.3)	398	76 (19.0)	1.05 (0.77–1.45)	.75
	Functional status^a
	No limitation	725	103 (14.2)	725	129 (17.8)	0.78 (0.61–1.02)	.06	.62
	Any limitation	263	48 (18.2)	263	54 (20.5)	0.88 (0.60–1.30)	.52
	Total Cholesterol
	<200 mg/dL	308	67 (21.8)	308	48 (15.6)	1.43 (0.99–2.07)	.060	.003
	>200 mg/dL	472	65 (13.8)	472	92 (19.5)	0.68 (0.50–0.94)	.019

Mortality	Age Category
	<76	587	64 (10.9)	587	86 (14.7)	0.76 (0.55–1.05)	.093	.047
	≥76	398	130 (32.7)	398	117 (29.4)	1.14 (0.89–1.47)	.30
	Functional status^a
	No limitation	725	134 (18.5)	725	146 (20.1)	0.93 (0.73–1.17)	.52	.92
	Any limitation	263	59 (22.4)	263	66 (25.1)	0.91 (0.64–1.29)	.60
	Total Cholesterol
	<200 mg/dL	308	65 (21.1)	308	79 (25.7)	0.83 (0.60–1.15)	.27	.79
	>200 mg/dL	472	82 (17.4)	472	92 (19.5)	0.88 (0.65–1.18)	.39

Table 3. Hazard Ratios (95% Confidence Intervals) for Major Cardiovascular Events and Mortality Stratified by Age, Functional Status, and Total Cholesterol

Outcome

Sub-group

Statin

No Statin

HR (95% CI)

P-value

P-interaction

Total number

Number with event (%)

Total number

Number with event (%)

Major CVD Events

Age Category

<76

587

79 (13.5)

587

93 (15.8)

0.83 (0.61–1.11)

.21

.27

≥76

398

77 (19.3)

398

76 (19.0)

1.05 (0.77–1.45)

.75

Functional status^a

No limitation

725

103 (14.2)

725

129 (17.8)

0.78 (0.61–1.02)

.06

.62

Any limitation

263

48 (18.2)

263

54 (20.5)

0.88 (0.60–1.30)

.52

Total Cholesterol

<200 mg/dL

308

67 (21.8)

308

48 (15.6)

1.43 (0.99–2.07)

.060

.003

>200 mg/dL

472

65 (13.8)

472

92 (19.5)

0.68 (0.50–0.94)

.019

Mortality

Age Category

<76

587

64 (10.9)

587

86 (14.7)

0.76 (0.55–1.05)

.093

.047

≥76

398

130 (32.7)

398

117 (29.4)

1.14 (0.89–1.47)

.30

Functional status^a

No limitation

725

134 (18.5)

725

146 (20.1)

0.93 (0.73–1.17)

.52

.92

Any limitation

263

59 (22.4)

263

66 (25.1)

0.91 (0.64–1.29)

.60

Total Cholesterol

<200 mg/dL

308

65 (21.1)

308

79 (25.7)

0.83 (0.60–1.15)

.27

.79

>200 mg/dL

472

82 (17.4)

472

92 (19.5)

0.88 (0.65–1.18)

.39

Statins for Primary Prevention of Cardiovascular Events and Mortality in Older Men

Abstract and Introduction

Abstract

Introduction

Tables

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

Email This

Feedback