Download Statins , Aspirin, B-Blockers and ACE inhibitors

Statins, Aspirin, Beta Blockers, ACE Inhibitors
Prevention
Dr Selwyn Wong
Cardiologist
Ascot and Middlemore Hospitals
Primary vs Secondary Prevention
NZ Primary Care Guidelines - Lipids
• Lipid levels (TC about 4–8 mmol/L) in people without CVD
should be interpreted in the context of their cardiovascular
risk.
• Recommended starting doses for statin treatment:
-Known CVD or CVD risk >20%, simvastatin 40 mg
-5-year CVD risk 15–20% simvastatin 20 mg and uptitrate
• If LDL-C targets are not met, options include increasing
simvastatin to 80 mg, substituting atorvastatin or combining
simvastatin with nicotinic acid or ezetimibe
Maximum Simvastatin Dose
June 8, 2011
• Increased risk of muscle injury cited.
“The U.S. Food and Drug Administration today is
announcing safety label changes for the cholesterollowering medication simvastatin because the highest
approved dose--80 milligram (mg)--has been associated
with an elevated risk of muscle injury or myopathy,
particularly during the first 12 months of use”
• Risk increased in elderly and renal impairment
Statin Debate – Wall St Journal Jan 2012
WSJ Statin Debate; Yes
• No sense why a medication that slows the progression of
hardening of the arteries would be harmful the day or week
before a heart attack, but helpful the day or week after a
heart attack.
• Evidence supports the selective use in high risk for heart
disease. Similarly, they have been shown to do the same in
patients without heart disease, but who are at high risk of
developing heart disease
• Generic statins cost about $50 a year
• Initiation of medication motivates patients with realisation
of how serious their cardiovascular risk actually is.
Dr. Blumenthal is a professor of medicine and director of the Johns Hopkins Ciccarone Center for the
Prevention of Heart Disease and editor in chief of "Preventive Cardiology—A Companion to
Braunwald's Heart Disease."
WSJ Statin Debate; No
• Leap of logic: Drs treated millions of healthy people with
statins to prevent heart disease.
• No evidence that taking statins prolongs life. Using the
most optimistic projections, for every 100 healthy people
who take statins for five years, one or two will avoid a heart
attack. One will develop diabetes.
• WOSCOPs – “high-risk group of men for whom the
benefits of statins were most likely to outweigh the
risks; ..smokers and obese, and some had heart disease.
Those results can't be extrapolated to most Americans
taking statins
Dr. Redberg is a professor of medicine and director of women's cardiovascular services at the
University of California, San Francisco.
WSJ Statin Debate; No
• Fortunately, there is a proven, widely available treatment
for people at high risk for heart disease that does prolong
survival. This treatment is cheaper and more effective than
any statin or other known drug, with virtually no adverse
side effects. The treatment, which has been available for
decades, involves almost no additional costs to patients,
insurance companies or the government. Numerous
studies have shown dramatic results in not only lowering
cholesterol, but in preventing heart attacks and in
prolonging life. This treatment is proper diet and exercise.
• Statins present a moral hazard, since some people will
make less effort to follow a healthy diet and get regular
physical activity because they feel falsely reassured by
their medications
WSJ Statin Debate; Poll
FDA Warning 29/2/2012
“FDA added new safety warnings to statin drugs noting
increased risks of Type 2 diabetes and memory loss”
• Statins may increase users’ risk of brain-related effects
like memory loss and confusion.
• Statins’ labels will now also warn patients and doctors that
the drugs may cause a small increase in blood sugar levels
and Type 2 diabetes.
Significant increase in the risk of DM associated with highdose statin therapy.
• JUPITER - 27% increase in diabetes mellitus
• PROVE-IT TIMI 22 substudy showed that high-dose
atorvastatin can worsen glycemic control.
Statin Debate- JAMA April 2012
Statin Debate- JAMA April 2012
Should a 55-year-old man who is otherwise well, with
systolic blood pressure of 110 mm Hg, total cholesterol of
6.5mmol/L, and no family history of premature CHD be
treated with a statin?
JAMA Statin Debate - No
• Meta-analysis of 11 trials including 65 229 persons with
244 000 person-years of follow-up in healthy but high-risk
men and women showed no reduction in mortality
• 2011 Cochrane review among persons without
documented coronary disease came to similar conclusions.
• Data from observational studies - much higher rates for
statin-associated myopathy and other adverse events in
actual use than the 1% to 5% rate reported in clinical trials.
• Numerous anecdotal reports/small trial have suggested
that statin therapy causes cognitive impairment. True extent
of cognitive impairment associated with statins remains
understudied.
JAMA Statin Debate - No
• The risk of diabetes; JUPITER, which found a 3% risk of
developing diabetes in the rosuvastatin group, significantly
higher than in the placebo group.
• Do the potential benefits outweigh the potential risks
-Based on all current evidence, a healthy man with elevated
cholesterol will not live any longer if he takes statins.
-For every 100 patients with elevated cholesterol levels who
take statins for 5 years, an MI will be prevented in 1 or 2
patients.
-However, 1 or more patients will develop diabetes and
20% or more will experience disabling symptoms, including
muscle weakness, fatigue, and memory loss.
Statin Debate- JAMA April 2012
JAMA Statin Debate - Yes
• WOSCOPS (Pravastatin 40 mg)
6595 men TC 7.0 ± 0.6mmol/L
31% reduction in MI and CHD-related death
• AFCAPS/TexCAPS (Lovastatin 20 to 40 mg)
6605 asymptomatic
LDL 5.7±0.5 mmol/L, low HDL 0.9± 0.1mmol/L
37% reduction1st major CE, 40% reduction in MI
• JUPITER (Rosuvastatin 20 mg)
17 802 healthy men and women
Normal LDL-C < 3.4 mmol/L and elevated hsCRP
44% reduction MI, CVA and revascularization
20% reduction total mortality
JAMA Statin Debate - Yes
• Patient in this common clinical scenario would have an
“intermediate” 10-year risk for developing CHD (~10%)
• Coronary Artery Calcium scan to reclassify intermediate
risk patients
• 50% chance CAC score of 0 - estimated 10-year CHD
event rate of less than 2%
• simple presence of CAC increases that risk nearly 4-fold
• 13% chance CAC score >100, - estimated 10-year CHD
event rate >12%
Statins – What to do??
Total cholesterol > 8mmol/L - treat
Total cholesterol 4-8mmol/L; risk assess NZGG
≥20% treat, ≥15% lifestyle/treat,
≥10% statins or CAC
• Atorvastatin or Simvastatin ?initially low dose
• Rosuvastatin now a viable option
• Efficacy of treatment never proven in an individual patient!!
Statins and Plaque Rupture
Aspirin in Primary Prevention
• Based on evidence from nine large-scale primary
prevention trials of men and women without established
cardiovascular disease (CVD), aspirin produces a
statistically significant and clinically important reduction in
the risk of a first MI.
• However, aspirin has not been shown to lead to a
statistically significant reduction in the rates of stroke or
cardiovascular death.
• The totality of randomized evidence suggests no
differences in response to aspirin between men and
women
Aspirin in Primary Prevention
LANCET 2009 Meta analysis 6 trials, 95,000 men and
women, aspirin (75-500mg/day) v placebo
Serious vascular events - 0.51%/yr aspirin v 0.57%/yr
controls. Driven by 1st non-fatal MI (0.18 versus 0.23%/yr).
Aspirin significantly é rate of major GI/extracranial bleeds
(0.10 v 0.07%/yr). ê similar for women and men.
Archives of IM 2012 Meta analysis 9 trials, n=100 000.
Mean follow-up of six years, aspirin treatment ê total CVE
by 10%, driven primarily by ênonfatal MI, but there was a
30% é risk of nontrivial bleeding events. The number
needed to treat to prevent one cardiovascular event was
120, compared with 73 for causing a nontrivial bleed.
Aspirin in Primary Prevention
• Low-risk patients (10-yr risk <10 %), the absolute benefit
on occlusive vascular events may be less than the absolute
risk of major bleeding.
• Moderate risk patients (10-yr risk 10-19%) the
randomized data on benefits and risks are sparse, so
clinical decision making should be made on an individual
basis. In these patients it should also be noted that
aggressive risk-preventative strategies (i.e. statins) will
reduce both MI and CVA with little hazard.
Available data suggest that daily doses of aspirin between
75 and 325 mg are equally safe and effective.
Beta-Blockers in Primary Prevention
• Beta-blockers (BB) have been widely used in HTN and
recommended as first-line agents in guidelines.
• Meta-analyses - uncomplicated HTN v other agents
é risk of stroke, especially in elderly
No benefit for all-cause mortality, cardiovascular
morbidity/mortality.
• “pseudo-antihypertensive” efficacy (failure to lower central
aortic pressure), lack of effect on regression of target end
organ effects like left ventricular hypertrophy and
endothelial dysfunction, and adverse effects
• Risk benefit ratio for BB 1st line Rx is not acceptable
HTN Treatment in Primary Prevention
• In the absence of a specific indication, there are three main
classes of drugs that have been used for initial
monotherapy: thiazide diuretics, long-acting calcium
channel blockers, and ACE inhibitors or angiotensin II
receptor blockers (ARBs).
• Each of these classes of drugs has been equally effective
in monotherapy trials if the attained blood pressure is
similar.
• Beta blockers are NOT commonly used for initial
monotherapy in the absence of a specific indication, since
they may have an adverse effect on some cardiovascular
outcomes, particularly in older patients
HTN Target – ESH April 27 2012
"We just don't know."
• London, UK - That was the brave declaration from a
number of experts speaking at the European Society of
Hypertension (ESH)
• There is much that remains unknown in the field. Evidence
for seemingly straightforward issues, such as what should
be the ideal number to lower blood pressure to in different
groups of individuals, is lacking
• In the meantime, guidelines need to offer the best direction
they can for those who have the task of treating
hypertension, which is increasingly falling upon the
shoulders of general practitioners and family doctors
NZ Primary Care Guidelines
• Everyone with a BP 170/100 mm Hg should have drug
treatment and specific lifestyle advice
• BP range 115/70 - 170/100 mmHg, decisions to treat
should be based on the individual’s cardiovascular risk
• Most of the treatment benefit is achieved by reaching the
following BP levels:
<140/85 mm Hg in people without clinical CVD
<130/80 mm Hg in people with diabetes or CVD
<130/80 mm Hg in people with CKD and significant
albuminuria (urine protein/creatinine >100 mg/mmol)
ACEI in Primary Prevention
European Heart Journal Advance Access published April 17, 2012
“Angiotensin-converting enzyme inhibitors reduce mortality
in hypertension: a meta-analysis of randomized clinical
trials of renin–angiotensin–aldosterone system inhibitors
involving 158 998 patients”
RAAS inhibition was associated with a 5% reduction
in all-cause mortality (HR: 0.95, 95% CI: 0.91–1.00, P 1/4
0.032), and a 7% reduction in cardiovascular mortality
(HR: 0.93, 95% CI: 0.88–0.99, P 1/4 0.018).
The observed treatment effect resulted entirely from the
class of ACE inhibitors, which were associated with a
significant 10% reduction in all-cause mortality (HR: 0.90,
95% CI: 0.84–0.97, P 1/4 0.004)
ACEI in Primary Prevention
• ACE inhibitor/ARB may be more effective in younger
patients
• Calcium channel blocker may be more effective in elderly
and black patients
• DM with confirmed microalbuminuria should be treated
with an ACE inhibitor or angiotensin 2 receptor blocker
(ARB) whether or not hypertension is present
Statins, Aspirin, Beta Blockers, ACE Inhibitors
• Statins – all high-risk, moderate risk with discussion/
discretion
• Aspirin – risk equivalent of secondary prevention/high-risk
with discussion/discretion
• Beta-blockers – not a first-line agent in HTN
• ACE Inhibitors – appropriate as first-line agent