Download The Second Myocardial Infarction: Are We Preventing It

The Second Myocardial Infarction: Are We Preventing It?
Introduction:
We sought to determine the characteristics of patients who had experienced
a previous Acute Myocardial Infarction (AMI), and presented to Cardiac Care
Units (CCU’s) in Israel with an acute coronary event. We aimed to determine
the influence of independent predictors, and in particular- the effect of
secondary medical prevention on the second coronary event.
The Second MI:
Survivors of an acute myocardial infarct (AMI) are at an increased risk of a
recurrent ischemic event. In the Framingham study1, a second myocardial
infarction occurred in 13 percent of the men and in 40 percent of the women
within 5 years of the first infarction. It is important to note, that a large
proportion of deaths among patients with myocardial infarction occurs within
the first 24 hours after presentation2. Re-infarction is an important cause of
mortality in these patients, increasing the risk of death significantly345.
In the comparison of AMI survivors who were treated with either invasive
measures or with thrombolytic therapy, evidence shows a reduction in shortterm mortality and in the combined outcome of short-term mortality and
nonfatal reinfarction in the primary coronary angioplasty (PCI) approach.6 7 8
It has been shown that patients who present with an ACS have a worse
prognosis if they have had a prior coronary artery bypass grafting (CABG) 9
10 11 12 13 14
. On the other hand, in cases of a previous PCI, there seems to be
an advantage in the prognosis of second AMI’s. However, there is an increase
in the rate of recurrent AMI’s, percentage of multi-vessel disease cases, and
a higher rate of ventricular dysfunction in this group15 16
As mentioned above, reinfarction is more prevalent in female survivors of a
first event. Also, there is a higher early wave of mortality in women (45%)1
17
. In terms of subjective, quality of life issues, it seems that women benefit
less from PCI than men, in comparison with fibrinolytic therapy18.
Besides gender, there are other risk factors for reinfarction in the survivors of
a first event, some of which are known risk factors for a first event: Anterior
location of the first AMI, peripheral vascular disease, congestive heart failure,
diabetes, hypertension, three-vessel coronary disease, smoking, prior
angina, age, hypercholesterolemia, prior strokes, smoking and obesity 3 11 19 20
21 22
. Anterior location of the second AMI is also considered a poor prognostic
factor23.
Prevention of a second MI:
Current guidelines for secondary prevention of coronary heart disease are
becoming more aggressive in the approach to reduce risk factors in these
patients, due to a growing number of trials showing benefit in the prevention
of AMI survivors by behavioral and medical means. 24 These include complete
cessation of smoking, reduction of blood pressure to 140/90 or 130/80 in
diabetic and in patients with chronic renal disease, management of weight to
the goal of a BMI between 18.5 and 25 (waist circumference below 40 inches
for men, 35 inches for women) and physical activity performed at least 5
times a week, 30 minutes each time. Guidelines also include management of
diabetes to the HbA1c goal of under 7%, and a more aggressive approach in
the reduction of lipid management. A new addition to the 2006 guidelines is
the recommendation of influenza vaccination to all patients with
cardiovascular disease.
Medication that has been recommended in the secondary prevention of
coronary heart disease includes statins, angiotensin converting enzyme
(ACE) inhibitors and other renin- angiotensin-aldosterone system blockers,
beta blockers (BB’s) and antiplatelet therapy. Other treatments, such as
calcium- blockers, are considered second line medications, and should be
tailored to the needs of each patient.
A first step in the secondary management is the assessment of the patient
and his/her specific needs, such as the presence of left ventricular
dysfunction25. In most cases, this is followed by treatment with a
combination of the four classes of drugs: BB’s, ACE inhibitors, Aspirin and
statins. Treatment rates have been rising substantially in the last years26 27 28
29
. However, there is still a high prevalence of under treatment, especially in
the elderly, and high rates of therapy discontinuation. This has a direct effect
on the mortality rates of these patients30 31 32 33 34 35.
There have been several trials that had shown a benefit in the treatment of
BB’s after an AMI. In the AIRE (Acute Infarction Ramipril Efficacy) study,
usage of a BB has reduced mortality significantly (hazard ratio of 0.66)36. In
the BAHT (Beta-Blocker in Heart Attack Trial), BB showed a benefit in the
survival of high- risk patients. Benefit was found non-significant in other
groups37. Gottlieb et al had shown a benefit from BB therapy in AMI
survivors, even in patients with conditions that are often considered
contraindications to beta-blockade, such as heart failure, pulmonary disease ,
and older age38. The COMMIT (Clopidogrel and Metoprolol in Myocardial
Infarction Trial) study has shown benefit in patients treated with metoprolol
in terms of reduced reinfarction rates in these patients, but higher rates of
cardiogenic shock, and no benefit in survival39.
Treatment with ACE inhibitors has shown a persistent benefit in survival, in
survivors of a first AMI. In the SAVE (survival and ventricular enlargement)
trial, long term captopril treatment was associated with better survival,
independent of other means of secondary prevention40. In the AIRE trial
mentioned above, treatment with ramipril was associated with a hazard ratio
of 0.73 in comparison with placebo, in patients with clinical evidence of heart
failure after an AMI.41 In ISIS-4 (Fourth International Study of Infarct
Survival ) showed a 7% reduction in mortality after 35 days of treatment
with captopril, but a higher incidence of episodes of hypotension, to the
extent that the trial was terminated.42 In the study GISSI-3 (Gruppo Italiano
per lo Studio della Sopravvivenza nell'infarto Miocardico) lisinopril, started
within 24 h from AMI symptoms and continued for 6 weeks, produced
significant reductions in overall mortality (odds ratio 0.88) and in the
combined outcome measure of mortality and severe ventricular dysfunction
(0.90)43. It is important to note, that angiotensin receptor blockers were also
proved to be efficacious in improving mortality of such patients, as shown in
the OPTIMAAL trial44.
In the CARE (Cholesterol and Recurrent Events) Trial, pravastatin was
administered to patients with what was considered normal cholesterol levels
at the time, for 5 years. Compared to placebo, the statin reduced the rate of
nonfatal AMI and death from cardiovascular causes by 24 percent45. Later,
the MRC/BHF Study was published, in which 40mg of simvastatin was given
to proven coronary heart disease, other arterial disease or diabetes patients,
and was proven to reduce coronary events by about one quarter after five
years.46 In the PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and
Infection Therapy–Thrombolysis in Myocardial Infarction 22 Investigators)
Trial, a comparison was made between intensive statin therapy and lower
doses of statins, showing a benefit in survivors of coronary events in the
higher dosage 47.
As for antiplatelet therapy, one must consider both aspirin and clopidogrel as
possible medications. In the ATC (Antiplatelet Trialists' Collaboration) study,
it was shown that treatment with aspirin after AMI reduced risk of
reinfarction by 25%, and of death of all causes by 12% 48. In a different
COMMIT Trial, addition of 75mg clopidegrol to standard aspirin treatment had
reduced rates of death of all causes, reinfarction or stroke by 9%49. In the
CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial,
clopidogrel was added to aspirin for 3 to 12 months after non-ST elevation
AMI, and was compared to aspirin treatment alone. This resulted in a
reduction of 20% in one of the following: death of cardiovascular causes,
reinfarction or stroke50.
There is much emphasis on the in-hospital treatment of these patients, the
secondary prevention begun immediately after an AMI, and its immediate
results. Less is known regarding the effect of long term prevention, and
specifically- on the characterization of a second AMI, if one should occur, in
this regard.
In this study, we intend to investigate the nature of a second AMI, the
implications of secondary medical prevention on this event, and other
possible variables associated with it.
1
Prognosis after initial myocardial infarction: the Framingham study ; Am J Cardiol. 1979 Jul;44(1):53-9
2
Kleiman NS et al; Death and nonfatal reinfarction within the first 24 hours after presentation with an
acute coronary syndrome: experience from GUSTO-IIb. Global Utilization of Strategies for Total
Occlusion; Am Heart J. 1999 Jan;137(1):12-23
3
Kornowski R, Predictors and long-term prognostic significance of recurrent infarction in the year after a
first myocardial infarction. SPRINT Study Group. Am J Cardiol. 1993 Oct 15;72(12):883-8.
4
Janion M, Clinical course and long-term prognosis in patients with recurrent myocardial infarction, Pol
Arch Med Wewn. 2000 Jan-Feb;103(1-2):53-9.
5
Mueller HS, Prognostic significance of nonfatal reinfarction during 3-year follow-up: results of the
Thrombolysis in Myocardial Infarction (TIMI) phase II clinical trial. The TIMI Investigators, J Am Coll
Cardiol. 1995 Oct;26(4):900-7.
6
Karin B. et al ; Does PTCA in Acute Myocardial Infarction Affect Mortality and Reinfarction Rates?
A Quantitative Overview (Meta-Analysis) of the Randomized Clinical Trials, Circulation. 1995;91:476485.
7
Zijlstra F. et al; Long-Term Benefit of Primary Angioplasty as Compared with Thrombolytic Therapy for
Acute Myocardial Infarction, NEJM Volume 341:1413-1419.
8
Gottlieb S et al, Long-term (three-year) prognosis of patients treated with reperfusion or conservatively
after acute myocardial infarction. Israeli Thrombolytic Survey Group; J Am Coll Cardiol. 1999
Jul;34(1):70-82
9
Waters DD; Previous coronary artery bypass grafting as an adverse prognostic factor in unstable angina
pectoris, Am J Cardiol. 1986 Sep 1;58(6):465-9
10
Kleiman NS; Comparison of outcome of patients with unstable angina and non-Q-wave acute myocardial
infarction with and without prior coronary artery bypass grafting (Thrombolysis in Myocardial Ischemia III
Registry). Am J Cardiol. 1996 Feb 1;77(4):227-31
11
Wiseman A et al; Long-term prognosis after myocardial infarction in patients with previous coronary
artery bypass surgery, J Am Coll Cardiol. 1988 Oct;12(4):873-80.
12
Labinaz, M et al; Outcomes of Patients With Acute Coronary Syndromes and Prior Coronary Artery
Bypass Grafting; Results From the Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression
Using Integrilin Therapy (PURSUIT) Trial ;Circulation 2002;105:322
13
Stone GW et al, Clinical and angiographic outcomes in patients with previous coronary artery bypass
graft surgery treated with primary balloon angioplasty for acute myocardial infarction. Second Primary
Angioplasty in Myocardial Infarction Trial (PAMI-2) Investigators; J Am Coll Cardiol. 2000 Mar
1;35(3):605-11.
14
Peterson LR et al, Reperfusion therapy in patients with acute myocardial infarction and prior coronary
artery bypass graft surgery (National Registry of Myocardial Infarction-2); Am J Cardiol. 1999 Dec
1;84(11):1287-91.
15
Labinaz M et al; Outcomes of patients with acute coronary syndromes and prior percutaneous coronary
intervention: a pooled analysis of three randomized clinical trials. Eur Heart J. 2005 Jan;26(2):128-36
16
Labinaz M et al, Thrombolytic therapy for patients with prior percutaneous transluminal coronary
angioplasty and subsequent acute myocardial infarction. GUSTO-I Investigators. Global Utilization of
Streptokinase and t-PA for Occluded Coronary Arteries. Am J Cardiol. 1996 Dec 15;78(12):1338-44
17
Kornowsky R. et al; Clinical predictors of reinfarction among men and women after a first myocardial
infarction. SPRINT Study Group. Secondary Prevention Reinfarction Israeli Nifedipine Trial ; Cardiology,
1995;86(2):163-8
18
Mortensen OS, Gender differences in health-related quality of life following ST-elevation myocardial
infarction: women and men do not benefit from primary percutaneous coronary intervention to the same
degree. Eur J Cardiovasc Prev Rehabil. 2007 Feb;14(1):37-43.
19
Serrano M, Smoking cessation and risk of myocardial reinfarction in coronary patients: a nested casecontrol study; Rev Esp Cardiol. 2003 May;56(5):445-51
20
Taylor GJ et al, Predictors of clinical course, coronary anatomy and left ventricular function after
recovery from acute myocardial infarction; Circulation 1980, Vol 62, 960-970
21
Nigam A, Excess weight at time of presentation of myocardial infarction is associated with lower initial
mortality risks but higher long-term risks including recurrent re-infarction and cardiac death; Int J Cardiol.
2006 Jun 16;110(2):153-9.
22
Marschner IC et al, Long-term risk stratification for survivors of acute coronary syndromes. Results from
the Long-term Intervention with Pravastatin in Ischemic Disease (LIPID) Study. LIPID Study
Investigators; J Am Coll Cardiol. 2001 Jul;38(1):56-63.
23
Kornowski R et al, Prognostic significance of infarction location in patients with recurrent myocardial
infarction. SPRINT Study Group. Secondary Prevention Reinfarction Israel Nifedipine Trial; Cardiology.
1997 Sep-Oct;88(5):441-5.
24
Sidney C. et al; AHA/ACC Guidelines for Secondary Prevention for Patients with Coronary and Other
Atherosclerotic Vascular Disease: 2006 Update Endorsed by the National Heart, Lung, and Blood Institute;
Circulation6136-6121;111;6002
25
Amin A. et al, Improving the Management of Patients After Myocardial Infarction, from Admission to
Discharge; Clin Ther. 2006;28:1509-1539.
26
van der Elst ME et al, Preventive drug use in patients with a history of nonfatal myocardial infarction
during 12-year follow-up in The Netherlands: a retrospective analysis; Clin Ther. 2005 Nov;27(11):180614.
27
Haim M et al, Prognosis of patients with a first non-Q-wave myocardial infarction before and in the
reperfusion era. SPRINT and the Israeli Thrombolytic Survey Groups. Secondary Prevention Reinfarction
Israeli Nifedipine Trial; Am Heart J. 1998 Aug;136(2):245-51.
28
Boersma E et al, Blood pressure is insufficiently controlled in European patients with established
coronary heart disease; J Hypertens. 2003 Oct;21(10):1831-40.
29
Newby, L. K. et al.; Long-Term Adherence to Evidence-Based Secondary Prevention Therapies in
Coronary Artery Disease; Circulation 2006;113:203-212.
30
P. Michael Ho et al, Impact of Medication Therapy discontinuation on Mortality After Myocardial
Infarction; Arch Intern Med. 2006;166:1842-1847.
31
Goyal A et al , Outcomes associated with the use of secondary prevention medications after coronary
artery bypass graft surgery; Ann Thorac Surg. 2007 Mar;83(3):993-1001.
32
Shlipak MG et al, Comparison of the effects of angiotensin converting-enzyme inhibitors and beta
blockers on survival in elderly patients with reduced left ventricular function after myocardial infarction;
Am J Med. 2001 Apr 15;110(6):425-33.
33
Soumerai SB et al, Adverse outcomes of underuse of beta-blockers in elderly survivors of acute
myocardial infarction; JAMA. 1997 Jan 8;277(2):115-21.
34
Ho PM. et al, Impact of medication therapy discontinuation on mortality after myocardial infarction;
Arch Intern Med. 6002 Sep 25;166(17):1842-7.
35
EUROASPIRE II Study Group, Lifestyle and risk factor management and use of drug therapies in
coronary patients from 15 countries; principal results from EUROASPIRE II Euro Heart Survey
Programme; Eur Heart J. 6001 Apr;22(7):554-72.
36
K S Spargias et al, Beta Blocker treatment and other prognostic variables in patients with clinical
evidence of heart failure after acute myocardial infarction: evidence from the AIRE study; Heart
16–51:68;1111.
37
Viscoli CM, Beta-blockers after myocardial infarction: influence of first-year clinical course on longterm effectiveness; Ann Intern Med. 1993 Jan 15;118(2):99-105.
38
Gottlieb S. S et al, Effect of Beta-Blockade on Mortality among High-Risk and Low-Risk Patients after
Myocardial Infarction; N Engl J Med 1998; 339:489-497.
39
COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group, Early
intravenous then oral metoprolol in 45 852 patients with acute myocardial infarction: randomised placebo
controlled trial; Lancet16–1266 :122 ;6008 .
40
MA Pfeffer, Et al, Effect of captopril on mortality and morbidity in patients with left ventricular
dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The
(SAVE Investigators); N Engl J Med 1992; 327:669-677.
41
The Acute Infarction Ramipril Efficacy (AIRE) Study Investigators, Effect of ramipril on mortality and
morbidity of survivors of acute myocardial infarction with clinical evidence of heart failure; The Lancet ;
Oct 2, 1993; 342, 8875.
42
ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group A randomised factorial trial
assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients
with suspected acute myocardial infarction; Lancet 1995; 345, Issue 8951.
43
GISSI-3 (Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico), Effects of lisinopril
and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after
acute myocardial infarction; Lancet. 1994 May 7;343(8906):1115-22.
44
Dickstein et al, Effects of losartan and captopril on mortality and morbidity in high-risk patients after
acute myocardial infarction: The OPTIMAAL randomised trial; Lancet. 2002. Vol.360, pg. 752.
45
The Cholesterol and Recurrent Events Trial Investigators, The Effect of Pravastatin on Coronary Events
after Myocardial Infarction in Patients with Average Cholesterol Levels; N Engl J Med 1996; 335:10011009.
46
Heart Protection Study Collaborative Group, MRC/BHF Heart Protection Study of cholesterol lowering
with simvastatin in 20 536 high-risk individuals: a randomised placebo controlled trial; Lancet 2002; Pages
7-22.
47
The PROVE IT–TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis
in Myocardial Infarction 22) Investigators, Intensive versus Moderate Lipid Lowering with Statins after
Acute Coronary Syndromes; N Engl J Med 2004;350:1495-504.
48
Antiplatelet Trialists' Collaboration. Collaborative overview of randomized trials of antiplatelet therapyPrevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various
categories of patients BMJ. 1994;308:81-106.
49
COMMIT (ClOpidogrel and Metoprolol in Myocardial Infarction Trial) collaborative group, Addition of
clopidogrel to aspirin in 45 852 patients with acute myocardial infarction: randomised placebo-controlled
trial, Lancet 2005; 366: 1607–21.
50
Yusuf S. et al, for the CURE (CIopidogrel in Unstable Angina to Prevent Recurrent Events) Trial
Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes
without ST-segment elevation; N EnglJ Med.2001; 345:494-502.