A. Take Home: High Dose Better Than Low Dose Statin in Preventing CV Events
Total Page：16
File Type：pdf, Size：1020Kb
Cardiology 101:
Why we do what we do
1) Statin therapy
a. Take home: High dose better than low dose statin in preventing CV events
Cannon, C, et. al. Intensive vs. Moderate Lipid Lowering with Statins after ACS. NEJM April 8, 2004. Vol 350. No 15. Pg 1495-1504.
Trial compared Pravastatin 40 mg (goal LDL 100) to Atorvastatin 80 mg (goal LDL 70) in patients who were hospitalized in the last 10 days for ACS/USA.
- Pts were on no other lipid lowering drug.
- Study drugs could be increased if goal LDL not obtained
- Baseline: Age 60, 90% white, 80% male, avg LDL 106
- Primary End Point – (composite) death, MI, USA required hospitalization, revascularization/CABG and CVA
- Followed for 2.5 years
- Results – Composite endpoint significant
o Driven by decrease in revascularization and USA requiring hospitalization
o Death from any cause (P value 0.07) not statistically significant, but showed a trend towards longer life
2) ACE Inhibitors
a. Take home: CV events in diabetics with normal EFs may be reduced with ACEi
HOPE Trial – Effects of Angiotensin-Converting Enzyme Inhibitor, Ramipril, on CV Events in High-Risk Patients. NEJM January 20, 2000. Vol 342. No 3. Pg 145-151.
Trial compared patients with vascular disease or DM plus another CAD risk factor (HTN, HLD, tobacco, microalbumuria) without low EF or CHF Sx got either Ramipril 10 mg qd or placebo
- Hypothesis: increased rennin-aldo levels lead to progression of arthrosclerosis
- ACEi known to reduce risk of CAD events in patients with low EFs
- Baseline: Age 66, 80% CAD, 40% PAD, 40% DM, 139/80 Avg BP
- Primary End Point – (composite) MI, CVA or death from CV cause
- Followed for 5 years
- 80% still taking Ramipril at end of study (analyzed by ITT)
- 12% on placebo had received an ACEi by end of study
- Results – Composite endpoint significant o Decrease across the board in death from CV cause, CVA, and MI
o Secondary endpoint of death from any cause significant
. However study not powered to show this
o No real change in BP at end of study 136/77 Avg BP
o Results thought to be due to effects on Renin-Aldo level
o Treating 1000 pts with ACEi for 4 years prevents 150 CV events in 70 pts
3) Beta blockers
a. Take home: EF <35% = beta blocker
Carvedilol Heart Failure Study Group. The Effect of Carvedilol on Morbidity and Mortality in patients with Chronic Heart Failure. NEJM May 23, 1996. Vol 334. No 21. Pg 1349-1355.
Trial of patients with chronic heart failure (EF < 35%) were given either carvedilol or placebo. Other medical therapy remained constant.
- 1100 patients
- Baseline: Age 58, 75% male, 85% NYHA Class II or III
- Pts with EF < 35% already on medical therapy
- Excluded HR < 68 or on CCB
- Goal of 25 to 50 mg bid if tolerated
- Followed for 1 year, ITT analysis
- Primary End Point: Death at 60 days
o Statistically significant mortality benefit
o Stopped early due to benefit
o HR decreased by 12 beats/min in carvedilol group, no change in BP
o Adverse Rxn
. Increased dizziness, hypotension and diarrhea
4) Digoxin
a. Take home: only use digoxin for symptoms and watch out for toxicity
The Digitalis Investigation Group. The Effect of Digoxin on Mortality and Morbidity in Pts with heart failure. NEJM February 20, 1997. Vol 336. No. 8. Pg 525-533. Trial compared Pts with EF < 45%, already on ACEi, diuretics on digoxin to those on placebo.
- Baseline: Age 60, EF 28%, 78% male, 86% white, 53% class II, 33% class III/IV
- Followed for 4 years
- Primary End Point – mortality
- Results
o No difference in mortality b/w digoxin and placebo
o Fewer hospitalizations for worsening CHF
o Less deaths from worsening CHF in Digoxin arm
o More deaths from “other cardiac” in Digoxin arm (arrhythmias?)
o Dig level achieved ~1
5) Biventricular Pacing
a. Take home: Wide QRS, low EF, bad CHF then highly consider BiV (morbidity and likely mortality benefit)
COMPANION Investigators. Cardiac-Resynchronization Therapy with or without Implantable Defibrillator in Advanced Chronic Heart Failure. NEJM, May 20, 2004. Vol 350. No. 21. Pg 2140-2150.
Trial comparing Pts with NYHA Class III/IV heart failure (ischemic or nonischemic), EF <35%, QRS > 120 ms were assigned to optimal medical therapy (diuretic, ACEi, beta-blocker, spironolactone) or optimal medical therapy plus cardiac-resynchronization therapy with or without defibrillator.
- Baseline: Age 68, 69% male, 82% NYHA Class III, EF 20%, QRS 158
- Followed for 3 years, ITT
- Primary End Point – death or hospitalization from any cause
- Secondary End Point – death from any cause
- Results
o BiV and BiV-ICD both achieved statistically significant decrease in death or hospitalization from any cause
o Death from any cause (secondary end point) for BiV was nearly significant HR .76 with CI .58-1.01, p = .06, for BiV-ICD was significant
o Subgroup analysis showed increasing mortality benefit with increasing QRS 120-150 < 150-170 < 170+ and Class IV > III
o Significant crossover in medical management group to receiving BiV-ICD
o Quality of life and 6 minute walk both improved
6) ICD Implantation a. Take home: CAD + EF <30% = ICD
MADIT II Investigators. Prophylactic Implantation of a Defibrillator in Patients with Myocardial Infarction and Reduced Ejection Fraction. NEJM. March 21, 2002. Vol 346. No 12. Pg 677-883.
Trial of patients with prior MI and EF 30% or less to receive an implantable defibrillator or optimal medical therapy. No EP testing required prior for risk stratification.
- Prior MI defined by: q waves on EKG, positive biomarkers in hospitalization for suspected MI, wall motion abnormalities with evidence of CAD on angiography, fixed defect on nuclear stress
- Excluded: NYHA Class IV
- 1200 patients
- Baseline: Age 64, 84% male, 70% NYHA class I or II, 50% QRS > .12
- Followed for 4 years, ITT analysis
- Primary end point: death from any cause
o Statistically significant in HR .69 (.51-.93) number of deaths (p .016)
. Survival appears as early as 9 months
. Lower EF (< 25%) had a bigger benefit
. 31% reduction in risk of death
7) Aspirin
a. Take home: History of CAD = ASA
Berger, JS, Brown, DL, Becker, RC. Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis. Am J Med 2008; 121:43.
- Low dose ASA in secondary prevention of CVD
- Pts had either history of MI, stable angina or CVA/TIA
- 6 studies with 10,000 patients.
- Results
o 21% reduction in risk of CV events (nonfatal MI, nonfatal CVA and CV death)
o 13% reduction in all cause mortality
o Pts treated with ASA had statistically significant more bleeding
8) Heparin/LMWH a. Take home: Enoxaparin as good, maybe better than heparin
ESSENCE Investigators. A Comparison of LMWH with unfractionated heparin for unstable CAD. NEJM. August 14, 1997. Vol 337. No 7. Pg 447-452.
Trial of patients with USA or NSTEMI to receive either 1 mg/kg enoxaparin SQ bid or continuous IV heparin gtt therapy for 48 hrs to 8 days.
- Patients had angina at rest and at least 1 of the following
o ST depression, transient ST elevation, T wave changes, h/o MI or PCI/CABG
- Baseline: Age 64, 66% male, 42% FMHx, 55% HTN, 44% HLD, 22% DM, 24% tobacco
- Primary End Point: (composite) death, MI, or recurrent angina at 14 days
- Recurrent angina - - angina at rest + EKG changes
- Results
o Primary end point statistically significant
. Driven by decrease in MI and recurrent angina (310 events) vs. death (36 events)
o Secondary end point of 30 days also significant
. Again driven by MI and recurrent angina
o Subgroup analysis of death alone showed no improved survival at any time
o Increased risk of minor, but not major hemorrhage with enoxaparin
9) Thrombolytics
a. Take home: STEMI + no cath lab = t-PA. The sooner the better.
The GUSTO Investigators. An International Randomized Trial Comparing Four Thrombolytics Strategies for Acute Myocardial Infarction. NEJM September 2, 1993. Vol 329. No 10. Pg 673-682.
Trial compared the use of streptokinase and SQ heparin, streptokinase and IV heparin, t-PA and IV heparin, and streptokinase, t- PA and IV heparin.
- 40,000 patients in trial, multicenter, multinational
- Pts with 6 hours or less of symptoms plus at least 1 mm ST elevation
- Pts with h/o CVA, heavy bleeding, severe uncontrolled HTN (SBP >180) contraindicated
- All patients received ASA and beta blocker (unless contraindication)
- Baseline: Age 62, 75% male, 15% DM, BP 130/73, Time to treatment 160 minutes
- Primary End Point: death at 30 days o t-PA with IV heparin had statistically significant impact on mortality at 24 hr and 30 days without an increase nonfatal ischemic/hemm CVA
o Patency of artery 85% post t-PA
o Secondary outcomes showed lower CHF, arrhythmia, cardiogenic shock with t-PA
10) Coronary Angioplasty
a. Take home: STEMI + cath lab = angioplasty.
The GUSTO IIb Investigators. A clinical trial comparing primary coronary angioplasty with t-PA for acute myocardial infarction. NEJM June 5, 1997. Vol 336. No. 23. Pg 1621-1628.
Trial compared patients within 12 hours of acute myocardial infarction and evidence of ST elevation to primary angioplasty vs. t- PA.
- Experienced centers (200 angios/year)
- ~ 1000 patients
- ST Elevation (2 mm), Chest pain x 20 minutes, LBBB
- All patients received ASA, other meds at discretion of physician
- Baseline: Age 63, 75% male, 65% tobacco, 91% Killip class 1
- Median time to treatment: t-PA ~ 3 hr, Angioplasty ~ 4 hr
- Primary End Point: (composite) death, nonfatal reinfarction, and nonfatal disabling CVA at 30 days, secondary end point (prespecified): morality (all cause)
o Neither death, reinfarction, or CVA were statistically significant independently, but together the composite endpoint was
. Trend seen towards survival benefit (death actually most frequent event in composite end point death > reinfarction > CVA
. Trend seen that earlier arrival favored angioplasty, later arrival (>6 hr) favored t-PA
. Trend towards benefit at 6 months
11) Preoperative Risk Stratification
a. Take home: High risk vascular surgery + no USA = medical management of CAD
CARP Trial: McFalls, E. et. al. Coronary-Artery Revascularization before Elective Major Vascular Surgery. NEJM. December 30, 2004. Vol 351. No. 27. Pg 2795-2804.
Trial compared Pts who were undergoing AAA repair or PAD bypass receiving revascularization by PIC or CABG to medical management. - Had to have a stenosis > 70% on catheterization
- Must be at increased risk for perioperative cardiac complication as determined by cardiologist
o No set criteria as to who as at a higher risk, but said h/o DM, CVA, ESRD and stress imaging played a role
- Independent cardiologists decided b/w PCI or CABG
- Baseline: age 65, 40% angina, 43 h/o MI, 50% tobacco, EF 55%,
- Primary endpoint: Mortality
- 5859 pts screened 510 randomized
o Lots of exclusions
- 93% of revascularization arm underwent CABG or PCI
- Followed for 6 years
- Results
o No change in mortality between revascularization and medical management prior to surgery
o Increased wait time to surgery for revascularization group (approx 35 more days)
o Stable CAD does not need to be revascularized prior to major vascular surgery