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Heart to Heart: A Review of the Top

Cardiovascular Trials in 2015-2016 Alexander Kantorovich, PharmD, BCPS Clinical Assistant Professor

Chicago State University College of Pharmacy

Ayesha Khan, PharmD, BCPS Clinical Assistant Professor

Chicago State University College of Pharmacy

Disclosure and Conflict of Interest

Alexander Kantorovich and Ayesha Khan declare no

conflicts of interest, real or apparent, and no

financial interests in any company, product, or

service mentioned in this program, including grants,

employment, gifts, stock holdings, and honoraria.

Pharmacist Objectives

At the conclusion of this program, the

pharmacist will be able to:

1. Discuss recent cardiovascular literature related to pharmacy

practice

2. Apply trial results to various clinical and patient care

scenarios

3. Describe ongoing research and potential changes to the

cardiovascular landscape

Technician Objectives

At the conclusion of this program, the technician

will be able to:

1.

2.

3.

Pre-Test Questions

• Which new ticagrelor dose was approved based on the PEGASUS-TIMI 54 trial for patients 1-3 years post-ACS in combination with aspirin?

• Which of the following are limitations of the IMPROVE-IT trial?

• Both empagliflozin arms in the EMPA-REG OUTCOME Trial saw statistically significant reductions in the composite primary efficacy endpoint of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke?

• Which CHADS2 scores were underrepresented In the BRIDGE trial leading clinicians to be hesitant about applying the overall trial results to these patients?

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REVERSE-AD Background

• Dabigatran indicated for stroke prevention in atrial fibrillation, treatment of DVT/PE, and DVT prophylaxis post-THA

• Reversal of anticoagulant effect is desirable

– Clinically relevant bleeding

– Emergent procedure/surgery

• Previous data with HD, PCC, rFVIIa, FFP (results varied)

• Idarucizumab is a monoclonal antibody which binds free and thrombin-bound dabigatran

• FDA approved in October 2015

Praxbind injection (idarucizumab) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2015.

REVERSE-AD Overview

• International ongoing, Phase III, multicenter, prospective cohort study

• Two study groups– Group A: Life-threatening hemorrhage (n=51)

– Group B: Emergent procedure/surgery (n=39)

• Intervention– 5 g of IV idarucizumab as two 50-ml infusions no more than 15

minutes apart

• Outcomes– Primary: Maximum percentage reversal of anticoagulation effect

within 4 hours plasma based coagulation assays (dTT or ECT)• At 1, 2, 4, 12, 24 hours

– Secondary: Clinical outcomes regarding efficacy and safety• Assessed by treating clinicians

Pollack CV, et al. N Engl J Med. 2015;373(6):511-20.

REVERSE-AD Demographics

Group A (n = 51) Group B (n = 39)

Age, yr (median) 77.0 76.0

Male, (%) 63 46

Weight, kg (median) 70.5 73.0

Creatinine Clearance -no.(%)

<30 ml/min

30 to <50 ml/min

50 to <80 ml/min

≥80 ml/min

5 (10)

14 (27)

16 (31)

6 (12)

7 (18)

6 (15)

11 (28)

9 (23)

Dose of Dabigatran - no.(%)

150mg BID

110mg BID

75mg BID

14 (27)

34 (67)

1 (2)

15 (38)

24 (62)

0 (0)

Time since last dose

Median

no.(%)

<12hr

12 to <24hr

24 to <48hr

≥48hr

15.2

17 (33)

21 (41)

12 (24)

1 (2)

16.6

15 (38)

10 (26)

10 (26)

4 (10)

Type of bleed - no.(%)

Intracranial

Traumatic

Gastrointestinal

Other

18 (35)

9 (18)

20 (39)

1 (22)

-

-

-

-Pollack CV, et al. N Engl J Med. 2015;373(6):511-20.

REVERSE-AD Results

dTT ECT


REVERSE-AD Results

• Secondary Outcomes– Time to cessation of bleeding (Group A)

• Median of 11.4 hours

– Major intra- or post-operative bleeding (Group B)• 36 patients underwent procedures

– Normal hemostasis (91.7%)

– Mildly abnormal hemostasis (5.6%)

– Moderately abnormal hemostasis (2.8%)

– 5 thrombotic complications• Events occurred 2-26 days post-idarucizumab

• No patient was on anticoagulation at the time of the event

– 18 deaths • 9 in each group

• 5 fatal bleeding events


REVERSE-AD

• Limitations

– No control group

– Physician discretion on cessation of bleeding

– Over 50% of patients had blood products

administered

– Median of 15.4 hours since last dabigatran dose

was administered

– Lack of applicability of lab tests to everyday

clinical practice


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REVERSE-AD – Key Points

• Idarucizumab safely and effectively reversed dabigatran-induced anticoagulation– Rebound dabigatran effect seen at ~24 hours after

idarucizumab

• External validity to institutions without dTT or ECT difficult– Institution standardization (dTT vs. ECT vs. aPTT)

• Must consider time from last dose and renal function on whether to utilize idarucizumab

• Full REVERSE-AD trial forthcoming in next 1-2 years

• Cost = ~$2000 per 5g dose


ANNEXA-A/R Background

• Rivaroxaban and apixaban approved for stroke prevention in atrial fibrillation, treatment of DVT/PE, and DVT prophylaxis post-THA/TKA

– Rivaroxaban also approved for secondary VTE prevention

• Reversal of anticoagulant effect is desirable

– Clinically relevant bleeding

– Emergent procedure/surgery

• Andexanet Alfa is a recombinant-modified factor Xadecoy protein binding direct/indirect Xa inhibitors

– Enoxaparin

Siegal DM, et al. N Engl J Med 2015;373:2413-2424 .

ANNEXA-A/R Overview

• Randomized, double-blind, placebo-controlled trial or healthy volunteers

• Study groups/Intervention– ANNEXA-A Dosing (n=65):

• Apixaban 5 mg BID x 3.5 days then 400 mg bolus or 400 mg bolus + 4 mg/min for 120 min

– ANNEXA-R Dosing (n=80):• Rivaroxaban 20 mg daily x 4 days then 800 mg bolus or 800 mg

bolus + 8 mg/min for 120 min

• Outcomes– Primary: Mean percent change in anti–factor Xa activity

– Secondary: Thrombosis and bleeding


ANNEXA-A/R Demographics

Apixaban Rivaroxaban

Bolus Only Bolus + Infusion Bolus Only Bolus + Infusion

Andexanet

(n=24)

Placebo

(n=9)

Andexanet

(n=24)

Placebo

(n=8)

Andexanet

(n=27)

Placebo

(n=14)

Andexanet

(n=26)

Placebo

(n=13)

Median Age 60 58 56 58.5 56 53.5 56 57

Female (%) 45.8 33.3 29.2 37.5 33.3 42.9 42.3 46.2

Caucasian

(%)100 100 87.5 100 81.5 71.4 76.9 61.5

Mean

Creatinine0.8 0.8 0.9 0.9 0.9 0.8 0.9 0.9

ANNEXA-A/R Results

• Efficacy

– Bolus: 92-94% vs 18-21%

– Bolus + Infusion: 92-97% vs 33-42%

• Safety

– No thrombotic complications

– No excess thrombin generation

– No serious or severe adverse effects

– Little immunogenicity with andexanet alfa


ANNEXA-A/R – Key Points

• Limitations– Only evaluated healthy non-bleeding patients

– Studied population does not mirror demographics in true practice

– Different doses of andexanet are necessary for apixaban and rivaroxaban

• Andexanet reversed the effects of apixaban or rivaroxabanwith 2-5 minutes after administration compared to placebo

• No serious safety effects were seen with andexanet alfa

• Currently under FDA review for approval

• ANNEXA-4 Trial– Evaluating efficacy and safety of andexanet in patients with factor

Xa inhibitor- or enoxaparin–associated acute major bleeding


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Extended DAPT Background

• Millions of coronary stents are implanted annually– Drug-eluting stents (DES) exhibit increased rates of stent

thrombosis

– Recommendations for DAPT with DES range from 6-12 months

• Previous literature suggests continuing DAPT past 12 months reduces rates of MI weighed against increased bleeding

• Previous guidelines have recommended 12 months of DAPT after DES implantation– Optimal duration unknown

Mauri L, et al. N Engl J Med. 2014;371(23):2155-66.

Levine GN, et al. Circulation. 2011;124(23):e574-651.

DAPT Overview

• International, multicenter, randomized, placebo-controlled trial

• Two study groups– Continued thienopyridine for 30 months total (n=5,020)

• Clopidogrel ~66%

• Prasugrel ~33%

– Placebo (n=4,941)

• Outcomes– Primary: Stent thrombosis and major adverse

cardiovascular/cerebrovascular events

– Secondary: Moderate or severe bleeding according to GUSTO criteria

Mauri L, et al. N Engl J Med. 2014;371(23):2155-66.

DAPT Results

Continued

Thienopyridine

PlaceboP-Value

GUSTO Severe or Moderate 2.5% 1.6% 0.001

GUSTO Moderate 1.7% 1.0% 0.004

GUSTO Severe 0.8% 0.6% 0.15Mauri L, et al. N Engl J Med. 2014;371(23):2155-66.

DAPT Score

• DAPT ≥ 2

– NNB: 34

– NNH: 272

• DAPT <2

– NNB: 153

– NNH: 64

Yeh RW, et al. JAMA. 2016;315(16):1735-49.

DAPT Score

Yeh RW, et al. JAMA. 2016;315(16):1735-49.

DAPT – Keypoints

• Trial corroborated previous data from observational trials

• Only enrolled patients who tolerated 12 months of DAPT

• Not generalizable to other DES types– ~75% had everolimus or paclitaxel-eluting stents

• Ticagrelor was not utilized in the trial– PEGASYS

• 2016 ACC/AHA Guideline Focused Update on Duration of DAPT– Consider use of DAPT Score to stratify patients

– DAPT continuation given IIb recommendation

Levine GN, et al. J Am Coll Cardiol. 2016. pii: S0735-1097(16)01699-5. [Epub ahead of print]

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PEGASUS-TIMI 54 Overview

• International, multicenter, randomized, placebo-controlled trial

• Three study groups with MI 1-3 years prior to randomization– Ticagrelor 90 mg BID (n=7,050)

– Ticagrelor 60 mg BID (n=7,045)

– Placebo (n=7,067)

• Outcomes– Primary Efficacy: Composite of cardiovascular death, myocardial

infarction, or stroke

– Primary Safety: TIMI major bleeding

– Secondary: CV death, death, intracranial hemorrhage, and fatal bleeding

Bonaca MP, et al. NEJM. 2015;372(19):1791-1800.

PEGASUS-TIMI 54 Baseline

Characteristics


PEGASUS-TIMI 54 Results


PEGASUS-TIMI 54 – Key Points

• Trial corroborated previous data from observational trials

• Previous patient bleeding history was not described

• Enrolled high risk patients – applicability to low risk population?

• Must assess bleeding risk vs. the benefit of extended DAPT– NNT: 60 mg: 79; 90 mg: 84

– NNH: 60 mg: 81; 90 mg: 64

• Ticagrelor 60 mg BID dosing approved for ACS post-12 months of 90 mg BID


Assessment Question #1

Which new ticagrelor dose was approved based

on the PEGASUS-TIMI 54 trial for patients 1-3

years post-ACS in combination with aspirin?

A. 60 mg PO daily

B. 90 mg PO daily

C. 60 mg PO BID

D. 90 mg PO BID

EMPA-REG OUTCOME Background

• Diabetes increases risk of MI, HF, PAD, CVA, and mortality 2-4 fold

• Diabetes is one of the most controllable CV disease risk factors

• FDA mandates CV outcome analysis with new agents for type II DM– Mixed outcomes depending on drug class

• Rosiglitazone

• SGLT-2 inhibitors are newest class of agents for type II DM

Fox CS. Trends Cardiovasc Med. 2010;20(3):90-5.

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EMPA-REG OUTCOME Overview

• International, multicenter, randomized, double-blind, placebo-controlled trial

• Three study groups– Empagliflozin 10 mg daily

– Empagliflozin 25 mg daily

– Placebo

• Outcomes– Primary efficacy: Composite of death from CV causes, non-

fatal MI or stroke

– Secondary efficacy : Primary outcome + hospitalization for unstable angina

– Secondary safety: Adverse events

Zinman B, et al. N Engl J Med. 2015;373(22):2117-28.

EMPA-REG OUTCOME Results






EMPA-REG OUTCOME – Key Points

• First diabetes agent that reduced CV mortality and all cause mortality– Only in composite group, not each arm separately

– Possibly due to BP reduction (4 mmHg over placebo) or HDL elevation

– Advisory panel recommended labeled indication for CV mortality

• Most patients did not achieve goal A1c

• Lower rates of UTIs compared to other SGLT-2 studies

• Affect in acute setting unknown– Outpatient use

• Future Trials– CANVAS (canagliflozin)

– DECLARE-TIMI 58 (dapagliflozin)



Both empagliflozin arms in the EMPA-REG OUTCOME

Trial saw statistically significant reductions in the

composite primary efficacy endpoint of death from

cardiovascular causes, nonfatal myocardial infarction,

or nonfatal stroke?

A. True

B. False

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BRIDGE Background

• AF increases the risk of TE, which can lead to stroke, MI, & TIA

• Guidelines recommend bridging therapy with UFH or LMWH in:– AF with a mechanical heart valve

– History of stroke

– CHA2DS2-VASc score of at least 2

• Limited evidence on the use of bridging in NVAF

• Bridging Anticoagulation in Patients who Require Temporary Interruption of Warfarin Therapy for an Elective Invasive Procedure or Surgery (BRIDGE)– Forgoing bridging altogether non-inferior to bridging for the

prevention of perioperative arterial TE

– Superior to bridging in regard to the outcome of major bleeding

Douketis JD, et al. N Engl J Med. 2015;373(9):823-833.

BRIDGE Overview

• Randomized, double-blind, placebo-controlled trial

• Adult patients with chronic AF or flutter on warfarin and undergoing elective procedure

• At least one CHADS2 stroke risk factors: CHF or left ventricular dysfunction, HTN, age of 75 years or older, DM, or previous ischemic stroke, systemic embolism, or TIA

• Warfarin held 5 days prior to procedure

• Placebo subQ injections BID vs dalteparin 100 units/kg subQ BID

• Primary outcome: stroke, TIA, systemic embolism

• Safety: bleeding


BRIDGE Overview

Study Design


BRIDGE Results

• Mean CHADS2: 2.3

• 34% of patients were on aspirin therapy

– 59% continued this medicine peri-operatively

• 84% of procedures classified as “minor”


BRIDGE Key Points

• Patients requiring temporary discontinuation of warfarin therapy for elective invasive procedures do not require bridging therapy– Patients undergoing minor procedures with CHADS2 <4 do

not require bridging

– Patients with mechanical heart valves still require bridging

• Bridging increased bleeding risk without benefit of TE risk reduction

• Use of CHADS2 vs CHA2DS2VASc for stroke risk estimation

• Dalteparin not uniformly used in practice

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Which CHADS2 scores were underrepresented In the BRIDGE trial leading clinicians to be hesitant about applying the overall trial results to these patients?

A. 2

B. 3

C. 4

D. 5

ODYSSEY/OSLER Background

• PCSK9 inhibitors are a new class of lipid-lowering agents given as monthly or bimonthly subQinjection– Alirocumab

(Praluent®) approved in July 2015

– Evolocumab(Repatha™) approved in August 2015

– Bococizumabcurrently in phase 3 trials

ODYSSEY Overview

• Multicenter, randomized, double-blind, placebo-controlled study

• Heterozygous familiar hypercholesterolemia

• CHD or CHD risk equivalent

• LDL-C level ≥ 70 mg/dL

• Receiving maximum tolerated dose of statin therapy

• Received subQ alirocumab (150 mg) or placebo every 2 weeks for 78 weeks in a 2:1 ratio

• Primary efficacy: % change in LDL-C at week 24

• Post-hoc: major CV events

Robinson JG, et al. N Engl J Med. 2015;372:1489-1499.

ODDYSSEY Results

LDL-C reduction:

Week 24: -61% vs 0.8%*

Week 78: -52% vs 3.6%*

*p<0.0001

Post—hoc analysis:

1.7% vs 3.3 % (p=0.02)

ADR

Myalgias: 5.4% vs 2.9%

(p<0.05)

Calculated LDL cholesterol levels over time

Robinson JG, et al. N Engl J Med. 2015;372:1489-1499.

OSLER Overview

• OSLER 1 and 2 parent trials; multicenter, randomized, open-label controlled studies

• Variety of patients enrolled• All with LDL-C level ≥ 75 mg/dL

• +/- Heterozygous familiar hypercholesterolemia

• +/- background therapies

• +/- statin intolerance

• Evolocumab + standard therapy or standard therapy alone in a 2:1 ratio• 420 mg monthly or 140 mg every 2 weeks

• 60% LDL-C reduction in both regimens

• End points: adverse events, % LDL-C change, CV events

Sabatine MS, et al. N Engl J Med. 2015; 372(16)1500-9.

OSLER Results

Week 44:

LDL-C: 61% reduction

Non-HDL: 52%

Apo B: 47.3%

TG: 12.6%

*P< 0.001

CV events

0.95% vs 2.18%

(HR 0.47; 95% CI = 0.28 to 0.78; P = 0.003)

ADR

Neurocognitive: 0.9% vs 0.3%

Cumulative incidence of cardiovascular events in OSLER studies

Sabatine MS, et al. N Engl J Med. 2015; 372(16)1500-9.

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ODYSSEY/OSLER KeyPoints

• Both studies demonstrated additional 48-53% reduction of CV events when added to statin therapy

• Support notion the “lower is better” notion

• PCSK9 inhibitors seen as a new frontier in lipid management

• Role in patients with “resistant hyperlipidemia”

• Annual cost of therapy:• Alirocumab (Praluent®): $13,440

• Evolocumab (Repatha™): $13,015

IMPROVE-IT Background

• Statins widely used to reduce LDL cholesterol and the risk of CV events

• Residual CV risk despite optimal dosing and safety concerns of high-dose statins prompted additional therapy investigation

• Ezetimibe reduces cholesterol absorption from the intestine

• When added to statin therapy, patients can have an additional LDL cholesterol reduction of 24%

• Clinical outcomes and benefits of this therapy combination was unknown

Cannon CP, et al. N Engl J Med. 2015; 372:2387-2397

IMPROVE-IT Overview

• Randomized, placebo-controlled, blinded, parallel study design

• Population:– Hospitalization for STEMI, NSTEMI/UA <10 days

– Age ≥50 years

– ≥1 high-risk feature: new ST changes, positive troponin, diabetes mellitus, prior MI, peripheral arterial disease, cerebrovascular accident, prior coronary artery bypass grafting (CABG) >3 years, and/or multivessel coronary artery disease, LDL-C 50-125 mg/dl (50-100 mg/dl if prior lipid-lowering therapy)

• Two study groups– Simvastatin 40 mg (moderate intensity statin)

– Simvastatin 40 mg + ezetimibe 10 mg

• Outcomes– Primary efficacy: Composite of death from CV disease, major coronary event,

or nonfatal stroke

– Secondary efficacy: Composite death from any cause, adverse events


IMPROVE-IT Results

• Simvastatin-only– Baseline LDL: 95 mg/dl � 69.5 mg/dl

– HDL: increased by 0.6 mg/dl

• Ezetimibe + simvastatin– Baseline LDL: 95 mg/dl � 53.7 mg/dl

– Triglycerides: lowered by 16.7 mg/dl

• Primary endpoint (ezetimibe/simvastatin vs simvastatin only):– 32.7% vs 34.7% (HR 0.94, 95% CI 0.89-0.99; p=0.016)

– NNT: 50 patients to prevent one event in 6 years

• No difference seen in cancer incidence, myopathy (0.2% vs 0.1%, p=0.32), or transaminitis

• After ~6 years, 42% of patients in each group had discontinued the study medication– Discontinued due to adverse drug effect: 10.1% vs. 10.6%


IMPROVE-IT Key Points

• Ezetimibe 10mg/simvastatin 40mg is superior to simvastatin 40mg alone in reducing CV events (in post high-risk ACS patients)

• After ~6 years, 42% of patients in each group had discontinued the study medication

• Patients with an LDL-cholesterol <125 mg/dl were included in the study as, at the time of the study design, an LDL-cholesterol of <70 mg/dl was included in guidelines

• The findings support a “lower is better” hypothesis with LDL cholesterol– Correlation between degree of LDL-C lowering and clinical

benefit, without adverse effects


Comparative LDL-C Trials

Hassan M. Glob Cardiol Sci Pract. 2015; 2015(2):20.

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Which of the following are limitations of the

IMPROVE-IT trial?

A. Statin intensity studied does not match current

guidelines

B. Lower incidence of adverse effects seen with

simvastatin/ezetimibe

C. Large amounts of study drug discontinuation

D. Both A and C

HOPE-3 Background

• Previous landmark trials have studied the impact of cholesterol lowering in patients with high CV risk

• The Heart Outcomes Prevention Evaluation (HOPE)-3 trial was conducted specifically among persons who:

– Did not have CV disease

– Were at intermediate risk of CV disease

– Of various ethnic backgrounds

Yusuf S, et al. N Engl J Med. 2016; 374:2021-2031

HOPE-3 Overview

• Double-blind, randomized, placebo-controlled trial

• Population:• Intermediate risk men and women without CV disease

• Men ≥ 55 years of age; Women ≥65 years of age

• 2-by-2 factorial design• Rosuvastatin 10 mg + candesartan/HCTZ 16 mg/12.5 mg daily

• Rosuvastatin 10 mg + placebo daily

• Placebo + combination pill

• 2 placebos daily

• Outcomes• Co-primary outcomes (cardiovascular related death, non-fatal stroke,

or non-fatal myocardial infarction)

• Secondary safety: Adverse events


HOPE-3 Results

• Baseline LDL-C was 128 mg/dL and mean blood pressure (BP) was 138/82 mmHg

• After a study duration of 5.6 years:– Lowering of mean LDL-C by 35 mg/dL in the rosuvastatin group

compared to placebo

– Co-primary outcomes occurred significantly less frequently with rosuvastatin than placebo (3.7% versus 4.8 %; hazard ratio, 0.76; P=0.002)

– No difference in the incidence of diabetes was found in the rosuvastatin versus placebo group

– Myalgia symptoms were significantly higher (5.8% versus 4.7%; P=0.005) in statin group

– Reduction in mean SBP/DBP by 6/3 mmHg with anti-hypertensivescompared to placebo, however no significant benefit in reducing CV events observed


HOPE-3 Key Points

• Rosuvastatin 10 mg daily is more effective in preventing CV events than candesartan/HCTZ 16 mg/12.5 mg daily in relatively low-risk and ethnically diverse populations

• Although antihypertensives have been shown to reduce CV-events in patients with a systolic BP >160 mmHg, its role in intermediate risk persons with lower BP remains unclear – Use of higher antihypertensive doses may have provided

additional patient benefit in the study

• Results of the study support a risk-based approach to statin use, as opposed to an LDL-goal directed approach


SPRINT Background

• Hypertension is prevalent in patients >60 years of age in the U.S.

• BP control reduces the risk of CV disease outcomes (stroke, MI, HF)

• Optimal systolic blood pressure (SBP) target is uncertain• Goal <150 mm Hg vs <140 mm Hg vs <120 mm Hg?

• 2007 NHLBI expert panel hypothesized a lower SBP goal would reduce clinical events compared to standard goal

• The Systolic Blood Pressure Intervention Trial (SPRINT) compared the benefit of SBP <120 mm Hg vs <140 mm Hg

Wright JT Jr, et al. N Engl J Med. 2015;373(22):2103-2116.

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SPRINT Overview

• Randomized, controlled, open-label trial

Inclusion criteria Exclusion criteria

• Age ≥50 years

• Hypertension with SBP 130-

180 mm Hg

• At least one risk factor for

heart disease including

subclinical CV disease, CKD, 10-

year Framingham Risk Score

CV disease ≥15%, age >75

years

• Diabetes mellitus

• History of stroke

• eGFR <20 ml/min/1.73 m2 or end-

stage renal disease

• CV event, procedure, or

hospitalization for UA within last 3

months

• Symptomatic HF within the past 6

months or LVEF <35%

• (Others)


SPRINT Overview

• Thiazide-type diuretics (encouraged 1st

line)

• Chlorthalidone encouraged as primary

• Loop diuretics (for participants with advanced CKD)

• Beta-adrenergic blockers (for those with CAD)

• Amlodipine as the preferred calcium-channel blocker

• Azilsartan and azilsartan combined with chlorthalidone

• Primary composite outcome: MI, other acute coronary syndromes, stroke, HF, or death from cardiovascular causes

• Secondary outcomes: safety, adverse events

Eligible

Participants

SBP < 140 mm

Hg

SBP < 120 mm

Hg


SPRINT Results

• Study terminated early due to overwhelming benefit

• Primary endpoints significantly lower in intensive BP arm – 5.2% vs. 6.8%; HR 0.75, 95% CI [0.64-0.89]; p < 0.0001

– Rate of MI, ACS, & stroke similar in each group

– CHF: 1.3% vs. 2.1%, p = 0.002

– CV death: 0.8% vs. 1.4%, p = 0.0005

• Secondary endpoints– GFR decline similar in each arm

– Mortality : 3.3% vs. 4.5%, p = 0.0003

– Hypotension: 2.4% vs. 1.4%, p = 0.001

– Syncope: 2.3% vs. 1.7%, p = 0.05

– Hyponatremia: 3.8% vs. 2.1%, p < 0.001


SPRINT Key Points

• BP reading: average of 3 office readings taken with proper cuff size, 5 minutes of rest before measurement, and no conversation

• Results add to “how low should we go” discussion on BP target

• Hypertension treatment should be tailored based on underlying risk of CV outcomes (instead of absolute values alone)

• A similar approach has occurred in lipid management

• Results are contrary to ACCORD trial findings– Smaller study, diabetic patients

• Based on study population, results apply to ~1 in 12 Americans

• Risk (side effects) vs benefit should be individuated in each patient


Take Home Points Resources & References

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Speaker Contact Information

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