Trial Outcomes & Findings for Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina (NCT NCT01396395)

Results Overview

Myocardial ischemia attack was evaluated by 24-hour Holter monitoring based on the following criteria: 0.08 seconds after the J point in electrocardiogram (ECG) or compared with baseline levels, ST-segment with horizontal or downward sloping down greater than or equal to (\>=) 0.1 millivolts (mV), and lasted for \>= 1 minute, and at least 1 minute of interval with another ischemic attack, as one array myocardial ischemia.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

402 participants

Primary outcome timeframe

At Week 12

Results posted on

2016-04-14

Participant Flow

4 subjects randomized to standard+nicorandil group were included in standard group for safety analysis as they did not receive nicorandil. 1 subject randomized to standard group was included in standard+nicorandil group as nicorandil was received. Thus, safety set have 197 and 205 in Standard+nicorandil and standard group, respectively.

Participant milestones

Participant milestones
Measure	Standard Treatment Plus Nicorandil The subjects received nicorandil 5 milligram (mg) tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors (ACEIs) as permitted by disease condition or as per standard local practices or prescribed per discretion of the investigators.	Standard Treatment The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Overall Study STARTED	200	202
Overall Study Safety Analysis Set	197	205
Overall Study COMPLETED	160	175
Overall Study NOT COMPLETED	40	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Standard Treatment Plus Nicorandil The subjects received nicorandil 5 milligram (mg) tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors (ACEIs) as permitted by disease condition or as per standard local practices or prescribed per discretion of the investigators.	Standard Treatment The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Overall Study Withdrawal by Subject	10	12
Overall Study Protocol Violation	3	1
Overall Study Adverse Event	10	2
Overall Study Lost to Follow-up	17	11
Overall Study Other	0	1

Baseline Characteristics

Research on Nicorandil Treatment of Patients Diagnosed as CHD (Coronary Heart Disease) With Stable Angina

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Standard Treatment Plus Nicorandil n=200 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies ( aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.	Standard Treatment n=202 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.	Total n=402 Participants Total of all reporting groups
Age, Continuous	61.4 years STANDARD_DEVIATION 10.16 • n=5 Participants	60.8 years STANDARD_DEVIATION 9.94 • n=7 Participants	61.1 years STANDARD_DEVIATION 10.04 • n=5 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	74 Participants n=7 Participants	132 Participants n=5 Participants
Sex: Female, Male Male	142 Participants n=5 Participants	128 Participants n=7 Participants	270 Participants n=5 Participants

PRIMARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.

Myocardial ischemia attack was evaluated by 24-hour Holter monitoring based on the following criteria: 0.08 seconds after the J point in electrocardiogram (ECG) or compared with baseline levels, ST-segment with horizontal or downward sloping down greater than or equal to (\>=) 0.1 millivolts (mV), and lasted for \>= 1 minute, and at least 1 minute of interval with another ischemic attack, as one array myocardial ischemia.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=141 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=150 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Number of Myocardial Ischemia Attacks in 24 Hours	2.3 ischemic attacks per 24 hours Standard Deviation 8.46	3.8 ischemic attacks per 24 hours Standard Deviation 18.02

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure. Analysis was done only for subjects with myocardial ischemia attack.

The total myocardial ischemic burden was defined as the product of the decrease, total array and total time of ST-segment in symptomatic and asymptomatic myocardial ischemia subjects within 24 hours.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=133 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=146 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Change From Baseline in Total Myocardial Ischemic Burden at Week 12	-38.63 millimeter*minutes Standard Deviation 572.807	29.26 millimeter*minutes Standard Deviation 404.070

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure. Analysis was done only for subjects with myocardial ischemia attack.

The maximum ST- depression was evaluated from sum of all leads for all the subjects with myocardial ischemia attack. Absolute value of maximum ST-depression was used for calculation.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=133 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=146 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Change From Baseline in Maximum ST-depression at Week 12	0.25 millimeter Standard Deviation 3.598	0.36 millimeter Standard Deviation 3.563

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure. Analysis was done only for subjects with myocardial ischemia attack.

The maximum ST- depression was evaluated from sum of all leads for all the subjects with myocardial ischemia attack. The longest duration of ST segment depression of all leads for all the subjects with myocardial ischemia attack.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=133 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=146 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Change From Baseline in Longest Duration of ST Segment Depression at Week 12	-3.8 seconds Standard Deviation 37.75	3.4 seconds Standard Deviation 18.83

SECONDARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure. Analysis was done only for subjects with myocardial ischemia attack.

The percentage of subjects who experienced ischemic heart attack during the Six-minute walk test (6-MWT) were evaluated.The 6-MWT was the distance that a subject could walk in 6 minutes. Subjects were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. The 6-MWT was completed within 1-hour after wearing Holter.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=135 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=147 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Percentage of Subjects Experienced Ischemic Heart Attack During the Six-minute Walk Test	2.2 percentage of subjects	4.1 percentage of subjects

SECONDARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. "n" signifies the number of subjects evaluable for each category in each group for this outcome measure, respectively.

HRV is the degree of fluctuation in the length of the intervals between heart beats. All HRV parameters are calculated on 'normal-to-normal' (NN) inter-beat intervals (or NN intervals) caused by normal heart contractions. Standard deviation of all NN intervals (SDNN) and Standard deviation of the averages of NN intervals (SDANN) are the two time domain methods used to determine heart rate variability. Two variants of the SDNN, created by dividing the 24-hour monitoring period into 5-minute segments, are the SDNN index and the SDANN index. The SDNN index is the mean of all the 5-minute standard deviations of NN (normal RR) intervals during the 24-hour period, while the SDANN index is the standard deviation of all the 5-minute NN interval means.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=200 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=202 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Heart Rate Variability (HRV) Rate: Time Domain SDNN-24 hour (n=141, 149)	126.1 millisecond Standard Deviation 35.58	125.7 millisecond Standard Deviation 33.25
Heart Rate Variability (HRV) Rate: Time Domain SDANN index (n=141, 149)	116.9 millisecond Standard Deviation 37.44	116.7 millisecond Standard Deviation 33.65
Heart Rate Variability (HRV) Rate: Time Domain SDNN index (n=140, 147)	47.6 millisecond Standard Deviation 14.60	47.0 millisecond Standard Deviation 14.99

SECONDARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.

HRV is the degree of fluctuation in the length of the intervals between heart beats. All HRV parameters are calculated on 'normal-to-normal' (NN) inter-beat intervals (or NN intervals) caused by normal heart contractions. The HRV was evaluated based on frequency domain power-24 hours.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=140 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=147 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Heart Rate Variability (HRV) Rate: Frequency Domain Power-24 Hour	2397.0 millisecond square (ms^2) Standard Deviation 1527.37	2328.6 millisecond square (ms^2) Standard Deviation 1458.31

SECONDARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.

The number of ventricular tachycardia and premature ventricular beats that occurred within 24 hours.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=141 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=150 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Number of Arrhythmia Occurred Within 24 Hours Ventricular tachycardia	0.8 beats per 24 hours Standard Deviation 4.03	5.2 beats per 24 hours Standard Deviation 40.67
Number of Arrhythmia Occurred Within 24 Hours Premature ventricular beat	134.8 beats per 24 hours Standard Deviation 457.59	569.1 beats per 24 hours Standard Deviation 2538.17

SECONDARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.

The ECG QT dispersion was defined as the difference between the longest (QTmax) and the shortest (QTmin) QT intervals within a 12-lead ECG.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=74 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=69 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
ECG QT Dispersion	0.1298 milliseconds Standard Deviation 0.17240	0.1110 milliseconds Standard Deviation 0.15865

SECONDARY outcome

Timeframe: Baseline up to 12 Weeks

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=162 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=176 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Number of Subjects Experienced Angina Attack	48 subjects	70 subjects

SECONDARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.

The total number of times angina attacks occurred within a week (number of times/week)

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=45 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=70 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Frequency of Angina Attack	1 angina attacks per week Interval 1.0 to 2.0	2 angina attacks per week Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=26 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=48 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Number of Subjects Relieved From Angina Attack After the Consumption of Nitroglycerin	20 subjects	43 subjects

SECONDARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies the number of subjects evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=19 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=43 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Number of Nitroglycerin Tablets Consumed in a Week	1 tablets per week Interval 1.0 to 4.0	2 tablets per week Interval 1.0 to 2.0

SECONDARY outcome

Timeframe: At Week 12

Population: FAS included all randomized subjects who received at least one dose of study treatment. N (number of subjects analyzed) signifies number of subjects evaluable for this outcome measure.

The 6-MWT distance was the distance that a subject could walk in 6 minutes. Subjects were asked to perform the test at a pace that was comfortable to them, with as many breaks as they needed. The 6-MWT was completed within 1-hour after wearing Holter.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=152 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=164 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Walk Distance in Six Minute Walk (6-MWT) Test at Week 12	452.1 meters Standard Deviation 116.87	438.1 meters Standard Deviation 107.42

SECONDARY outcome

Timeframe: From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks )

Population: Safety analysis population included all the subjects who received at least one dose of the study drug. 4 subjects randomized to standard+nicorandil group were included in standard group for safety analysis as they did not receive nicorandil. 1 subject randomized to standard group was included in standard+nicorandil group as nicorandil was received.

An AE was defined as any new untoward medical occurrences/worsening of pre-existing medical condition without regard to possibility of causal relationship. SAE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs were defined as the AEs that occurred between first dose of study drug and up to 30 days after last dose that were absent before treatment or that worsened relative to pretreatment state.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=197 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=205 Participants The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation TEAEs	23 subjects	13 subjects
Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation SAEs	9 subjects	7 subjects
Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation AEs Leading to Death	1 subjects	1 subjects
Number of Subjects With Any Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Death, and AEs Leading to Discontinuation AEs Leading to Discontinuation	16 subjects	0 subjects

SECONDARY outcome

Timeframe: Baseline up to 12 Weeks

Population: Safety analysis population included all the subjects who received at least one dose of the study drug. 4 subjects randomized to standard+nicorandil group were included in standard group for safety analysis as they did not receive nicorandil. 1 subject randomized to standard group was included in standard+nicorandil group as nicorandil was received.

Compliance percent (%) was calculated by using the formula: (actual total dose divided by planned total dose) multiplied by 100. If subject compliance was less than 80% or greater than 120%, then that subject was considered as non compliant. The compliance of subjects taking nicorandil was evaluated.

Outcome measures

Outcome measures
Measure	Standard Treatment Plus Nicorandil n=191 Participants The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Number of Subjects Who Showed Compliance to Nicorandil	181 subjects	—

Adverse Events

Standard Treatment Plus Nicorandil

Serious events: 9 serious events

Other events: 12 other events

Deaths: 0 deaths

Standard Treatment

Serious events: 7 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Standard Treatment Plus Nicorandil n=197 participants at risk The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=205 participants at risk The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Nervous system disorders Dizziness	1.0% 2/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Nervous system disorders Headache	3.0% 6/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Gastrointestinal disorders Nausea	2.0% 4/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Cardiac disorders Chest pain	1.0% 2/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.49% 1/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).

Additional Information

Merck KGaA Communication Center

Merck Serono, a division of Merck KGaA

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	Standard Treatment Plus Nicorandil n=197 participants at risk The subjects received nicorandil 5 mg tablet orally three times daily for a period of 12 weeks along with one of the standard antianginal therapies (aspirin, beta-blockers, lipid lowering statins and angiotensin-converting enzyme inhibitors \[ACEIs\] as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators).	Standard Treatment n=205 participants at risk The subjects received one of the standard antianginal therapies which included but not limited to aspirin, beta blockers, lipid lowering statins and ACEIs as permitted by disease condition or as per standard local practices or prescribed per discretion of investigators.
Cardiac disorders Sudden death	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Cardiac disorders Cardiac sudden death	0.00% 0/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.49% 1/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Cardiac disorders Angina	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Cardiac disorders Supraventricular tachycardia	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Cardiac disorders Acute coronary syndrome	0.00% 0/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.49% 1/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Cardiac disorders Unstable angina	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Cardiac disorders Sick sinus syndrome	0.00% 0/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.49% 1/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Cardiac disorders Coronary artery disease	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.49% 1/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Metabolism and nutrition disorders Peripheral edema	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Metabolism and nutrition disorders Diabetic foot	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Metabolism and nutrition disorders Diabetes	0.00% 0/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.49% 1/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lymphoma	0.00% 0/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.49% 1/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Multiple myeloma	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Gastrointestinal disorders Gastric ulcer	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Gastrointestinal disorders Gastroenteritis'	0.00% 0/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.49% 1/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Gastrointestinal disorders Duodenal ulcer	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Investigations Increased blood pressure	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Renal and urinary disorders Chronic renal failure	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).
Eye disorders Glaucoma	0.51% 1/197 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).	0.00% 0/205 • From the first dose of study drug administration up to 30 days after the last dose of study drug administration (up to 16 weeks ).