1

Background

Chronic angina affects approximately 10.2 million Americans and has detrimental effects on the quality of life of those it afflicts . Current conventional medical therapy recommendations utilize coronary revascularization and antianginal drug therapy including beta blockers, long-acting nitrates and calcium channel blockers (CCB) . Despite these therapeutic modalities, patients often continue to experience chronic refractory angina.

In 2006, ranolazine was approved for the adjunct treatment of chronic angina and subsequently approved as monotherapy in 2008 . Ranolazine is a novel antianginal medication whose mechanism of action has not been fully elucidated . However, ranolazine does exhibit its antianginal effect without significant changes in hemodynamics . This unique feature is due to blockage of late sodium current. In ischemic myocytes, these channels increase intracellular sodium resulting in intracellular calcium overload. Intracellular calcium overload during diastole is believed to directly increase diastolic wall tension and perpetuate myocardial ischemia . Thus, by blocking the late sodium current, ranolazine decreases angina through a different mechanism than conventional antianginal drug therapy.

Within our institution, prior to initiation of ranolazine therapy, patients must have ≥3 angina episodes per week and are prescribed maximally tolerated conventional antianginal drug therapy including beta blockers and CCB. Antianginal drug therapy is considered to be maximized if the blood pressure is <130/80 mmHg and the heart rate is <70 beats per min (bpm), unless limited by intolerable side effects. Additionally, patients must receive long-acting nitrate therapy unless not tolerated. These criteria innately select a refractory angina population that may benefit from the addition of this novel agent. We describe the use of ranolazine in patients identified at our institution meeting the above criteria and who had pre- and postranolazine angina symptoms documented.

2

Results

2.1

Population

A total of 18 patients were identified and are described in this case series. Preranolazine characteristics of those patients are listed in Table 1 . All patients were white males with a median age of 66 years [interquartile range (IQR) 61–78]. Fifteen (83%) patients had a preexisting hypertension diagnosis. Prior to ranolazine, the median systolic blood pressure was 116.2 mmHg (IQR 105.3–124.9), diastolic blood pressure was 61.8 mmHg (IQR 57.5–69.1) and heart rate was 65 bpm (IQR 61.5–68.9). Optimal hemodynamic control was maintained after ranolazine initiation, with resulting median systolic blood pressure of 115 mmHg (IQR 105–123), diastolic blood pressure of 61 mmHg (IQR 56–68) and heart rate of 66 bpm (IQR 60–69). The rate–pressure product for each patient is reported in Table 2 . The percentage of conventional antianginal drug therapy used was as follows: beta blockers 94% ( n =17), CCB 61% ( n =11) and long-acting nitrates 83% ( n =15) ( Table 1 ). Two or more conventional antianginal agents were used in 16 (89%) of the patients. Additionally, 94% of the patients were taking both HMG CoA reductase inhibitor (statin) and antiplatelet therapy, and 78% were prescribed either an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) prior to ranolazine use.

Table 1

Preranolazine patient characteristics

Characteristic	n =18
Age, median (IQR), years	66 (61–78)
Male, no. (%)	18 (100)
White, no. (%)	18 (100)
Past medical history, no. (%)
Hypertension	15 (83)
Diabetes mellitus	10 (55)
PCI or CABG prior to study	18 (100)
Vitals prior to ranolazine therapy, median (IQR)
Systolic blood pressure, mmHg	116.2 (105.3–124.9)
Diastolic blood pressure, mmHg	61.8 (57.5–69.1)
Heart rate, bpm	65 (61.5–68.9)
Antianginals, no. (%)
Beta blocker	17 (94)
Metoprolol tartrate ( n =10)
Metoprolol succinate ( n =5)
Carvedilol ( n =2)
Calcium channel blocker	11 (61)
Amlodipine ( n =7)
Felodipine ( n =3)
Diltiazem ( n =1)
Long-acting nitrate	15 (83)
Isosorbide mononitrate ( n =10)
Isosorbide dinitrate ( n =3)
Nitroglycerin patch ( n =2)
Two or more antianginals	16 (89)
Other medications, no. (%)
Statin	17 (94)
Rosuvastatin ( n =7)
Simvastatin ( n =6)
Pravastatin ( n =4)
Antiplatelet	17 (94)
Aspirin plus clopidogrel ( n =13)
Aspirin ( n =3)
Clopidogrel ( n =1)
ACE inhibitor or ARB	14 (78)
Lisinopril ( n =12)
Enalapril ( n =1)
Valsartan ( n =1)

CABG=coronary artery bypass graft; PCI=percutaneous coronary intervention.

Table 2

Clinical information for 18 patients treated with ranolazine

Case	Age	Ranolazine dose (mg; twice a day)	Time to follow-up evaluation (days)	Left main disease	Number of coronary vessel territories involved	LVEF <40%	Rate–pressure product		CCS angina grade		Angina episodes per week		SLNTG use per week		Corrected QT
							Pretherapy	Posttherapy	Pretherapy	Posttherapy	Pretherapy	Posttherapy	Pretherapy	Posttherapy	Pretherapy	Posttherapy
1	79	500	20	Yes	3	No	7.1	10.9	III	II	56	5	–	–	445	455
2	65	500	14	No	3	No	8.0	7.7	II	I	21	1	21	3	433	408
3	56	1000	70	No	3	No	6.6	6.2	IV	II	7	0	21	0.3	–	443
4	78	500	49	No	2	Yes	8.3	6.4	II	I	3	0.3	4	0	408	389
5	67	500	35	No	3	No	7.7	8.2	III	III	14	14	14	14	402	444
6	87	1000	49	No	3	No	8.4	7.8	III	I	14	0	14	0	–	412
7	67	1000	106	No	3	No	8.6	8.0	IV	II	7	0	0.5	0	–	415
8	69	1000	63	No	3	Yes	6.0	5.7	IV	III	21	12	63	18	413	421
9	60	500	18	Yes	3	No	6.0	6.5	II	I	14	0	14	0	–	414
10	62	500	45	Yes	3	No	7.5	6.8	II	I	3	0	6	0	414	467
11	74	1000	84	No	3	No	10.2	10.0	III	I	105	0	0	0	–	409
12	62	500	133	Yes	3	Yes	6.7	7.2	III	II	21	4	–	–	444	434
13	85	500	28	Yes	3	No	7.0	8.1	II	II	3	2	–	–	–	450
14	49	500	12	Yes	3	No	6.7	6.4	III	III	14	14	0	0	435	494
15	64	500	42	No	3	No	7.9	7.7	III	II	14	14	0	0	–	419
16	78	500	42	No	2	No	6.7	6.7	II	I	7	0	1	0	436	398
17	80	500	92	No	2	No	7.7	7.3	III	I	14	0	–	–	403	417
18	56	1000	28	Yes	3	No	6.6	7.5	IV	II	56	28	42	21	454	407

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